Posts Tagged ‘breast cancer management’

Examples of Surgical Procedures [4.4]

Writer and Curator: Larry H. Bernstein, MD, FCAP 

It is not possible to discuss surgical procedures without a firsthand knowledge of the principles of surgical, radiation and medical oncology and the current interdisciplinary approach to the care of the patient with cancer with respect to the type of cancer, the stage, the patient health status, the preoperative preparation, the assessment of treatment for cure or of palliation, and the postoperative plan for management of the patient.

Cancer surgery has evolved over the decades from a radical ‘one size fits all’ approach to a patient-specific, cancer-specific direction, which means that surgeons rely on their multidisciplinary partners in the assessment of patients. As surgeons are frequently the first specialists involved with most solid tumors, familiarity with pre-operative imaging, pathological biopsy and patient-selection, careful surgical technique and staging are fundamental to the surgeon’s armamentarium.

Surgical resection of cancers remains the cornerstone of treatment for many types of cancers. Historically, surgery was the only effective form of cancer treatment, but developments in radiation therapy and chemotherapy have demanded that surgeons work with the other disciplines of medicine in order to achieve best results for the patient with cancer.

This type of interaction between the medical disciplines together with the supportive care groups required by cancer patients is defined as multidisciplinary care. It is now widely recognized that for optimal treatment of cancer a multidisciplinary team with the surgeon as part of this team is essential.

Surgery is effective treatment for cancer if the disease is localized. Defining the extent of the cancer before surgery has become much more accurate with modern imaging methods including computed tomography (CT), positron emission tomography (PET) scanning and high resolution ultrasound. The exploratory operation to determine the extent of disease, or attempting a ‘curative’ resection when the disease has already spread beyond the bounds of a ‘surgical’ cure, is not part of the modern surgical treatment of cancer. Oncological trained surgeons are now distinguished from more general surgeons because of the particular needs of the cancer patients.

Clinical trials are required to evaluate new treatments and treatment combinations. The struggle against the scourge of cancer has seen an explosion in basic research directed towards cancer. This academic element to cancer care is a constant feature as all those involved in cancer care endeavor to advance the understanding of the management of cancer patients.

Three main questions to consider are implied from the preceding:

What is the type of cancer?

In most cases, this requires a tissue diagnosis. In modern oncology, it is unusual or inappropriate to start treatment based on clinical diagnosis alone without tissue diagnosis. Tissue diagnosis is also important to perform molecular studies to select appropriate targeted therapies.

What is the extent of the spread of the cancer?

This is answered by staging scans including CT scans, bone scans and PET scans.

Is it curable or not curable?

This depends on the type of cancer and the presence or absence of and the extent of metastasis.

For curable cancers, rate of cure is determined by prognostic factors (for example: tumor size and nodal status in breast cancer).

For incurable cancers, duration of survival is expressed in median survival rather than in absolute time frame.

Most solid tumors require adequate and site-specific imaging. This facilitates diagnosis and staging of the primary tumor and staging for distal metastases. Not all modalities are appropriate for all sites. For example mammography using the BIRADS system and ultrasound are used in breast cancers to assess a primary breast cancer. Meanwhile, an esophageal cancer requires a CT and a low rectal cancer will be best assessed with MRI or endorectal ultrasound, while a thyroid cancer is best evaluated with neck ultrasound.

One of the biggest challenges for the surgeon is to choose the correct surgery for the correct patient and with the tumor type and biology in mind. Although surgery removes a tumor and provides further pathological information to estimate prognosis and influence adjuvant therapies, the surgery cannot cause more morbidity than the cancer and must achieve surgical goals without compromising tumor biology.

The TNM staging system (American Joint Commission on Cancer AJCC) is devised for cancers to allow an assessment of T- tumor, N- nodal metastases and M- distal metastases. The goal of having a site-specific staging system is to estimate prognosis, facilitate treatment planning including the sequence of treatments and allow comparisons of treatment for different stages. Generally, a combination of different ‘T’, ‘N’, and ‘M’ allows the cancer to be grouped into stages. Stages I-IV usually depict a tumor in the following state: Stage 1- early and superficial cancer, Stage 2- locally advanced, Stage 3- regionally advanced with lymph node metastases and Stage 4- distant metastatic disease.

Despite suggestive imaging, a cancer is not diagnosed until histopathological biopsy. Biopsies where tissue (as opposed to cells) are provided to the pathologist increase the accuracy of the pre-operative diagnosis but may not always be feasible. Biopsies may be undertaken percutaneously — for example, a core biopsy of the breast, fine needle aspiration of thyroid or endoscopically such as in gastric cancer or colon cancer.

A biopsy should confirm the tumor type, grade, may show lymphovascular invasion and in some cases, special immunohistochemical stains may be performed to assess hormone receptor status such as in breast cancer or flow cytometry may be performed to assess subtypes such as in lymphoma. Staging may also require a biopsy of draining lymph nodes.

The aims of any cancer surgery are to remove the cancer with an adequate margin of normal tissue with minimal morbidity. Clear margins have an impact on local control.  Many solid tumors require removal of the draining lymph nodes for the purpose of staging and/or to achieve local control. Surgery has become more conservative with the advent of sentinel node biopsy, and is frequently used in breast cancer and melanoma. The sentinel node biopsy is a  staging tool to predict prognosis and influence use of adjuvant therapies. Surgery is performed for cure by removing the primary cancer and lymph nodes.

When tumors are locally advanced, a neoadjuvant approach with chemotherapy, radiotherapy or targeted therapies may be important to ‘control’ the growth of a tumor, down-stage a tumor to render it operable, or because the impact of systemic disease risk may outweigh those of local control. Similarly, patients with metastatic disease may still require surgery to prevent complications of the primary tumor, such as bowel obstruction from a colon cancer.

The preceding paragraphs define the discipline of surgical oncology. In summary, surgical oncology is the involvement of a specialty trained surgeon as part of a multidisciplinary team program, the use of appropriate surgery in an adequately staged patient and the involvement of the surgeon in academic programs particularly involved with clinical trials.

The use of effective techniques in the operating theater, the careful management of the patient undergoing surgery and supportive post-operative care are similar requirements to those of all other disciplines of surgery.

Communication with the patient and family, the obtaining of informed consent and the careful honest, realistic but where possible optimistic explanation of the results of surgery, are all matters of high importance to all surgical practice. However, the ability to talk sympathetically to cancer patients and their family is particularly important in the field of surgical oncology.

Multidisciplinary care

Surgeons need to understand the principles and practical consequences of the treatment offered by radiation oncologists, medical oncologists and the paramedical disciplines in order to be able to work in a team to treat cancer patients.

Principles of cancer surgery
Dr. Anita Skandarajah MBBS MD FRACS — Author
Cancer Council Australia Oncology Education Committee — Co-author

Principles of surgery for malignant disease


Surgical resection has the potential to cure early or localized cancers which have not metastasized. In general early cancers equate with curability. For example, a malignant polyp in the colon is usually curable by surgery. However, this does not always hold true. Small breast cancers may metastasize early with cure not inevitable from surgical excision alone. Screening for cancer to detect early asymptomatic cancers is now commonplace.

For screening to be effective, the test must be able to detect a common cancer at a stage when it can be cured by treatment. For screening to be effective it must be introduced on a population basis. The most effective screening program has been cervical screening where, since its introduction, there has been a substantial fall in mortality from cervical cancer in all age groups. Similar less dramatic effect is seen with breast cancer screening by mammography.

Surgeons are involved in screening programs performing endoscopies and biopsies (e.g. abnormal Barrett’s mucosa), excising polyps from the colons at colonoscopy and biopsying mammographically detected breast lesions.


A tissue diagnosis is essential prior to the creation of any management plan for a cancer patient. The consequences of many cancer treatments are so severe that only rarely can treatment be commenced without a pathological diagnosis. Tissue is obtained by fine needle aspiration, core biopsy or by excisional biopsy.

Assessment of the patient

An important early part of the assessment of a patient with cancer is to determine the psychological and physical fitness of the patient. An idea of the ‘health’ of the patient can be gained from a simple clinical assessment, the Eastern Cooperative Oncology Group (ECOG) status. Patients who are ECOG 3 or lower will usually have a poor outcome from any treatment including major surgery.

All patients undergoing major surgery need assessment of the clinical status including, where appropriate, tests of cardiac function, for example scans and angiography if indicated, respiratory status by lung function tests and renal function tests including creatinine clearance.

Staging of malignant disease

Accurate staging of the extent of disease is of great importance in formulating a treatment plan. Clinical stage is that defined by clinical examination and imaging of the patient. It is often not accurate but with the use of high quality CT and PET scanning the accuracy is improved. Pathological staging is that defined after excisional surgery by the anatomical pathologist. It is accurate in defining the extent of disease associated with a primary tumor. The staging system is varied according to the primary site of the tumor.

Rectal cancers have a long-standing clinical and pathological staging system known as the Cuthbert-Dukes staging system. Dukes A is local disease in the rectum not invading muscularis propria; Dukes B, the tumour has extended through the wall of the bowel; and Dukes C, where there is lymph node involvement. Dukes D is when distant metastases are present. The Dukes system is commonly used alongside the TNM system.

Methods of clinical staging include radiological methods such as CT, MRI and ultrasound. Within the area of nuclear medicine are PET scanning and nuclear scanning generally (e.g. bone scanning). Laparoscopy is an added staging method which detects intra-abdominal tumors.

Decision about treatment at the multidisciplinary conference

Armed with information about the diagnosis of the cancer, the extent of the disease, that is the clinical stage of the disease and the fitness of the patient, decisions can be made about the most appropriate treatment program. Ideally consultation with a multidisciplinary team occurs at this stage, however if the decision regarding surgery is straightforward, the multidisciplinary conference usually occurs after the surgery when a pathological stage has been determined. However many cancers require down-staging with radiotherapy or chemotherapy prior to surgery, and multidisciplinary consultations early are important to facilitate this process.

The provision of written information to the patient and family, with careful and repeated discussions, is necessary to ensure that the patient can give informed consent to any treatment plan offered. Patients have the right to refuse all or some of the treatment plan and they are encouraged to be part of the decision making process.

At this stage discussions regarding involvement in research projects, use of resected tissues and involvement in clinical trials need to be commenced.

Principles of operative surgical oncology

The technical issues in surgical oncology are not different from other surgical intervention. Open surgery, laparoscopic surgery, robotic surgery, ablative interventions and other technical interventions all have a place in modern surgical oncology. However some important oncological principles exist which must be followed by the surgeon for a satisfactory outcome.

Definition of curative surgery

Despite modern staging methods, occult tumor spread is still discovered by the surgeon, for example small-volume peritoneal disease or unsuspected nodal disease. Frozen section examination of the disease is necessary to confirm the diagnosis. So-called curative surgery is only performed when a total excision of the tumor is possible. The primary tumor and the associated lymph node drainage fields are excised in continuity. A measure of the adequacy of the oncological surgical operation is demonstrated by the findings on pathological examination of the specimen. The operative specimens need to be correctly orientated by the surgeon to allow the pathologist to carefully examine and interpret the specimen given to him. The key issues are:

  • whether the margins of the specimen removed are clear of tumor
  • the total number of lymph nodes excised together with the number of involved lymph nodes.
  • Standards exist for the adequacy of the surgical excision to be assessed in many tumors.

Palliative surgery

Here the operation is performed to overcome some symptom-producing consequence of the tumor either by resection or bypass. This is to remove a potentially symptomatic lesion even though a cure is known to be impossible.
Examples include the following:

In case of pyloric obstruction from an advanced cancer of the stomach, a gastrojejunostomy will provide good palliation of vomiting.

Resection of a bleeding cancer of the colon is justified even in the presence of metastases.

Many other examples exist. ‘Tailoring’ this type of surgery to the needs of the patient without undue morbidity or loss of quality of life is an important role for an oncological surgeon.

Margins of surgical excision

The degree to which normal tissues should be removed with the primary tumor is a subject constantly being researched. A universal rule is not possible to formulate. In general a margin of 2-5 cm is suggested. Particular examples follow:

For excision of melanomas the depth of excision is more important than the extent of surrounding skin. A margin of 2 cm usually suffices in contrast to the 5 cm previously practiced.

However for esophageal resection the majority of the esophagus needs to be resected because the tumor does spread up and down in the submucosal plane.

Soft tissue sarcomas may spread along aponeurotic planes so that complete excision requires the resection of the entire muscle group and fascial compartment to encompass this type of spread.

The recognition that spread of rectal cancer occurs into perirectal tissues has led to the use of the total mesorectal excision of the rectum to improve the completeness of resection.

The principle of complete local excision with an adequate margin is paramount in surgical oncology and it needs to be achieved in different ways depending on the type of tumor being resected.

Lymph node resection

Traditionally the draining lymph nodes from a primary tumor are excised with the local lesion. The main benefit of this removal is increased staging information, which will affect the decisions regarding post-operative adjuvant therapy. In some situations there may be a survival benefit from removal of early-involved lymph nodes. However prophylactic excision of uninvolved nodes does not provide a survival advantage to the patient and exposes the patient to increased morbidity from the node removal. An example is the prophylactic removal of groin lymph nodes (radical groin dissection), when these glands are not involved. This operation is nowadays not performed when the glands are clinically not involved as randomized controlled trials have shown that survival rates have not improved but the morbidity from the operation is significant. Poor skin healing and swelling of the affected leg are two such complications.


It is necessary to undertake rehabilitation of the cancer patient who has undergone major a resection. This usually involves the allied health disciplines, part of the oncology team. The type and duration of the process will vary according to the type of tumor and surgery performed.

Follow-up of patient after initial treatment

A program of follow-up is required for cancer patients after their initial treatment. This is for two main reasons. This is to observe the patient and investigate when appropriate to detect recurrent disease, which can then be treated effectively. By definition this is only likely to be useful to the patient when strong effective postoperative therapies are available which will have a real impact on the control of cancer.


The principles of surgical oncology can be applied to many of the systemic practices of surgery. In simple terms the surgeon operating on cancer patients in the 21st century must have some understanding of the malignant process, be prepared to work as part of a team and offer multidisciplinary care, communicate well with a very concerned sometimes desperate group of patients, operate with a high level of skill and perform an adequate cancer operation, help the patient rehabilitate from the treatment and finally be prepared to be involved in the advancing area of surgical science as applied to cancer patients. As God knows, surgeons cannot cure all cancers on their own.

Principles of Surgical Oncology    (Apr 08, 2009) Lawrence D. Wagman, MD, FACS

Surgical oncology, as its name suggests, is the specific application of surgical principles to the oncologic setting. These principles adapt standard surgical approaches to the unique situations that arise when treating cancer patients.

The surgical oncologist must be knowledgeable about all of the available surgical and adjuvant therapies, both standard and experimental, for a particular cancer. This enables the surgeon not only to explain the various treatment options to the patient but also to facilitate and avoid interfering with future therapeutic options.

Invasive diagnostic modalities

As the surgeon approaches the patient with a solid malignancy or abnormal nodal disease or the rare individual with a tissue-based manifestation of a leukemia, selection of a diagnostic approach that will have a high likelihood of a specific, accurate diagnosis is paramount. The advent of high-quality invasive diagnostic approaches guided by radiologic imaging modalities has limited the open surgical approach to those situations where the disease is inaccessible, a significant amount of tissue is required for diagnosis, or a percutaneous approach is too dangerous (due, for example, to a bleeding diathesis, critical intervening structures, or the potential for unacceptable complications, such as pneumothorax).

Lymph node biopsy

The usual indication for biopsy of the lymph node is to establish the diagnosis of lymphoma or metastatic carcinoma. Each situation should be approached in a different manner.

Lymphoma The initial diagnosis of lymphoma should be made on a completely excised node that has been minimally manipulated to ensure that there is little crush damage. When primary lymphoma is suspected, the use of needle aspiration does not consistently allow for the complete analyses described above and can lead to incomplete or inaccurate diagnosis and treatment delays.

Carcinoma The diagnosis of metastatic carcinoma often requires less tissue than is needed for lymphoma. Fine-needle aspiration (FNA), core biopsy, or subtotal removal of a single node will be adequate in this situation. The use of immunocytochemical analyses can be successful in defining the primary site, even on small amounts of tissue.

Head and neck adenopathy The head and neck region is a common site of palpable adenopathy that poses a significant diagnostic dilemma. Nodal zones in this area serve as the harbinger of lymphoma (particularly Hodgkin lymphoma) and as sites of metastasis from the mucosal surfaces of the upper digestive tract; nasopharynx; thyroid; lungs; and, occasionally, intra-abdominal sites, such as the stomach, liver, and pancreas. The surgical oncologist must consider the most likely source of the disease prior to performing the biopsy. FNA or core biopsy becomes a valuable tool in this situation, as the tissue sample is usually adequate for basic analysis (cytologic or histologic), and special studies (eg, immunocytochemical analyses) can be performed as needed.

Biopsy of a tissue-based mass

Several principles must be considered when approaching the seemingly simple task of taking a tissue biopsy. As each of the biopsy methods has unique risks, yields, and costs, the initial choice can be a critical factor in the timeliness and expense of the diagnostic process.

Mass in the digestive tract In the digestive tract, biopsy of a lesion should include a representative amount of tissue taken preferably from the periphery of the lesion, where the maximum amount of viable malignant cells will be present. The biopsy must be of adequate depth to determine penetration of the tumors. This is particularly true for carcinomas of the oral cavity, pharynx, and larynx.

Breast mass Although previously a common procedure, an open surgical biopsy of the breast is rarely indicated today. Palpable breast masses that are highly suspicious (as indicated by physical findings and mammography) can be diagnosed as malignant with close to 100% accuracy with FNA. However, because the distinction between invasive and noninvasive diseases is often required prior to the initiation of treatment, a core biopsy, performed either under image guidance (ultrasonography or mammography) or directly for palpable lesions, is the method of choice.

An excellent example of the interdependence of the method of tissue diagnosis and therapeutic options is the patient with a moderate-sized breast tumor considering breast conservation who chooses preoperative chemotherapy for downsizing of the breast lesion. The core biopsy method establishes the histologic diagnosis, provides adequate tissue for analyses of hormone-receptor levels and other risk factors, causes little or no cosmetic damage, does not perturb sentinel node analyses, and does not require extended healing prior to the initiation of therapy. In addition, a small radio-opaque clip can be placed in the tumor to guide the surgical extirpation. This step is important because excellent treatment responses can make it difficult for the surgeon to localize the original tumor site.

Mass in the trunk or extremities For soft-tissue or bony masses of the trunk or extremities, the biopsy technique should be selected on the basis of the planned subsequent tumor resection. The incision should be made along anatomic lines in the trunk or along the long axis of the extremity. When a sarcoma is suspected, FNA can establish the diagnosis of malignancy, but a core biopsy will likely be required to determine the histologic type and plan neoadjuvant therapy.

Specific Surgical References

Adjuvant chemotherapy after preoperative (chemo)radiotherapy and surgery for patients with rectal cancer: a systematic review and meta-analysis of individual patient data
AJ Breugom, M Swets, Jean-François Bosset, L Collette, ..CJH van de Velde
Lancet (Oncology) 2015; 16: 200-207.

Background The role of adjuvant chemotherapy for patients with rectal cancer after preoperative (chemo)radiotherapy and surgery is uncertain. We did a meta-analysis of individual patient data to compare adjuvant chemotherapy with observation for patients with rectal cancer. Methods We searched PubMed, Medline, Embase, Web of Science, the Cochrane Library, CENTRAL, and conference abstracts to identify European randomized, controlled, phase 3 trials comparing observation with adjuvant chemotherapy after preoperative (chemo)radiotherapy and surgery for patients with non-metastatic rectal cancer. The primary endpoint of interest was overall survival. Findings We analyzed data from four eligible trials, including data from 1196 patients with TNM stage II or III disease, who had an R0 resection, had a low anterior resection or an abdominoperineal resection, and had a tumor located within 15 cm of the anal verge. We found no significant differences in overall survival between patients who received adjuvant chemotherapy and those who underwent observation (hazard ratio [HR] 0·97, 95% CI 0·81–1·17; p=0·775); there were no significant differences in overall survival in subgroup analyses. Overall, adjuvant chemotherapy did not significantly improve disease-free survival (HR 0·91, 95% CI 0·77–1·07; p=0·230) or distant recurrences (0·94, 0·78–1·14; p=0·523) compared with observation. However, in subgroup analyses, patients with a tumor 10–15 cm from the anal verge had improved disease-free survival (0·59, 0·40–0·85; p=0·005, p interaction=0·107) and fewer distant recurrences (0·61, 0·40–0·94; p=0·025, p interaction=0·126) when treated with adjuvant chemotherapy compared with patients undergoing observation. Interpretation Overall, adjuvant fluorouracil-based chemotherapy did not improve overall survival, disease-free survival, or distant recurrences. However, adjuvant chemotherapy might benefit patients with a tumor 10–15 cm from the anal verge in terms of disease-free survival and distant recurrence. Further studies of preoperative and postoperative treatment for this subgroup of patients are warranted.

Breast-conserving surgery with or without irradiation in women aged 65 years or older with early breast cancer (PRIME II): a randomised controlled trial
IH Kunkler, LJ Williams, WJL Jack, DA Cameron, JM Dixon, et al.
Lancet Oncol 2015; 16: 266–73

Background For most older women with early breast cancer, standard treatment after breast-conserving surgery is adjuvant whole-breast radiotherapy and adjuvant endocrine treatment. We aimed to assess the effect omission of whole-breast radiotherapy would have on local control in older women at low risk of local recurrence at 5 years. Methods Between April 16, 2003, and Dec 22, 2009, 1326 women aged 65 years or older with early breast cancer judged low-risk (ie, hormone receptor-positive, axillary node-negative, T1–T2 up to 3 cm at the longest dimension, and clear margins; grade 3 tumor histology or lympho-vascular invasion, but not both, were permitted), who had had breast conserving surgery and were receiving adjuvant endocrine treatment, were recruited into a phase 3 randomized controlled trial at 76 centers in four countries. Eligible patients were randomly assigned to either whole-breast radiotherapy (40–50 Gy in 15–25 fractions) or no radiotherapy by computer-generated permuted block randomization, stratified by center, with a block size of four. The primary endpoint was ipsilateral breast tumor recurrence. Follow-up continues and will end at the 10-year anniversary of the last randomized patient. Analyses were done by intention to treat. The trial is registered on, number ISRCTN95889329.n Findings 658 women who had undergone breast-conserving surgery and who were receiving adjuvant endocrine treatment were randomly assigned to receive whole-breast irradiation and 668 were allocated to no further treatment. After median follow-up of 5 years (IQR 3·84–6·05), ipsilateral breast tumor recurrence was 1·3% (95% CI 0·2–2·3; n=5) in women assigned to whole-breast radiotherapy and 4·1% (2·4–5·7; n=26) in those assigned no radiotherapy (p=0·0002). Compared with women allocated to whole-breast radiotherapy, the univariate hazard ratio for ipsilateral breast tumor recurrence in women assigned to no radiotherapy was 5·19 (95% CI 1·99–13·52; p=0·0007). No differences in regional recurrence, distant metastases, contralateral breast cancers, or new breast cancers were noted between groups. 5-year overall survival was 93·9% (95% CI 91·8–96·0) in both groups (p=0·34). 89 women died; eight of 49 patients allocated to no radiotherapy and four of 40 assigned to radiotherapy died from breast cancer. Interpretation Postoperative whole-breast radiotherapy after breast-conserving surgery and adjuvant endocrine treatment resulted in a significant but modest reduction in local recurrence for women aged 65 years or older with early breast cancer 5 years after randomization. However, the 5-year rate of ipsilateral breast tumor recurrence is probably low enough for omission of radiotherapy to be considered for some patients.
Disease-free survival after complete mesocolic excision compared with conventional colon cancer surgery: a retrospective, population-based study   CA Bertelsen, AU Neuenschwander, JE Jansen, M Wilhelmsen, et al.
Lancet Oncol 2015; 16: 161–68

Background Application of the principles of total mesorectal excision to colon cancer by undertaking complete mesocolic excision (CME) has been proposed to improve oncological outcomes. We aimed to investigate whether implementation of CME improved disease-free survival compared with conventional colon resection. Methods Data for all patients who underwent elective resection for Union for International Cancer Control (UICC) stage I–III colon adenocarcinomas in the Capital Region of Denmark between June 1, 2008, and Dec 31, 2011, were retrieved for this population-based study. The CME group consisted of patients who underwent CME surgery in a centre validated to perform such surgery; the control group consisted of patients undergoing conventional colon resection in three other hospitals. Data were collected from the Danish Colorectal Cancer Group (DCCG) database and medical charts. Patients were excluded if they had stage IV disease, metachronous colorectal cancer, rectal cancer (≤15 cm from anal verge) in the absence of synchronous colon adenocarcinoma, tumor of the appendix, or R2 resections. Survival data were collected on Nov 13, 2014, from the DCCG database, which is continuously updated by the National Central Office of Civil Registration. Findings The CME group consisted of 364 patients and the non-CME group consisted of 1031 patients. For all patients, 4-year disease-free survival was 85·8% (95% CI 81·4–90·1) after CME and 75·9% (72·2–79·7) after non-CME surgery (log-rank p=0·0010). 4-year disease-free survival for patients with UICC stage I disease in the CME group was 100% compared with 89·8% (83·1–96·6) in the non-CME group (log-rank p=0·046). For patients with UICC stage II disease, 4-year disease-free survival was 91·9% (95% CI 87·2–96·6) in the CME group compared with 77·9% (71·6–84·1) in the non-CME group (log-rank p=0·0033), and for patients with UICC stage III disease, it was 73·5% (63·6–83·5) in the CME group compared with 67·5% (61·8–73·2) in the non-CME group (log-rank p=0·13). Multivariable Cox regression showed that CME surgery was a significant, independent predictive factor for higher disease-free survival for all patients (hazard ratio 0·59, 95% CI 0·42–0·83), and also for patients with UICC stage II (0·44, 0·23–0·86) and stage III disease (0·64, 0·42–1·00). After propensity score matching, disease-free survival was signifi cantly higher after CME, irrespective of UICC stage, with 4-year disease-free survival of 85·8% (95% CI 81·4–90·1) after CME and 73·4% (66·2–80·6) after non-CME (log-rank p=0·0014). Interpretation Our data indicate that CME surgery is associated with better disease-free survival than is conventional colon cancer resection for patients with stage I–III colon adenocarcinoma. Implementation of CME surgery might improve outcomes for patients with colon cancer.

Biomolecular and clinical practice in malignant pleural mesothelioma and lung cancer: what thoracic surgeons should know
I Opitza, R Bueno, E Lim, H Pass, U Pastorino, M Boeri, G Rocco, et al.
European J Cardio-Thor Surg 46(2014):602–606

Today, molecular-profile-directed therapy is a guiding principle of modern thoracic oncology. The knowledge of new biomolecular technology applied to the diagnosis, prognosis, and treatment of lung cancer and mesothelioma should be part of the 21st century thoracic surgeons’ professional competence. The European Society of Thoracic Surgeons (ESTS) Biology Club aims at providing a comprehensive insight into the basic biology of the diseases we are treating. During the 2013 ESTS Annual Meeting, different experts of the field presented the current knowledge about diagnostic and prognostic biomarkers in malignant pleural mesothelioma including new perspectives as well as the role and potential application of microRNA and genomic sequencing for lung cancer, which are summarized in the present article.


Principles of Surgical Therapy in Oncology
Michael S. Sabel, Kathleen M. Diehl, and Alfred E. Chang
With the expansion of the multidisciplinary approach to cancer, the role of the surgeon has changed significantly. In addition to the well-established curative role, surgeons are often asked to obtain tissue for diagnosis and staging, debulk tumors as part of multimodality therapy, palliate incurable patients, or prevent cancer by the surgical removal of nonessential organs. As the management of cancer is altered by new discoveries in genetics, molecular biology, immunology, and improved therapeutics, so too will the functions of the surgical oncologist change. With our increased understanding of the genetic predisposition to cancer, the surgeon is increasingly being asked to remove healthy organs to prevent malignancy. However, as other effective methods of prevention are developed, such as chemoprevention or gene therapy, this role will certainly diminish. Improving imaging technologies may have diminished the need for surgical intervention for staging (such as in Hodgkin’s lymphoma), but the expanded use of neoadjuvant therapies often requires interventions to accurately assess response to therapy. In addition, harvesting tumors may become increasingly important for molecular staging as well as identifying molecular targets for specific therapies. It is therefore imperative for surgical oncologists to remain up-to-date on the newest approaches to cancer therapy, both multidisciplinary and experimental, and be prepared to adapt to the changing requirements for surgery.

The major objective for surgery of the primary cancer is to achieve optimal local control of the lesion. Local control is defined as the elimination of the neoplastic process and establishing a milieu in which local tumor recurrence is minimized. Historically, this was achieved with radical extirpative surgeries that shaped the surgical oncologists’ major objective, namely, avoiding a local recurrence. Before William Halsted’s description of the radical mastectomy, surgical

treatment of breast cancer resulted in a dismal local control rate of less than 30%. The reason why Halsted’s procedure was adopted as a standard approach was because he achieved greater than 90% local control, despite the fact that the overall survival of his patients was not improved.4 The latter was due to the locally advanced stage of the patients who were treated in those days. This consideration ushered in the concept of en bloc removal of adjacent tissue when removing a primary cancer. Halsted’s mastectomy involved the removal of adjacent skin (often necessitating a skin graft), underlying pectoral muscles, and axillary lymph nodes (Figure 4.1). One of the major principles of surgical therapy of the primary tumor is to obtain adequate negative margins around the primary tumor, which could mean different operative approaches depending on the tumor type and its local involvement with adjacent structures. For example, the removal of a primary colon cancer that involves an adjacent loop of small bowel or bladder requires the en bloc resection of the primary tumor along with removal of the involved segment of small bowel and bladder wall. This approach avoids violation of the primary tumor margins that could lead to tumor spillage and possible implantation of malignant cells in the surrounding normal tissues. Aside from biopsies of the primary tumor, the lesion should not be entered during a definitive resection. In fact, any biopsy tract or incision that was performed before the tumor resection should be included in the procedure to reduce the risk of local recurrence (Figure 4.2). The risk of local recurrence for all solid malignancies is clearly increased if negative margins are not achieved. The adequacy of the negative margin has been defined for most tumor types either from retrospective clinical experience or prospective clinical trials. For example, a 5-cm margin is an adequate bowel margin for primary colon cancers that has been established from clinical experience. Likewise, it is accepted that a 2-cm distal margin for rectal cancers results in adequate local control. Through several prospective, randomized clinical trials, the margins of excision for primary cutaneous melanomas differ according to the thickness of the primary (see Chapter 60). It was a commonly held notion that the development of a local recurrence would in itself result in metastatic disease with decreased overall survival. However, this has not been borne out in the context of prospective trials as described here. The emergence of multimodal therapy has dramatically affected the surgical approach to many primary cancers, especially when surgical resection of the tumor is combined with radiotherapy. Local control is significantly improved after surgical resection of breast, rectal, sarcoma, head and neck, and pancreatic primary cancers. In fact, the addition of radiation therapy as an adjunctive therapy has allowed for less-radical procedures to be performed with an improvement in the quality of life of patients. A prime example of this is in breast cancer. Several clinical trials have demonstrated that the overall survival of patients with invasive breast cancer was comparable if treated by mastectomy versus lumpectomy plus adjuvant radiotherapy.

The regional lymph nodes represent the most prevalent site of metastasis for solid tumors. Because of this, the involvement of the regional lymph nodes represents an important prognostic factor in the staging of the cancer patient. For this reason, the removal of the regional lymph nodes is often performed at the time of resection of the primary cancer. Besides staging information, a regional lymphadenectomy provides regional control of the cancer. Examples of this are patients with melanoma who have tumor metastatic to lymph nodes. It is well documented that the removal of these regional lymph nodes can result in long-term survival benefit in approximately 20% to 40% of individuals depending upon the extent of nodal involvement. Hence, the removal of regional lymph nodes can be therapeutic. The controversies regarding regional lymphadenectomy for solid malignancies have related to the timing of the procedure as well as the extent of the procedure. For some visceral solid tumors such as gastric and pancreatic cancers, the extent of lymphadenectomy at the time of primary tumor resection has been hypothesized to be important in optimizing local and regional control and has an impact on improving overall survival. This concept has not been borne out in prospective randomized trials of gastric cancer in which the extent of lymphadenectomy has been examined.

Based on these trials, the more-extended lymphadenectomy appears to result in more accurate staging of patients at a cost of increased morbidity. For nonvisceral solid tumors such as melanoma, breast cancers, and head and neck squamous cancers, the elective removal of regional lymph nodes at the time of primary tumor resection has been postulated to result in better survival outcomes compared to taking the wait-and-watch approach. The latter involves performing a lymphadenectomy only when the patient relapses in a nodal basin that would then necessitate a therapeutic lymph node dissection. In prospective randomized clinical studies evaluating elective versus therapeutic lymph node dissection in various tumor types, there was no survival advantage for performing elective lymph node dissections (Table 4.2). It is apparent from these controversies that the initial removal of regional lymph nodes is most important for its staging impact, rather than its therapeutic effect. The introduction of selective lymphadenectomy based upon the concept of the sentinel lymph node has dramatically improved our ability to stage the regional lymph nodes of certain cancers. This is reviewed in more detail in the Diagnosis and Staging section of this chapter.

One of the earliest examples of surgical prophylaxis is the recommendation for total proctocolectomy for subsets of patients with chronic ulcerative colitis. Patients with pancolitis, onset of disease at a young age, and a long duration of colitis are at high risk of developing colorectal cancer.36 Other clinical diseases of the large intestine also illustrate the role of proctocolectomy in cancer prevention. Familial adenomatous polyposis coli (FAP) syndrome, defined by the diffuse involvement of the colon and rectum with adenomatous polyps often in the second or third decade of life, almost always predisposes to colorectal cancer if the large intestine is left in place. However, the role of screening and prophylactic proctocolectomy changed dramatically with the identification of the gene responsible for FAP, the adenomatous polyposis coli (APC) gene, located on the long arm of chromosome 5 (5q21).37 Now, children of families in which an APC mutation has been identified can have genetic testing before polyps become evident. Carriers can have screening and surgical resection once polyps appear, usually in the late teens or early twenties. Although not ideal, the palatability of proctocolectomy in this population was furthered with the description of the total abdominal colectomy, mucosal proctectomy, and ileoanal pouch anastomosis.38

Another example of prophylactic surgery is the bilateral mastectomy for women at high risk of developing breast cancer. Before the identification of the BRCA genes, prophylactic mastectomies were typically reserved as an option for women with lobular carcinoma in situ (LCIS). However, with the identification of BRCA1 and BRCA2, the role of prophylactic mastectomies has been greatly expanded. For women with BRCA1 or BRCA2 mutations, the lifetime probability of breast cancer is between 40% and 85%.41–43 Because mastectomy cannot remove all breast tissue, women can expect a 90% to 94% risk reduction with prophylactic surgery.44 Schrag et al. calculated the estimated gain in life expectancy after prophylactic surgery versus no operation in women with either a BRCA1 or BRCA2 mutation and found a 30-year-old woman would be expected to gain 2.9 to 5.3 years of life, depending on her family history.45 However, potential benefits of prophylactic mastectomy must be weighed against quality of life issues and the morbidity of the surgery.46 In addition, other methods for prophylaxis, such as tamoxifen chemoprevention or bilateral oophorectomy, must be considered. Along with the increased risk of breast cancer with BRCA1/2 mutations, the risk of ovarian cancer is also increased. Bilateral oophorectomy after childbearing is complete not only reduces the risk of ovarian cancer47 but may also decrease the risk of breast cancer.48 A detailed discussion must be held with each patient considering bilateral mastectomies regarding the risks and benefits, the knowns and unknowns. It is becoming increasingly important that today’s surgical oncologist have a clear understanding of genetics and inherited risk.

Increased genetic knowledge has also changed our approach to thyroid cancer. Medullary thyroid cancer (MTC) is a wellestablished component of multiple endocrine neoplasia syndrome type 2a (MEN 2a) or type 2b (MEN 2b). Previously, family members at risk for MEN 2 underwent annual screening for elevated calcitonin levels; however, this only detected MTC after it developed. In 1993 it was identified that mutations in the RET proto-oncogene were present in almost all cases of MEN 2a and 2b. Now family members of MEN patients can be screened for the presence of a RET mutation. Those without the mutation need not undergo additional screening, whereas those with the mutation should undergo total thyroidectomy at a young age (6 years for MEN 2a, infancy for MEN 2b).49

The readers are reminded that older or elderly patients will increasingly make up the population of patients with cancer. Currently 60% of all malignancies, and 70% of all cancer deaths, occur in people over the age of 65.58 In addition to the previously mentioned considerations, assessment of the older patient should include evaluation of activities of daily living, depression, cognitive function, current medications and potential medication interactions, and available social support.59–62

  1. Lewison EF. Breast Cancer and Its Diagnosis and Treatment. Baltimore: Williams & Wilkins, 1955.
  2. Rutledge RH. Theodore Billroth: a century later. Surgery (St. Louis) 1995;118:36–43.
  3. Weir R. Resection of the large intestine for carcinoma. Ann Surg 1886;1886(3):469–489.
  4. Halsted WS. The results of operations for the cure of cancer of the breast performed at the Johns Hopkins Hospital from June 1889 to January 1894. Ann Surg 1894;320(13):497–555.
  5. Clark JG. A more radical method for performing hysterectomy for cancer of the cervix. Johns Hopkins Bull 1895;6:121.
  6. Crile G. Excision of cancer of the head and neck. JAMA 1906; XLVII:1780.
  7. Miles WE. A method for performing abdominoperineal excision for carcinoma of the rectum and terminal portion of the pelvic colon. Lancet 1908;2:1812–1813.
  8. Krakoff IH. Progress and prospects in cancer treatment: the Karnofsky legacy. J Clin Oncol 1994;12:432–438.
  9. Farber S, Diamond LK, Mercer RD, et al. Temporary regressions in acute leukemia in children produced by folic acid antagonist, aminopteroyl-glutamic acid. N Engl J Med 1948;238: 693.
  10. Huggins CB, Hodges CV. Studies on prostatic cancer: the effect of castration, of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate. Cancer Res 1941;1:293–297.
  11. Lawrence W Jr, Wilson RE, Shingleton WW, et al. Surgical oncology in university departments of surgery in the United States. Arch Surg 1986;121:1088–1093.
  12. Fisher B, Remond C, Poisson R, et al. Eight-year results of a randomized clinical trial comparing total mastectomy and lumpectomy with or without irradiation in the treatment of breast cancer. N Engl J Med 1989;320:822–828.

Quality of surgery: has the time come for colon cancer?
Lancet (Oncology)   Feb 2015; 16

Major improvements in outcomes for rectal cancer have occurred in the 30 years since the introduction of total mesorectal excision and multidisciplinary treatment.1 This situation should continue to improve with more radical surgery for low rectal cancer. Pioneering work by leaders of rectal cancer surgery was initially ignored and it took the independent reproduction of the improved outcomes in single hospital and small regional studies before large-scale regional and national training programs led to major reductions in local recurrence, significant improvements in survival, and major financial savings occurred around the world. Colon cancer accounts for around 70% of bowel cancer and although survival has improved, it has not been to the same extent as that for rectal cancer, with substantial variation remaining between hospitals for operative cases. Historical reports have shown significantly improved survival in colon cancer following surgical standardization,2–4 and excellent results from Japan have largely been ignored.5 The rectal cancer story is repeating itself. Colonic cancer resection in western countries is unfortunately still viewed as a routine procedure with little concern surrounding these major variations in outcome. Indeed the focus has been on laparoscopic surgery rather than optimisation of the surgery. In The Lancet Oncology, a paper by Claus Anders Bertelsen and colleagues,6 and the debate it should generate, is a key step to reproduce the benefits of optimum rectal cancer surgery in colonic cancer, and hints at what could be achievable by the routine adoption of high-quality surgery. In this detailed report, the researchers show that implementation of complete mesocolic excision (CME) with central vascular ligation (CVL) results in a major improvement in survival. By simply visiting and adopting the methods of expert surgeons in Erlangen, led by Werner Hohenberger,4 and by quality controlling their surgery through mesocolic grading, routine specimen photography, and internal and external pathology audit,7 the researchers have independently reproduced results from Erlangen and Japan. The improvement in outcome described could be attributable to two specific variables; first, CME, which comprises the intact removal of the mesocolon and its lymphatic drainage within embryological planes. This procedure should be routine; it does not increase risks to the patient and might seem obvious since careful dissection following anatomical planes is a basic principle of surgery and such planes were described in the early 20th century, but on close scrutiny surgical planes are very variable and must be improved.8,9 Second, but more controversially, is the role of CVL. This procedure entails more radical central dissection, with potential risk to major vessels, nerves, and organs such as the pancreas. In Erlangen, Japan, and now in Hillerød, such surgery seems to be safe, but several important questions remain. How much benefit does it convey in addition to mesocolic surgery? What is the learning curve and is this achievable for all surgeons? Can it be safely achieved laparoscopically? Is the same benefi t derived for all stages of disease?

Radiation therapy in the locoregional treatment of triple-negative breast cancer
Meena S Moran
Lancet Oncol 2015; 16: e113–22

This Review assesses the relevant data and controversies regarding the use of radiotherapy for, and locoregional management of, women with triple-negative breast cancer (TNBC). In view of the strong association between BRCA1 and TNBC, knowledge of baseline mutation status can be useful to guide locoregional treatment decisions. TNBC is not a contraindication for breast conservation therapy because data suggest increased locoregional recurrence risks (relative to luminal subtypes) with breast conservation therapy or mastectomy. Although a boost to the tumour bed should routinely be considered after whole breast radiation therapy, TNBC should not be the sole indication for postmastectomy radiation, and accelerated delivery methods for TNBC should be off ered on clinical trials. Preliminary data implying a relative radioresistance for TNBC do not imply radiation omission because radiation provides an absolute locoregional risk reduction. At present, the integration of subtypes in locoregional management decisions is still in its infancy. Until level 1 data supporting treatment decisions based on subtypes are available, standard locoregional management principles should be adhered to.


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Recent comprehensive review on the role of ultrasound in breast cancer management

Writer, reporter and curator: Dror Nir, PhD

The paper below by R Hooley is a beautifully written review on how ultrasound could (and should) be practiced to better support breast cancer screening, staging, and treatment. The authors went as well into the effort of describing the benefits from combining ultrasonography with the other frequently used imaging modalities; i.e. mammography, tomosynthesis and MRI. Post treatment use of ultrasound is not discussed although this is a major task for this modality.

I would like to recommend giving attention to two very small (but for me very important) paragraphs: “Speed of Sound Imaging” and “Lesion Annotation”


Breast Ultrasonography: State of the Art

Regina J. Hooley, MDLeslie M. Scoutt, MD and Liane E. Philpotts, MD

Department of Diagnostic Radiology, Yale University School of Medicine, 333 Cedar St, PO Box 208042, New Haven, CT 06520-8042.

Address correspondence to R.J.H. (e-mail:

Ultrasonography (US) has become an indispensable tool in breast imaging. Breast US was first introduced in the 1950s by using radar techniques adapted from the U.S. Navy (1). Over the next several decades, US in breast imaging was primarily used to distinguish cystic from solid masses. This was clinically important, as a simple breast cyst is a benign finding that does not require further work-up. However, most solid breast lesions remained indeterminate and required biopsy, as US was not adequately specific in differentiating benign from malignant solid breast masses. However, recent advances in US technology have allowed improved characterization of solid masses.

In 1995, Stavros et al (2) published a landmark study demonstrating that solid breast lesions could be confidently characterized as benign or malignant by using high-resolution grays-cale US imaging. Benign US features include few (two or three) gentle lobulations, ellipsoid shape, and a thin capsule, as well as a homogeneously echogenic echotexture. Malignant US features include spiculation, taller-than-wide orientation, angular margins, microcalcifications, and posterior acoustic shadowing. With these sonographic features, a negative predictive value of 99.5% and a sensitivity of 98.4% for the diagnosis of malignancy were achieved. These results have subsequently been validated by others (3,4) and remain the cornerstone of US characterization of breast lesions today. These features are essential in the comprehensive US assessment of breast lesions, described by the Breast Imaging and Reporting Data System (BI-RADS) (5).

US is both an adjunct and a complement to mammography. Advances in US technology include harmonic imaging, compound imaging, power Doppler, faster frame rates, higher resolution transducers, and, more recently, elastography and three-dimensional (3D) US. Currently accepted clinical indications include evaluation of palpable abnormalities and characterization of masses detected at mammography and magnetic resonance (MR) imaging. US may also be used as an adjuvant breast cancer screening modality in women with dense breast tissue and a negative mammogram. These applications of breast US have broadened the spectrum of sonographic features currently assessed, even allowing detection of noninvasive disease, a huge advance beyond the early simplistic cyst-versus-solid assessment. In addition, US is currently the primary imaging modality recommended to guide interventional breast procedures.

The most subtle US features of breast cancers are likely to be best detected by physicians who routinely synthesize findings from multiple imaging modalities and clinical information, as well as perform targeted US to correlate with lesions detected at mammography or MR imaging. Having a strong understanding of the technical applications of US and image optimization, in addition to strong interpretive and interventional US skills, is essential for today’s breast imager.


Optimal Imaging Technique

US is operator dependent, and meticulous attention to scanning technique as well as knowledge of the various technical options available are imperative for an optimized and accurate breast US examination. US is an interactive, dynamic modality. Although breast US scanning may be performed by a sonographer or mammography technologist, the radiologist also benefits greatly from hands-on scanning (Fig 1). Berg et al (6) demonstrated that US interpretive performance was improved if the radiologist had direct experience performing breast US scanning, including rescanning after the technologist. Real-time scanning also provides the opportunity for thorough evaluation of lesions and permits detailed lesion analysis compared with analyzing static images on a workstation. Subtle irregular or indistinct margins, artifacts, and architectural distortions may be difficult to capture on static images. Real-time scanning also allows the operator to assess lesion mobility, location, and relationship to adjacent structures and allows direct assessment of palpable lesions and other clinical findings. Moreover, careful review of any prior imaging studies is imperative to ensure accurate lesion correlation.



The US examination is generally well tolerated by the patient. Gentle but firm transducer pressure and optimal patient positioning are essential, with the patient’s arm relaxed and flexed behind the head. Medial lesions should generally be scanned in the supine position, and lateral lesions, including the axilla, should usually be scanned with the patient in the contralateral oblique position. This allows for elimination of potential artifact secondary to inadequate compression of breast tissue.


Gray-Scale Imaging

Typical US transducers used in breast imaging today have between 192 and 256 elements along the long axis. When scanning the breast, a linear 12–5-MHz transducer is commonly used. However, in small-breasted women (with breast thickness < 3 cm) or when performing targeted US to evaluate a superficial lesion, a linear 17–5-MHz transducer may be used. Such high-frequency transducers provide superb spatial and soft-tissue resolution, permitting substantially improved differentiation of subtle shades of gray, margin resolution, and lesion conspicuity in the background of normal breast tissue (Fig 2). However, the cost of such a high insonating frequency is decreased penetration due to attenuation of the ultrasound beam, making visualization of deep posterior tissue difficult (ie, greater than 3 cm in depth by using a linear 17–5-MHz transducer or greater than 5 cm in depth by using a linear 12–5-MHz transducer).



During the initial US survey of the region of interest in the breast, the depth should be set so that the pectoralis muscle is visualized along the posterior margin of the field of view. Initial gain settings should be adjusted so that fat at all levels is displayed as a midlevel gray. Simple cysts are anechoic. Compared with breast fat, most solid masses are hypoechoic, while the skin, Cooper ligaments, and fibrous tissue are echogenic. Time gain compensation, which adjusts image brightness at different depths from the skin to compensate for attenuation of the ultrasound beam as it penetrates into the breast tissue, may be set manually or, with appropriate equipment, may be adjusted automatically during real-time scanning or even during postprocessing of the image.

When searching for a lesion initially identified at mammography or MR imaging, careful correlation with lesion depth and surrounding anatomic structures is imperative. Lesion location may be affected by the patient’s position, which differs during mammography, US, and MR imaging examinations. Attention to surrounding background tissue may assist in accurate lesion correlation across multiple modalities. If a mass identified at mammography or MR imaging is surrounded entirely by fat or fibroglandular tissue, at US it should also be surrounded by hypoechoic fat or echogenic fibroglandular tissue, respectively. Similarly, careful attention to the region of clinical concern is necessary when scanning a palpable abnormality to ensure that the correct area is scanned. The examiner should place a finger on the palpable abnormality and then place the transducer directly over the region. Occasionally, the US examination may be performed in the sitting position if a breast mass can only be palpated when the patient is upright.

After a lesion is identified, or while searching for a subtle finding, the depth or field of view may be adjusted as needed. The depth should be decreased to better visualize more superficial structures or increased to better visualize deeper posterior lesions. The use of multiple focal zones also improves resolution at multiple depths simultaneously and should be used, if available. Although this reduces the frame rate, the reduction is typically negligible when scanning relatively superficial structures within the breast. If a single focal zone is selected to better evaluate a single lesion, the focal zone should be centered at the same level as the area of interest or minimally posterior to the area of interest, for optimal visualization.


Spatial Compounding, Speckle Reduction, and Harmonic Imaging

Spatial compound imaging and speckle reduction are available on most high-end US units and should be routinely utilized throughout the breast US examination. Unlike standard US imaging, in which ultrasound pulses are transmitted in a single direction perpendicular to the long axis of the transducer, spatial compounding utilizes electronic beam steering to acquire multiple images obtained from different angles within the plane of imaging (79). A single composite image is then obtained in real-time by averaging frames obtained by ultrasound beams acquired from these multiple angles (10). Artifactual echoes, including speckle and other spurious noise, as well as posterior acoustic patterns, including posterior enhancement (characteristic of simple cysts) and posterior acoustic shadowing (characteristic of some solid masses), are substantially reduced. However, returning echoes from real structures are enhanced, providing improved contrast resolution (9) so that ligaments, edge definition, and lesion margins, including spiculations, echogenic halos, posterior and lateral borders, as well as microcalcifications, are better defined. Speckle reduction is a real-time postprocessing technique that also enhances contrast resolution, improves border definition, is complementary to spatial compounding, and can be used simultaneously.

When a lesion is identified, harmonic imaging may also be applied—usually along with spatial compounding—to better characterize a cyst or a subtle solid mass. The simultaneous use of spatial compounding and harmonic imaging may decrease the frame rate, although this usually does not impair real-time evaluation. Harmonic imaging relies on filtering the multiple higher harmonic frequencies, which are multiples of the fundamental frequencies. All tissue is essentially nonlinear to sound propagation and the ultrasound pulse is distorted as it travels through breast tissue, creating harmonic frequencies (9). The returning ultrasound signal therefore contains both the original fundamental frequency and its multiples, or harmonics. Harmonic imaging allows the higher harmonic frequencies to be selected and used to create the gray-scale images (89). Lower-frequency superficial reverberation echoes are thereby reduced, allowing improved characterization of simple cysts (particularly if small) through the elimination of artifactual internal echoes often seen in fluid. Harmonic imaging also improves lateral resolution (10) and may also improve contrast between fatty tissue and subtle lesions, allowing better definition of subtle lesion margins and posterior shadowing (Fig 3).





Speed of Sound Imaging

Conventional US systems set the speed of sound in tissue at a uniform 1540 m/sec (10). However, the speed of sound in tissues of different composition is variable and this variability may compromise US image quality. Breast tissue usually contains fat, and the speed of sound in fat, of approximately 1430–1470 m/sec, is slower than the assumed standard (11). Accurate speed of sound imaging, in which the US transducer may be optimized for the presence of fat within breast tissue, has been shown to improve lateral resolution (12). Additionally, it can be used to better characterize tissue interfaces, lesion margins, and microcalcifications (13) and may also be useful to identify subtle hypoechoic lesions surrounded by fatty breast tissue. Speed of sound imaging is available on most high-end modern US units and is an optional adjustment, depending on whether predominately fatty, predominately dense, or mixed breast tissue is being scanned.


 Lesion Annotation

When a mass is identified and the US settings are optimized, the mass should be scanned with US “sweeps” through the entire lesion in multiple planes. Images of the lesion in the radial and antiradial views should be captured and annotated with “right” or “left,” clock face position, and centimeters from the nipple. Radial and anti-radial scanning planes are preferred over standard transverse and sagittal scanning planes because scanning the breast along the normal axis of the mammary ducts and lobar tissues allows improved understanding of the site of lesion origin and better visualization of ductal extension and helps narrow the differential diagnosis (14). Images should be captured with and without calipers to allow margin assessment on static images. Lesion size should be measured in three dimensions, reporting the longest horizontal diameter first, followed by the anteroposterior diameter, then the orthogonal horizontal.


 Extended-Field-of-View Imaging

Advanced US technology permits extended-field-of-view imaging beyond the footprint of the transducer. By using a freehand technique, the operator slides the transducer along the desired region to be imaged. The resultant images are stored in real-time and, by applying pattern recognition, a single large-field-of-view image is obtained (7). This can be helpful in measuring very large lesions as well as the distance between multiple structures in the breast and for assessing the relationship of multifocal disease (located in the same quadrant as the index cancer or within 4–5 cm of the index cancer, along the same duct system) and/or multicentric disease (located in a different quadrant than the index cancer, or at a distance greater than 4–5 cm, along a different duct system).


 Doppler US

Early studies investigating the use of color, power, and quantitative spectral Doppler US in the breast reported that the presence of increased vascularity, as well as changes in the pulsatility and resistive indexes, showed that these Doppler findings could be used to reliably characterize malignant lesions (15,16). However, other investigators have demonstrated substantial overlap of many of these Doppler characteristics in both benign and malignant breast lesions (17). Gokalp et al (18) also demonstrated that the addition of power Doppler US and spectral analysis to BI-RADS US features of solid breast masses did not improve specificity. While the current BI-RADS US lexicon recommends evaluation of lesion vascularity, it is not considered mandatory (5).

Power Doppler is generally more sensitive than color Doppler to low-flow volumes typical of breast lesions. Light transducer pressure is necessary to prevent occlusion of slow flow owing to compression of the vessel lumen. Currently both power and color Doppler are complementary tools to gray-scale imaging, and power Doppler may improve sensitivity in detecting malignant breast lesions (18,19). Demonstration of irregular branching central or penetrating vascularity within a solid mass raises suspicion of malignant neovascularity (20). Recently, the parallel artery and vein sign has been described as a reliable feature that has the potential to enable prediction of benignity in solid masses so that biopsy may be avoided. In a single study, a paired artery and vein was present in 13.2% of over 1000 masses at US-guided CNB and although an infrequent finding, the specificity for benignity was 99.3% and the false-negative rate was only 1.4%, with two malignancies among 142 masses in which the parallel artery and vein sign was identified (21).

Color and power Doppler US are also useful to evaluate cysts and complex cystic masses that contain a solid component. High-grade invasive cancer and metastatic lymph nodes may occasionally appear anechoic. Demonstration of flow within an otherwise simple appearing cyst, a complicated cyst, or a complex mass confirms the presence of a suspicious solid component, which requires biopsy. In addition, twinkle artifact seen with color Doppler US is useful to identify a biopsy marker clip or subtle echogenic microcalcifications (Fig 4). This Doppler color artifact occurs secondary to the presence of a strong reflecting granular surface and results in a rapidly changing mix of color adjacent to and behind the reflector (22). Care must be taken to avoid mistaking twinkle artifact for true vascular flow and, if in doubt, a spectral Doppler tracing can be obtained, as a normal vascular waveform will not be seen with a twinkle artifact.







At physical examination, it has long been recognized that malignant tumors tend to feel hard when compared with benign lesions. US elastography can be used to measure tissue stiffness with the potential to improve specificity in the diagnosis of breast masses. There are two forms of US elastography available today: strain and shear wave. With either technique, acoustic information regarding lesion stiffness is converted into a black-and-white or color-scaled image that can also be superimposed on top of a B-mode gray-scale image.

Strain elastography requires gentle compression with a US probe or natural motion (such as heart beat, vascular pulsation, or respiration) and results in tissue displacement, or strain. Strain (ie, tissue compression and motion) is decreased in hard tissues compared with soft tissue (23). The information obtained with strain elastography provides qualitative information, although strain ratios may be calculated by comparing the strain of a lesion to the surrounding normal tissue. Benign breast lesions generally have lower ratios in comparison to malignant lesions (24,25).

Shear-wave elastography is based on the principle of acoustic radiation force. With use of light transducer pressure, transient automatic pulses can be generated by the US probe, inducing transversely oriented shear waves in tissue. The US system captures the velocity of these shear waves, which travel faster in hard tissue compared with soft tissue (26). Shear-wave elastography provides quantitative information because the elasticity of the tissue can be measured in meters per second or in kilopascals, a unit of pressure.

Elastography features such as strain ratios, size ratios, shape, homogeneity, and maximum lesion stiffness may complement conventional US in the analysis of breast lesions. Malignant masses evaluated with elastography tend to be more irregular, heterogeneous, and typically appear larger at elastography than at grayscale imaging (Fig 5) (27,28). Although malignant lesions generally also exhibit maximum stiffness greater than 80–100 kPa (28,29), caution is necessary when applying these numerical values to lesion analysis. Berg et al (28) reported three cancers among 115 masses with maximum stiffness between 20 and 30 kPa, for a 2.6% malignancy rate; 25 cancers among 281 masses with maximum stiffness between 30 and 80 kPa, for an 8.9% malignancy rate; and 61 cancers among 153 masses with maximum stiffness between 80 and 160 kPa, for a 39.9% malignancy rate (28). Invasive cancers with high histologic grade, large tumor size, nodal involvement, and vascular invasion have also been shown to be significantly correlated with high mean stiffness at shear-wave elastography (30).



Elastography may be useful in improving the specificity of US evaluation of BI-RADS 3 and 4A lesions, including complicated cysts. Berg and colleagues (28) showed that by using qualitative shear-wave elastography and color assessment of lesion stiffness, oval shape, and a maximum elasticity value of less than 80 kPa, unnecessary biopsy of low-suspicion BI-RADS 4A masses could be reduced without a significant loss in sensitivity. Several investigators have proposed a variety of imaging classifications using strain elastography, mostly based on the color pattern (27,31,32). A “bull’s eye” artifact has also been described as a characteristic feature present in benign breast cysts, which may appear as a round or oval lesion with a stiff rim associated with two soft spots, one located centrally and the other posteriorly (33).

Despite these initial promising studies regarding the role of US elastography in the analysis of breast lesions, limitations do exist. Strain and shear-wave elastography are quite different methods of measuring breast tissue stiffness, and the application of these methods varies across different commercial manufacturers. Inter- and intraobserver variability may be relatively high because the elastogram may be affected by differences in degree and method of compression. With strain elastography, a quality indicator that is an associated color bar or numerical value may be helpful to ensure proper light compression. Shear-wave elastography has been shown to be less operator-dependent, as tissue compression is initiated by the US probe in a standard, reproducible fashion (34) and only light transducer pressure is necessary. In addition, there is currently no universal color-coding standard and, depending on the manufacturer and/or operator preference, stiff lesions may be arbitrarily coded to appear red while soft lesions appear blue, or vice versa. Some elastography features such as the “bull’s eye” artifact are only seen on specific US systems. Lesions deeper than 2 cm are less accurately characterized by means of elastography. Moreover, one must be aware that soft cancers and hard benign lesions exist. Therefore, careful correlation of elastography with B-mode US features and mammography is essential. Future studies and further technical advances, including the creation of more uniformity across different US manufacturers, will ultimately determine the usefulness of elastography in clinical practice.

Three-dimensional US

Both handheld and automated high-resolution linear 3D transducers are now available for use in breast imaging. With a single pass of the ultrasound beam, a 3D reconstructed image can be formed in the coronal, sagittal, and transverse planes, potentially allowing more accurate assessment of anatomic structures and tumor margins (Fig 6). Few studies regarding the performance of 3D US in the breast exist, but a preliminary study demonstrated improved characterization of malignant lesions (35). Automated supine whole-breast US using 3D technology is now widely available for use in the screening setting (see section on screening breast US). Three-dimensional US may also be used in addition to computed tomography for image-guided radiation therapy (36) and has a potential role in assessing tumor response to neoadjuvant chemotherapy.




US Features of Benign and Malignant Breast Lesions


Although for many years the main function of breast US was to differentiate cysts from solid masses, this differentiation can at times be problematic, particularly if the lesion is small or located deep in the breast. Simple cysts are defined as circumscribed, anechoic masses with a thin imperceptible wall and enhanced through transmission (provided spatial compounding is not used). By convention, simple cysts may also contain up to a single thin septation. Simple cysts are confidently characterized with virtually 100% accuracy at US (14,37), provided that they are not very small (< 5 mm in size) or not located in deep tissue. Complicated cysts are hypoechoic with no discernable Doppler flow, contain internal echoes, and may also exhibit indistinct margins, and/or lack posterior acoustic enhancement. Clustered microcysts consist of a cluster of tiny (<2–3 mm in size) anechoic foci with thin (< 0.5 mm in thickness) intervening septations.

Complicated cysts are very common sonographic findings and the majority are benign. In multiple studies, which evaluated over 1400 complicated cysts and microcysts, the malignancy rate ranged from 0% to 0.8% (3844). Most complicated cysts and clustered microcysts with a palpable or mammographic correlate are classified as BI-RADS 3 and require short-interval imaging follow-up or, occasionally, US-guided aspiration. However, in the screening US setting, if multiple and bilateral complicated and simple cysts are present (ie, at least three cysts with at least one cyst in each breast), these complicated cysts can be assessed as benign, BI-RADS 2, requiring no additional follow-up (38).

Complicated cysts should never demonstrate internal vascularity at color Doppler interrogation. The presence of a solid component, mural nodule, thickened septation, or thickened wall within a cystic mass precludes the diagnosis of a benign complicated cyst. These complex masses require biopsy, as some cancers may have cystic components. The application of compound imaging and harmonics, color Doppler, and potentially elastography may help differentiate benign complicated cysts from malignant cystic-appearing masses and reduce the need for additional follow-up or biopsy.

Solid Masses

Sonographic features of benign-appearing solid masses include an oval or ellipsoid shape, “wider-than-tall” orientation parallel to the skin, circumscribed margins, gentle and smooth (less than three) lobulations, as well as absence of any malignant features (2,45) (Fig 2b). Lesions with these features are commonly fibroadenomas or other benign masses and can often be safely followed, even if the mass is palpable (4648). Malignant features of solid masses include spiculations, angular margins, marked hypoechogenicity, posterior acoustic shadowing, microcalcifications, ductal extension, branching pattern, and 1–2-mm microlobulations (2,45) (Figs 1b,56). These are also often taller-than-wide lesions with a nonparallel orientation to the skin and may occasionally be associated with thickened Cooper ligaments and/or or skin thickening. Most cancers have more than one malignant feature, spiculation being the most specific and angular margins the most common (2).

There is, however, considerable overlap between these benign and malignant US features and careful scanning technique, as well as direct correlation with mammography, is essential. For example, some high-grade invasive ductal carcinomas with central necrosis, as well as the well-differentiated mucinous and medullary subtypes, may present as circumscribed, oval, hypoechoic masses that may look like complicated cysts with low-level internal echoes at US. Benign focal fibrous breast tissue or postoperative scars can appear as irregular shadowing masses on US images. Furthermore, while echogenic lesions are often benign and frequently represent lipomas or fibrous tissue, echogenic cancers do rarely occur (Figs 78) (49,50). The presence of a single malignant feature, despite the presence of multiple benign features, precludes a benign classification and mandates biopsy, with the exception of fat necrosis and postoperative scars exhibiting typical benign mammographic features. Likewise, a mass with a benign US appearance should be biopsied if it exhibits any suspicious mammographic features.




 Ductal Carcinoma in Situ

Ductal carcinoma in situ (DCIS) is characteristically associated with microcalcifications detected at mammography, but may also be detected at US since they are often associated with a subtle hypoechoic mass, which may indicate an invasive mammographically occult component. US features associated with DCIS most commonly include a hypoechoic mass with an irregular shape, microlobulated margins, no posterior acoustic features, and no internal vascularity. Ductal abnormalities, intracystic lesions, and architectural distortions may also be present (5153). Noncalcified DCIS manifesting as a solid mass at US is more frequently found in non–high-grade than high-grade DCIS, which is more often associated with microcalcifications and ductal changes (54). US can depict microcalcifications, particularly those in clusters greater than 10 mm in size and located in a hypoechoic mass or a ductlike structure (Fig 9) (55). Malignant calcifications are more likely to be detected sonographically than are benign calcifications, which may be obscured by surrounding echogenic breast tissue (55,56). Although US is inferior to mammography in the detection of suspicious microcalcifications, the main benefit of US detection of DCIS is to identify the invasive component and guide biopsy procedures.





Breast US in Clinical Practice

Current indications for breast US as recommended by the American College of Radiology Practice Guidelines include the evaluation of palpable abnormalities or other breast symptoms, assessment of mammographic or MR imaging–detected abnormalities, and evaluation of breast implants (57). Additionally, US is routinely used for guidance during interventional procedures, treatment planning for radiation therapy, screening in certain groups of women, and evaluation of axillary lymph nodes. Much literature has been written on these uses and a comprehensive discussion is beyond the scope of this article. A few important and timely topics, however, will be reviewed.




The BI-RADS US lexicon was introduced in 2003, and subsequently, there have been several studies assessing the accuracy of BI-RADS US classification of breast lesions. Low to moderate interobserver agreement has been found in the description of margins (especially noncircumscribed margins), echogenicity, and posterior acoustic features. Abdullah et al (58) reported low interobserver agreement especially for small masses and for malignant masses. Given the importance of margin analysis in the characterization of benign and malignant lesions, this variability is potentially problematic. Studies have also shown variable results in the use of the final assessment categories. In clinical settings, Raza et al (46) showed inconsistent use of the BI-RADS 3 (probably benign) category in 14.0% of cases when biopsy was recommended. Abdullah et al also demonstrated fair and poor interobserver agreement for BI-RADS 4 (suspicious for malignancy) a, b, and c subcategories (58). However, Henig et al (59) reported more promising results, with malignancy rates in categories 3, 4, and 5 to be similar to those seen with mammographic categorization (1.2%, 17%, and 94%, respectively).


 Evaluation of Mammographic Findings

Targeted US is complementary to diagnostic mammography because of its ability to differentiate cystic and solid lesions.US is also useful in the work up of subtle asymmetries, as it can help identify or exclude the presence of an underlying mass. True hypoechoic lesions can often be differentiated from prominent fat lobules by scanning in multiple planes, because true lesions usually do not blend or elongate into adjacent tissue. With the introduction of digital breast tomosynthesis for mammographic imaging, US will play yet another important role. As mammographic lesions can often be detected, localized, and have adequate margin assessment on 3D images, patients with lesions detected on digital breast tomosynthesis images at screening may often be referred directly to US, avoiding additional mammographic imaging and its associated costs and radiation exposure (Fig 10). This will place an even greater importance on high-quality US.






Evaluation of the Symptomatic Patient:Palpable Masses, Breast Pain, and Nipple Discharge

US is essential in the evaluation of patients with the common clinical complaint of either a palpable mass or focal persistent breast pain. Unlike focal breast pain, which may be occasionally associated with benign or malignant lesions, diffuse breast pain (bilateral or unilateral), as well as cyclic breast pain, requires only clinical follow-up, as it is usually physiologic with an extremely low likelihood of malignancy (60,61). In patients with isolated focal breast pain, the role of sonography may be limited to patient reassurance (61). In women younger than 30 years of age, with a palpable lump or focal breast pain, US is the primary imaging test, with a sensitivity and negative predictive value of nearly 100% (62). Symptomatic women older than 30 years usually require both US and mammography, and in these patients, the negative predictive value approaches 100% (63,64). Lehman et al (65) demonstrated that in symptomatic women aged 30–39 years, the risk of malignancy was 1.9% and the added value of adjunct mammography in addition to US was low. Identification of a benign-appearing solid lesion at US in a symptomatic woman can negate the need for needle biopsy, as many of these masses can safely be monitored with short-interval follow-up US (4648), usually performed at 6 months. A suspicious mass identified at US can promptly undergo biopsy with US guidance.

US can also be used as an alternative or an addition to ductography in patients who present with unilateral, spontaneous bloody, clear, or serosanguinous nipple discharge (66). Among women with worrisome nipple discharge, ductography can demonstrate an abnormality in 59%–82% of women (67,68), MR imaging may demonstrate a suspicious abnormality in 34% of women (68), and US has been shown to demonstrate a subareolar mass or an intraductal mass or filling defect in up to 14% of women (67). If US can be used to identify a retroareolar mass or an intraductal mass, US-guided biopsy can be performed and ductography may be avoided (Fig 11). US may be limited, however, as small peripherally located intraductal masses or masses without an associated dilated duct may not be identified. Therefore, galactography, MR imaging, and/or major duct excision may still be necessary in the symptomatic patient with a negative US examination.


Finally, in the pregnant or lactating patient who presents with a palpable breast mass, focal breast pain, or bloody nipple discharge, US is also the initial imaging modality of choice. Targeted US examination in these patients can be used to identify most benign and malignant masses, including fibroadenomas, galactocoeles, lactating adenomas, abscesses, and invasive carcinomas. In a recent study by Robbins et al (69), a negative predictive value of 100% was found among 122 lesions evaluated with US in lactating, pregnant, or postpartum women. This is much higher than the pregnancy-associated breast cancer sensitivity of mammography, which has been reported in the range of 78%–87% (70,71). The diminished sensitivity of mammography is likely due to increased parenchymal density seen in these patients. However, since lactating breast parenchyma is more echogenic than most breast masses, hypoechoic breast cancers are more readily detected at US in pregnant patients.



Supplemental Screening Breast US

Because of the known limitations of mammography, particularly in women with dense breast tissue, supplemental screening with whole-breast US, in addition to mammography, is increasingly gaining widespread acceptance. Numerous independent studies have demonstrated that the addition of a single screening or whole-breast US examination in women with dense breast tissue at mammography will yield an additional 2.3–4.6 mammographically occult cancers per 1000 women (7280). Mammographically occult cancers detected on US images are generally small node-negative invasive cancers (Fig 12) (81). However, few studies have investigated the performance of incident screening breast US, and the optimal screening US interval is unknown. Berg and colleagues (82) recently demonstrated that incident annual supplemental screening US in intermediate- and high-risk women with mammographically dense breast tissue enabled detection of an additional 3.7 cancers per 1000 women screened.


Handheld screening breast US is highly operator-dependent and the majority of screening breast US studies have relied on physician-performed examinations. As per the ACRIN 6666 protocol, a normal screening US examination should consist of a minimum of one image in each quadrant and one behind the nipple (83). Two studies have also demonstrated that technologist-performed handheld screening breast US can achieve similar cancer detection rates (76,78).

Automated whole-breast US is a recently developed alternative to traditional handheld screening breast US, in which standardized, uniform image sets may be readily obtained by a nonradiologist. Automated whole-breast US systems may utilize a standard US unit and a linear-array transducer attached to a computer-guided mechanical arm or a dedicated screening US unit with a 15-cm wide transducer (84,85). With these systems, over 3000 overlapping sagittal, transverse, and coronal images are obtained and available for later review by the radiologist, with associated 3D reconstruction. The advantages include less operator dependence, increased radiologist efficiency, and increased reproducibility, which could aid in follow-up of lesions.

A multi-institutional study has shown that supplemental automated whole-breast US can depict an additional 3.6 cancer per 1000 women screened, similar to physician-performed handheld screening US (85). However, disadvantages include the limited ability to scan the entire breast, particularly posterior regions in large breasts, time-consuming review of a large number of images by the radiologist, and the need to recall patients for a second US examination to re-evaluate indeterminate findings. Moreover, few investigators have compared the use of handheld with automated breast US screening. A single small recent study by Chang et al (86) demonstrated that of 14 cancers initially detected at handheld screening, only 57%–79% were also detected by three separate readers on automated whole-breast US images, with the two cancers missed by all three readers at automated whole-breast US, each less than 1 cm in size.

The use of supplemental screening breast US, performed in addition to mammography, remains controversial despite proof of the ability to detect small mammographically occult cancers. US has limited value for the detection of small clustered microcalcifications without an associated mass lesion. Low positive predictive values of biopsies performed of less than 12% have been consistently reported (77,87). No outcome study has been able to demonstrate a direct decrease in patient mortality due to the detection of these additional small and mammographically occult cancers. This would require a long, randomized screening trial, which is not feasible. Rationally, however, the early detection and treatment of additional small breast cancers should improve outcomes and reduce overall morbidity and mortality. Many insurance companies will not reimburse for screening breast US and historically, this examination has not been widely accepted in the United States.

Nevertheless, because of both the known efficacy of supplemental screening breast US and overall increased breast cancer awareness, more patients and clinicians are requesting this examination. In fact, some states now mandate that radiologists inform women of their breast density and advise them to discuss supplemental screening with their doctors. Although supplemental screening breast MR imaging is usually preferred for women who are at very high risk for breast cancer (ie, women with a lifetime risk of over 20%, for example those women who are BRCA positive or have multiple first-degree relatives with a history of premenopausal breast cancer), screening breast US should be considered in women at very high risk for breast cancer who cannot tolerate breast MR imaging, as well as those women with dense breast tissue and intermediate risk (ie, lifetime risk of 15%–20%, for example those women whose only risk factor is a personal history of breast cancer or previous biopsy of a high-risk lesion), or even average risk. Future studies are needed to establish strategies to reduce false-positive results and continue to optimize both technologist-performed handheld screening US and automated whole-breast US in women with mammographically dense breast tissue.


 Use of US for MR Imaging–depicted Abnormalities

MR imaging of the breast is now an integral part of breast imaging, most commonly performed to screen high-risk women and to further assess the stage in patients with newly diagnosed breast cancers. While MR has a higher sensitivity than mammography for detecting breast cancer, the specificity is relatively low (88). Lesions detected on MR images are often mammographically occult, but many can be detected with targeted US (Fig 13). Besides further US characterization of an MR imaging–detected lesion, US may be used to guide intervention for lesions initially detected at MR imaging. US-guided biopsies are considerably less expensive, less time consuming, and more comfortable for the patient than MR imaging–guided biopsies.



Some suspicious lesions detected at MR imaging will represent invasive ductal or lobular cancers, but many may prove to be intraductal disease, which can be challenging to detect at US. Meticulous scanning technique is required for an MR imaging–directed US examination, with knowledge of subtle sonographic signs and close correlation with the MR imaging findings and location. Precontrast T1 images are helpful to facilitate localization of lesions in relation to fibroglandular tissue (89). Because MR imaging abnormalities tend to be vascular, increased vascularity may also assist in detection of a subtle sonographic correlate (90). Having the MR images available for simultaneous review while performing the US examination will ideally permit such associative correlation. At the authors’ facility, computer monitors displaying images from the picture archiving and communication system are available in all US rooms for this purpose.

Recent studies have shown that 46%–71% of lesions at MR imaging can be detected with focused US (9094). Enhancing masses detected on MR images are identified on focused US images in 58%–65% of cases compared with nonmass enhancement, which is identified on focused US images in only 12%–32% of cases (9092). Some studies have shown that US depiction of an MR imaging correlate was independent of size (91,93,95). However, Meissnitzer et al (92) showed that size dependence is also important: For masses 5 mm or smaller, only 50% were seen, versus 56% for masses 6–10 mm, 73% for masses 11–15 mm, and 86% for masses larger than 15 mm. Likewise, this study also demonstrated that for nonmass lesions, a US correlate was found for 13% of those measuring 6–10 mm, 25% of those 11–15 mm, and 42% of those larger than 15 mm (92). In addition, many of these studies determined that when a sonographic correlate was discovered, the probability of malignancy was increased (9092). Since typical US malignant features such as spiculation and posterior shadowing may be absent and the pretest probability is higher for MR imaging–detected lesions, a lower threshold for biopsy should be considered when performing MR imaging–directed US compared with routine targeted US (90) or screening US.

Because lesions are often very subtle at MR-directed US examination and because of differences in patient positioning during the two examinations, careful imaging–histologic correlation is required when performing US-guided biopsy of MR imaging–detected abnormalities. For lesions sampled with a vacuum-assisted device and US guidance, Sakamoto et al (96) found a higher rate of false-negative biopsy results for MR imaging–detected lesions than for US-detected lesions, suggesting that precise US-MR imaging correlation may not have occurred. Meissnitzer et al (92) showed that although 91% of MR imaging–detected lesions had an accurate US correlate, 9% were found to be inaccurate. With ever-improving techniques and experience in breast US, the US visualization of MR imaging–detected abnormalities will likely continue to improve. Nevertheless, if a suspicious lesion is not identified sonographically, MR imaging–guided biopsy should still be performed, because the malignancy rate of sonographically occult MR imaging–detected lesions has been shown to range from 14% to 22% (91,95).



Preoperative Staging of Cancer with US

Breast MR imaging has been shown to be more sensitive than US in the detection of additional foci of mammographically occult disease in women with newly diagnosed breast cancer (9799). Nevertheless, when a highly suspicious mass is identified at mammography and US, immediate US evaluation of the remainder of the ipsilateral breast, the contralateral breast, and the axilla should be considered. If additional lesions are identified, preoperative staging with MR imaging can be avoided and US-guided biopsy can be promptly performed, saving the patient valuable time and expense (100). In a study by Moon et al (101), of 201 patients with newly diagnosed breast cancer, staging US demonstrated mammographically occult multifocal or multicentric disease in 28 patients (14%) and contralateral breast cancers in eight patients (4%), resulting in a change in therapy in 32 patients (16%).

US can also be used to identify abnormal axillary, supraclavicular, and internal mammary lymph nodes. Abnormal lymph nodes characteristically demonstrate focal or diffuse cortical thickening (≥3 mm in thickness), a round (rather than oval or reniform) shape, loss of the echogenic fatty hilum and/or nonhilar, disorganized, irregular blood vessels (102,103) (Fig 14). A positive US-guided CNB or fine-needle aspiration of a clinically abnormal axillary lymph node in a patient with a known breast cancer can aid patient management, by avoiding the need for sentinel node biopsy and allowing the patient instead to proceed directly to axillary lymph node dissection or neoadjuvant chemotherapy.



 Interventional Breast US

US-guided interventional procedures have increased in volume in recent years and US is now the primary biopsy guidance technique used in many breast imaging centers. Most palpable lesions, as well as lesions detected at mammography, MR imaging, or screening US, can be sampled with US. With current high-resolution transducers, even suspicious intraductal microcalcifications may be detected and sampled.

While US-guided procedures require technical skills that must be developed and can be challenging, once mastered this technique allows precise real-time sampling of the lesion, which is not possible with either stereotactic or MR imaging–guided procedures. US-guided procedures do not require ionizing radiation or intravenous contrast material. US procedures are more tolerable for patients than stereotactic (104) or MR imaging–guided procedures because US-guided procedures are faster and more comfortable, as breast compression and uncomfortable biopsy coils or tables are not necessary and the procedure may be performed with the patient supine (104106).

Most literature has shown that automated 14-gauge CNB devices are adequate for the majority of US-guided biopsies (107115). Image-guided CNB is preferable to fine-needle aspiration cytology of breast masses because of superior sensitivity, specificity, and diagnostic accuracy (116). DCIS, malignant invasion, and hormone receptor status of invasive breast cancers can be determined with CNB samples, but not with fine-needle aspiration cytology. Fine-needle aspiration may be performed, however, in complicated cysts and symptomatic simple cysts. In these cases, the cyst aspirate fluid can often be discarded; cytology is usually only necessary if the fluid is frankly bloody (117).

The choice of performing fine-needle aspiration or CNB of a suspicious axillary lymph node depends on radiologist preference and the availability of an experienced cytopathologist, although CNB is usually more accurate than fine-needle aspiration biopsy (118,119). Fine-needle aspiration may be preferred for suspicious deep lymph nodes in proximity to the axillary vessels, whereas CNB may be preferred in large nodes with thickened cortices, particularly if determination of hormone receptor status or immunohistochemistry is desired, since more tissue is required for these assays. If lymphoma is suspected, a core should be placed in saline and also in conventional formalin.

While the underestimation rate of malignancy can be considerable for high-risk lesions such as atypical hyperplasia, such histology is not commonly found in lesions undergoing US-guided CNB. Multiple studies have shown a false-negative rate for US CNB biopsy of around 2%–3% (107115). Although the contiguous and larger samples obtained with a vacuum-assisted biopsy device undoubtedly reduce sampling error, the vacuum-assisted biopsy is a more expensive and more invasive procedure (109). In the authors’ experience, vacuum-assisted US biopsy is to be considered for small masses, intraductal or intracystic lesions, or lesions with subtle microcalcifications. These may be difficult to adequately sample with a spring-loaded automatic firing device. Alternatively, for more accurate sampling of such challenging cases, as well as some axillary lymph nodes and masses smaller than 1 cm in size, automated CNB needles designed to place the inner trough of the needle within a lesion before firing can be utilized (Fig 15). With this technique, the sampling trough of the CNB needle can be clearly visualized within the lesion before the overlying outer sheath is fired. Regardless of needle choice, a postbiopsy clip marker should be placed followed by a postbiopsy mammogram to document clip position. This will assist with follow-up imaging, facilitating mammography and/or MR imaging correlation.




There has been recent interest in the percutaneous removal of benign breast lesions by using US-guided vacuum-assisted biopsy. While in general, proved benign concordant lesions can safely remain in the breast, some patients desire removal. Percutaneous US-guided removal with a vacuum-assisted biopsy device can replace surgical removal in some cases, particularly for small lesions (1 cm in size or less). Several reports have shown promising results demonstrating rates of complete lesion excision, varying from 61% to 94% (120124). Dennis et al (125) demonstrated that vacuum-assisted US-guided biopsy could be used to excise intraductal lesions resulting in resolution of problematic nipple discharge in 97% of patients. Even on long-term follow-up, most studies show low rates of residual masses, more commonly observed in larger fibroadenomas.


 Intraoperative Breast US

The use of two-dimensional and 3D intraoperative US may decrease the incidence of positive margins and decrease re-excision rates (126130) particularly in the setting of lumpectomy for palpable cancers, when US is used to assess the adequacy of surgical margins to determine the need for additional tissue removal. Similarly, intraoperative US has also been utilized to improve detection and removal of metastatic lymph nodes during sentinel lymph node assessment (131).


Future Directions

Intravenous US microbubble contrast agents have been used to enhance US diagnosis by means of analysis, enhancement patterns, the rates of uptake and washout, and identification of tumor angiogenesis. In addition, preliminary research has shown that intravenous US contrast agents may be able to depict tissue function with the potential to deliver targeted gene therapy to selected tumor cells (132). However, there are currently no intravenous US contrast agents approved for use in breast imaging by the U.S. Food and Drug Administration. Other potential advances in breast US include fusion imaging, which involves the direct overlay of correlative MR imaging with targeted US. Another evolving area is that of US computer-aided detection, which may be of particular benefit when combined with automated whole-breast screening US.



Technical advances in US now allow comprehensive US diagnosis, management, and treatment of breast lesions. Optimal use of US technology, meticulous scanning technique with careful attention to lesion morphology, and recognition and synthesis of findings from multiple imaging modalities are essential for optimal patient management. In the future, as radiologists utilize US for an ever-increasing scope of indications, become aware of the more subtle sonographic findings of breast cancer, and apply newly developing tools, the value of breast US will likely continue to increase and evolve.



  • • Breast US is operator dependent; knowledge and understanding of the various technical options currently available are important for image optimization and accurate diagnosis.
  • • US is an interactive, dynamic modality and real-time scanning is necessary to assess subtle findings associated with malignancy.
  • • Ability to synthesize the information obtained from the breast US examination with concurrent mammography, MR imaging, and clinical breast examination is necessary for accurate diagnosis.
  • • The use of screening breast US in addition to mammography, particularly in women with dense breast tissue, is becoming more widely accepted in the United States.
  • • Breast US guidance is the primary biopsy method used in most breast imaging practices, and the radiologist should be familiar with various biopsy devices and techniques to adequately sample any breast mass identified at US.


Disclosures of Conflicts of Interest: R.J.H. No relevant conflicts of interest to disclose. L.M.S. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: educational consultant in vascular US to Philips Healthcare; payment for lectures on breast US from Educational Symposia; payment for development of educational presentations from Philips Healthcare. Other relationships: none to disclose. L.E.P. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: consultant to Hologic. Other relationships: none to disclose.


BI-RADS = Breast Imaging and Reporting Data System

CNB = core needle biopsy

DCIS = ductal carcinoma in situ

3D = three dimensional


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