Efficacy of Ovariectomy in Presence of BRCA1 vs BRCA2 and the Risk for Ovarian Cancer
Reporter: Aviva Lev-Ari, PhD, RN
UPDATED on 3/8/2014
Tel Aviv Researchers Find New Way To Fight Ovarian Cancer
By NoCamels Team March 03, 2014 0 Comments
Ovarian cancer accounts for more deaths of American women than any other cancer of the female reproductive system. According to the American Cancer Society, one in 72 American women will be diagnosed with ovarian cancer, and one in 100 will ultimately die of the condition.
Now Prof. Dan Peer of Tel Aviv University’s Department of Cell Research and Immunology has proposed a new strategy to tackle an aggressive subtype of ovarian cancer using a new nanoscale drug-delivery system designed to target specific cancer cells. He and his team have devised a cluster of nanoparticles called gagomers, made of fats and coated with a kind of polysugar. When filled with chemotherapy drugs, these clusters accumulate in tumors, producing dramatically therapeutic benefits.
The objective of Peer’s research is two-fold: to provide a specific target for anti-cancer drugs to increase their therapeutic benefits, and to reduce the toxic side effects of anti-cancer therapies. The study was published in February in the journal “ACS Nano”.
Why chemotherapy fails
According to Peer, traditional courses of chemotherapy are not an effective line of attack. Chemotherapy’s failing lies in the inability of the medicine to be absorbed and maintained within the tumor cell long enough to destroy it. In most cases, the chemotherapy drug is almost immediately ejected by the cancer cell, severely damaging the healthy organs that surround it, leaving the tumor cell intact.
But with their new therapy, Peer and his colleagues saw a 25-fold increase in tumor-accumulated medication and a dramatic dip in toxic accumulation in healthy organs. Tested on laboratory mice, the gagomer mechanism effects a change in drug-resistant tumor cells. Receptors on tumor cells recognize the sugar that encases the gagomer, allowing the binding gagomer to slowly release tiny particles of chemotherapy into the cancerous cell. As more and more drugs accumulate within the tumor cell, the cancer cells begin to die off within 24-48 hours.
“Tumors become resistant very quickly. Following the first, second, and third courses of chemotherapy, the tumors start pumping drugs out of the cells as a survival mechanism,” said Peer. “Most patients with tumor cells beyond the ovaries relapse and ultimately die due to the development of drug resistance. We wanted to create a safe drug-delivery system, which wouldn’t harm the body’s immune system or organs.”
A personal perspective
Peer chose to tackle ovarian cancer in his research because his mother-in-law passed away at the age of 54 from the disease. “She received all the courses of chemotherapy and survived only a year and a half,” he said. “She died from the drug-resistant aggressive tumors.
“At the end of the day, you want to do something natural, simple, and smart. We are committed to try to combine both laboratory and therapeutic arms to create a less toxic, focused drug that combats aggressive drug-resistant cancerous cells,” said Peer. “We hope the concept will be harnessed in the next few years in clinical trials on aggressive tumors,” said Peer.
SOURCE
http://nocamels.com/2014/03/tel-aviv-researchers-find-new-way-to-fight-ovarian-cancer/
Does BRCA1 Warrant Early Ovariectomy?
Published: Feb 24, 2014 | Updated: Feb 25, 2014
Carriers of BRCA 1/2 mutations had an 80% lower risk of ovarian cancer if they underwent bilateral oophorectomy, a study involving almost 6,000 women showed.
Of 186 ovarian, fallopian, and peritoneal cancers diagnosed during follow-up, 108 (4.8%) occurred in women who did not undergo oophorectomy, 23 (1.1%) in women who had oophorectomy at enrollment, and 55 (4%) in women who underwent oophorectomy after enrollment. Oophorectomy also was associated with a 77% reduction in the hazard for all-cause mortality, owing primarily to the effect on ovarian and breast cancer risk.
Almost all of the risk reduction resulted from reduced risk among carriers of the more common BRCA1 mutation.
The findings suggest that BRCA1 mutation carriers should consider oophorectomy as soon as possible after determining mutation status but by age 35 in all cases, Steven A. Narod, MD, of the University of Toronto, and co-authors concluded in an article published online in the Journal of Clinical Oncology (JCO).
“To me, waiting to have oophorectomy until after 35 is too much of a chance to take,” Narod said in a statement. “These data are so striking that we believe prophylactic oophorectomy by age 35 should become a universal standard for women with BRCA1 mutations.”
“Women with BRCA2 mutations, on the other hand, can safely delay surgery until their 40s, since their ovarian cancer risk is not as strong.”
The recommendation for oophorectomy before age 35 differs from current recommendations, which specify an age rage of 35 to 40 and when childbearing is complete, said Noah D. Kauff, MD, of Memorial Sloan-Kettering Cancer Center in New York City. Moreover, the data do not appear to support prophylactic oophorectomy before age 35.
“The results in the study really do not suggest an increased risk of ovarian cancer prior to age 40 that has been reported in other studies,” Kauff, who was not involved in the study, told MedPage Today. “Approximately 2% to 3% of women in this study, not the 4% the authors said was their estimated number in the conclusion. This is the same number we have been quoting to women for the last decade.”
“It is not at all clear that the authors’ conclusion that you must have your ovaries out by age 35 is actually warranted by this data,” he added.
Narod and colleagues, as well as other investigators, have previously shown that prophylactic oophorectomy reduces the risk of ovarian and breast cancer. However, the optimal age for surgery remained unclear.
Building on results from their earlier work, the authors sought to inform the age decision by analyzing data from an ongoing study of women who have BRCA1/2 mutations. At the time of the analysis, 5,783 women had been enrolled at sites in North America, Austria, France, Italy, Norway, and Poland.
The study population consisted of 2,270 women who did not undergo oophorectomy, 2,123 who had undergone oophorectomy at baseline, and 1,390 who had the surgery after enrollment in the study. The patients had a mean age of 46 at enrollment, ranging from 42 in the no-oophorectomy group to 50.5 in the women who had undergone oophorectomy at enrollment.
Among women with intact ovaries, 98 of 108 ovarian cancers occurred in BRCA1 carriers and 10 BRCA2 mutation carriers. Cancer diagnosis occurred most often during ages 50 to 59 for BRCA1 carriers and 60 to 69 for the BRCA2 carriers.
The authors found that 46 occult cancers were found at oophorectomy, including 27 classified as ovarian, 18 as primary fallopian tube carcinoma, and one as peritoneal. Of 44 cancers diagnosed at oophorectomy in BRCA1 carriers, three were diagnosed in women ≤40. The youngest patient was 34 at diagnosis. An additional 19 BRCA1-related cancers were diagnosed in women 40 to 49.
The two BRCA2-related cancers diagnosed at oophorectomy involved women older than 60.
Primary peritoneal cancer after oophorectomy accounted for the remaining 32 cases, 28 involving BRCA1 carriers and four in BRCA2 carriers. Mean age at diagnosis was 51.6 and ranged from 36 to 69.
The investigators performed an adjusted analysis of the impact of oophorectomy on the risk of ovarian, fallopian-tube, and primary peritoneal cancer (BRCA1 and BRCA2 combined). The analysis yielded a hazard ratio of 0.20 versus the non-oophorectomy group (95% CI 0.13-0.30, P<0.001).
The authors estimated the effect of oophorectomy on all-cause mortality to age 70. The analysis produced an adjusted hazard ratio of 0.23 (95% CI 0.13-0.39, P<0.001).
The magnitude of mortality reduction was similar in patients with a family history of breast cancer, leading the authors to conclude that “genetic testing is likely to be beneficial in countries where patients who test positive for a mutation have access to salpingo-oophorectomy, even if limited resources are available for other aspects of care.”
The findings provide important information to guide clinical decision making for women who harbor BRCA1, said Don Dizon, MD, of the Massachusetts General Hospital Cancer Center in Boston.
“These results could make a real difference for women with BRCA mutations, who face tough decisions about whether and when to undergo a prophylactic oophorectomy,” said Dizon, who also is a spokesperson for the American Society of Clinical Oncology, which publishesJCO. “For women with BRCA1 mutations, these results suggest that surgery should be performed as soon as it is practical.”
The association between oophorectomy and all-cause mortality provides reassurance that removal of the ovaries confers long-lasting benefits, he added.
Narod and coauthors disclosed no relevant relationships with industry.
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