Spring 2008
Contents
Raising Awareness and Growing FORCE
Setting a Hereditary Cancer Research Agenda
Differences in Breast Cancer Risk Reduction
Preimplantation Genetic Diagnosis
(to search past issues of our newsletter)
Differences in Breast Cancer Risk Reduction for BRCA1 and BRCA2
by Margaret Snow, MD and Lisa Held
In 2002, two landmark studies, one by Dr. Noah Kauff at Memorial Sloan Kettering and another by Dr. Tim Rebbeck, lead investigator of the PROSE study, demonstrated the benefits of removing the ovaries of BRCA carriers. When women’s ovaries and tubes were removed before menopause, their breast cancer risk was reduced by as much as 75 percent.
New research involving several large cancer centers and recently published in the Journal of Clinical Oncology showed the level of breast cancer risk reduction may differ between BRCA1 and BRCA2 carriers. This study followed BRCA carriers who were deciding whether or not to remove both ovaries to lower their risk of breast cancer and ovarian cancer. It was one of only a few investigations that examined distinct risk reduction in BRCA2 carriers, separate from women with BRCA1 mutations.
BRCA2 study participants who had oophorectomy were 72 percent less likely to get breast cancer. For BRCA1 patients, the study suggested a 29 percent reduction in breast cancer risk. Although the reason for this difference is unknown, the authors suggest that ovary removal may be more protective for women with BRCA2 mutations because BRCA2 breast cancers are more likely to be estrogen receptor positive, and removing the ovaries before menopause leaves the body with little estrogen to stimulate cancer cells . Breast cancers in BRCA1 mutation carriers are usually estrogen and progesterone receptor negative.
Although dividing the study groups into BRCA1 and BRCA2 carriers produced specific results of each it did have one unfortunate result: it reduced the total participants in each group. Because few participants developed cancer during the research, the results included large “confidence intervals.” This means that although the data suggests that BRCA1 and BRCA2 carriers have differing levels of protection from oophorectomy, researchers could not conclude without question that the difference in risk reduction between the two groups was different. The study had another limitation: half of the women followed had their ovaries removed after age 45. Further research is needed to show whether oophorectomy before age 45 may offer more protection for BRCA1 carriers than the protection shown in this study, and to prove that the difference in risk reduction in BRCA1 compared to BRCA2 carriers was not random.
As expected, the study also found that removing their ovaries protected women with BRCA1 mutations against ovarian cancer. After oophorectomy, women with BRCA1 mutations were much less likely to develop ovarian cancer compared to women who did not have surgery. Even after removing the ovaries, a risk remains for primary peritoneal cancer, a cancer of the abdominal lining that behaves like ovarian cancer and is treated the same way.
Although removing the ovaries and tubes is expected to offer similar protection from ovarian cancer in BRCA2 carriers, in this study the number of BRCA2 carriers with ovarian cancer was too small to show a difference.
The authors of the study support the practice of offering ovarian removal as a cancer prevention strategy both for BRCA1 and BRCA2 carriers.
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