What makes this study unique is that it is a large, multi-center study that not only looked at the effectiveness of these prevention techniques overall for women with BRCA mutations but also sorted the data to look separately at the effectiveness of preventive surgeries for women with BRCA1 mutations versus BRCA2 mutations. The study also sorted the data to look at women who had already been diagnosed with breast cancer at the time of prophylactic oophorectomy versus those who had never had a cancer diagnosis. This data is important because many women still come to genetic testing only after a breast cancer diagnosis and these women need to know that what effect removing their ovaries will have on their risk for another breast cancer as well as their risk for ovarian cancer. Finally, the study looked not only at the risk of developing cancer, but also the risk of dying from breast cancer, ovarian cancer, or from any other cause.
So far, the headlines focus only on the overall findings of the study that these preventive surgeries do reduce both breast and ovarian cancer risk in the women who choose them as well as reducing our overall risk of death. This is indeed good news for those of us facing and making the though decisions to remove our body parts in hopes for a longer, cancer-free life. But those of us with BRCA mutations need and want the details of the study. JAMA has made the full text of the study available online free (at least for now). You can find it here.
Some of the study findings are striking, which probably accounts for why nearly every major news outlet has done a story on this in the past 24 hours. CNN reported: "Study: Breast, ovary removal cuts cancer risk in high-risk women." ABC Evening News on Tuesday August 31st titled its story: "Removing Ovaries and Breasts to Cut Cancer" and profiled FORCE Outreach Coordinator Lisa Schlager and her gut wrenching decisions to have preventive surgeries as part of its coverage. NPR's All Things Considered had more extensive coverage. It profiled a woman who made the tough decision to have preventive surgery, interviewed one of the researchers on the study, and talked with Dr. Ken Offit, chief of the Clinical Genetics Service at Memorial Sloan-Kettering Cancer Center about the importance of the study. The All Things considered stories can be found here and here.
The study found that preventive mastectomy is highly effective for preventing breast cancer and in fact none of the women in the study who had preventive mastectomies went on to develop breast cancer during the three years of follow-up. While this is indeed good news for the thousands of BRCA-positive women who, like me, have made the painful choice to give up their breasts for a cancer-free future, what I really want to know is whether my breast cancer risk will remain low for the rest of my life. Other studies seem to indicate that the answer will be yes, but the women in the PROSE study, from whom the data for this study was compiled, and other women, will need to be followed for many more years to get additional reassurance on this answer.
Another striking finding is that none of the women with BRCA2 mutations who have had both preventive mastectomies and preventive oophorectomies went on to develop cancer, but this good news is tempered by the fact that the study only included fifty-six such women. This highlights the fact that these preventive surgery decisions are difficult and many women with BRCA mutations are not opting for surgery, at least not immediately. Only ten percent of the women in the study opted for preventive mastectomies although 38 percent had prophylactic bilateral oophorectomies. Additionally, and perhaps more significantly, none of the BRCA2-positive women who had oophorectomies went on to develop primary peritoneal cancer. This was a larger group of women because some women chose oophorectomies but chose to keep their breasts.
The study confirmed what had been reported in multiple earlier studies about the breast cancer risk reduction from premeopausal oophorectomy. Namely, oophorectomy prior to age 50 reduces breast cancer risk for both BRCA1 and BRCA2 women, although perhaps to a different extent. Oophorectomy after the age of fifty did not result in any change in breast cancer risk although it remained highly effective at reducing future ovarian cancer risk. This study found that premenopausal ooporectomy conferred a 64 percent reduction in breast cancer risk for BRCA2 carriers but only a 37 percent risk reduction for BRCA1 carriers. The study authors speculate that this may be due to the fact that many BRCA1 breast cancers are estrogen negative but clearly more research is needed on this issue.
The ovarian cancer risk reduction for BRCA1 is also not as high as for BRCA2 carriers, although it is still excellent. Whereas none of the BRCA2 carriers who chose preventive oophorectomy developed primary peritoneal cancer, BRCA1 carriers who had preventive surgery had an 86 percent reduction in ovarian cancer risk with approximately 1 percent of such women developing peritoneal cancer following preventive oophorectomy (ten BRCA1-positive women developed peritoneal cancer after surgery). This may be due to the fact that BRCA1 carriers have a higher overall risk of ovarian cancer or may be due to the molecular features of BRCA1 ovarian cancers that are not yet understood.
The finding regarding risk reduction for women who have already been diagnosed with breast cancer are significant. Unfortunately, removing the ovaries after breast cancer does not reduce the risk of another breast cancer for these women. But these women receive the same ovarian cancer risk reduction as women who have not had a breast cancer diagnosis.
An issue that needs more research is the ideal timing of when a woman should have an oophorectomy. Because ovarian cancer is difficult to detect at a stage when it will not be fatal, many doctors recommend that BRCA-positive women remove their ovaries as soon as they are done having children. But very early surgical menopause, especially under age 45 without supplemental hormones, may cause other health risks. The study authors noted that:
Precise estimates of risk reduction following risk reducing salpingo-oophorectomy are needed to balance the increasingly recognized health risks caused by premature menopause.Specifically, as we discussed in Positive Results, the decision of when to remove the ovaries comes down to a cost-benefit analysis. We and our doctors must weigh the risks of breast and ovarian cancer caused by our BRCA mutation if we keep our ovaries versus the risks of premature menopause, especially under the age of 45. We need to know if hormone replacement will negate any portion of the risk reduction benefit of these surgeries. The study authors note the need for further research on this issue but do note that research to date does not show any increase in breast cancer risk with hormone use in BRCA-positive young women. We also need to know that removing our ovaries at a young age does not increase our risk of death from other causes because studies in the general population do show an increased risk of all cause death in women who remove their ovaries under the age of 45, especially if they do not have replacement hormones up to at least age 45. Ovarian cancer risk in BRCA1-positive women under the age of 45 is significant enough that doctors strongly recommend removing the ovaries as soon as childbearing is complete. This new study confirms that these women are making the right decision.
The study also confirms that women like me who also choose prophylactic mastectomies are reducing our future breast and ovarian cancer risk to the lowest possible level and are undoubtedly extending our lives, regardless of whether we are BRCA1 or BRCA2. Finally, for those women who are considering BRCA testing but worry that knowing their risk will be a burden, this study should provide reassurance that if you do test positive for a BRCA mutation, there are steps you can take to protect your life from these cancers.
Women who are considering genetic testing or who have tested positive for BRCA mutations need to more than the headlines. They need to understand the complexities of breast and ovarian cancer risk conferred by BRCA mutations and all the options that are available to protect their lives, as well as the consequences of those options. This is the reason we wrote Positive Results.
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