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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.

Risk Management Guidelines

The National Comprehensive Cancer Network (NCCN) risk guidelines for people with a PTEN mutation include:

For both men and women

  • Clinical breast examination, beginning at age 25 or 5 - 10 years earlier than the earliest known breast cancer in the family.

For women

  • Training in breast selfexamination, with regular monthly practice, beginning at age 18.
  • Annual mammogram and breast MRI screening starting at ages 30 - 35, or 5 - 10 years earlier than the earliest known breast cancer in the family (but not earlier than age 25).
  • Premenopausal women should undergo annual blind endometrial aspiration biopsies starting at ages 35 - 40 or 5 years before the earliest case of endometrial cancer in the family.
  • Postmenopausal women should receive an annual endometrial ultrasound.

Reference

ND Kauff, SM Domchek, TM Friebel, et al. Risk-Reducing Salpingo-Oophorectomy for the Prevention of BRCA1- and BRCA2- Associated Breast and Gynecological Cancer. A Multicenter, Prospective Study. Journal of Clinical Oncology, March 10, 2008; Vol . 26, No . 8: p . 1331-1337.

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