By Dr. Kathleen Ruddy

Approximately 10% of breast cancer cases diagnosed in the United States are associated with a genetic, inherited predisposition to the disease. Of these patients, the majority carry a mutation in one of two genes, BRCA 1 and BRCA 2. These mutations are inherited from either parent and are passed to children in the same manner as, say, eye color. There are a variety of mutations that may occur on the BRCA genes, and all are associated with a range of increased risk for several cancers, including breast, ovarian, pancreatic, colon, and (in male carriers) prostate. Women who carry a BRCA mutation are at an especially high lifetime risk for breast and ovarian cancer. Surgical removal of the breasts and ovaries reduces the risk and mortality associated with these tumors, but does not completely eradicate it because residual cells that harbor the BRCA mutation are invariable left behind and still retain the potential to produce tumors. Given below are current estimates of the value of surgical interventions aimed at reducing the risk for breast and ovarian cancer incidence and mortality in women who carry a BRCA mutation.

How significant is the risk of breast or ovarian cancer in women who carry a BRCA mutation?

Women who carry a BRCA mutation are at a 5-20 fold increased risk of developing breast or ovarian cancer. The risk for these tumors is somewhat broad because there is a variety of mutations that can occur, each with its own specific risk profile. In addition, other known risk factors for breast cancer, such as use of oral contraceptives, smoking, and alcohol ingestion, can interact with the BRCA mutation to increase the overall risk for malignancy.

What is the preventive benefit of prophylactic mastectomy in BRCA carriers?

On average, women who carry a BRCA mutation can expect to have a 90% reduction in their risk for breast cancer if they have their breasts removed. Risk reduction does not achieve 100% efficacy because even during the most thorough mastectomy, some BRCA mutated cells are invariably left behind such that a small, but significant, risk for breast cancer persists.

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Some women may elect an aggressive breast cancer screening program as an alternative to prophylactic mastectomy. An annual mammogram and an annual breast MRI, staggered so that one of each screening method is performed every six months, yields a survival benefit that approaches 95% of that achieved by prophylactic mastectomy. For this reason, many women choose prophylactic removal of the ovaries, which reduces the risk of breast cancer by 50%, and aggressive screening with mammogram and breast MRI rather than surgical removal of the breasts.

What is the preventive benefit of prophylactic ovary removal in BRCA carriers?

Prophylactic removal of the ovaries can reduce the risk of ovarian cancer in BRCA carriers by as much as 85% if it is performed before age 50. Because the risk of ovarian cancer in BRCA carriers increases every year as they get older, the greatest survival benefit is achieved if the ovaries are removed prior to menopause, preferably as soon as childbearing is complete.

Is there any other benefit of prophylactic removal of the ovaries in BRCA carriers?

Yes, removal of the ovaries by age 50 reduces the risk for breast cancer approximately 50%. The reason removing the ovaries lowers breast cancer risk is that breast cancer is, in large part, dependent on the presence of estrogen for growth and development. This is why removing the source of estrogen made by the ovaries serves to cut the risk for breast cancer in half.

What is the most successful surgical intervention to improve survival in BRCA carriers?

At this time, the most successful surgical intervention to improve survival in women who carry a BRCA mutation is a combined prophylactic mastectomy and removal of the ovaries. The best overall survival benefit is found in women who have a prophylactic mastectomy by age 25 and a prophylactic removal of the ovaries by age 40. BRCA carriers who chose this combined surgical prophylaxis can achieve an overall survival that approaches normal; that is, a survival that is similar to women who do not carry a BRCA mutation.

Women who inherit a mutation in BRCA genes are at an increased risk for breast, ovarian, pancreatic, and colon cancer. Surgical removal of the breasts can reduce the risk for breast cancer by as much as 90%. Surgical removal of the ovaries can reduce the risk for ovarian cancer by 85% and the risk of breast cancer by 50%. Because the risk for breast and ovarian cancer in BRCA carriers increases significantly every year of their life, it is generally recommended that prophylactic surgical procedures be offered to these women between the ages of 25-50 to maximize the preventive benefit of these risk reduction strategies.

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