Should Older Women Be Tested For BRCA Mutation: Should They Have Prophylactic Surgery?

Should Older Women Be Tested For BRCA Mutation: Should They Have Prophylactic Surgery?

Most genetic testing and preventive measures are carried out in women less than 50 years. A multinational, multi-institutional group of scientists studied BRCA1 and BRCA2-positive patients from ages 50 to 75 to estimate the cumulative risk of all cancers. There were 2211 women included in the initial analysis, 1470 of which had a BRCA1 pathogenic variant and 741 had a BRCA2 pathogenic variant. The median follow-up time was 8.8 years (0.1 – 24.5 years).

There were 333 cancers diagnosed in the cohort, representing 15% of the women included in the analysis. The authors noted that the actuarial risk of any cancer (except skin cancer) from age 50 to 75 was 47% (49% in BRCA1 patients and 43% for BRCA2 patients). The actuarial risk of breast cancer from age 50 to 75 was 32% for BRCA1 patients and 25% for BRCA2 patients. The actuarial risk of ovarian/fallopian/peritoneal cancer was 13% in patients with a BRCA1 mutation compared to 7% for patients with a BRCA2 mutation.

Of the entire cohort, 15.4% had prophylactic bilateral mastectomy before age 50 and 43.4% had ovaries and tubes removed before age 50. Seventy-six women took tamoxifen as chemoprevention before age 50 and 43 took raloxifene. The analysis was repeated for women who had taken no preventive measures before age 50. The risk of breast cancer in the group who took no preventive measures was 56% for BRCA1 patients and 45% for BRCA2 patients. The risk of ovarian/fallopian/peritoneal cancer from age 50 to 75 in this same group who took no preventive measures was 35% for BRCA1 patients and 28% for BRCA2 patients. In patients having a preventive mastectomy five cases of invasive breast cancer were diagnosed; four of which had a history of DCIS before or at the time of preventive mastectomy.

“Combined, these data confirm the benefit of genetic testing in older women to provide them with options for cancer risk reduction.” Many women carrying a breast cancer gene mutation opt for enhanced surveillance (mammograms and MRIs) as opposed to prophylactic surgery. Enhanced surveillance, however, attempts to diagnose cancer early as opposed to preventing cancer. Unfortunately, it is not always successful. Of the 232 breast cancers diagnosed in patients who were undergoing surveillance, 68% required chemotherapy as part of their treatment The authors suggest that cancer risk in patients with BRCA mutations is not yet lowered to what is observed in the general population. They believe that most of this cancer risk can be attributed to the limited uptake of risk-reduction surgery. In women who had both ovaries and both breasts removed the overall cancer risk was only 9%. This is substantially lower than the risk in the average population and highlights the effectiveness of genetic testing and prophylactic surgery in decreasing the incidence of cancer in patients with BRCA mutations.

Dr. Alan Stolier, MD, FACS, clinical breast oncologist

Dr. Alan Stolier, MD, FACS, clinical breast oncologist, shares his expert medical perspective with a series of educational and scientific articles.