The Likelihood Of Breast Cancer Development In BRCA Women Beyond Age 60

Implications For Surveillance and Prophylactic Surgery

The question remains whether the risk of breast cancer in BRCA1/BRCA2 mutation carriers beyond age 60 is enough to justify intensive screening or prophylactic surgery. The mean age of breast cancer diagnosis in women with BRCA1/BRCA2 mutations is approximately 45 years and 49 years respectively. Many women do not receive a positive genetic test result until they have passed this peak risk period. To make informed decisions regarding cancer screening and preventative surgeries, it is crucial to provide precise estimates of cancer risks tailored to the age of older individuals carrying mutations but without cancer.

Although most guidelines suggest that individuals undergo yearly screening and MRI scans until they reach age 50, policies vary significantly for those older than this age. Though bilateral mastectomy is the most effective means of breast cancer prevention, in older women the benefit is offset by operative risk and competing causes of death. In addition, the incidence of breast cancer declines because of a reduction in life expectancy. Recently, a multi-institutional, multinational prospective study of breast cancer risk was carried out among women with BRCA mutations who were cancer-free at age 60 (Stjepanovic et al. Breast Cancer Research and Treatment, 2021; 187:515 – 523). Eighty-eight centers in 16 countries participated in the study.

A total of 699 women (463 BRCA1 and 236 BRCA2 carriers) were cancer free on their 60th birthday and followed in this study. The mean follow-up was 7.9 years. In this cohort of women, 81 breast cancers were diagnosed after age 60 (14.8%). Of these 61 were invasive and 20 were DCIS. The annual rate of invasive cancer for BRCA1 carriers was 1.8% between ages 60 and 70 and 1.7% between 70 and 80. The annual rate of invasive cancer for BRCA2 carriers between ages 60 and 70, and 70 and 80 was 1.9% and 1.2% respectively. The annual risk for the development of DCIS was 0.3% for BRCA1 carriers and 1.1% for BRCA2 carriers. For individuals with BRCA1 mutations, the total risk of developing breast cancer (including both invasive and in situ types) between the ages of 60 and 80 was 24.1%, while those with BRCA2 mutations had a cumulative risk of 32.2% during the same time. If one includes only invasive cancers the cumulative risk from age 60 to 80 was 20.1% for BRCA1 carriers and 17.3% for BRCA2 carriers. Using statistical methodology (Cox proportional hazards model), the authors noted that the risk of breast cancer was not modified by oophorectomy, using hormone replacement therapy, or family history of breast cancer.

Forty-one percent (25) of the 61 patients were screened-detected, and even this group of patients had a 28.7% node positivity rate. Of the patients who were not screen-detected, 23.1% were node positive. More astounding, of the seven patients whose cancers were detected by MRI alone, 2 were node positive.

Conclusions

In BRCA carriers, the risk of breast cancer remains high even after age 60. The annual risk of invasive cancer from age 60-80 was 1.8% for BRCA1 carriers and 1.7% for BRCA2 carriers. This is similar to the risk reported for younger people in other studies. This observation casts serious doubt on the assumption that women BRCA carriers over the age of 60 are less susceptible to breast cancer than their younger counterparts. The authors noted that “the data support a model where the risk of cancer follows a stochastic pattern and is relatively steady from age 40 until age 80 (with no apparent peak).

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