Breast Cancer Risk Before and After Menopause

Commentary by Bernard A. Eskin, MS, MD, and Ari D Brooks, MD

This well-powered study of hormonal status/exposure and subsequent risks of breast cancer used the power of meta-analysis to confirm what we have known for over 30 years based on another powerful statistical tool: multivariate analysis. In 1989, Mitchell Gail and colleagues at the National Cancer Institute published a retrospective review of factors associated with the development of breast cancer in a prospective longitudinal study of over 280,000 women.^[1,2] The Gail model demonstrated to us that factors such as age, family history, and prior breast biopsies can be used to predict breast cancer risk. More relevant to this paper, early menarche and late menopause were identified as risk factors for subsequent breast cancer development in the Gail model, but perhaps not as well quantified as in the current study. This current study showed that for every year younger a woman is when she begins menarche, there is an increase in RR by a factor of 1.05 for breast cancer; for each additional year before menopause, there is an increase by a factor of 1.029. The implications of this finding are important, namely that serum estrogen level (SEL) exposure is a quantifiable risk factor for subsequent development of breast cancer. Some other important associated findings are the increased risk for ER-positive cancers over ER-negative, and increased risk for lobular carcinoma over ductal.

We have previously reported the timeline for decrease in SEL in postmenopause.^[3]We believe that this study confirms the role of peripheral estrogen in breast cancer risk. While the risk of breast cancer decreases in the years post-menopause, the magnitude of the decrease was less in women with a body mass index over 25. These women presumably have a higher serum SEL than their thinner counterparts, but we have shown that SEL does not drop immediately postmenopause, perhaps explaining why the incidence of breast cancer does not decrease immediately in the postmenopause years. The SEL stays elevated, but slowly decreases, until a woman is over age 65; and we have described these years as the geripause. A minimum SEL is always present from sources other than the ovary. According to the data presented here, it appears that as time passes from menopause onset, breast cancer risk decreases. However, data from the American Cancer Society shows that breast cancer incidence in the United States remains just as high in the 6th and 7th decades.^[4] It is probable that the peripheral source SEL is responsible for levels of malignancy. This study represents a great leap in quantitative risk assessment, but clearly there are other risk factors we need to measure.