Background: Women with menopausal symptoms have been reported to have reduced risk of breast cancer, possibly reflecting differences in endogenous hormone levels. We examined the associations between menopausal symptoms and breast cancer in women under age 50.
Methods: We carried out a sister-controlled case-control study, the Two Sister Study, comparing 1422 women with breast cancer diagnosed before age 50 and their 1669 sisters who were free of breast cancer and had enrolled in the prospective Sister Study cohort. History and age at first occurrence of menopause-associated symptoms (e.g. hot flashes, poor sleep or night sweats) were ascertained using computer-assisted telephone interviews. To equalise opportunity for exposure, we assessed exposures in relation to a sibship-based index age (the minimum of the age at diagnosis of the case sister and the age at interview of her control sister(s)), and estimated odds ratios using conditional logistic regression with adjustment for menopausal status and birth order.
Findings: Having had menopause-associated symptoms (n=706) prior to the index age was associated with reduced risk of young-onset breast cancer (odds ratio (OR), 0.49; 95% confidence interval (CI), 0.40-0.61). Similar results were seen for hot flashes and for "other" menopausal symptoms. The association between menopausal symptoms and breast cancer risk was somewhat stronger for oestrogen receptor positive tumours than for oestrogen receptor negative tumours (heterogeneity p=0.07). Menopausal status, age at menopause, BMI and hormone replacement therapy did not modify the associations, but the inverse association between menopausal symptoms and breast cancer attenuated with increasing index age (p<0.01).
Interpretation: Menopause-associated symptoms were associated with markedly reduced risk of young-onset breast cancer. Further studies are needed to confirm the association and elucidate possible pathways.
Published by Elsevier Ltd.