Menopausal hormone therapy after breast cancer

There is now resounding evidence that use of exogenous hormones by postmenopausal women increases risk for breast cancer [1-3]. Likewise, obesity among postmenopausal women with breast cancer is a major determinant of relapse and mortality [4,5], being directly related to poor outcomes. On the other hand, tamoxifen provides lasting reduction in risk for recurrence and mortality [6], an effect that is independent of adjuvant chemotherapy. Despite this evidence relating endogenous and exogenous hormones to breast cancer risk and outcomes, debate continues regarding the use of postmenopausal hormones for symptom relief among women with breast cancer. Col and colleagues [7], in this issue of Breast Cancer Research, report a systematic review in which they identified eight observational studies and two randomized controlled trials of postmenopausal hormone therapy. They note that the combined results for the two trials show increased risk for recurrence (relative risk [RR] = 3.4, 95% confidence interval [CI] = 1.6 to 7.3), which contrasts with the findings of the observational results, which show a decrease in risk (RR = 0.6, 95% CI = 0.5–0.8). While noting heterogeneity between the results according to study design, Col and colleagues do not explore the data to describe the possible sources of heterogeneity [8,9] beyond study design. As noted below, the quality of data reporting limits their ability in this regard.Biologic evidence supports estrogenic exposures being related to incidence and poor outcome among women with breast cancer. Weight after diagnosis is a strong predictor of outcome [4], and weight gain after diagnosis is associated with increased recurrence and mortality [5]. There are direct positive relations between adiposity and circulating estrogens [10], and between adult weight gain and postmenopausal breast cancer risk [11], and circulating endogenous hormones represent the primary explanation for this positive relation between adiposity and postmenopau