Menopausal hormone therapy and breast cancer: what is the evidence from randomized trials?

Abstract

The relationship between menopausal hormone therapy (HT) and breast cancer is complex and further complicated by misinformation, perception and overgeneralization of data. These issues are addressed in this mini-review through the lens of the Women’s Health initiative (WHI) that has colored the view of HT and breast cancer. In the WHI, unopposed conjugated equine estrogen (CEE) REDUCED breast cancer risk and mortality. In the WHI CEE plus continuously combined medroxyprogesterone acetate (MPA) trial, although the hazard ratio (HR) was elevated it was statistically non-significant for an association between CEE+MPA and breast cancer. In fact, the increased HR was NOT due to an increased breast cancer incidence rate in women randomized to CEE+MPA therapy but rather due to a DECREASED and unexpectedly low breast cancer rate in the subgroup of women with prior HT use randomized to PLACEBO. For women who were HT naïve when randomized to WHI, the breast cancer incidence rate was not affected by CEE+MPA therapy relative to placebo for up to 11 years of follow-up. The current state of science indicates that HT may or may not cause breast cancer but the totality of data neither establish nor refute this possibility. Further, any association that may exist between HT and breast cancer appears to be rare and no greater than other medications commonly used in clinical medicine.

Carotid Atherosclerosis Progression in Postmenopausal Women Receiving a Mixed Phytoestrogen Regimen: Plausible Parallels with Kronos Early Estrogen Replacement Study

“…Phytoestrogen preparations can be used as a long-term treatment because of the virtual absence of side effects. One of the current concerns in the development of therapeutic strategies for late postmenopausal women is the association of HT with the development of breast cancer [37]. However, phytoestrogen therapy appears to be rather safe in this regard.…”

Menopause Medicine: Past, Present, and Future

“…The apparent "harm" reported for combined MHT in the WHI has been overstated. 8,10,11 In the WHI, MHT caused no increase in breast cancer among first-time users. The small increase in breast cancer rates (8/10,000 users per year) seen in former MHT users in the combined estrogen-progestin trial appears to have resulted from an unexplained decrease in breast cancer diagnoses among women assigned to placebo.…”

“…After five decades of study, no conclusive evidence, including the WHI combined CEE/MPA (conjugated equine estrogen/ medroxyprogesterone acetate) trial, proves that MHT causes breast cancer and, in fact, the overwhelming preponderance of data, including the WHI combined CEE/MPA trial, show that estrogen/progestogen therapy has a null effect on breast cancer. 11 Undoubtedly, some will challenge this assertion by citing biological plausibility and the accumulated evidence from observational studies. Nevertheless, the impact of MHT on breast cancer, if any, is small, and the potential preventive benefits for cardiovascular disease are enormous.…”

Traitement de la ménopause : passé, présent et futur

“…Le « danger » apparent de l'HTM combin ee qu'a rapport e l' etude WHI a et e exag er e 8,10,11 . Dans l' etude, l'HTM n'a entraîn e aucune augmentation du risque de cancer du sein chez les nouvelles utilisatrices.…”

“…Apr es cinquante ann ees d' etudes, aucune donn ee concluante, y compris les donn ees tir ees de l'essai de la WHI sur l'hormonoth erapie combin ee EEC-AMPR (oestrog enes equins conjugu es et ac etate de m edroxyprogest erone), ne prouve que l'HTM cause le cancer du sein. En fait, la vaste majorit e des donn ees, notamment celles de l'essai de la WHI sur la combinaison EEC-AMPR, indique que l'hormonoth erapie oestrog ene-progestatif n'a aucune incidence sur le risque de cancer du sein 11 .…”