Reliable evidence from placebo-controlled, randomized, clinical trials for menopausal hormone therapy's influence on incidence and deaths from breast cancer

ABSTRACT

In an invited editorial, Dr Shapiro proposes that vaginal bleeding leading to unblinding and subsequent detection bias explains the breast cancer increase seen with estrogen plus progestin in the Women's Health Initiative (WHI) clinical trial¹. In the context of a uniform detection program of protocol-mandated annual mammography and breast examinations, such a proposal is medically implausible. Dr Shapiro suggests detection bias would identify a larger number of ‘slowly growing tumors that would otherwise remain clinically silent’. The findings of more advanced cancers with increased deaths from breast cancer in the estrogen plus progestin group refute this conjecture. During early post-intervention phases of both WHI hormone therapy trials, when breast cancer detection bias is asserted by Dr Shapiro because participants had been informed of randomization assignment, breast cancer incidence rates were lower (rather than higher) than during intervention. Thus, Dr Shapiro's claims are directly refuted by findings from the WHI randomized clinical trials. Health-care providers should be aware that randomized clinical trial evidence supports estrogen plus progestin increasing breast cancer incidence and deaths from breast cancer. In contrast, among women with prior hysterectomy, randomized clinical trial evidence supports estrogen alone reducing breast cancer incidence and deaths from breast cancer.

Key words::

• PLACEBO-CONTROLS
• RANDOMIZED CLINICAL TRIAL
• BREAST CANCER
• ESTROGEN
• ESTROGEN PLUS PROGESTIN
• BREAST CANCER

Conflict of interest Dr Chlebowski reported being a consultant for AstraZeneca, Novartis, Amgen, Genomic Health and Novo Nordisk; receiving funding support from Amgen; and serving on the speaker's bureau for Novartis and Genentech.

Source of funding The WHI program is funded by the National Heart, Lung, and Blood Institute at the National Institutes of Health, U.S. Department of Health and Human Services through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN 268201100003C, HHSN268201100004C, HHSN2712011 00004C.