title: 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 trial (1) . 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.
authors.affiliation: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center , Torrance, CA , USA.
authors.forename: R T
authors.initials: RT
authors.lastname: Chlebowski
authors.forename: G L
authors.initials: GL
authors.lastname: Anderson
authors.forename: R L
authors.initials: RL
authors.lastname: Prentice
authors.forename: J E
authors.initials: JE
authors.lastname: Rossouw
authors.forename: A K
authors.initials: AK
authors.lastname: Aragaki
authors.forename: J E
authors.initials: JE
authors.lastname: Manson
mesh_terms: D015982:Bias; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality*; D015914:Estrogen Replacement Therapy / Q000379:methods*; D004967:Estrogens / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008327:Mammography; D017698:Postmenopause; D011372:Progestins / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic
chemical_list: D004967:Estrogens; D011372:Progestins
keywords: BREAST CANCER; ESTROGEN; ESTROGEN PLUS PROGESTIN; PLACEBO-CONTROLS; RANDOMIZED CLINICAL TRIAL