title: Changing concepts: Menopausal hormone therapy and breast cancer.
abstract: Hormone therapy is still used by millions of women for menopausal symptoms. Concerns regarding hormone therapy and breast cancer were initially based on case reports and retrospective case-control studies. However, recent results from large prospective cohort studies and the Women's Health Initiative (WHI) randomized placebo-controlled hormone therapy trials have substantially changed concepts regarding how estrogen alone and estrogen plus progestin influence breast cancer. The preponderance of observational studies suggested that estrogen alone and estrogen plus progestin both increased the risk of breast cancer, with cancers commonly diagnosed at an early stage. However, substantially different results emerged from the WHI randomized hormone therapy trials. In the WHI trial evaluating estrogen plus progestin in postmenopausal women with an intact uterus, combined hormone therapy statistically significantly increased the risk of breast cancer and hindered breast cancer detection, leading to delayed diagnosis and a statistically significant increase in breast cancer mortality. By contrast, estrogen alone use by postmenopausal women with prior hysterectomy in the WHI trial did not substantially interfere with breast cancer detection and statistically significantly decreased the risk of breast cancer. Differential mammography usage patterns may explain differences between observational study and randomized trial results. In clinical practice, hormone therapy users have mammograms more frequently than nonusers, leading to more and earlier stage cancer detection. By contrast, in the WHI randomized trials, mammogram frequency was protocol mandated and balanced between comparison groups. Currently, the different effects of estrogen plus progestin vs estrogen alone on breast cancer are not completely understood.
authors.affiliation: Los Angeles Biomedical Research Institute at Harbor, UCLA Medical Center, 1124 W. Carson St, Torrance, CA 90502, USA. rowanchlebowski@gmail.com
authors.forename: Rowan T
authors.initials: RT
authors.lastname: Chlebowski
authors.forename: Garnet L
authors.initials: GL
authors.lastname: Anderson
mesh_terms: D000368:Aged; D001706:Biopsy / Q000706:statistics & numerical data; D001943:Breast Neoplasms / Q000139:chemically induced* / Q000737:chemistry / Q000175:diagnosis* / Q000453:epidemiology / Q000473:pathology; D004334:Drug Administration Schedule; D015914:Estrogen Replacement Therapy / Q000009:adverse effects* / Q000379:methods*; D004967:Estrogens / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D015994:Incidence; D008593:Menopause; D008875:Middle Aged; D011372:Progestins / Q000008:administration & dosage / Q000009:adverse effects; D011634:Public Health; D016032:Randomized Controlled Trials as Topic; D011960:Receptors, Estrogen / Q000032:analysis / Q000187:drug effects; D011980:Receptors, Progesterone / Q000032:analysis / Q000187:drug effects; D012306:Risk
chemical_list: D004967:Estrogens; D011372:Progestins; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone