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The Year in Basic Science: update of estrogen plus progestin therapy for menopausal hormone replacement implicating stem cells in the increased breast cancer risk.

ABSTRACT: This transcript is based on my The Year in Basic Science lecture at ENDO 2008. I reviewed current data surrounding hormone replacement therapy and the relationship between systemic estrogen plus progestin (E+P) treatment and increased breast cancer risk, and I explored the hypothesis that women who develop breast cancer while on E+P had occult, undiagnosed disease before they started therapy. Beginning with recent hormone replacement therapy data focusing on E+P and its association with breast cancer to set the stage, the lecture then reviewed our newly published data that progestins expand breast cancer stem cells. Finally, the issues of occult or undiagnosed breast cancer in presumably healthy women, and of tumor dormancy in breast cancer survivors, were brought to bear on the discussion. Taken together, these apparently disparate themes allowed me to suggest the idea that systemic progestins have the ability to reawaken cancers that were presumed to be either nonexistent or cured. To avoid this potentially devastating outcome while retaining the benefits of E+P, I advocated the use of local P delivery methods, rather than the currently popular systemic routes.

SUBMITTER: Horwitz KB

PROVIDER: S-EPMC2626201 | biostudies-literature | 2008 Dec

REPOSITORIES: biostudies-literature

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The Year in Basic Science: update of estrogen plus progestin therapy for menopausal hormone replacement implicating stem cells in the increased breast cancer risk.

Horwitz Kathryn B KB

Molecular endocrinology (Baltimore, Md.) 20081009 12

This transcript is based on my The Year in Basic Science lecture at ENDO 2008. I reviewed current data surrounding hormone replacement therapy and the relationship between systemic estrogen plus progestin (E+P) treatment and increased breast cancer risk, and I explored the hypothesis that women who develop breast cancer while on E+P had occult, undiagnosed disease before they started therapy. Beginning with recent hormone replacement therapy data focusing on E+P and its association with breast c ...[more]

PMID: 18845670

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Project description:CONTEXT:In the Women's Health Initiative randomized, placebo-controlled trial of estrogen plus progestin, after a mean intervention time of 5.6 (SD, 1.3) years (range, 3.7-8.6 years) and a mean follow-up of 7.9 (SD, 1.4) years, breast cancer incidence was increased among women who received combined hormone therapy. Breast cancer mortality among participants in the trial has not been previously reported. OBJECTIVE:To determine the effects of therapy with estrogen plus progestin on cumulative breast cancer incidence and mortality after a total mean follow-up of 11.0 (SD, 2.7) years, through August 14, 2009. DESIGN, SETTING, AND PARTICIPANTS:A total of 16,608 postmenopausal women aged 50 to 79 years with no prior hysterectomy from 40 US clinical centers were randomly assigned to receive combined conjugated equine estrogens, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5 mg/d, or placebo pill. After the original trial completion date (March 31, 2005), reconsent was required for continued follow-up for breast cancer incidence and was obtained from 12,788 (83%) of the surviving participants. MAIN OUTCOME MEASURES:Invasive breast cancer incidence and breast cancer mortality. RESULTS:In intention-to-treat analyses including all randomized participants and censoring those not consenting to additional follow-up on March 31, 2005, estrogen plus progestin was associated with more invasive breast cancers compared with placebo (385 cases [0.42% per year] vs 293 cases [0.34% per year]; hazard ratio [HR], 1.25; 95% confidence interval [CI], 1.07-1.46; P = .004). Breast cancers in the estrogen-plus-progestin group were similar in histology and grade to breast cancers in the placebo group but were more likely to be node-positive (81 [23.7%] vs 43 [16.2%], respectively; HR, 1.78; 95% CI, 1.23-2.58; P = .03). There were more deaths directly attributed to breast cancer (25 deaths [0.03% per year] vs 12 deaths [0.01% per year]; HR, 1.96; 95% CI, 1.00-4.04; P = .049) as well as more deaths from all causes occurring after a breast cancer diagnosis (51 deaths [0.05% per year] vs 31 deaths [0.03% per year]; HR, 1.57; 95% CI, 1.01-2.48; P = .045) among women who received estrogen plus progestin compared with women in the placebo group. CONCLUSIONS:Estrogen plus progestin was associated with greater breast cancer incidence, and the cancers are more commonly node-positive. Breast cancer mortality also appears to be increased with combined use of estrogen plus progestin. TRIAL REGISTRATION:clinicaltrials.gov Identifier: NCT00000611.

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The Year in Basic Science: update of estrogen plus progestin therapy for menopausal hormone replacement implicating stem cells in the increased breast cancer risk.

Publications

The Year in Basic Science: update of estrogen plus progestin therapy for menopausal hormone replacement implicating stem cells in the increased breast cancer risk.

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