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Hormone Replacement Therapy and Breast Cancer
Systematic Evidence Reviews, No. 14
Linda L Humphrey, MD, MPH.
Author Information and AffiliationsStructured Abstract
Objective:
To evaluate and update the prior review evaluating the risk of breast cancer and breast cancer (BCA) death associated with the use of postmenopausal hormone replacement therapy (HRT) by reviewing the medical literature which has been published since the last US Preventive Services Task Force update.
Data Source:
All English language studies identified in the Medline database from 1992-2000 and all previously published meta-analyses. In addition, reference lists of key articles, letters, and editorials were reviewed for all related studies, including those pre-dating the database search.
Study Selection:
All studies that evaluated breast cancer incidence or mortality as a primary or secondary outcome in association with hormone replacement therapy published between 1992-2000. Studies evaluating the effect of hormone replacement therapy on breast density were also reviewed.
Data Extraction:
The following studies met inclusion criteria: 8 meta-analyses from the years 1988-1997, 1 nested case-control study, 14 case-control studies, and 15 cohort studies all evaluating breast cancer incidence, mortality, or both. Of the 15 cohort studies, 10 represented unique cohorts and of the 14 case control studies, 2 involved updates of the same case set. Data from each study were abstracted to prepared forms. When more than one study from the same population was reported, data from the most recent publication were reviewed. If data from the same population were analyzed by cohort and by case-control analysis, both results were reported if they evaluated different outcomes. In addition, several studies evaluating breast density and HRT were reviewed, and the best studies summarized.
Data Synthesis:
For ever or short-term use of estrogen, 7 of the 8 meta-analyses, 8 of the 11 case-control studies, and 6 of the 7 cohort studies evaluating incidence showed no increase in breast cancer with hormone replacement therapy. Of the original studies reviewed evaluating incidence, 12 of 19 showed no increased risk of breast cancer with long duration ERT or HRT use. However, 5 of the meta-analyses showed increased risk with duration over 5 years and 2 important cohort studies showed increased risk with longer duration use. Eleven original studies evaluated combined estrogen and progestin, and one showed increased risk of BCA with short-term use; 3 of the 5 evaluating duration with combined therapy showed increased risk that was statistically significant. Current use of ERT was associated with significantly increased risk of breast cancer in two of the best cohort studies; use of combined therapy was associated with increased risk in 3 studies. Six recent cohort studies (1992-2000) evaluated breast cancer mortality in association with hormone use: 1 showed increased risk of death, 4 showed decreased risk of death, and one showed no association. Several recent studies show that post-menopausal estrogen therapy is associated with increased breast density by mammography and that adding progesterone to estrogen results in even greater increases in breast density. Finally, there is evidence suggesting an important interaction between HRT and alcohol use and HRT and lower body weight.
Conclusions:
The association of short-term hormone replacement therapy with the development of breast cancer is uncertain based on multiple studies with inconsistent findings. Among studies indicating increased risk, the risk is largely confined to current and long-term use (>5–10 years), and the risk is relatively small (RR 1.2–1.5). Reduced mortality is a fairly consistent finding among the studies evaluating breast cancer mortality and HRT use. The addition of progesterone to estrogen and current, as well as long-term, use may be associated with breast cancer risk above that of estrogen itself. Although the biological plausibility of an association between postmenopausal hormone use and breast cancer is high, the studies showing risk or benefit from the use of post-menopausal hormones are limited by the observational nature of the epidemiologic data existing to date. Data from randomized controlled trials are needed to validly evaluate the relationship.
Contents
- Preface
- 1. Introduction
- 2. Methods
- 3. Results
- Does short-term use of exogenous postmenopausal estrogen increase the risk of breast cancer?
- Does long-term use of postmenopausal estrogen increase the risk of breast cancer?
- Is combination therapy with estrogen and progesterone (CHRT) associated with increased risk of breast cancer?
- Does current ERT or CHRT increase the risk of Breast Cancer?
- Does exogenous estrogen and/or estrogen plus progesterone increase the risk of fatal breast cancer?
- Are there subpopulations of women at higher risk of breast cancer in association with hormone replacement therapy?
- Does hormone replacement therapy change breast density on mammograms?
- Does hormone replacement therapy influence prognostic characteristics?
- 4. Discussion
- 5. Research Priorities
- Addendum
- Evidence Tables
- Appendix 1. Search Strategy
- Appendix 2. Search Results
- Appendix 3. Criteria for Grading the Internal Validity of Individual Studies
- Appendix 4. Study Summaries
- References
Prepared for: Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services.1 Contract No. 290-97-0018, Task Order No. 2, Technical Support of the U.S. Preventive Services Task Force. Prepared by: Oregon Health Sciences University Evidence-based Practice Center, Portland, Oregon.
This report may be used, in whole or in part, as the basis for development of clinical practice guidelines and other quality enhancement tools, or a basis for reimbursement and coverage policies. AHRQ or U.S. Department of Health and Human Services endorsement of such derivative products may not be stated or implied.
AHRQ is the lead Federal agency charged with supporting research designed to improve the quality of health care, reduce its cost, address patient safety and medical errors, and broaden access to essential services. AHRQ sponsors and conducts research that provides evidence-based information on health care outcomes; quality; and cost, use, and access. The information helps health care decisionmakers—patients and clinicians, health system leaders, and policymakers—make more informed decisions and improve the quality of health care services.
The authors of this report are responsible for its content. Statements in the report should not be construed as endorsement by the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services of a particular drug, device, test, treatment, or other clinical service.
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- Review Postmenopausal hormone replacement therapy: scientific review.[JAMA. 2002]Review Postmenopausal hormone replacement therapy: scientific review.Nelson HD, Humphrey LL, Nygren P, Teutsch SM, Allan JD. JAMA. 2002 Aug 21; 288(7):872-81.
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