Abstract
Objectives
To assess the extent to which prior hormone therapy modifies the breast cancer risk
found with estrogen plus progestin (E + P) in the Women's Health Initiative (WHI) randomized trial.
Methods
Subgroup analyses of prior hormone use on invasive breast cancer incidence in 16,608
postmenopausal women in the WHI randomized trial of E + P over an average 5.6 years of follow-up.
Results
Small but statistically significant differences were found between prior HT users
and non-users for most breast cancer risk factors but Gail risk scores were similar.
Duration of E + P use within the trial (mean 4.4 years, S.D. 2.0) did not vary by prior use. Among
4311 prior users, the adjusted hazard ratio (HR) for E + P versus placebo was 1.96 (95% confidence interval [CI]: 1.17–3.27), significantly
different (p = 0.03) from that among 12,297 never users (HR 1.02; 95% CI: 0.77–1.36). The interaction
between study arm and follow-up time was significant overall (p = 0.01) and among never users (p = 0.02) but not among prior users (p = 0.10). The cumulative incidence over time for the E + P and placebo groups appeared to cross after about 3 years in prior users, and after
about 5 years in women with no prior use. No interaction was found with duration (p = 0.08) or recency of prior use (p = 0.17). Prior hormone use significantly increased the E + P hazard ratio for larger, more advanced tumors.
Conclusion
A safe interval for combined hormone use could not be reliably defined with these
data. However, the significant increase in breast cancer risk in the trial overall
after only 5.6 years of follow-up, initially concentrated in women with prior hormone
exposure, but with increasing risk over time in women without prior exposure, suggests
that durations only slightly longer than those in the WHI trial are associated with
increased risk of breast cancer. Longer-term exposure and follow-up data are needed.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to MaturitasAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial.JAMA. 2002; 288: 321-333
- Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women: the Women's Health Initiative randomized trial.JAMA. 2003; 289: 3243-3253
- The use of estrogens and progestins and the risk of breast cancer in postmenopausal women.N Engl J Med. 1995; 332: 1589-1593
- Relationship between long durations and different regimens of hormone therapy and risk of breast cancer.JAMA. 2003; 289: 3254-3263
- Hormone replacement therapy containing progestins and given continuously increases breast carcinoma risk in Sweden.Cancer. 2003; 97: 1387-1392
- Breast cancer and hormone-replacement therapy in the Million Women Study.Lancet. 2003; 362: 419-427
- Effect of hormone replacement therapy on breast cancer risk: estrogen versus estrogen plus progestin.J Natl Cancer Inst. 2000; 92: 328-332
- Menopausal estrogen and estrogen–progestin replacement therapy and breast cancer risk.JAMA. 2000; 283: 785-791
FDA News Release. FDA Approves New Labels for Estrogen and Estrogen with Progestin Therapies for Postmenopausal Women Following Review of Women's Health Initiative Data. January 8, 2003. Available at http://www.fda.gov/cder/drug/infopage/estrogens_progestins. Last accessed on June 15, 2006.
- National use of postmenopausal hormone therapy: annual trends and response to recent evidence.JAMA. 2004; 291: 47-53
- Design of the Women's Health Initiative clinical trial and observational study.Control Clin Trials. 1998; 19: 61-109
- Implementation of the Women's Health Initiative study design.Ann Epidemiol. 2003; 13: S5-S17
- The Women's Health Initiative recruitment methods and results.Ann Epidemiol. 2003; 13: S18-S77
- Outcomes ascertainment and adjudication methods in the Women's Health Initiative.Ann Epidemiol. 2003; 13: S122-S128
- Projecting individualized probabilities of developing breast cancer for white females who are being examined annually.J Natl Cancer Inst. 1989; 81: 1879-1886
- Hot flushes, menstrual status, and hormone levels in a population-based sample of midlife women.Obstet Gynecol. 1996; 88: 437-442
- Androgens and estrogen in relation to hot flashes during the menopausal transition.Maturitas. 2002; 41: 69-77
- Elevated serum estradiol and testosterone concentrations are associated with a high risk for breast cancer.Ann Intern Med. 1999; 130: 270-277
- Short-term biologic response to withdrawal of hormone replacement therapy in patients with invasive breast carcinoma.Cancer. 2003; 98: 2539-2546
- Response after withdrawal of tamoxifen and progestogens in advanced breast cancer.Ann Oncol. 1992; 3: 587-588
- Estrogen, estrogen plus progestin therapy and risk of breast cancer.Clin Cancer Res. 2005; 11: 909s-917s
Article info
Publication history
Published online: July 03, 2006
Accepted:
May 5,
2006
Received in revised form:
April 28,
2006
Received:
November 23,
2005
Identification
Copyright
© 2006 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
