New reports spark more questions on HT risks
Just-published papers in the Journal of the American Medical Association add to heightened concern regarding hormone therapy (HT).1,2 One report suggests that estrogen plus progestin HT use heightens the risk for breast cancers, which are diagnosed at a more advanced stage compared with placebo use, and increases the frequency of abnormal mammograms.1
The second paper, which focuses on long- term HT use among older women, indicates that combination therapy poses an increase in breast cancer risk, regardless of the pattern of progestin use.2
How are clinicians interpreting these data? Much of the reaction is in response to the first report, which updates results from the original Women’s Health Initiative (WHI) data released in 2002.3 Many are puzzled by findings, which seem to contradict earlier studies of the subject.
"The Collaborative Report, for example, found that among a reanalysis of 57 studies (52,705 cancers vs. 108,411 controls) that cancers diagnosed while a woman was on HT were better differentiated, had less lymph involvement;4 overall, the Collaborative Report contradicts what was found in the WHI," observes Susan Wysocki, RNC, NP, president and chief executive officer of the Washington, DC-based National Association of Nurse Practitioners in Women’s Health (NPWH). "Clearly, we need to know more about what these disparities are about."
Wulf Utian, MD, PhD, executive director of the Cleveland-based North American Menopause Society (NAMS), says that the WHI report’s finding of delay in diagnosis and increased size of tumor, does need further examination; however, there was no increase in mortality, he notes.
To help clinicians sort through the data, NPWH will offer two sessions focusing on hormone therapy at its October 2003 annual meeting. NAMS will address the data in a report on postmenopausal HT use from its 2003 HT Advisory Panel. Results will be issued at the September 2003 NAMS Annual Meeting in Miami Beach and posted on its web site, www.menopause.org.
"There may be a small increase in breast cancers with estrogen-progestin therapy, or this treatment stimulates pre-existing tumors to grow," comments Leon Speroff, MD, professor of obstetrics and gynecology at Oregon Health Sciences University in Portland. "I don’t believe it is appropriate to discard the large body of literature indicating that tumors in hormone users are better-differentiated, lower grade and stage disease, with better outcomes."
Look at the research
The WHI report is an updated analysis of data that show that after an average of 5.6 years, 245 of the 8,506 women on combination therapy and 185 of the 8,102 women on placebo developed breast cancer. Of the total cancers, 349 cases were invasive, a type of breast cancer with a greater chance of spreading to other parts of the body.
The breast cancers in the estrogen plus progestin group had similar characteristics to those in the placebo group; however, the tumors in the combination HT group tended to be larger and more advanced. More women had abnormal mammograms in the estrogen plus progestin group (9.4%) compared to the placebo group (5.4%); this pattern continued until the study ended.1
Women in the WHI study received placebo or combined conjugated equine estrogens (0.625 mg/d) plus medroxyprogesterone acetate (2.5 mg/d), manufactured as Prempro (Wyeth Pharmaceuticals, Collegeville, PA).
Keep in mind that the WHI report demonstrated there was no increase in the risk of invasive breast cancer until after five years of use, points out Anita Nelson, MD, professor in the obstetrics and gynecology department at the University of California in Los Angeles (UCLA) and medical director of the women’s health care clinic and nurse practitioner training program at Harbor-UCLA Medical Center in Torrance. Never-users had no increase in breast cancer risk over the control group for the full five years; it was only the women who had used HT before they entered the study who had any increase in risk, she observes.
David Archer, MD, professor of obstetrics and gynecology and director of the Clinical Research Center at the Eastern Virginia Medical Center in Norfolk, sees the report as a recapitulation of the data that were issued in 2002, with two new points: increased mammographic density and increased size of tumor.
"Mammographic density should not delay diagnosis of breast lesions, and tumor size is not as important as nodal involvement," he comments.
What will be the outcome for hormone therapy in light of the new data?
"I think the bottom line, at the moment, is that we will see a tendency toward the same history as we saw with oral contraceptives of reducing dosages in anticipation that lower doses may have the same symptom efficacy but have lower risk profiles," observes Utian.
References
1. Chlebowski RT, Hendrix SL, Langer RD, et al. Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women. The Women’s Health Initiative Randomized Trial. JAMA 2003; 289:3,243-3,253.
2. Li CI, Malone KE, Porter PL, et al. Relationship between long durations and different regimens of hormone therapy and risk of breast cancer. JAMA 2003; 289:3,254-3,263.
3. Writing Group for the Women’s Health Initiative Investigators. 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.
4. Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and hormone replacement therapy: Collaborative reanalysis of data from 51 epidemiological studies of 52,705 women with breast cancer and 108,411 women without breast cancer. Lancet 1997; 350:1,047-1,059.
Resources
The National Association of Nurse Practitioners in Women’s Health’s (NPWH) annual conference will be held Oct. 15-18, 2003, in Savannah, GA. Registration costs for NPWH members: $315 for early registration (postmarked by Aug. 29); $365 for regular registration (postmarked by Oct. 1). Nonmember registration is $390. Registration may be entered on-line at www.npwh.org; also the registration form may be printed and mailed to RSG Consulting, 75 Dogwood Road, Cortlandt Manor, NY 10567, or fax to (914) 734-8055 (credit card registrants only). For more information on the conference, contact: Alyssa Arceneaux, NPWH, 503 Capitol Court N.E., Suite 300, Washington, DC 20002. Telephone: (202) 543-9693, ext. 1. Email: [email protected].
The North American Menopause Society’s annual meeting is scheduled for Sept. 17-20, 2003, in Miami Beach, FL. Registration costs are $545 for members; $645 for nonmembers. All registration fees must be received by Sept. 3; after that date, participants must register at the conference. Visit the NAMS web site, www.menopause.org, for more information.
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