Postmenopausal hormone therapy and the risk of breast cancer: A clinician’s view
Introduction
Decision-making regarding postmenopausal hormone therapy has always been a time-consuming process requiring an educated dialogue between patient and clinician. The major concern has been the potential risk of breast cancer associated with hormonal treatment, and this concern has been intensified by recent epidemiologic reports. Despite this new information, decisions are still difficult because the epidemiologic conclusions are not overwhelming in strength, and there are disagreements among the studies. Most importantly, it is not established whether there is a slight increase in breast cancer risk with hormone therapy or whether the epidemiologic results reflect the effect of hormones on pre-existing tumors. This brief review focuses on a critical analysis of the two studies that have had a major public impact in an effort to achieve the most useful clinical conclusions.
Section snippets
The Women’s Health Initiative
On 31 May 2002, the Data and Safety Monitoring Board (DMSB) made its periodic review of the data accumulated by the Women’s Health Initiative (WHI). The DMSB made two recommendations that were made public on 9 July 2002: (1) to discontinue the trial arm administering daily 0.625 mg conjugated estrogens combined with 2.5 mg medroxyprogesterone acetate or placebo and (2) to continue the trial arm comparing daily unopposed estrogen (0.625 mg conjugated estrogens) with placebo in hysterectomized women
The Million Women Study
The Million Women Study recruited 1,084,110 women between 1996 and 2001 from those invited by the UK National Health Service Breast Screening Programme to have screening mammography every 3 years (about half had ever used postmenopausal hormone therapy) [9]. The Study data were recorded from questionnaires returned prior to mammography, and the women were followed to determine cancer incidence and death. The Study is noteworthy for its large numbers and adjustments for the well-recognized
Summary and conclusion
The WHI agrees with some case-control and cohort studies indicating that long-term current use of combined estrogen and progestin has a slightly increased risk of breast cancer. It is still not clear whether this finding is due to an effect of hormonal therapy on pre-existing tumors.
The epidemiologic data indicate that a positive family history of breast cancer should not be a contraindication to the use of postmenopausal hormone therapy.
Women who develop breast cancer while using
Note added in proof
The estrogen-only arm of the WHI failed to observe an increase in breast cancer; indeed, the risk of breast cancer was reduced in the treatment group, although it just failed to reach statistical significance [39]:Empty Cell Estrogen only Placebo Hazard ratio Invasive breast cancer 94 cases 124 cases 0.77 (0.59–1.01)
It is important to keep in mind that the participants in the two arms of the WHI were not identical [40]. The estrogen-only arm had 5859 fewer participants, making it more susceptible to a loss of
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2006, Primary Care - Clinics in Office PracticeCitation Excerpt :Although the WHI and the Million Women Study showed increased breast cancer rates in users of combined HRT, the breast tumors that were found in the WHI were less localized and were associated with more positive lymph nodes [14]. A subsequent analysis of the data showed improved survival rates in postmenopausal women who were taking HRT and subsequently diagnosed with breast cancer [15]. Some investigators postulate that HRT makes patients' breasts more dense, which makes mammography more difficult to read, and, thus, delays the diagnosis [15].
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