Estrogen replacement therapy in patients with early breast cancer

OBJECTIVE: Most physicians believe that estrogen replacement therapy is contraindicated once a patient is diagnosed with breast cancer. Recently, several studies have shown that estrogen replacement therapy may be safely used in patients with early breast cancer that has been treated successfully. These women can have severe menopausal symptoms and are at risk for osteoporosis. We reviewed the current status of women in our practice with breast cancer who received estrogen replacement therapy, who did not receive hormone replacement therapy, and who did not receive estrogenic hormone replacement therapy. STUDY DESIGN: The study group consisted of 123 women (mean age, 65.4 +/- 8.85 years) who were diagnosed with breast cancer in our practice, including 69 patients who received estrogen replacement therapy for < or = 32 years after diagnosis. The comparative groups were 22 women who used nonestrogenic hormones for < or = 18 years and 32 women who used no hormones for < or = 12 years. The group who did not receive estrogenic hormone replacement therapy received androgens with or without progestogens (such as megestrol acetate). Of the 63 living hormone users, 56 women are still being treated in our clinic, as are 15 of the 22 subjects who receive nonestrogenic hormone replacement therapy. Follow-up was done through the tumor registry at University Hospital; those patients whose tumor records were not current were contacted by telephone. RESULTS: There were 18 deaths in the 123 patients: 6 patients who received estrogen replacement therapy (8.69%), 2 patients who received nonestrogenic hormone replacement therapy (9.09%), and 10 patients who received no hormone replacement therapy (31.25%). Of the 18 deaths, 9 deaths were from breast cancer (mortality rate, 7.3%); 3 deaths were from lung cancer; 1 death was from endometrial cancer; 1 death was from myocardial infarction; 1 death was from renal failure; and 3 deaths were from cerebrovascular accidents. The 9 deaths from breast cancer included one patient who received nonestrogenic hormone replacement therapy (mortality rate, 4.5%), 6 patients who received no hormone replacement therapy (mortality rate, 11.3%), and 2 patients who received estrogen replacement therapy (mortality rate, 4.28%). The 9 non-breast cancer deaths included 4 patients who received estrogen replacement therapy (endometrial cancer [1 death], lung cancer [1 death], cerebrovascular accident [1 death], and renal failure [1 death]), 1 patient who did not receive estrogenic hormone replacement therapy group (myocardial infarction), and 4 patients who used no hormones (lung cancer, 2 deaths; stroke, 2 deaths). Carcinoma developed in one patient in the estrogen replacement therapy group in the contralateral breast after 4 years of hormone replacement therapy; she is living and well 2.5 years later with no evidence of disease. Metastatic breast cancer developed in one patient after 8 years of hormone replacement therapy; she is living with disease. CONCLUSION: Estrogen replacement therapy apparently does not increase either the risk of recurrence or of death in patients with early breast cancer. These patients may be offered estrogen replacement therapy after a full explanation of the benefits, risks, and controversies.     

Postmenopausal hormone replacement and cardiovascular disease: incorporating research into practice

The long-standing practice of prescribing hormones to postmenopausal women was based in part on the observation that following menopause, women's incidence of cardiovascular diseases such as atherosclerosis, myocardial infarction, and cerebral vascular accident increased. Recent large-scale research has shown an increase in cardiovascular events for postmenopausal women receiving estrogen replacement in oral form. This article examines research on positive effects of hormone replacement therapy, discusses what is known about the development of cardiovascular disease in women, and evaluates recent research that has shown increased cardiovascular risk in women receiving hormone replacement. It concludes with recommendations for preventing cardiovascular disease in women. This is essential information for nurses, who need to be informed of ways to maintain their own health while serving as sources of health information for the public at large.     

Risk of myocardial infarction, angina and stroke in users of oral contraceptives: an updated analysis of a cohort study

Objectives To investigate risk of myocardial infarction, angina and stroke in users of contraceptive pills compared with users of other methods of contraception.
Design Prospective cohort study, with recruitment between 1968 and 1974 and annual follow up until the age of 45 years. After this age, only women who had never used oral contraception or those who had used it for eight or more years continued to be followed up annually until July 1994.
Setting Seventeen family planning clinics in England and Scotland.
Population 17,032 women aged between 25 and 39 years at entry to the study.
Main outcome measures Occurrence of angina, myocardial infarction or stroke that was associated with either hospital admission or outpatient referral to hospital or death.
Results Increased risk of myocardial infarction in oral contraceptive users was observed only in women who were heavy smokers at entry to the study. In this subgroup the relative risk of a myocardial infarction was 4.2 (95% CI 1.4–16.6) in ever users of oral contraception compared with non-users, 4–9 (1.2–23.6) in current users, and 4–0 (1.3–16.2) in ex-users. In all current users the relative risk of angina was 0.5 (0.1–1.4), and the relative risk of ischaemic stroke was 2.9 (1.3–6.7). The increased risk of ischaemic stroke did not persist in ex-users.
Conclusions Use of oral contraception is associated with increased risk of ischaemic stroke and increased risk of myocardial infarction (only in heavy smokers), but no increased risk of angina. These increased risks need to be considered within the context of the very low absolute risks of cardiovascular disease in this population. 5880 women need to take oral contraception for one year to cause one extra stroke, and 1060 women who are heavy smokers need to take it for one year to cause one extra myocardial infarction.     

Hormone replacement therapy and risk of malignancy

PURPOSE OF REVIEW: The fact that today our concern is oriented towards the risks rather than the benefits of hormone replacement therapy could be the clearest message about our current position. The safety of hormone replacement therapy, an estrogen-progestin combination which has been sympathetic to and supportive of disturbing menopausal symptoms of women, is seriously challenged. RECENT FINDINGS: Four randomized trials have now reported on the results of hormone replacement therapy in major potentially fatal conditions, in more than 20,000 women studied for about 5 years. The main concern regarding the increased risk of malignancy in healthy postmenopausal women in western countries has been breast cancer. It is estimated to cause an extra case in about six per 1000 users aged 50-59 and 12 per 1000 aged 60-69. Over the same period the estimated risk of endometrial cancer rates are not increased, with a relative risk of 0.76 per 1000 users aged 50-59. Overall, however, the increased incidence of malignancies is greater than any reduction, one per 230 users aged 50-59 and one per 150 aged 60-69. Randomized trials examining other important but rarer malignancies, like ovarian, gall bladder and urinary bladder cancer, are either nonexistent or too small to reliably describe any effects of hormone replacement therapy. SUMMARY: Conclusively epidemiological evidence suggests that hormone replacement therapy is associated with a small but substantial increase in breast cancer risk and combined estrogen-progesterone regimens further increase this hazard. Additionally, the evidence from the recent double blind placebo controlled randomized trial on the slight increase in the incidence of adverse cardiovascular events, has turned our orientation away from hormone replacement therapy as a long term therapy in postmenopausal women. In this review, the effort is to approach comprehensively and globally the information on the risks of hormone replacement therapy on several cancer sites.     

Use of hormone replacement therapy among Danish nurses in 1993

BACKGROUND: To describe the prevalence of women using systemic hormone replacement therapy in various age groups. To identify their reasons for choosing or not choosing the therapy, reasons for discontinuing the treatment, the prevalence of side effects among current users, and to estimate the duration of treatment. METHODS: The study is based on postal questionnaires sent to 23,000 female Danish nurses above the age of 44 years. Out of these 19,953 (86%) responded. The questionnaire gave information on age, use of hormone replacement therapy, use of oral contraceptives, family predisposition and diseases. Duration of hormone replacement therapy was calculated by Cox regression analysis. Chi square tests were used to evaluate differences and 5% was used as the level of significance. RESULTS: Overall, 6673 (33%) had ever used hormone replacement therapy. The prevalence was highest in the age group 55-59, where 29.3% were currently using hormones. The most cited reasons for choosing hormone replacement therapy were vasomotor symptoms (62%) and prevention of osteoporosis (44%). Among never users 43% had not experienced climacteric symptoms, 24% found the therapy unnatural, and 22% were afraid of side effects. It was estimated that 70% still were using hormones five years after the start of therapy, 57% after ten years, and 48% after fifteen years. Women with a family history of osteoporosis used hormones longer than women without this predisposition. CONCLUSIONS: One third of all the women had ever used hormone replacement therapy and more than half of ever users used the therapy for more than ten years.     

Could androgens protect middle-aged women from cardiovascular events? A population-based study of Swedish women: The Women's Health in the Lund Area (WHILA) Study.

OBJECTIVE: The aim of this analysis was to delineate perceived associations between androgens and cardiovascular events in perimenopausal women. DESIGN: A cross-sectional, population-based study of 6440 perimenopausal women aged 50-59 years, living in Southern Sweden. In all, 461 (7.1%) women were premenopausal (PM), 3328 (51.7%) postmenopausal without hormone therapy (HT) (PM0) and 2651 (41.2%) postmenopausal with HT (PMT). For further comparisons, 104 women (1.6%) who reported cardiovascular disease (CVD) were studied in detail; 49 had had a myocardial infarction, 49 a stroke and six women both events. For each woman with CVD, two matched controls were selected (n=208). RESULTS: In the matched controlled series, androstenedione levels were lower (p<0.005) in cases. Cases with hormone therapy had also lower testosterone levels than matched controls (p=0.05). In the total cohort, by using multiple logistic regression analyses, testosterone was positively associated with low density lipoprotein cholesterol (p<0.001) and high density lipoprotein cholesterol (HDL-C) (p<0.001) in all women, but negatively associated with levels of triglycerides in both the PM0 (p<0.001) and PMT (p<0.001) groups. Androstenedione levels were positively associated with HDL-C (p<0.05) and negatively with triglycerides (p<0.05) in the PM group. CONCLUSION: Women with cardiovascular disease had lower serum androgen levels, particularly women using hormone replacement therapy, even when controlled for lipids and other potential risk factors.     

Effect of long-term hormone substitution therapy on serum TSH level in postmenopausal women

OBJECTIVE: Dysfunction's of the thyroid gland are one of the most important endocrinological diseases. We report serum TSH levels in postmenopausal women before and during long-term hormone replacement therapy. MATERIAL AND METHODS: 107 postmenopausal patients participated in this study. Criteria for inclusion were: no known thyroid dysfunction and request for hormone replacement. Before starting therapy TSH serum levels were measured in each patient. If basal levels were within normal range TSH serum levels were reported over 4 years of hormone replacement therapy. RESULTS: More than 10% of the postmenopausal women showed pathological TSH-levels without clinical symptoms requiring further diagnostic. During subsequent treatment cycles (4 years) serum TSH in euthyroid patients did not show significant changes. Women using hormone replacement therapy developed no new manifestation of thyroid disease. CONCLUSION: In euthyroid women using long-term hormone replacement therapy are no changes in thyroid function caused by hormone replacement therapy to expect.     

A study of hormone replacement therapy in postmenopausal women with ischaemic heart disease: the Papworth HRT atherosclerosis study

Objective To assess the possible benefit of hormone replacement therapy (HRT) in the secondary prevention of ischaemic heart disease.
Design A prospective randomised trial of transdermal HRT in women with definite ischaemic heart disease.
Setting A regional cardiac unit.
Population Postmenopausal women with angiographically ischaemic heart disease.
Methods A total of 255 postmenopausal women with angiographically proven ischaemic heart disease were recruited and randomised; 134 were treated with transdermal HRT and 121 acted as controls. The women were seen at six monthly intervals. The primary end points, which were determined by a blinded assessor, were admission to hospital with unstable angina, proven myocardial infarction or cardiac death. A total of 53 (40%) patients withdrew from the HRT group and eight (7%) from the control group. The mean duration of follow up was 30.8 months.
Main outcome measures Admission to hospital with unstable angina, proven myocardial infarction or cardiac death.
Results During follow up, there were 53 primary end-point events in the HRT group and 37 in the control group. Using an intention-to-treat analysis, the primary end-point event rate was 15.4 events per 100 patient years for the HRT group compared with 11.9 for the control group (event rate ratio 1.29 (95% CI 0.84–1.95,   P = 0.24  )). Using a per-protocol analysis, there was an event rate ratio of 1.49 (  0.93–2.36, P = 0.11  ) for the HRT arm compared with the control arm. Particularly during the first two years of follow up, the HRT group had a higher, but not statistically significant, event rate than the control group.
Conclusion Our findings suggest that transdermal HRT should not be commenced for the purpose of secondary prevention in postmenopausal women with angiographically proven ischaemic heart disease.     

Assessment by quantitative ultrasonometry of the effects of hormone replacement therapy on bone mass

OBJECTIVE: This study was undertaken to evaluate the impact of hormone replacement therapy on results of quantitative ultrasonometry of the heel. STUDY DESIGN: A total of 2006 healthy perimenopausal women (mean age, 52.2 (10.3 years) were recruited in 5 German centers: 611 women (30%) had received hormone replacement therapy and 1395 (70%) had not. About 90% of the hormone replacement therapy users were current users, and the rest had stopped <6 months before the study. Speed of sound, broadband ultrasonographic attenuation, and the stiffness index were compared among the following groups: all users and nonusers of hormone replacement therapy, hormone replacement therapy users and nonuser control subjects matched for age and body mass index, and hormone replacement therapy users grouped in relation to the duration of hormone replacement therapy use and age and control subjects matched for body mass index. RESULTS: Women who were using hormone replacement therapy had significantly higher values (P <.001) than did nonusers for all ultrasonographic variables, even after we controlled for age and body mass index. Women who had used hormone replacement therapy for >3 years had significantly higher values (P <.001) than did matched control subjects for all variables. Differences increased with the duration of hormone replacement therapy use. CONCLUSION: Quantitative ultrasonometric measurement at the heel differentiates hormone replacement therapy users from nonusers, reflects duration of hormone replacement therapy use, and could be useful in both clinical trials and patient management.     

Continuous combined hormone replacement therapy and risk of endometrial cancer

OBJECTIVE: Postmenopausal women who receive sequential hormone replacement therapy with estrogen combined with progestogen for 10 to 24 d/mo for a prolonged period may have an elevated endometrial cancer risk relative to those who have never received hormone replacement therapy. We investigated whether daily use of estrogen and progestogen (continuous combined hormone replacement therapy) could diminish any excess endometrial cancer risk.Study Design: A population-based study in Washington State obtained interview data from 969 women aged 45 to 74 years with endometrial cancer diagnosed during 1985 through 1991 or 1994 through 1995 and from 1325 age-matched control subjects selected primarily by random digit dialing. Women who had received only continuous combined hormone replacement therapy were compared with women who had only received another hormone replacement therapy regimen or who had never received hormone replacement therapy. RESULTS: The risk of endometrial cancer among users of continuous combined hormone replacement therapy (n = 9 case patients, n = 33 control subjects) relative to women who had never received hormone replacement therapy was 0.6 (95% confidence interval, 0.3-1.3); the risk relative to women who received hormone replacement that included progestogen for 10 to 24 d/mo was 0.4 (95% confidence interval, 0.2-1.1). Most continuous combined hormone replacement therapy use was short-term (<72 months) or recent (in the previous 24 months). CONCLUSION: Women who had received continuous combined hormone replacement therapy for several years did not appear to be at any increased risk for endometrial cancer relative to women who had never received hormone replacement therapy and may in fact be at decreased risk for endometrial cancer.     

Hormone therapy and cardiovascular disease: a systematic review and meta-analysis

BACKGROUND: Despite decades of evidence from observational studies, the use of hormone therapy for the prevention of cardiovascular disease (CVD) among postmenopausal women is controversial. The recent completion of several randomised clinical trials examining the effects of hormone therapy on CVD presents an opportunity to provide a more precise estimate of the cardiovascular risks of hormone therapy. OBJECTIVE: To summarise the effects of hormone therapy on CVD in postmenopausal women. SEARCH STRATEGY: MEDLINE, EMBASE, the Cochrane Library, DARE and CENTRAL were searched for clinical trials reporting mortality and/or CVD outcomes in association with hormone therapy. Bibliographies and editorials were also reviewed. All studies were reviewed and rated for quality independently by two reviewers. SELECTION CRITERIA: High quality, randomised placebo-controlled clinical trials of hormone therapy (duration greater than one year) in non-hospitalised postmenopausal women were included. DATA COLLECTION AND ANALYSIS: Summary relative risks were estimated for all-cause mortality, coronary heart disease (CHD) mortality, non-fatal acute myocardial infarction (AMI) and all stroke. MAIN RESULTS: Seven randomised clinical trials met the inclusion criteria. The use of hormone therapy had no significant effect on all-cause mortality, non-fatal AMI or CHD mortality, with relative risks of 1.02 [95% confidence interval (CI) 0.93-1.13], 1.00 (0.88-1.14) and 0.99 (0.82-1.21), respectively. For all stroke, the summary relative risk was 1.29 (1.13-1.48). AUTHOR'S CONCLUSIONS: This systematic review, incorporating the latest available trial data, shows that hormone therapy does not significantly change the risk of all-cause morality, CHD death or non-fatal AMI but increases the risk of stroke in postmenopausal women.     

Management of preterm prelabour rupture of membranes: an audit. How do the results compare with clinical practice guidelines?

BACKGROUND: Preterm prelabour rupture of membranes is a common clinical event. It is associated with infection in approximately 50% of cases. Clinical practice guidelines have been developed at the Royal Women's Hospital, Melbourne, Australia for investigation and management of this condition. AIM: To perform an audit of management of women presenting with this diagnosis and assess how inpatient management compares with the Hospital's current clinical practice guideline and how the clinical practice guideline compares with the evidence in the literature. METHODS: Retrospective audit over a 3-month period collecting data on maternal age, gestation, microbiological results, other investigations, pharmacological treatment and outcome. RESULTS: All the 56 women admitted for this reason received at least one dose of antibiotic, most commonly erythromycin. More than two thirds of patients had the antibiotic changed at least once during their admission. Ten patients were prescribed intravenous antibiotics without a clear indication. Sixty-four percent received steroids for lung maturation of the neonate and 30% received tocolysis with nifedipine. Almost two thirds of patients delivered within 7 days and there were four neonatal deaths. CONCLUSION: In general management of women with premature rupture of membranes is in keeping with the current clinical practice guideline at the Royal Women's Hospital although antibiotic prescribing and management of Group B streptococcus colonisation could be improved. In addition, routine measurement of C reactive protein should cease. The current clinical practice guideline should be modified to reflect the current evidence in the literature.     

Postpartum acute myocardial infarction

We report a postpartum acute myocardial infarction that occurred during the first week after cesarean section delivery. We also calculated the rate of postpartum myocardial infarction as related to all women with myocardial infarctions seen in our hospital.(Am J Obstet Gynecol 1997;177:1553-5.)     

Menopausal hormones and risk of ovarian cancer

OBJECTIVE: The objective of this study was to determine if use of menopausal hormones was associated with ovarian cancer and if risk varied by type of hormone used. STUDY DESIGN: Data from a population-based, case-control study of ovarian cancer in North Carolina (364 cases, 370 controls, all postmenopausal) were analyzed to evaluate the relationship between menopausal hormones and ovarian cancer. Logistic regression analyses were used to calculate odds ratios (OR) and 95% CIs associated with various patterns of hormone use. RESULTS: Ovarian cancer cases were more likely than controls to report long-term use (>or=10 years) of unopposed estrogens (OR 2.2; 95% CI 1.2-4.1). No relationship was observed for estrogen always used with progestin. CONCLUSION: Hormone replacement therapy used according to current recommendations should not increase risk of ovarian cancer; however, clinicians should be aware of possible increased risk among women with a long history of estrogen replacement therapy.     

Comparative cardiovascular effects of different progestins in menopause.

Progesterone receptors are present in the arterial wall and it is, therefore, likely that the arterial effects of progestins are mediated through progesterone receptors as well as through down-regulation of the estradiol receptor. Progestin therapy affects arterial function, as it can stabilize arteries in a state of vasomotor instability, but may also induce vasoconstriction of estrogenized vessels. Thus, the cardiovascular effects of progestins may influence the cardioprotective effect of estrogens. There has been some concern that a combined estrogen-progestogen therapy may attenuate some of estrogen's beneficial effects on cardiovascular health. This is a reflection of the past epidemiologic studies which have used primarily unopposed estrogen. The PEPI trial is the only large-scale, long-term study to compare directly the effects of different combined hormone replacement therapy regimens upon plasma lipids in healthy women. This study has shown that the adjunctive clinical impact of different progestogens on the beneficial effect of estrogen replacement therapy is trivial. It has never been proved that in normocholesterolemic women, e.g., those included in the PEPI trial, the increase in HDL reduces cardiovascular mortality or morbidity. Based on the results of PEPI, hormone replacement therapy has positive effects on key heart disease risk factors and endometrial tissue, and the magnitude of those effects does not differ significantly across the hormone replacement therapy regimens used. At present there are only few and inconclusive data available on the vascular effect of progestins in menopausal women. Some studies found that progestins reduced the beneficial effect of estrogens, while others did not. Our group has recently shown that different estrogen-progestin treatments have different effects upon vascular reactivity and that a careful selection of the progestin to be added to estrogen is of capital importance to preserve, or even enhance the positive vascular effects of estrogens. Few epidemiological studies have investigated the effect of adding a progestin to estrogen therapy upon cardiovascular mortality and morbidity, and all have suggested that hormone replacement therapy may be more effective than estrogen replacement alone in reducing cardiovascular events in primary prevention. The results of the recently published Heart and Estrogen/progestin Replacement Study (HERS) have added some critical data on the effect of hormone replacement therapy for secondary prevention in women with coronary artery disease. The study, however, is affected by several important methodological and statistical problems, which make its interpretation difficult and its conclusions useless for clinical practice. The results of the study should be evaluated with caution by physicians who give advice on hormone replacement therapy, and no woman should be taken off hormone replacement therapy because of HERS. Of importance, the results of HERS should not be used to suggest alternative forms of treatment, especially the selective estrogen receptor modulators (SERMs), for cardiovascular protection in postmenopausal women.     

Effect of oral hormone replacement therapy on plasma homocysteine levels

BACKGROUND: Various inherited or acquired conditions can lead to mild or severe hyperhomocysteinemia, which has toxic effects on the vascular endothelium. It has been reported that hormone replacement therapy is associated with decreased homocysteine plasma levels, but this is still a controversial issue. PURPOSE: To compare homocysteine plasma levels in women before and after 3 months of oral hormone replacement therapy. METHODS: Twenty-four women were selected to take part in the study. Blood samples were collected immediately before hormone replacement therapy (cyclic association of 2 mg of estradiol valerate and 1 mg of cyproterone acetate) and three months after the beginning of hormone replacement therapy. Samples collected before hormone replacement therapy were used as controls. Plasma homocysteine levels and the presence of C677T mutation in the methylene tetrahydrofolate reductase gene were evaluated in all participants. RESULTS: The methylene tetrahydrofolate reductase gene mutation was detected in 8 women (33.3%) in heterozygosis, in 3 (12.5%) in homozygosis, and 13 women (54.2%) did not present the mutation. No significant differences were observed in homocysteine levels before and after three months of oral hormone replacement therapy, regardless of the C677T genotype. CONCLUSIONS: The results obtained indicate that homocysteine plasma levels are not affected after three months of oral hormone replacement therapy.     

Hormone substitution after carcinoma

OBJECTIVE: The colorectal carcinoma is one of the most frequent malignomas in western countries. Therefore the gynecologist often will be confronted with the question whether a hormone replacement with sexual steroids is allowed after a curative operation. MATERIAL AND METHODS: Basing on the data of several international publications we have substituted in an own study from 1989 to 1997 42 women with colon and 10 with rectal cancer after successful operation with a combined preparation. RESULTS: In the meantime it could be proved that in the cells of colorectal carcinomas estrogen and progesterone receptors are absent or only existing in a low concentration. Thus analogous to the receptor positive breast cancer the hormone replacement therapy also after curative treatment of a colorectal cancer should be justified. Therefore the benefit of the individual hormone replacement therapy shouldn't be withheld from these women without worsening the prognosis. CONCLUSIONS: After palliative therapy and in the case of a relapse a combined hormone replacement can be an act for diminishing the disease and should be recommended after a corresponding clearing-up and weighing the risk.     

Incidence of breast cancer in a 22-year study of women receiving estrogen-progestin replacement therapy.

OBJECTIVE: To review the incidence of breast cancer in a continuous 22-year study of conjugated estrogen-medroxyprogesterone acetate hormone replacement therapy. METHODS: Eighty-four pairs of continuously hospitalized postmenopausal women who were matched for age, smoking history, and medical diagnosis were treated with estrogen-progestin hormone replacement therapy or placebo in a prospective and double-blind manner for 10 years. In the subsequent 12 years, the women were offered the choice of starting, stopping, or continuing hormone replacement therapy. RESULTS: After the initial 10 years, the incidence of breast cancer in the placebo group was 4.8%, whereas no cancers were found in the hormone replacement therapy group (P = .12). After an additional 12 years of follow-up, the overall incidence of breast cancer in the women who had never taken hormone replacement therapy was 11.5%, whereas no breast cancers had developed in the women who had ever taken hormone replacement therapy (P < .01). CONCLUSIONS: These data suggest that the 22-year administration of estrogen-progestin hormone replacement therapy did not increase the incidence of breast cancer in a small group of continuously hospitalized postmenopausal women.