Virginia L. Ernster

PURPOSE: To critically review the risks and benefits of hormone therapy for asymptomatic postmenopausal women who are considering long-term hormone therapy to prevent disease or to prolong life. DATA SOURCES: Review of the English-language literature since 1970 on the effect of estrogen therapy and estrogen plus progestin therapy on endometrial cancer, breast cancer, coronary heart disease, osteoporosis, and stroke. We used standard meta-analytic statistical methods to pool estimates from studies to determine summary relative risks for these diseases in hormone users and modified lifetable methods to estimate changes in lifetime probability and life expectancy due to use of hormone regimens. RESULTS: There is evidence that estrogen therapy decreases risk for coronary heart disease and for hip fracture, but long-term estrogen therapy increases risk for endometrial cancer and may be associated with a small increase in risk for breast cancer. The increase in endometrial cancer risk can probably be avoided by adding a progestin to the estrogen regimen for women who have a uterus, but the effects of combination hormones on risk for other diseases has not been adequately studied. We present estimates for changes in lifetime probabilities of disease and life expectancy due to hormone therapy in women who have had a hysterectomy; with coronary heart disease; and at increased risk for coronary heart disease, hip fracture, and breast cancer. CONCLUSIONS: Hormone therapy should probably be recommended for women who have had a hysterectomy and for those with coronary heart disease or at high risk for coronary heart disease. For other women, the best course of action is unclear.

OBJECTIVE: To determine the efficacy of screening mammography by age, number of mammographic views per screen, screening interval, and duration of follow-up. DESIGN: Literature review and meta-analysis. DATA IDENTIFICATION AND ANALYSIS: Literature search of English-language studies reported from January 1966 to October 31, 1993, using MEDLINE, manual literature review, and consultation with experts. A total of 13 studies were selected, and their results were combined using meta-analytic techniques based on the assumption of fixed effects. MAIN RESULTS: The overall summary relative risk (RR) estimate for breast cancer mortality for women aged 50 to 74 years undergoing screening mammography compared with those who did not was 0.74 (95% confidence interval [CI], 0.66 to 0.83). The magnitude of the benefit in this age group was similar regardless of number of mammographic views per screen, screening interval, or duration of follow-up. In contrast, none of the summary RR estimates for women aged 40 to 49 years was significantly less than 1.0, irrespective of screening intervention or duration of follow-up. The overall summary RR estimate in women aged 40 to 49 years was 0.93 (95% CI, 0.76 to 1.13); the summary RR estimate for those studies that used two-view mammography was 0.87 (95% CI, 0.68 to 1.12) compared with 1.02 (95% CI, 0.73 to 1.44) for those studies that used one-view mammography, and for those studies with 7 to 9 years of follow-up, the summary RR estimate was 1.02 (95% CI, 0.82 to 1.27) compared with 0.83 (95% CI, 0.65 to 1.06) for those studies with 10 to 12 years of follow-up. CONCLUSION: Screening mammography significantly reduces breast cancer mortality in women aged 50 to 74 years after 7 to 9 years of follow-up, regardless of screening interval or number of mammographic views per screen. There is no reduction in breast cancer mortality in women aged 40 to 49 years after 7 to 9 years of follow-up. Screening mammography may be effective in reducing breast cancer mortality in women aged 40 to 49 years after 10 to 12 years of follow-up, but the same benefit could probably be achieved by beginning screening at menopause or 50 years of age.

OBJECTIVE: To assess the association of unopposed estrogen or estrogen plus progestin and the risk of developing endometrial cancer or dying of that disease. DATA SOURCES: A literature search of English-language studies was performed using MEDLINE, a review of bibliographies, and consultations with experts. METHODS OF STUDY SELECTION: We identified 30 studies with adequate controls and risk estimates. DATA EXTRACTION AND SYNTHESIS: Risk estimates were extracted by two authors and summarized using meta-analytic methods. The summary relative risk (RR) was 2.3 for estrogen users compared to nonusers (95% confidence interval [CI] 2.1-2.5), with a much higher RR associated with prolonged duration of use (RR 9.5 for 10 or more years). The summary RR of endometrial cancer remained elevated 5 or more years after discontinuation of unopposed estrogen therapy (RR 2.3). Interrupting estrogen for 5-7 days per month was not associated with lower risk than daily use. Users of unopposed conjugated estrogen had a greater increase in RR of developing endometrial cancer than users of synthetic estrogens. The risk for endometrial cancer death was elevated among unopposed estrogen users (RR 2.7, 95% CI 0.9-8.0). Among estrogen plus progestin users, cohort studies showed a decreased risk of endometrial cancer (RR 0.4), whereas case-control studies showed a small increase (RR 1.8). CONCLUSIONS: Endometrial cancer risk increases substantially with long duration of unopposed estrogen use, and this increased risk persists for several years after discontinuation of estrogen. Although not statistically significant, the risk of death from endometrial cancer among unopposed estrogen users is increased, similar to the increased risk of developing the disease. Data regarding risk for endometrial cancer among estrogen plus progestin users are limited and conflicting.

OBJECTIVE: To describe trends in incidence and treatment for ductal carcinoma in situ (DCIS) of the breast in the United States between 1973 and 1992 and to estimate total numbers of in situ cases diagnosed and numbers treated by mastectomy since 1983, when screening mammography for breast cancer began to become widespread. DESIGN: Analysis of population-based breast cancer incidence data collected by the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program since 1973 and treatment data collected by the SEER program since 1983. STUDY POPULATION: All women in the geographic areas af the United States included in the SEER program. MAIN OUTCOME MEASURES: Annual age-adjusted and age-specific incidence rates for DCIS; time trends in distribution of cases by type of treatment; percentage of cases treated by mastectomy by geographic area; and estimated numbers for the entire United States of DCIS cases, mastectomies for DCIS, and cases attributable to mammography. RESULTS: There was a marked increase in DCIS incidence beginning in the early 1980s. Average annual increases in rates between 1973 and 1983 and between 1983 and 1992 changed from 0.3% to 12.0% among women aged 30 to 39 years, from 0.4% to 17.4% among women aged 40 to 49, and from 5.2% to 18.1% among women aged 50 years or older. The total estimated number of DCIS cases in the United States in 1992 (23,368) was 200% higher than expected based on 1983 rates and trends between 1973 and 1983. Between 1983 and 1992, there was a marked decline in the proportion of DCIS cases treated by mastectomy (from 71% to 43.8%) and an increase in those treated by lumpectomy (from 25.6% to 53.3%). In 1992, 23.3% of cases were treated by lumpectomy and radiation, 30.2% by lumpectomy alone, and 2.6% with no surgery. Treatment patterns varied substantially by geographic area, with 57.7% of cases in New Mexico treated by mastectomy in 1992 compared with 28.8% in Connecticut. Despite the decline in the proportion of cases treated by mastectomy, the increased DCIS incidence rates resulted in an increase in the absolute number of cases treated by mastectomy until 1990 (n=10,657); in 1992, there were an estimated 10,242 DCIS cases treated by mastectomy. CONCLUSIONS: Incidence rates of DCIS of the breast have increased dramatically since 1983. This increase correlates with the widespread adoption of modern mammographic screening. While early detection of invasive breast cancer is beneficial, the value of DCIS detection is currently unknown. There is cause for concern about the large number of DCIS cases that are being diagnosed as a consequence of screening mammography, most of which are treated by some form of surgery. In addition, the proportion of cases treated by mastectomy may be inappropriately high, particularly in some areas of the United States.

BACKGROUND: With the large number of women having mammography-an estimated 28.4 million U.S. women aged 40 years and older in 1998-the percentage of cancers detected as ductal carcinoma in situ (DCIS), which has an uncertain prognosis, has increased. We pooled data from seven regional mammography registries to determine the percentage of mammographically detected cancers that are DCIS and the rate of DCIS per 1000 mammograms. METHODS: We analyzed data on 653 833 mammograms from 540 738 women between 40 and 84 years of age who underwent screening mammography at facilities participating in the National Cancer Institute's Breast Cancer Surveillance Consortium (BCSC) throughout 1996 and 1997. Mammography results were linked to population-based cancer and pathology registries. We calculated the percentage of screen-detected breast cancers that were DCIS, the rate of screen-detected DCIS per 1000 mammograms by age and by previous mammography status, and the sensitivity of screening mammography. Statistical tests were two-sided. RESULTS: A total of 3266 cases of breast cancer were identified, 591 DCIS and 2675 invasive breast cancer. The percentage of screen-detected breast cancers that were DCIS decreased with age (from 28.2% [95% confidence interval (CI) = 23.9% to 32.5%] for women aged 40-49 years to 16.0% [95% CI = 13.3% to 18.7%] for women aged 70-84 years). However, the rate of screen-detected DCIS cases per 1000 mammograms increased with age (from 0.56 [95% CI = 0.41 to 0.70] for women aged 40-49 years to 1.07 [95% CI = 0.87 to 1.27] for women aged 70-84 years). Sensitivity of screening mammography in all age groups combined was higher for detecting DCIS (86.0% [95% CI = 83.2% to 88.8%]) than it was for detecting invasive breast cancer (75.1% [95% CI = 73.5% to 76.8%]). CONCLUSIONS: Overall, approximately 1 in every 1300 screening mammography examinations leads to a diagnosis of DCIS. Given uncertainty about the natural history of DCIS, the clinical significance of screen-detected DCIS needs further investigation.