Estrogen-progestin replacement and risk of breast cancer
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Biomedical subjects
Publications and source records attributed to L Brinton.
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CONTEXT: Whether menopausal hormone replacement therapy using a combined estrogen-progestin regimen increases risk of breast cancer beyond that associated with estrogen alone is unknown. OBJECTIVE: To determine whether increases in risk associated with the estrogen-progestin regimen are greater than those associated with estrogen alone. DESIGN: Cohort study of follow-up data for 1980-1995 from the Breast Cancer Detection Demonstration Project, a nationwide breast cancer screening program. SETTING: Twenty-nine screening centers throughout the United States. PARTICIPANTS: A total of 46355 postmenopausal women (mean age at start of follow-up, 58 years). MAIN OUTCOME MEASURE: Incident breast cancers by recency, duration, and type of hormone use. RESULTS: During follow-up, 2082 cases of breast cancer were identified. Increases in risk with estrogen only and estrogen-progestin only were restricted to use within the previous 4 years (relative risk [RR], 1.2 [95% confidence interval [CI], 1.0-1.4] and 1.4 [95% CI, 1.1-1.8], respectively); the relative risk increased by 0.01 (95% CI, 0.002-0.03) with each year of estrogen-only use and by 0.08 (95% CI, 0.02-0.16) with each year of estrogen-progestin-only use among recent users, after adjustment for mammographic screening, age at menopause, body mass index (BMI), education, and age. The P value associated with the test of homogeneity of these estimates was .02. Among women with a BMI of 24.4 kg/m2 or less, increases in RR with each year of estrogen-only use and estrogen-progestin-only use among recent users were 0.03 (95% CI, 0.01-0.06) and 0.12 (95% CI, 0.02-0.25), respectively. These associations were evident for the majority of invasive tumors with ductal histology and regardless of extent of invasive disease. Risk in heavier women did not increase with use of estrogen only or estrogen-progestin only. CONCLUSION: Our data suggest that the estrogen-progestin regimen increases breast cancer risk beyond that associated with estrogen alone.
OBJECTIVE: It was our aim to evaluate the hypothesis that molar pregnancy is a marker of increased risk for cancer. STUDY DESIGN: This was a nationwide cohort study of 1520 women, identified from the Danish National Register of Patients, in whom a molar pregnancy was diagnosed during the period 1977-1992 and of 1295 male partners of these women, traced in the Danish Central Population Register. RESULTS: Linkage of the female roster with the Danish Cancer Registry through 1994 revealed 19 cases of gestational choriocarcinoma, whereas 0.04 was expected from the rates for the general population. Twenty cases of cancers of other types were observed with 24.9 expected (standardized incidence ratio, 0.8; 95% confidence interval, 0.5-1.2), but no specific type of cancer other than gestational choriocarcinoma occurred at a rate significantly different from that expected. Among the 1295 male partners notified in the Central Population Register, a total of 22 cancers were observed with 21.9 expected (standardized incidence ratio, 1.0; 95% confidence interval, 0.7-1.5). CONCLUSION: Molar pregnancy is not associated with an increased risk for cancer other than gestational carcinoma.
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Endometrial cancers may be divided into two groups, reflecting differences in clinical behavior and pathogenesis. Endometrioid adenocarcinoma, which accounts for the majority of endometrial cancers, typifies the group of endometrial carcinomas that develop from atypical endometrial hyperplasia in the setting of excess estrogenic stimulation. In contrast, serous carcinomas are representative of endometrial tumors that occur in older women who have endometrial atrophy and lack the typical endometrial cancer risk factors reflecting unopposed estrogen exposure. Serous carcinomas are frequently associated with p53 abnormalities and appear to develop from a surface lesion termed endometrial intraepithelial carcinoma. Although serous carcinomas are rare, these highly aggressive tumors account for a disproportionate number of endometrial cancer deaths. Further delineation of the estrogen-dependent and estrogen-independent pathways of endometrial carcinogenesis may be useful in developing comprehensive chemopreventive approaches for endometrial cancer.
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A population-based national cancer registry has documented strikingly different regional incidence rates of cervical cancer in the Republic of Panama. Such regional differences in disease rates could represent regional differences in the occurrence of risk factors, in particular, human genital papillomaviruses (HPV). This study enrolled newly diagnosed invasive cancer patients in the Republic of Panama over an 18-mo period. Behavioral risk factors were measured by interviewing cases and matched controls. In addition, DNA extracted from biopsies of the cancers was tested for HPV sequences. Early age at first coitus, multiple pregnancies, and nonparticipation in Pap smear screening programs were significant risk factors for cervical cancer in this population. These factors and low levels of education occurred more frequently among women residing in regions with higher cancer rates than women residing in the region with lower cancer rates. HPV DNA was detected most frequently (70%) among cases from the region with the lowest cancer rate (30 of 100,000) and least frequent (54%) among cases where the cancer rate was the highest (51 of 100,000). The observations suggest that risk factors other than HPV contribute to the differences in cervical cancer rates among women residing in various regions of Panama.
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