Hormone-related factors and risk of breast cancer in relation to estrogen receptor and progesterone receptor status

Risk factors were examined for subgroups of breast cancer characterized by estrogen receptor (ER) and progesterone receptor (PR) status. Data from the Carolina Breast Cancer Study, a population-based, North Carolina case-control study of 862 breast cancer cases aged 20-74 years diagnosed during 1993-1996 and 790 controls frequency matched on race and age, were obtained by personal interview. ER and PR status was retrieved from medical records (80%) or was determined in the authors' laboratory (11%) but was missing for 9% of cases. The receptor status distribution was as follows: 53% ER+PR+, 11% ER+PR-, 8% ER-PR+, and 28% ER-PR-. Several hormone-related factors were associated with stronger increased risks for ER+PR+ than for ER-PR- breast cancer: the elevated odds ratios were strongest for ER+PR+ breast cancer among postmenopausal women who had an early age at menarche (odds ratio (OR) = 1.6, 95% confidence interval (CI): 1.0, 2.4), nulliparity/late age at first full-term pregnancy (OR = 1.7, 95% CI: 0.9, 3.2 and OR = 1.6, 95% CI: 1.0, 2.7, respectively), or a high body mass index (OR = 1.6, 95% CI: 0.9, 3.0) and among pre-/perimenopausal women who had a high waist-hip ratio (OR = 1.9, 95% CI: 1.2, 3.1). In contrast, family history of breast or ovarian cancer and medical radiation exposure to the chest produced higher odds ratios for ER-PR- than for ER+PR+ breast cancer, especially among pre-/perimenopausal women.     

Alcohol consumption and breast cancer risk in the Women's Health Study

The authors assessed the association between moderate alcohol consumption and breast cancer risk in the Women's Health Study (United States, 1992-2004). During an average of 10 years of follow-up, 1,484 cases of total breast cancer (1,190 invasive and 294 in situ) were documented among 38,454 women who, at baseline, were free of cancer and cardiovascular disease and provided detailed dietary information, including alcohol consumption, for the preceding 12 months. Higher alcohol consumption was associated with a modest increase in breast cancer risk; the multivariable relative risks for > or =30 g/day of alcohol vs. none were 1.32 (95% confidence interval (CI): 0.96, 1.82) for total breast cancer and 1.43 (95% CI: 1.02, 2.02) for invasive breast cancer. An increased risk was limited to estrogen receptor (ER)- and progesterone receptor (PR)-positive tumors; the multivariable relative risks for an increment of 10 g/day of alcohol were 1.11 (95% CI: 1.03, 1.20) for ER+PR+ tumors (804 cases), 1.00 (95% CI: 0.81, 1.24) for ER+PR- tumors (125 cases), and 0.99 (95% CI: 0.82, 1.20) for ER-PR- tumors (167 cases). The association also seemed strongest among those taking postmenopausal hormones currently, but the test for interaction was not significant. The findings from this prospective study suggest that moderate alcohol consumption increases breast cancer risk.     

Dietary phytoestrogens are not associated with risk of overall breast cancer but diets rich in coumestrol are inversely associated with risk of estrogen receptor and progesterone receptor negative breast tumors in Swedish women

Results from epidemiological and experimental studies indicate that phytoestrogens may protect against breast cancer. Because one of the biological effects of phytoestrogens is probably estrogenic, it's possible that the preventive effect on breast cancer differs by estrogen receptor (ER) or progesterone receptor (PR) status of the tumor. We evaluated the associations between dietary phytoestrogen (isoflavonoids, lignans, and coumestrol) intake and risk of breast cancer and whether the ER/PR statuses of the tumor influence this relationship. In 1991-2 a prospective population-based cohort study among Swedish pre- and postmenopausal women was performed, making questionnaire data available for 45,448 women. A total of 1014 invasive breast cancers were diagnosed until December 2004. Cox proportional hazards models were performed to estimate multivariate risk ratios, 95% CI for associations with risk of breast cancer. Intakes of lignan, isoflavonoid, or coumestrol were not associated with breast cancer risk overall or before or after 50 y of age. The effects of lignans or isoflavonoids were independent of receptor status. However, intake of coumestrol was associated with decreased risk of receptor negative tumors (ER-PR-) but not positive tumors. The risk of ER-PR- tumors was significantly lower (50%) in women with intermediate coumestrol intake compared with those who did not consume any. In conclusion, we found no association between intake of isoflavonoids or lignans and breast cancer risk. Our results of a decreased risk of ER-PR- tumors in women with intermediate intake of coumestrol could be due to chance because of the low intake. The results should be confirmed in other studies.     

Association between family history of cancer and breast cancer defined by estrogen and progesterone receptor status

There are recent data to suggest that risk factors for breast cancer may differ according to whether the tumor expresses detectable levels of the estrogen receptor (ER) and progesterone receptor (PR). While a family history of breast cancer is one of the most consistent predictors of the disease, we recently reported a modest inverse association with ER+PR− tumors. However, the definition of a family history of cancer did not consider second-degree relatives or cancer sites that may be etiologically related. The current report presents additional data analysis from the Iowa Women's Health Study, a prospective population-based cohort study conducted among 41,837 postmenopausal women. At baseline in 1986, respondents provided information on family history of cancers of the breast, ovaries, or uterus/endometrium in their mothers, sisters, daughters, maternal and paternal grandmothers, and maternal and paternal aunts. Data on family history of prostate cancer in fathers and brothers and age at onset of breast cancer in mothers and sisters were collected in 1992. Cohort members were followed for cancer incidence through the statewide tumor registry. After 7 years and more than 235,000 person-years of follow-up, 939 incident cases of breast cancer were identified. Information was obtained from the tumor registry on ER (+/−) and PR (+/−) status for 610 cases (65.0%). A family history of breast cancer in first-degree relatives was associated with increased risk (relative risk [RR] = 1.4; 95% confidence interval [CI]: 1.1–1.6) for all receptor-defined subtypes of breast cancer except ER+PR− tumors (RR = 0.7; 95% CI: 0.3–1.4). These results were unchanged when data on second-degree relatives were included. When the onset of breast cancer in relatives occurred at or before the age of 45 years, increased risks were evident only for ER−PR+ and ER−PR− tumors (RR = 2.3 and 3.3, respectively). Conversely, when relatives were affected with breast cancer after the age of 45 years, increased risks were most apparent for ER+PR+ and ER−PR+ tumors (RR = 1.3 and 3.2, respectively). A family history of prostate cancer in first-degree relatives was associated with a 1.2-fold increased risk of breast cancer (95% CI: 0.98–1.50), largely a reflection of the association with ER−PR− tumors (RR = 1.5; 95% CI: 0.8–3.0). The small numbers of cases in some categories and the corresponding wide CIs preclude definitive conclusions, but these data are at least suggestive that joint stratification of breast tumors on ER and PR status may be useful in partitioning breast cancer families into more homogeneous subsets. © 1996 Wiley-Liss, Inc.     

Long-term Dietary Acrylamide Intake and Breast Cancer Risk in a Prospective Cohort of Swedish Women

The association between dietary acrylamide intake and the incidenceof invasive breast cancer was examined among 61,433 Swedishwomen who were cancer free and completed a food frequency questionnairein 1987–1990 and again in 1997. During a mean follow-upof 17.4 years, a total of 2,952 incident cases of breast cancerwere diagnosed in the cohort. In multivariate analyses controllingfor breast cancer risk factors, no statistically significantassociation was observed between long-term acrylamide intake(assessed at baseline and in 1997) and the risk of breast cancer,overall or by estrogen receptor (ER) and progesterone receptor(PR) status. The multivariate rate ratios comparing extremequartiles of acrylamide intake were 0.91 (95% confidence interval(CI): 0.80, 1.02) for overall breast cancer, 0.89 (95% CI: 0.74,1.08) for ER+PR+ tumors, 1.17 (95% CI: 0.84, 1.64) for ER+PR–tumors, and 0.91 (95% CI: 0.61, 1.38) for ER–PR–tumors. The association between acrylamide intake and breastcancer risk did not differ by smoking status. These findingsfor Swedish women do not support the hypothesis that dietaryacrylamide is positively associated with risk of breast cancer,at least not within the ranges of acrylamide consumed by thispopulation. acrylamide; breast neoplasms; cohort studies; diet; prospective studies     

Food Sources of Fat and Sex Hormone Receptor Status of Invasive Breast Tumors in Women of the Malmö Diet and Cancer Cohort

We examined associations between food intakes and incident breast cancer, defined by estrogen receptor (ER) and progesterone receptor (PR) status in the Malmö Diet and Cancer cohort (～17,000 women aged 45–73 yr). The hazard ratios (HRs) of ER+PR+ (n = 270), ER+PR? (n = 87), and ER?PR? (n = 61) tumors and all cancer (n = 544) were estimated after 10 yr of follow-up. In multivariate analysis of ER+PR+ tumors, a protective linear risk trend, indicating change between adjoining food categories, was seen with yogurt (HR = 0.89, 95% CI = 0.80–0.99), but increased risks with eggs (HR = 1.10, 95% CI = 1.01–1.20) and dried soups/sauces (HR = 1.10, 95% CI = 1.00–1.22). In ER?PR? tumors, vegetable-oil-based margarine (HR = 1.31, 95% CI = 1.09–1.59) and dried soups/sauces (HR = 1.31 95% CI = 1.05–1.64) showed increased risks. Heterogeneity was observed between ER+PR+ and ER?PR? tumors for vegetable-oil-based margarine (P < 0.01). Regular milk showed decreased, and dried soups/sauces increased, risk with all breast cancer. The study suggests that fat-containing food may contribute both to hormonal and nonhormonal mechanisms in breast tumor development and supports observations of positive associations between characteristics of Westernized diets and postmenopausal breast cancer.     

Intake of Energy-Dense Foods,Fast Foods,Sugary Drinks,and Breast Cancer Risk in African American and European American Women

Limiting energy-dense foods, fast foods, and sugary drinks that promote weight gain is a cancer prevention recommendation, but no studies have evaluated intake in relation to breast cancer risk in African American (AA) women. In a case-control study with 1692 AA women (803 cases and 889 controls) and 1456 European American (EA) women (755 cases and 701 controls), odds ratios (OR) and 95% confidence intervals (CI) for risk were computed, stratifying for menopausal and estrogen receptor (ER) status. Among postmenopausal EA women, breast cancer risk was associated with frequent consumption of energy-dense foods (OR = 2.95; 95% CI: 1.66–5.22), fast foods (OR = 2.35; 95% CI: 1.38–4.00), and sugary drinks (OR = 2.05; 95% CI: 1.13–3.70). Elevated risk of ER+ tumors in EA women was associated with energy-dense (OR = 1.75; 95% CI: 1.14–2.69) and fast foods (OR = 1.84; 95% CI: 1.22–2.77). Among AA women, frequent fast food consumption was related to premenopausal breast cancer risk (OR = 1.97; 95% CI: 1.13–3.43), and with ER+ tumors. Energy adjustment attenuated risk estimates in AA women, while strengthening them among EA women. Frequent consumption of energy-dense and fast foods that have poor nutritive value appeared to increase breast cancer risk in AA and EA women, with differences by menopausal status and ER status.     

Dietary Mushroom Intake and the Risk of Breast Cancer Based on Hormone Receptor Status

Although many studies have documented the antitumor activities of mushrooms, the association between mushroom intake and breast cancer, defined by hormone receptor status, has received minimal empirical investigation. This study evaluated the association between mushroom intake and the risk of breast cancer according to hormone receptor status among Korean women. Mushroom intake and breast cancer risk were examined among 358 breast cancer patients and 360 cancer-free controls. Intake of mushrooms was assessed using a quantitative food frequency questionnaire. Greater mushroom intake was related to lower risk of breast cancers among premenopausal women (odds ratio [OR] = 0.35, 95% confidence interval [CI] = 0.13–0.91 for the highest vs. the lowest quartile intake). The association was stronger for premenopausal women with estrogen receptor (ER)+/progesterone receptor (PR) + tumors (OR = 0.30, 95% CI = 0.11–0.79 for the highest vs. the lowest quartile intake) than those with ER–/PR– tumors. Our results suggest that high consumption of mushrooms might be related to lower risks for breast cancers among premenopausal women; this association may be more robust among women with hormone receptor positive tumors.     

Diet and expression of estrogen alpha and progesterone receptors in malignant mammary tissue

Estrogen receptor (ER) and/or progesterone receptor (PR) expression has been associated with more favorable breast cancer prognosis. Results on the differential association of diet with ER and/or PR positive and negative tumors have been inconclusive. In a large case-control study conducted in Athens, Greece, we investigated whether diet is associated with the expression of ER-alpha or PR in mammary tumors of 421 women with histologically confirmed breast cancer. Diet was assessed through an extensive food frequency questionnaire and results were analyzed using multiple logistic regression. After controlling for non-nutritional variables and mutually adjusting for energy-generating nutrients and ethanol, carbohydrate intake was inversely associated with ER-alpha (P = 0.04) and PR (P = 0.10) expression. The odds ratios (OR) per one standard deviation increment were 0.69 with 95% confidence interval (95% CI) 0.48-0.98 for ER-alpha and 0.72 (95% CI 0.49-1.07) for PR expression. No consistent or statistically significant associations were noted for any of the other energy-generating nutrients or food groups examined. Although in these data no strong relations of qualitative aspects of diet with hormone receptor expression in breast cancer tumors were evident, the inverse association of carbohydrate intake with ER-alpha, and perhaps PR, expression merits further study in future investigations.     

Effect of Dietary Intake of Isoflavones on the Estrogen and Progesterone Receptor Status of Breast Cancer

To examine if higher intake of isoflavones prior to diagnosis was associated with a positive status of estrogen receptors (ER) and progesterone receptors (PR) in breast tumor tissue, a retrospective study was conducted in 2004 to 2005 in 756 Chinese women with histologically confirmed breast cancer. We administered a food frequency questionnaire by face-to-face interview to assess the intake of the isoflavones daidzein and genistein. Unconditional logistic regression analysis was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) adjusted for potential confounders. Comparing the highest to lowest intake quartiles, the adjusted ORs for daidzein were 1.94 (95% CI = 1.20–3.32) and 2.18 (95% CI = 1.28–3.73) for ER positive and PR positive tumors, respectively, in premenopausal patients. The ORs for both ER and PR positive status combined were 2.48 (95% CI = 1.37–4.49) for daidzein and 1.94 (95% CI = 1.21–3.14) for genistein in premenopausal patients with statistically significant tests for trend. There was little or no evidence of associations in postmenopausal patients. We conclude that higher intake of daidzein and genistein before diagnosis was associated with ER and PR positive status in premenopausal Chinese women with breast cancer. The association might confer a more favorable prognosis.     

Vitamin D from dietary intake and sunlight exposure and the risk of hormone-receptor-defined breast cancer

Evidence has emerged for a role of vitamin D in the development of breast cancer, and there is some suggestion that its antiproliferative effect is greater in hormone-receptor-positive cells. Few epidemiologic studies have considered the association between vitamin D and hormone-receptor-defined breast cancer, and the results are conflicting. Considering 759 cases and 1,135 controls from a case-control study (Ontario, Canada, 2003-2005), the authors examined the association between vitamin D intake at specific ages and combined estrogen-receptor- (ER) and progesterone-receptor- (PR) defined breast cancer. While increased intake of vitamin D (from the sun and diet) was most consistently associated with a significantly reduced risk of ER+/PR+ tumors (e.g., odds ratio = 0.76, 95% confidence interval: 0.59, 0.97 for use of cod liver oil during adolescence), comparable nonsignificant associations were found for receptor-negative (ER-/PR-) (odds ratio = 0.74, 95% confidence interval: 0.53, 1.04) and mixed (ER+/PR-) (odds ratio = 0.79, 95% confidence interval: 0.51, 1.22) tumors. This study suggests that vitamin D is associated with a reduced risk of breast cancer regardless of ER/PR status of the tumor. Future studies with a larger number of receptor-negative and mixed tumors are required.     

Associations of weight,weight change,and body mass with breast cancer risk in Hispanic and non-Hispanic white women

PURPOSE: A wealth of studies have examined the effects of weight, weight gain, and obesity on breast cancer risk; however, few have examined this relationship in Hispanic white women, a population with the highest rate of obesity in the U.S. METHODS: A population-based case-control study was conducted in New Mexico of Hispanic (n = 694) and non-Hispanic (n = 813) white women with incident breast cancer during the period of January 1, 1992 through December 31, 1994. Conditional logistic regression models were fitted to estimate the relative risk of breast cancer for levels of weight, weight change, and body mass index (BMI) and to assess differences in the effects by ethnicity, menopausal status, early life BMI, and estrogen receptor/progesterone receptor (ER/PR) expression in tumors. RESULTS: Weight change from age 18 to usual adult weight was associated with increased risk of breast cancer among Hispanics [4th quartile vs. baseline, odds ratio (OR): 2.41; 95% confidence interval (CI): 1.45-4.03] with no substantial variation by menopausal status. In non-Hispanic white women, weight change was a risk factor for those in the post-menopausal group (4th quartile vs. baseline, OR: 2.27; 95% CI: 1.09-4.73). The effect of usual BMI (test for interaction p = 0.04) and weight change (test for interaction p = 0.03) differed by ethnicity. Increased risk from weight gain was largely restricted to women who were lean at age 18 and those with ER(+)/PR(+) tumors. Height, weight at age 18, and BMI at age 18 were not associated with risk in either ethnic group. CONCLUSIONS: Weight change and obesity are risk factors for breast cancer in both Hispanic and non-Hispanic white women. However, the risk for Hispanic women is evident independent of menopausal status, while the risk for non-Hispanics is apparent in post-menopausal women. Due to the increasing prevalence of adult obesity, particularly among Hispanic women, adult weight gain may be an important modifiable risk factor for the primary prevention of breast cancer among Hispanic populations.     

Diet and Expression of Estrogen Alpha and Progesterone Receptors in Malignant Mammary Tissue

Estrogen receptor (ER) and/or progesterone receptor (PR) expression has been associated with more favorable breast cancer prognosis. Results on the differential association of diet with ER and/or PR positive and negative tumors have been inconclusive. In a large case-control study conducted in Athens, Greece, we investigated whether diet is associated with the expression of ER-alpha or PR in mammary tumors of 421 women with histologically confirmed breast cancer. Diet was assessed through an extensive food frequency questionnaire and results were analyzed using multiple logistic regression. After controlling for non-nutritional variables and mutually adjusting for energy-generating nutrients and ethanol, carbohydrate intake was inversely associated with ER-alpha (P = 0.04) and PR (P = 0.10) expression. The odds ratios (OR) per one standard deviation increment were 0.69 with 95% confidence interval (95% CI) 0.48-0.98 for ER-alpha and 0.72 (95% CI 0.49–1.07) for PR expression. No consistent or statistically significant associations were noted for any of the other energy-generating nutrients or food groups examined. Although in these data no strong relations of qualitative aspects of diet with hormone receptor expression in breast cancer tumors were evident, the inverse association of carbohydrate intake with ER-alpha, and perhaps PR, expression merits further study in future investigations.     

Dietary intakes of total and specific lignans are associated with clinical breast tumor characteristics

Dietary lignans may affect breast cancer by modifying tumor characteristics likely to affect prognosis. We investigated usual dietary intakes of total and specific lignans with tumor characteristics in 683 women with breast cancer and 611 healthy women without breast cancer enrolled in the Data Bank and BioRepository at Roswell Park Cancer Institute (RPCI). Clinicopathologic data were abstracted from the RPCI breast cancer database. Dietary lignan intakes were calculated from FFQ. OR and 95% CI were estimated with logistic regression adjusting for potential confounders and stratified by menopausal status. Women in the highest compared to the lowest tertile of total lignan intakes had a 40-50% lower odds of breast cancer regardless of menopausal status and substantially reduced odds of an invasive tumor, especially among premenopausal women [OR 0.48 (95% CI 0.26-0.86)]. Lignan intakes were inversely associated with odds of grade 3 tumors among premenopausal women. Lignan intakes were inversely associated with risk of estrogen receptor (ER) negative (ER(-)) breast cancer among premenopausal women [OR 0.16 (95% CI 0.03-0.44)] and particularly triple negative tumors [ER(-), progesterone receptor negative, HER2 negative; OR 0.16 (95% CI 0.04-0.62)]. There were significant differences in the contribution to these effects by specific lignans, especially matairesinol and lariciresinol. In summary, in this case-control study of dietary lignan intakes and breast cancer, we found that higher lignan intakes were associated with lower risks of breast cancer with more favorable prognostic characteristics. Future investigations are warranted to explore the strong associations observed with ER(-) cancer in premenopausal women.     

Residential and occupational exposures to 50-Hz magnetic fields and breast cancer in women: a population-based study

A case-control study was conducted to investigate whether residential and occupational exposures to magnetic fields increased the risk for breast cancer among women. Cases of breast cancer diagnosed during 1980-1996 were identified in a cohort of women living near a high-voltage power line in Norway in 1980 or between 1986 and 1996. Each case was matched by year of birth, municipality, and first year of entry into the cohort with two randomly selected controls without cancer. Residential exposure to magnetic fields was calculated as that generated by the lines before diagnosis, and occupational exposure was based on exposure matrix data. Women with residential exposure had an odds ratio of 1.58 (95% confidence interval (CI): 1.30, 1.92) when compared with unexposed women. The odds ratios for exposed women versus unexposed women with estrogen receptor (ER)-positive and ER-negative breast cancer were 1.33 (95% CI: 0.93, 1.90) and 1.40 (95% CI: 0.78, 2.50), respectively (ER status was available for 44% of the cases). Women with the highest occupational exposure had an odds ratio of 1.13 (95% CI: 0.91, 1.40) when compared with those unexposed at work. The findings suggest an association between exposure to magnetic fields and breast cancer in women.     

Environmental tobacco smoke and breast cancer incidence

To evaluate whether environmental tobacco smoke (ETS) influences breast cancer incidence, data from a population-based case-control study were analyzed. Respondents with available ETS information assessed by in-person questionnaires included 1356 newly diagnosed cases and 1383 controls. Relative to nonsmokers who reported no residential ETS exposure throughout the life course, the odds ratios (OR) for breast cancer were not substantially elevated in relation to ETS exposure, active smoking, or a joint measure of active and passive smoking (OR, 1.15, 95% CI, 0.90, 1.48). An increased OR, however, was noted among nonsmokers who lived with a smoking spouse for over 27 years (2.10, 95% CI, 1.47, 3.02), although no dose-response was evident. Also, among women with hormone-receptor-positive tumors only, the OR for both active and passive smoking was increased (1.42 for ER+ PR+, 95% CI, 1.00, 2.00). Our data suggest that if there is an effect for ETS on breast cancer, that effect is restricted to selected subgroups of women, such as those with long-term exposure from a smoking spouse.     

Selected antioxidants and risk of hormone receptor-defined invasive breast cancers among postmenopausal women in the Women's Health Initiative Observational Study

BACKGROUND: Few studies have evaluated carotenoids and vitamins C and E in association with the risk of breast cancers defined by estrogen receptor (ER) and progesterone receptor (PR) status. OBJECTIVE: We examined the associations between dietary and supplemental intakes of these nutrients and risk of breast cancers jointly defined by both ER and PR status among postmenopausal women. DESIGN: Our investigation was conducted in the Women's Health Initiative Observational Study. After following 84 805 women for an average of 7.6 y, 2879 incident invasive breast cancer cases had been ascertained, of whom 2509 had receptor data. We used Cox proportional hazards models to assess the associations of interest. RESULTS: Dietary alpha-carotene (highest versus lowest quintile: RR = 0.83; 95% CL = 0.70, 0.99; P for trend = 0.019), beta-carotene (highest versus lowest quintile: RR = 0.78; 95% CL = 0.66, 0.94; P for trend = 0.021), and lycopene (highest versus lowest quintile: RR = 0.85; 95% CL = 0.73, 1.00; P for trend = 0.064) were inversely associated with risk of ER+PR+breast cancer, but not with other breast cancer groups jointly defined by ER and PR status. Total or supplemental beta-carotene and dietary intakes of lutein+zeaxanthin and beta-cryptoxanthin were not associated with breast cancers defined by ER and PR status. Vitamin E (regardless of source) and dietary vitamin C were not associated with breast cancer. However, total and supplemental vitamin C intake had weak positive associations with breast cancer overall. CONCLUSION: Dietary intake of certain carotenoids might be differentially associated with risk of invasive breast cancers jointly defined by ER and PR status among postmenopausal women.     

Breast cancer risk and ovariectomy, hysterectomy, and tubal sterilization in the women's contraceptive and reproductive experiences study

Removal or impairment of ovaries before menopause may affect a woman's breast cancer risk by altering her cumulative exposure to ovarian hormones. The Women's Contraceptive and Reproductive Experiences Study, a population-based, multicenter case-control study of incident invasive breast cancer, recruited women aged 35-64 years (4,490 cases and 4,611 controls) who provided data on ovariectomy, hysterectomy, and tubal sterilization during in-person interviews. Controls were frequency-matched to cases by age, race, and study site. Unconditional logistic regression analysis was used. Women who had not undergone premenopausal reproductive surgery were the referent group. Bilateral ovariectomy was associated with reduced breast cancer risk overall (odds ratio (OR) = 0.59, 95% confidence interval (CI): 0.50, 0.69) and among women <45 years of age (ORs ranged from 0.31 to 0.52), but not among those who were older at surgery. It was also associated with a reduced risk for estrogen and progesterone receptor-positive tumors (OR = 0.63, 95% CI: 0.52, 0.75) but not receptor-negative tumors. Hysterectomy with ovarian conservation (OR = 0.83, 95% CI: 0.72, 0.96) and hysterectomy with partial ovary removal (OR = 0.73, 95% CI: 0.59, 0.91) were also associated with lower risk. No association with breast cancer risk was observed with tubal sterilization only or partial ovariectomy without hysterectomy. Reproductive organ surgeries may alter ovarian hormone levels, thereby affecting breast cancer risk.     

Infertility and breast cancer: a population-based case-control study

To investigate whether a history of infertility affects a woman's risk of developing breast cancer, the authors analyzed case-control data collected between 1980 and 1982 as part of the Cancer and Steroid Hormone Study. The 4,730 cases were women aged 20-54 years with a first diagnosis of breast cancer ascertained from eight population-based cancer registries; the 4,688 controls were women randomly selected from the general population of these same eight areas. After controlling for age, age at first birth, and parity, the odds ratio (OR) for breast cancer associated with infertility was 1.01 (95% confidence interval (CI) 0.89-1.15) among gravid women. Controlling for age, the odds ratio was 0.82 (95% CI 0.59-1.14) among nulligravid women. Women who reported that the reason for their infertility was a problem with their ovaries had a risk similar to that for women without a history of infertility (OR = 0.75, 95% CI 0.48-1.24). Women whose physicians reported that the reason for their infertility was anovulation or Stein-Leventhal syndrome also had risks similar to those for women without a history of infertility (OR = 1.26 (95% CI 0.67-2.34) and OR = 1.13 (95% CI 0.46-2.78), respectively). Menopausal status, age at menarche, history of spontaneous abortions, drinking or smoking behavior, use of exogenous hormones, or family history of breast cancer did not appreciably alter the observed odds ratios. If infertility has an effect on breast cancer that is independent of age at first birth, then the effect is small.