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.     

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.     

Dietary B vitamin and methionine intakes and breast cancer risk among Chinese women

Methionine, folate, vitamin B(6), vitamin B(12), niacin, and riboflavin intakes may be related to breast carcinogenesis. These associations may vary by breast cancer type. Using the prospective cohort Shanghai Women's Health Study (1997-2008) including 718 Chinese breast cancer cases, the authors evaluated baseline dietary intake of these factors and breast cancer risk and whether the associations varied by menopausal status and estrogen receptor (ER) and progesterone receptor (PR) status. They estimated associations using hazard ratios and 95% confidence intervals from Cox proportional hazards regression models and stratified analyses by menopausal status and ER/PR status. Lowest quantile of intake was used as the comparison group. For postmenopausal women, dietary intakes of methionine and B vitamins were not associated with breast cancer risk. For premenopausal women, higher intake of folate was associated with decreased breast cancer risk (hazard ratio = 0.58, 95% confidence interval: 0.34, 0.99 for the highest vs. lowest quintile of intake). Only niacin intake was associated with ER+/PR+ breast cancer risk (hazard ratio = 1.62, 95% confidence interval: 1.07, 2.46; P for trend = 0.04 for the highest vs. lowest quartile of intake). Findings support the hypothesis that high folate intake may reduce breast cancer risk and that the association may vary by menopausal and ER/PR status.     

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.     

Fruit, vegetable, and animal food intake and breast cancer risk by hormone receptor status

The effects of diet on breast cancer are controversial and whether the effects vary with hormone receptor status has not been well investigated. This study evaluated the associations of dietary factors with risk for breast cancer overall and by the hormone receptor status of tumors among Chinese women. The Shanghai Breast Cancer Study, a large, population-based, case-control study, enrolled 3,443 cases and 3,474 controls in 1996-1998 (phase I) and 2002-2005 (phase II); 2676 cases had estrogen receptor (ER) and progesterone receptor (PR) data. Dietary intake was assessed using a validated, quantitative, food frequency questionnaire. Odds ratios (OR) and 95% confidence intervals (95% CI) were derived from multivariate, polychotomous, unconditional logistic regression models. Total vegetable intake was inversely related to breast cancer risk, with an adjusted OR for the highest quintile of 0.80 (95% CI = 0.67-0.95; P trend = 0.02). Reduced risk was also related to high intake of allium vegetables (P trend = 0.01) and fresh legumes (P trend = 0.0008). High intake of citrus fruits and rosaceae fruits were inversely associated with breast cancer risk (P trend = 0.003 and 0.004, respectively), although no consistent association was seen for total fruit intake. Elevated risk was observed for all types of meat and fish intake (all P trend < 0.05), whereas intakes of eggs and milk were associated with a decreased risk of breast cancer (both P trend <0.05). There was little evidence that associations with dietary intakes varied across the 4 tumor subtypes or between ER+/PR+ and ER-/PR- tumors (P for heterogeneity >0.05). Our results suggest that high intake of total vegetables, certain fruits, milk, and eggs may reduce the risk of breast cancer, whereas high consumption of animal-source foods may increase risk. The dietary associations did not appear to vary by ER/PR status.     

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.     

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.     

Risk of breast cancer classified by joint estrogen receptor and progesterone receptor status among women 20-44 years of age

To gain insight into whether breast cancer tumors jointly classified by estrogen receptor (ER) and progesterone receptor (PR) status represent diseases with differing etiologies, data from a population-based case-control study of US women 20-44 years of age were analyzed. Cases included 1,556 women diagnosed between 1990 and 1992. Age- and geographic-frequency-matched controls included 1,397 women identified by random digit dialing. Heterogeneity between ER+PR+ and ER-PR- tumors was most pronounced in relation to age, race, and recreational exercise at 12-13 years of age. Multivariate-adjusted odds ratios for ER+PR+ tumors were 0.64 (95% confidence interval (CI): 0.47, 0.89) for 30-34 versus 40-44 years of age, 0.89 (95% CI: 0.63, 1.25) for Black versus White race, and 0.84 (95% CI: 0.68, 1.03) for exercise at 12-13 years of age above versus at or below the median. Corresponding odds ratios for ER-PR- tumors were 1.24 (95% CI: 0.86, 1.77), 1.51 (95% CI: 1.07, 2.14), and 1.15 (95% CI: 0.90, 1.48). Risk of ER-PR- cancer in relation to menstrual and reproductive (parity and lactation) characteristics, alcohol consumption, and family history of breast cancer was similar to that observed for ER+PR+ tumors. These findings only modestly support the hypothesis that hormonally related risk factors have differing relations with ER+PR+ versus ER-PR- tumors among younger women.     

Fruit,Vegetable, and Animal Food Intake and Breast Cancer Risk by Hormone Receptor Status

The effects of diet on breast cancer are controversial and whether the effects vary with hormone receptor status has not been well investigated. This study evaluated the associations of dietary factors with risk for breast cancer overall and by the hormone receptor status of tumors among Chinese women. The Shanghai Breast Cancer Study, a large, population-based, case-control study, enrolled 3,443 cases and 3,474 controls in 1996–1998 (phase I) and 2002–2005 (phase II); 2676 cases had estrogen receptor (ER) and progesterone receptor (PR) data. Dietary intake was assessed using a validated, quantitative, food frequency questionnaire. Odds ratios (OR) and 95% confidence intervals (95% CI) were derived from multivariate, polychotomous, unconditional logistic regression models. Total vegetable intake was inversely related to breast cancer risk, with an adjusted OR for the highest quintile of 0.80 (95% CI = 0.67–0.95; P trend = 0.02). Reduced risk was also related to high intake of allium vegetables (P trend = 0.01) and fresh legumes (P trend = 0.0008). High intake of citrus fruits and rosaceae fruits were inversely associated with breast cancer risk (P trend = 0.003 and 0.004, respectively), although no consistent association was seen for total fruit intake. Elevated risk was observed for all types of meat and fish intake (all P trend < 0.05), whereas intakes of eggs and milk were associated with a decreased risk of breast cancer (both P trend <0.05). There was little evidence that associations with dietary intakes varied across the 4 tumor subtypes or between ER+/PR+ and ER-/PR- tumors (P for heterogeneity >0.05). Our results suggest that high intake of total vegetables, certain fruits, milk, and eggs may reduce the risk of breast cancer, whereas high consumption of animal-source foods may increase risk. The dietary associations did not appear to vary by ER/PR status.     

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.     

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.     

Dietary folate, vitamin B6, vitamin B12 and methionine intake and the risk of breast cancer by oestrogen and progesterone receptor status

Few studies have evaluated the relationship between the consumption of dietary folate and one-carbon metabolism-related nutrients and breast cancer risk defined by oestrogen receptor (ER) and progesterone receptor (PR) status. The objective of the present study was to examine the associations between dietary folate, vitamin B6, vitamin B12, and methionine intake and the risk of breast cancer by ER and PR status among Chinese women in Guangdong. A hospital-based case-control study was conducted from June 2007 to August 2008, with 438 cases and 438 age (5-year interval)- and residence (rural/urban)-matched controls. Dietary intake information was assessed using a validated FFQ administered through a face-to-face interview. Unconditional logistic regression models were used to calculate multivariate-adjusted OR and 95 % CI. A significant inverse association was found between dietary folate and vitamin B6 intake and breast cancer risk. The adjusted OR of the highest v. the lowest quartile were 0·32 (95 % CI 0·21, 0·49; P(trend) < 0·001) for dietary folate and 0·46 (95 % CI 0·30, 0·69; P(trend) < 0·001) for vitamin B6. No associations were observed for vitamin B12 and methionine intake. A significant inverse association between dietary folate intake and breast cancer risk was observed in all subtypes of ER and PR status. These findings suggest that dietary folate and vitamin B6 intakes were inversely associated with breast cancer risk. The inverse association did not differ by ER and/or PR status.     

Dietary Acrylamide and the Risk of Endometrial Cancer: An Italian Case-Control

The role of dietary acrylamide on the risk of hormone-related, and specifically endometrial, cancers is debated. Epidemiological data are scanty. Thus, we examined the relation between acrylamide intake and endometrial cancer risk in a case-control study conducted between 1992 and 2006 in 3 Italian areas. Cases were 454 women with incident, histologically confirmed endometrial cancer. Controls were 908 age-matched women admitted to the same network of hospitals of cases for acute, non-neoplastic conditions. We calculated multivariate odds ratios (OR) and 95% confidence intervals (CI) using logistic regression models. The OR of endometrial cancer for increasing quintiles of dietary acrylamide, as compared to the lowest one, were 1.02 (95% CI: 0.67–1.54), 1.20 (95% CI: 0.80–1.80), 1.00 (95% CI: 0.65–1.54) and 1.17 (95% CI: 0.73–1.85). The OR for an increase of 10 μg/day of dietary acrylamide was 1.00 (95% CI: 0.91–1.10). In subgroup analyses, the ORs for high vs. low acrylamide intake were 1.28 (95% CI: 0.73–2.25) in never smokers and 1.14 (95% CI: 0.45–2.90) in ever smokers. Our data do not support an association between dietary acrylamide intake and endometrial cancer.     

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.     

Fish intake is positively associated with breast cancer incidence rate

Animal studies have, in general, been supportive of a protective effect of fish and fish (n-3) PUFA against breast cancer risk; but the epidemiologic evidence of such a relationship is limited. Case-control and cohort studies have rarely shown significant associations. The association between total fish intake and the effect of fat content and preparation method of the fish, in relation to the incidence rate ratios of breast cancer, were investigated among postmenopausal women. We also investigated the effect of fish intake with respect to estrogen receptor expression of breast cancer tumors. A total of 23,693 postmenopausal women from the prospective study "Diet, Cancer and Health" were included in the study. During follow-up, 424 women were diagnosed with breast cancer. The incidence rate ratio (IRR) and 95% CI per each additional 25 g of mean daily intake of fish were 1.13 (CI, 1.03-1.23). Analysis of fatty fish gave IRR of 1.11 (CI, 0.91-1.34), and the result for lean fish was 1.13 (CI, 0.99-1.29). When fish intake was stratified into three types of preparation methods, the IRR for fried fish was 1.09 (CI, 0.95-1.25), for boiled fish 1.09 (CI, 0.85-1.42), and for processed fish 1.12 (CI, 0.93-1.34). The IRR per additional 25 g of mean daily intake of fish was 1.14 (CI, 1.03-1.26) for estrogen receptor-positive (ER+) and 1.00 (CI, 0.81-1.24) for estrogen receptor-negative (ER-) breast cancer. In conclusion, this study showed that higher intakes of fish were significantly associated with higher incidence rates of breast cancer. The association was present only for development of ER+ breast cancer.     

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.     

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.     

Effect of dietary intake of phytoestrogens on estrogen receptor status in premenopausal women with breast cancer

Although many dietary studies have focused on breast cancer risk, few have examined dietary influence on tumor characteristics such as estrogen receptor (ER) status. Because phytoestrogens may modulate hormone levels and ER expression, we analyzed ER status and phytoestrogen intake in a case-case study of 124 premenopausal breast cancer patients. We assessed intake with a food-frequency questionnaire and obtained ER status from medical records. Rather than focusing on risk, we evaluated whether low intakes were more strongly associated with ER-negative tumors than with ER-positive disease. In logistic regression adjusting for potential confounders, threefold greater risks of ER-negative tumors relative to ER-positive tumors were associated with low intake of the isoflavones genistein (odds ratio, OR=3.50; 95% confidence interval, CI=1.43-8.58) and daidzein (OR=3.10; 95% CI=1.31-7.30). Low intake of the flavonoid kaempferol (OR=0.36; 95% CI=0.16-0.83), the trace element boron (OR=0.33; 95% CI=0.13-0.83), and the phytosterol beta-sitosterol (OR=0.42; 95% CI=0.18-0.98) were associated with decreased risk of ER-negative tumors relative to ER-positive disease. Other phytoestrogens were not significantly associated with ER status. Thus, in premenopausal patients, some phytoestrogens may affect breast carcinogenesis by influencing ER status. Such findings suggest new directions for mechanistic research on dietary factors in breast carcinogenesis that may have relevance for prevention and clinical treatment.     

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 folate intake, alcohol, and risk of breast cancer in a prospective study of postmenopausal women.

Low B-vitamin intake may increase risk of breast cancer through decreased DNA repair capacity. Alcohol intake increases risk for breast cancer, with evidence from prospective studies of an interaction between alcohol and folate. We explored dietary intake of folate and other B vitamins with risk of breast cancer in a cohort study of 34,387 postmenopausal women. To measure diet, we mailed a food frequency questionnaire; we estimated nutrient intakes and categorized them into four levels: <10th, 11th-30th, 31st-50th, and >50th percentiles. Through 12 years of follow-up, we identified 1,586 cases of breast cancer in the cohort at risk. We estimated relative risks (RRs) and 95% confidence intervals (CIs) through Cox regression models adjusted for age, energy, and other risk factors. Women in the lowest 10th percentile of folate intake from diet alone were at modestly increased risk of breast cancer relative to those above the 50th percentile: RR = 1.21 (95% CI = 0.91--1.61). We examined the joint association of folate intake and alcohol use on risk of breast cancer, with the reference group defined as women with high folate (>50th percentile) and no alcohol use. The RRs of breast cancer associated with low dietary folate intake were 1.08 (95% CI = 0.78--1.49) among nondrinkers, 1.33 (95% CI = 0.86--2.05) among drinkers of < or = 4 gm per day, and 1.59 (95% CI = 1.05--2.41) among drinkers of > 4 gm per day. These results suggest that the risks of postmenopausal breast cancer may be increased among women with low intakes of folate if they consume alcohol-containing beverages.