The current prospective study was designed to evaluate how alcohol-related risk varies by breast cancer subtype among postmenopausal women. The consumption of alcohol is a well-established risk factor for breast cancer. The influence of alcohol on risk of breast cancer is thought to be primarily hormonally driven, implying that alcohol intake may be more strongly associated with hormonally-sensitive types of breast cancer. The study included 87,724 participants in the Women's Health Initiative Observational Study prospective cohort from 1993 to 1998 who reported their own alcohol consumption. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable adjusted Cox regression models. All statistical tests were two-sided. A total of 2,944 invasive breast cancers were diagnosed in the study group during the follow-up period, which lasted until September 15, 2005. Alcohol consumption was found to be associated with increased risk of invasive breast cancer overall, as well as invasive lobular carcinoma and hormone receptor-positive tumors when examined by subtype. Alcohol intake was also found to be more strongly related to risk of certain breast cancer types than others. Compared with those who reported no use of alcohol, women who consumed seven or more alcoholic beverages per week had almost two times the risk of hormone receptor-positive (ER+/PR+) invasive lobular carcinoma (HR = 1.82, 95% CI = 1.18-2.81). The women who had seven or more drinks per week also had a slightly increased risk of invasive ductal carcinoma, but this association was not statistically significant (HR = 1.14, 95% CI = 0.87-1.50). The absolute rate of hormone receptor-positive lobular cancer among never drinkers was 5.2 per 10,000 person-years compared to 8.5 for current drinkers. On the other hand, for hormone receptor-positive ductal breast cancer, the rates were 15.2 and 17.9 per 10,000 person-years, respectively. The authors conclude that alcohol use may be more strongly associated with the risk of hormone-sensitive breast cancers than hormone-insensitive subtypes, suggesting distinct etiologic pathways for these two breast cancer subtypes.

The present prospective study was designed to examine the association between alcohol consumption and risk of ductal carcinoma in situ (DCIS) in postmenopausal women. Previous population studies have reported an association between higher alcohol consumption and a modest increase in risk of invasive breast cancer, studies have not examined the association with risk of DCIS. The association between adulthood alcohol consumption (assessed at baseline) and subsequent risk of DCIS was examined in a cohort of 63,822 postmenopausal women participating in the Women's Health Initiative clinical trials. Alcohol consumption was assessed by a semiquantitative food-frequency questionnaire. Mammography was protocol-mandated in the trials. DCIS cases were verified using central pathology report review. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). A total of 489 cases of DCIS were diagnosed in the study group after a median follow-up of 8.0 years. In the primary analysis, invasive breast cancer was treated as a competing risk, and follow-up time was censored at the date that any invasive breast cancer was diagnosed. After adjustment for covariates, the risk of DCIS among women who consumed 14 or more servings of alcohol per week was slightly lower that that of nondrinkers, but this result was not statistically significant (HR = 0.87, 95% CI = 0.50-1.51). Alcohol consumption also was not found to be associated with risk by DCIS grade (high-grade or low-/moderate-grade). The authors conclude that alcohol consumption was not associated with risk of DCIS in this large cohort of postmenopausal women. If the findings are confirmed by other studies, this would suggest that alcohol may have an effect later in the carcinogenic process.

The present prospective study was designed to investigate the influence of nonvitamin, nonmineral supplements on risk of breast cancer. The use of such specialty supplements has greatly increased over recent decades. Some of these supplements may have anti-inflammatory or anticancer activities. In addition, supplements taken to relieve symptoms of menopause have been associated with reduced risk of breast cancer in two case-control studies. However, until now there have been no prospective studies of the association between the long-term use of such supplements and risk of breast cancer. The study included 35,016 postmenopausal members of the VITamins And Lifestyle (VITAL) Cohort residing in western Washington State and aged 50 to 76. The women, who did not have a history of breast cancer, completed a 24-page baseline questionnaire about their use of non-vitamin, non-mineral supplements during the period 2000 to 2002. Questions were designed to assess the recency (current versus past), frequency (days per week), and duration (number of years) of specialty supplement use. The Surveillance, Epidemiology and End Results (SEER) registry was used to find new breast cancer diagnoses among the women. Cox proportional hazards models were used to calculate multivariable-adjusted hazards ratios (HR) and 95% confidence intervals (CIs). During the period 2000 to 2007, 880 of the study participants were diagnosed with invasive breast cancer. Current use of fish oil was found to be associated with reduced risk of breast cancer (HR = 0.68; 95% CI = 0.50-0.92). Ten-year average use was suggestive of reduced risk (P trend = 0.09). When analyzed according to histological subtype, the results held for ductal but not lobular tumors. The remaining specialty supplements were not found to be associated with breast cancer risk. In particular, use of supplements sometimes taken for menopausal symptoms (black cohosh, dong quai, soy, or St. John's wort) was not found to be associated with breast cancer risk. The authors conclude that fish oil may be inversely associated with breast cancer risk.

The present study was designed to investigate the mechanisms by which curcumin, an active constituent of turmeric, inhibits breast cancer cell growth. Curcumin has been reported to inhibit cell proliferation and induce apoptosis of a board range of cancer cells. In the study, the authors examined the effect of curcumin on NFκB, cell cycle regulatory proteins, and matrix metalloproteinases in MDA-MB-231 and BT-483 breast cancer cells. Cell proliferation, the activity of matrix metalloproteinase-1, 3, 9, cell cycle regulatory proteins, and the expression of NFκB in breast cancer cells all were assessed. Curcumin was found to inhibit proliferation of MDA-MB-231 and BT-483 cells in a time- and dose-dependent manner. Treatment with curcumin resulted in reductions in the expression of cyclin D1 in MDA-MB-231 cells and the expression of CDK4 in BT-483 cells. Compared with untreated cells, matrix metalloproteinase1 mRNA expression declined significantly in curcumin treated BT-483 and MDA-MB-231 cells. The authors conclude that curcumin reduces proliferation and invasion by down-regulating NFκB inducing genes.

The present study was designed to examine the association between alcohol consumption and breast cancer in postmenopausal women by breast cancer type. The study group included 184,418 postmenopausal women 50 to 71 years old in the National Institutes of Health-AARP Diet and Health Study (1995–2003). A mailed questionnaire was used at baseline to assess alcohol use, diet, and potential risk factors for cancer. Relative risks and 95% confidence intervals were calculated by using Cox proportional hazards regression. State cancer registries were used to identify breast cancer cases and estrogen receptor and progesterone receptor status. During a mean seven year follow-up period, 5,461 breast cancer cases were identified. Alcohol consumption was found to be significantly positively associated with risk of breast cancer: Even a moderate amount of alcohol (greater than 10 g/day) was shown to significantly increase risk of breast cancer. In a comparison of greater than 35 g per day versus no alcohol intake, the multivariate relative risks were found to be 1.35 (95% confidence interval (CI): 1.17-1.56) for total breast cancer, 1.46 (95% CI: 1.22-1.75) for ductal breast cancer, and 1.52 (95% CI: 0.95-2.44) for lobular tumors. The multivariate relative risk for estrogen receptor-positive/progesterone receptor-positive (ER+/PR+) tumors was 1.46 (95% CI: 1.12-1.91) for greater than 35 g per day versus no alcohol intake. The estrogen receptor-positive/progesterone receptor-negative (ER+/PR-) multivariate relative risk was 1.13 (95% CI: 0.73-1.77) for greater than 20 g versus no alcohol intake. The estrogen receptor-negative/progesterone receptor-negative (ER-/PR-) multivariate relative risk was 1.21 (95% CI: 0.79-1.84) for greater than or equal to 20 g versus no alcohol intake. The authors conclude that moderate consumption of alcohol is associated with breast cancer, especially hormone receptor-positive tumors.

The present large U.S. population study was designed to examine the association between regular tea consumption and breast cancer risk. The study included 5,082 women with breast cancer aged 20 - 74 years from cancer registries in Wisconsin, Massachusetts, and New Hampshire, as well as 4,501 age-matched controls from lists of licensed drivers and Medicare beneficiaries. Study participants completed a structured telephone interview to elicit information on usual tea consumption five years prior to the interview and other breast cancer risk factors. Logistic regression was used to calculate covariate-adjusted odds ratios and 95% confidence intervals. Tea consumption was found not to be associated with breast cancer risk overall (P for trend = 0.18). However, when analyzed by age, women under 50 who consumed three or more cups of tea per day were found to have a 37% lower breast cancer risk compared to women under 50 reporting no tea consumption (age and study site-adjusted odds ratios, 0.63; 95% confidence interval, 0.44-0.89; P = 0.01) with a significant test for trend (P = 0.01). The inverse association noted among younger women was found for both in situ and invasive breast cancer, and for ductal as well as lobular breast cancer. These results were not altered after adjusting for established risk factors. The authors conclude that there was evidence in the study to support a potential beneficial impact on breast cancer risk associated with moderate levels of tea consumption (at least three cups per day) among younger women. Further research is needed to confirm this association.

The current study was designed to assess the influence of the phytoestrogens genistein and apigenin on breast cancer growth. Genistein and apigenin are present in several commercial supplements designed to be used for postmenopausal symptoms and breast health. Both flavonoids were found to stimulate proliferation of estrogen receptor-positive/progesterone receptor-positive (ER+/PR+) MCF-7 and estrogen receptor alpha (ERα-positive) T47D breast cancer cells. However, the compounds did not stimulate the proliferation of ERα-negative MDA-MB-435 breast cancer cells. Genistein was observed to be more efficient in this regard due to its higher binding affinity for ERα. Similarly to actions previously described for estradiol (E2), both genistein and apigenin were found to down regulate ERα and enhance estrogen response element-dependent gene expression. An additional finding that genistein antagonizes the anti-proliferative effect of hydroxytamoxifen indicates that certain phytoestrogens may be detrimental for women with breast cancer who are being treated with tamoxifen. The authors conclude that because of their ability to stimulate breast cell growth, the use of phytoestrogen supplements in postmenopausal women could be detrimental.

The current study was designed to examine serum progesterone levels and progesterone receptor expression in normal mammary glands and corresponding mammary tumors in rats fed a soy protein isolate or casein diet (control diet). Previously, the authors showed that lifetime exposure of Sprague-Dawley rats to a diet made with soy protein isolate as the only protein source protected against chemically-induced mammary tumorigenesis, relative to the control (casein) diet. However, in the soy protein isolate-fed rats that developed tumors, there was a higher proportion of tumors with infiltrating ductal carcinoma (IDC) than with ductal carcinoma in situ (DCIS), compared to the tumors of the casein-fed rats. This suggests potential unfavorable effects of soy components on tumor progression. The present study focused on progesterone. An inverse associated between serum progesterone levels and breast cancer risk has been reported in premenopausal women. Also, the breast tissue of women consuming dietary soy supplements has been reported to have increased progesterone receptor (PR) expression, whereas the breast tissue of women on soy-based diets has been found to be decreased. In the study, the expression of progesterone receptor A (PR-A) and progesterone receptor B (PR-B) isoforms in pathologically normal mammary glands and corresponding mammary tumors (IDC and DCIS) were evaluated. In addition, the serum progesterone levels of rats fed soy protein isolate or casein and exposed to the carcinogen N-nitroso-N-methylurea (NMU) were examined. PR-A levels were found to be higher in normal mammary glands in the soy protein isolate-fed rats than in the casein group, while PR-B levels did not differ with diet. The ratio of PR-A/PR-B was four-fold higher in the soy protein isolate relative to the casein group in normal mammary glands, but was not different in tumor tissues. The increased PR-A/PR-B ratio in the soy protein isolate group was accompanied by increased levels of HER-2/neu oncogene, whose up-regulated expression is reported in invasive breast cancers. Serum progesterone levels were found to be significantly lower (P<0.01) in tumor-bearing rats fed soy protein isolate than those fed casein, while no differences (P=0.259) were observed for serum estrogen. The authors comment that since breast cancer patients with mammary PR-A greater than PR-B expression have been found to be less responsive to endocrine therapy than those with higher PR-B expression, the finding of increased expression of PR-A with dietary soy in rats with NMU-induced tumors may have important implications for women with benign or malignant breast cancer consuming soy-based diets.

The present study was designed to evaluate curcumin's effect on gene expression in a preclinical model for ductal carcinoma in situ (DCIS). The amplification or over-expression of oncogene HER-2/neu is found in up to 30% of DCIS breast cancer lesions. Previous work from the authors' laboratory demonstrated preventive action of curcumin (diferuloylmethane) due to cytostatic arrest of growth (S:G2/M phase of cell cycle), as well as induction of apoptosis in a mouse model for breast cancer. 184-B5 immortalized normal breast epithelial cells, established from reduction mammoplasty, lack anchorage-independent growth and are non-cancerous. A preclinical epithelial cell culture model for DCIS was developed with transformed 184-B5/HER cells which exhibits hyperproliferation, shorter population doubling time, higher saturation density, high anchorage independent growth and tumorigenicity. In the study, normal or transformed cells were treated for 24 hours with 0 uM or 20 uM curcumin. Exposure of curcumin to regular 184-B5 cells demonstrated no change in the expression of genes related to cell cycle or apoptosis, in other words, a non-responsive effect. On the other hand, curcumin treated 184-B5/HER cells evinced upregulation of the apoptosis-related genes BAX and TRAF1. Downregulated genes included cyclins A and B, CDC 2, 20 and 25C and BUB1. The authors conclude that curcumin exerts its anti-proliferative activity by reduction of cell cycle progression in S:G2/M and by induction of apoptosis through BAX and TRAF1 related mechanisms, effects that were not observed under identical conditions in normal cells.

The current case-control study was designed to examine the relationship between alcohol consumption and the risk of the most hormonally-responsive breast cancer types (i.e., lobular or hormone receptor positive breast cancers). The study included 975 women 65 to 79 years of age diagnosed with invasive breast cancer during 1997–1999 in Washington State, as well as 1,007 controls. Ever-use of alcohol over the past 20 years was found to be associated with a 1.3-fold [95% confidence interval (CI), 1.0–1.5] increased risk of breast cancer, although this increase was mostly accounted for by women who drank at least 30.0 g per day of alcohol [OR, 1.7; CI: 1.1–2.6]. Ever-use of alcohol also was found to be associated with a 1.8-fold (CI: 1.3–2.5) increased risk of lobular cancer compared to a 1.2-fold (CI: 0.9–1.4) increased risk of ductal cancer. Ever-users of alcohol had an increase in risk of ER+/PR+ tumors (OR, 1.3; CI: 1.1–1.7), but no impact was observed for their risks of ER-/PR- or ER+/PR- breast cancer. The authors conclude that alcohol use appears to be more strongly associated with lobular and hormone receptor-positive cancers than it is with other types of breast cancer.