Dietary intake of selected fatty acids,cholesterol and carotenoids and estrogen receptor status in premenopausal breast cancer patients

Although a wealth of research has focused on the influence of diet on breast cancer risk, the relationships between dietary factors and tumor characteristics of breast cancer, like estrogen receptor (ER) status, are not well characterized. In a case-case study, we evaluated self-reported dietary intake for five individual carotenoids, selected fatty acids, and cholesterol 1 year before diagnosis in 34 premenopausal breast cancer patients with ER-negative tumors and 86 premenopausal breast cancer patients with ER-positive tumors from The University of Texas M. D. Anderson Cancer Center. In multivariate logistic regression analysis adjusted for age, body mass index, and ethnicity, high intakes of linoleic acid were associated with more than a threefold greater risk of ER-negative disease than ER-positive disease (odds ratio (OR) = 3.48, 95% confidence interval (CI) = 1.42–8.54), whereas high cholesterol intake was associated with lower risk of ER-negative disease (OR = 0.35, 95% CI = 0.14–0.92). In a model evaluating carotenoids, selected fatty acids, and cholesterol together, the association with high intake of linoleic acid remained statistically significant (OR = 3.96, 95% CI = 1.53–10.25), while those for high intake of cholesterol (OR = 0.38, 95% CI = 0.14–1.03) and low intake of cryptoxanthin (OR = 0.43, 95% CI = 0.17–1.06) were of marginal significance. While no striking associations were observed for the intakes of total carotenoids, selected fatty acids, and cholesterol, our analysis revealed an association for the consumption of a specific fatty acid (i.e., linoleic acid), suggesting dietary influence of this factor on ER status in premenopausal breast cancer patients. However, larger studies are needed to clarify the role of micronutrients in ER status in breast cancer.     

A maternal high‐fat diet during pregnancy in rats results in a greater risk of carcinogen‐induced mammary tumors in the female offspring than exposure to a high‐fat diet in postnatal life

The association between a high‐fat diet and breast cancer risk is controversial. We hypothesized that the exposure of rats to a high‐fat diet in utero via the maternal diet would result in a greater risk of carcinogen‐induced mammary tumors than high‐fat diet exposure in postnatal life. Rats were exposed to a high‐fat diet with 40% of the energy source as safflower oil in utero (In utero group), at postnatal days 30–50 (Puberty group), postnatal days 150–170 (Adult group), postnatal days 1–230 (Postnatal group) or for their whole life from in utero (Whole group). Chow diet‐fed rats were used as the Nonexposure group. Mammary tumor incidence was significantly higher in the In utero (60%), Postnatal (61%) and Whole (91%) groups than in the Nonexposure group (32%), but there was no significant difference between the Puberty (44%), Adult (44%) and Nonexposure groups. Arachidonic acid levels were 10 times higher in mammary tumor tissue than in the normal mammary gland across all groups and were positively correlated with tumor weight. We conclude that the timing, but not the duration, of high‐fat diet exposure makes rats more susceptible to carcinogen‐induced mammary tumors and that exposure in utero to a maternal high‐fat diet during pregnancy is more important in increasing the risk of mammary tumors in the female offspring than exposure of the offspring to the same high‐fat diet later in life. © 2009 UICC     

Alcohol intake and risk of breast cancer defined by estrogen and progesterone receptor status--a meta-analysis of epidemiological studies

The association between alcohol consumption and an increased risk of breast cancer has been established. It is still unclear however, whether this relationship differs across the estrogen receptor (ER) and progesterone receptor (PR) tumors subtypes. To provide a quantitative assessment of the association between alcohol intake and the risk of ER-/PR-defined breast cancer, we conducted a meta-analysis of cohort and case-control studies. Studies were identified by a literature search of PubMed through April 20, 2007 and by searching the reference lists of relevant articles. Summarized risk estimates (REs) with 95% confidence intervals (CIs) were calculated using random-effects models. The summarized results of the meta-analysis comparing the highest versus the lowest consumption categories showed statistically significant higher risks of developing all ER+ (27%), all ER- (14%), ER+PR+ (22%) and ER+PR- (28%), but not ER-PR- tumors. The dose-response meta-analysis showed that an increase in alcohol consumption of 10 g of ethanol per day was associated with statistically significant increased risks for all ER+ (12%), all ER- (7%), ER+PR+ (11%) and ER+PR- (15%), but not ER-PR-. A statistically significant heterogeneity of the REs across all ER+ versus ER-PR- was observed (p(heterogeneity) = 0.02). The summarized results from studies with adjustment for postmenopausal hormone use, body mass index and family history of breast cancer were higher and statistically significantly different from those without. The observed positive associations with alcohol for ER+PR+ and ER+PR- tumors cannot be explained by estrogen-dependent pathway only. Further studies need to clarify the biological mechanisms.     

Dietary fiber intake and risk of postmenopausal breast cancer defined by estrogen and progesterone receptor status--a prospective cohort study among Swedish women

There is few data on the association between dietary fiber intake and estrogen receptor (ER)/progesterone receptor (PR)-defined breast cancer risk. We evaluated the association between dietary fiber and ER/PR-defined breast cancer risk stratified by postmenopausal hormone use, alcohol intake, and family history of breast cancer in the population-based Swedish Mammography Screening Cohort comprising 51,823 postmenopausal women. Fiber intake was measured by food-frequency questionnaire collected in 1987 and 1997. Relative risks (RRs) were estimated by hazard ratio derived from Cox proportional hazard regression models. During an average of 8.3-year follow-up, 1,188 breast cancer cases with known ER/PR status were diagnosed. When comparing the highest to the lowest quintile, we observed non-significant inverse associations between total fiber intake and the risk of all tumor subtypes; the multivariate-adjusted RRs were 0.85 (95% CI: 0.69-1.05) for overall, 0.85 (0.64-1.13) for ER+PR+, 0.83 (0.52-1.31) for ER+PR- and 0.94 (0.49-1.80) for ER-PR-. For specific fiber, we observed statistically significant risk reductions for overall (34%) and for ER+PR+ (38%) for the highest versus lowest quintile of fruit fiber, and non-significant inverse associations for other subtypes of cancer and types of fiber. Among ever-users of postmenopausal hormone (PMH), total fiber intake and especially cereal fiber were statistically significantly associated with approximately 50% reduced risk for overall and ER+PR+ tumors when comparing the highest to the lowest quartile, but no association was observed among PMH never users. Our results suggest that dietary fiber intake from fruit and cereal may play a role in reducing breast cancer risk.     

Dietary patterns and the risk of postmenopausal breast cancer

The association between individual foods and breast cancer has been inconsistent. Therefore, we examined the association between diet and risk of postmenopausal breast cancer by the alternative approach of dietary patterns. Dietary patterns were identified with factor analysis from food consumption data collected from a food frequency questionnaire in 1984. Relative risks were computed using proportional hazard models and adjusted for known risk factors for breast cancer. Between 1984 and 2000, we ascertained 3,026 incident cases of postmenopausal breast cancer. We identified 2 major dietary patterns. The prudent pattern is characterized by higher intake of fruits, vegetables, whole grains, low-fat dairy products, fish and poultry, while the Western pattern is characterized by higher intake of red and processed meats, refined grains, sweets and desserts and high-fat dairy products. Neither of the patterns was associated with overall risk of postmenopausal breast cancer. However, a positive association between the Western pattern score was observed among smokers at baseline (relative risk = 1.44, comparing top to bottom quintiles; 95% CI = 1.02-2.03; p for trend = 0.03). An inverse association was observed between the prudent pattern and estrogen receptor-negative cancer (relative risk = 0.62; 95% CI = 0.45-0.88; p for trend = 0.006). Among the major food groups, higher consumptions of fruits (relative risk for 1 serving/day increase = 0.88; 95% CI = 0.80-0.97; p = 0.009) and vegetables (relative risk = 0.94; 95% CI = 0.88-0.99; p = 0.03) were significantly associated with decreased risk for ER(-) breast cancer. In conclusion, we did not observe an overall association between the prudent or Western pattern and overall breast cancer risk. However, a Western-type diet may elevate risk of breast cancer among smokers, and a prudent diet may protect against estrogen receptive-negative tumors.     

Prediction of hormone responsiveness by mammographic parenchymal pattern in advanced primary breast cancer

Summary Ninety-two women with advanced, unilateral breast cancer were classified according to the Wolfe and Nottingham classifications of mammographic parenchymal pattern (MPP). Both classifications of MPP were significantly correlated to the estrogen receptor (ER) status of the breast carcinoma, but could not be used for prediction of response to hormonal therapy. Age distribution was significantly different among Wolfe types as well as between ER groups, but a multiple regression analysis showed that both age and Wolfe pattern were significant and independent predictors of the ER status.     

Adjuvant dietary fat intake reduction in postmenopausal breast cancer patient management

Management of localized breast cancer now commonly involves a breast-sparing approach combined with systemic adjuvant therapy resulting in improved cosmetic results and patient survival. Reducing dietary fat intake represents a conceptually new approach to further improve outcome of patients with resected breast cancer. The rationale supporting evaluation of dietary fat reduction in the management of patients with localized breast cancer is based on: (1) epidemiologic observations (along with biochemical and hormonal correlates) of major differences in stage-by-stage survival of patients with localized breast cancer comparing outcome in countries with low fat (Japan) versus high fat (U.S.A.) dietary intakes; (2) relationships between dietary fat intake and factors prognostic of clinical outcome in patients with established breast cancer; (3) effects of weight gain (especially that associated with adjuvant chemotherapy) on breast cancer clinical outcome; (4)in vivo animal studies demonstrating adverse influence of increased dietary fat intake (especially linoleic acid) on growth and metastatic spread of mammary cancer; (5) direct adverse effects of increased linoleic acid on human breast cancer growthin vitro; (6) plausible mechanisms which could mediate the effects of dietary fat intake reduction on breast cancer growth and metastatic spread; (7) demonstration of adherence to dietary fat reduction regimens in ongoing clinical feasibility studies including those involving postmenopausal patients with resected breast cancer; and (8) favorable sample size requirements for definitive assessment of dietary fat intake reduction influence on breast cancer growth and metastases (using as endpoints relapse-free survival and overall survival) in postmenopausal breast cancer patients with localized disease.     

Maternal height, pregnancy estriol and birth weight in reference to breast cancer risk in Boston and Shanghai

Birth weight has been positively associated with breast cancer risk in adult life and is positively associated with the principal pregnancy estrogen estriol. Birth weight is lower among Chinese women than among Caucasian women, but paradoxically, pregnancy estriol levels are higher among the former than the latter. We studied a cohort of 317 Caucasian pregnant women in Boston, MA, and 339 Chinese pregnant women in Shanghai, China. We investigated whether maternal height, which is inversely associated with pregnancy estriol levels, interacts with this hormone in relation to birth weight, thus accommodating the apparently contradictory ecologic and analytic evidence concerning the role of pregnancy estrogens on breast cancer risk in the offspring. In both Boston and Shanghai, there was a positive association of pregnancy estriol with birth weight among taller women, whereas among shorter women the association was essentially null. The relevant interaction terms were highly significant in Boston (p approximately 0.006), whereas in Shanghai, where pregnant women were generally shorter, the interaction term was suggestive (p approximately 0.14). We conclude that maternal height should be considered an important risk factor for breast cancer in the offspring since it is a crucial determinant of birth weight, both directly and through positive interaction with the principal pregnancy estrogen estriol.     

Dietary fat intake and risk of epithelial ovarian cancer by tumour histology

Background:

Studies of fat intake and epithelial ovarian cancer (EOC) risk have reported inconsistent findings, hence we hypothesised that associations may vary by histologic subtype.

Methods:

We evaluated fat intake in a New England case–control study including 1872 cases and 1978 population-based controls (1992–2008). Epithelial ovarian cancer risk factors and diet were assessed using a food frequency questionnaire at enrolment. Logistic regression was used to estimate associations between fat intake and EOC risk and polytomous logistic regression was used to test whether associations varied by histologic subtype.

Results:

We observed a decreased risk of EOC when comparing the highest vs lowest quartiles of intake of omega-3 (odds ratio (OR)=0.79, 95% confidence interval (CI) 0.66–0.96, P-trend=0.01) and omega-6 (OR=0.77, 95% CI 0.64–0.94, P-trend=0.02) and an increased risk with high consumption of trans fat (OR=1.30, 95% CI 1.08–1.57, P-trend=0.002). There was no significant heterogeneity by tumour histologic subtype; however, we observed a strong decreased risk for endometrioid invasive tumours with high intake of omega-3 (quartile (Q) 4 vs Q1, OR=0.58, 95% CI 0.41–0.82, P-trend=0.003).

Conclusions:

These findings suggest that higher intake of omega-3 may be protective for EOC overall and endometrioid tumours in particular, whereas greater consumption of trans fat may increase risk of EOC overall.     

Haplotypes of the estrogen receptor beta gene and breast cancer risk

Exposure to exogenous (oral contraceptives, postmenopausal hormone therapy) and endogenous (number of ovulatory cycles, adiposity) steroid hormones is associated with breast cancer risk. Breast cancer risk associated with these exposures could hypothetically be modified by genes in the steroid hormone synthesis, metabolism and signaling pathways. Estrogen receptors are the first step along the path of signaling cell growth and development upon stimulation with estrogens. The National Cancer Institute Breast and Prostate Cancer Cohort Consortium has systematically selected haplotype tagging SNPs in genes along the steroid hormone synthesis, metabolism and binding pathways, including the estrogen receptor beta (ESR2) gene. Four htSNPs tag the 6 major (>5% frequency) haplotypes of the ESR2 gene. These polymorphisms have been genotyped in 5,789 breast cancer cases and 7,761 controls nested within the American Cancer Society Cancer Prevention Study II, European Prospective Investigation into Cancer and Nutrition, Multiethnic Cohort, Nurses' Health Study and Women's Health Study cohorts. None of the SNPs were independently associated with breast cancer risk. One haplotype of the ESR2 gene was associated with breast cancer risk before correction for multiple testing (OR 1.17, 95% CI 1.07-1.28, p = 0.0007). This haplotype remained associated with breast cancer risk after adjustment for multiple testing using a permutation procedure. There was no statistically significant heterogeneity in SNP or haplotype odds ratios across cohorts. These data suggest that inherited variants in ESR2 (while possibly conferring a small increased risk of breast cancer) are not associated with appreciable (OR > 1.2) changes in breast cancer risk among Caucasian women.     

乳腺癌内分泌治疗耐药相关机制的研究进展

内分泌治疗作为雌激素受体（estrogen receptor,ER）阳性乳腺癌的主要治疗方案被广泛应用。他莫西芬（tamoxifen,Tam）是乳腺癌内分泌治疗最常用的药物,它通过与雌激素竞争性结合ERα来降低雌激素的生物学活性,抑制细胞的增殖,从而治疗乳腺癌。然而,肿瘤细胞所表现出的原发性或获得性的他莫西芬耐药使得其临床应用受到了限制,寻找克服他莫西芬耐药的治疗策略已经刻不容缓。目前为止,他莫西芬耐药的相关机制已部分明确,但仍需进一步研究。有证据表明ERα、生长因子受体信号通路及microRNA的表达异常等多种机制均与他莫西芬耐药有关。本文对他莫西芬耐药的相关机制进行了具体分析,以期为ER阳性乳腺癌的治疗提供新思路。     

Dietary lignan intakes and risk of breast cancer by tumor estrogen receptor status

We examined the association of dietary lignan intake with estrogen receptor negative (ER−) and ER positive (ER+) breast cancer risk in a breast cancer case–control study. Among premenopausal women only, there was a reduced risk of ER− breast cancer for those in the highest compared to the lowest quartile of lignan intake suggesting that the observed negative association of lignans with breast cancer may be limited to ER− tumors.     

Atributable risk of breast,prostate, and lung cancer in Hawaii due to saturated fat

The dietary data from case-control studies of breast, prostate, and lung cancer in Hawaii revealed that saturated fat was a risk factor for these malignancies. The dietary intakes from the three studies were used to calculate the attributable risk (AR) due to saturated fat. For all ethnic groups combined, the ARs for the highest quartiles of intake were 14.9 percent for female breast cancer, 13.0 percent for prostate cancer, and 23.1 percent for male lung cancer. Our results suggested that a reduction of saturated fat to the lowest quartiles of intake could result in a 10 to 20 percent decrease in risk for these three cancers in Hawaii. We also examined the ethnic-specific risks associated with saturated fat consumption among the Japanese and the Caucasians in the three studies. The ARs for the highest quartiles of intake were notably higher among the Caucasians than the Japanese, primarily due to the difference in their dietary patterns. Although the calculated AR due to saturated fat was higher among the Caucasians than among the Japanese, all persons in the population would derive considerable benefit by reducing their intake of this nutrient.Authors are with the Epidemiology Program, Cancer Research Center of Hawaii, University of Hawaii, 1236 Lauhala Street, Honolulu, HI 96813, USA. Address correspondence to Dr Hankin. This study was supported in part by NIH Grant PO1 CA 33619.     

Autoimmune diseases and breast cancer risk by tumor hormone‐receptor status among elderly women

The female preponderance of many autoimmune diseases suggests a possible hormonal etiology. Little research exists on systemic and organ‐specific autoimmune diseases and risk of breast cancer by tumor estrogen receptor (ER)‐ and progesterone receptor (PR)‐ status. Here, we evaluate associations between selected systemic and organ‐specific autoimmune diseases and breast cancer risk overall and by tumor ER‐ and PR‐status. We used linked Surveillance, Epidemiology and End Results (SEER)‐Medicare data, with first female breast cancer cases ages ≥66 years identified by SEER registries (years 1992–2011; N = 209,929). We selected female controls (N = 200,000) from a stratified 5% random sample of Medicare recipients who were alive and breast cancer‐free. We assessed exposures until 12 months before breast cancer diagnosis/selection using Medicare claims data. We estimated odds ratios (OR) and 99.9% confidence intervals (CI) using unconditional and multinomial logistic regression. We found reduced breast cancer risk among those with rheumatoid arthritis (OR = 0.84; 99.9% CI 0.79–0.89), systemic lupus erythematosus (OR = 0.82; 99.9% CI 0.70–0.97) and pernicious anemia (OR = 0.90; 99.9% CI 0.83–0.97) and increased risk among those with psoriasis (OR = 1.16; 99.9% CI 1.06–1.27). Statistically significant alterations in risk for rheumatoid arthritis were limited to ER‐positive (+) breast cancer, whereas those for the other three conditions were further limited to ER+/PR+ breast cancer. However, only differences for rheumatoid arthritis by ER‐status were statistically significant (p‐heterogeneity = 0.0001). The reasons for these associations need to be investigated in future studies accounting for host characteristics and autoimmune disease treatment.     

Dietary acrylamide intake and risk of breast cancer in the UK women's cohort

Background:

No studies to date have demonstrated a clear association with breast cancer risk and dietary exposure to acrylamide.

Methods:

A 217-item food frequency questionnaire was used to estimate dietary acrylamide intake in 33 731 women aged 35–69 years from the UK Women''s Cohort Study followed up for a median of 11 years.

Results:

In all, 1084 incident breast cancers occurred during follow-up. There was no evidence of an overall association between acrylamide intake and breast cancer (hazard ratio=1.08 per 10 μg day⁻¹, 95% CI: 0.98–1.18, P_trend=0.1). There was a suggestion of a possible weak positive association between dietary acrylamide intake and premenopausal breast cancer after adjustment for potential confounders (hazard ratio=1.2, 95% CI: 1.0–1.3, P_trend=0.008). There was no suggestion of any association for postmenopausal breast cancer (hazard ratio=1.0, 95% CI: 0.9–1.1, P_trend=0.99).

Conclusions:

There is no evidence of an association between dietary acrylamide intake and breast cancer. A weak association may exist with premenopausal breast cancer, but requires further investigation.     

Dietary fat and breast cancer risk in the Swedish women's lifestyle and health cohort

We investigated whether dietary intakes of total fat, monounsaturated fat (MUFA), polyunsaturated fat (PUFA) and saturated fat (SFA) were associated with breast cancer risk in a prospective cohort of 49 261 Swedish women (30-49 years at enrolment), which yielded 974 breast cancer cases by December 2005. Further, we evaluated if associations differed by oestrogen and/or progesterone receptor tumour status. Total fat, MUFA, PUFA or SFA were not associated with risk overall. However, women in the highest MUFA and PUFA quintile intake had a reduced breast cancer risk after age 50 years (hazard ratios: 95% confidence interval=0.45: 0.25-0.99 and 0.54: 0.35-0.85, respectively) compared to women in the lowest quintile. The associations did not differ by oestrogen or progesterone receptor status. Despite the negative findings, type of fat during premenopausal years may have later differential effects on risk.     

Polymorphisms in the estrogen receptor beta gene and risk of breast cancer: no association

Polymorphisms in the estrogen receptor beta (ER) gene may influence the cellular growth regulating effects of estradiol. In this first association study about breast cancer risk and polymorphisms in the ER gene we have screened 219 Finnish sporadic breast cancer cases and 248 ethnically matched male controls. No difference in the allele distribution of the six studied polymorphisms was found between the breast cancer and control groups.     

The effect of dietary fat on breast cancer survival among Caucasian and Japanese women in Hawaii

182 Japanese and 161 Caucasian breast cancer patients participated in an epidemiologic case-control study from 1975–1980. They were subsequently followed until the end of 1987 to determine their survival status. Among the Japanese, patients with regional or distant disease had a relative risk (RR) of death of 13.0 (95% Confidence Interval (CI), 4.3–39.1) compared to those within situ or localized disease, and obese patients had a RR of death of 3.5 (95% CI, 1.3–10.0) compared to non-obese subjects. Among the Caucasians, patients with advanced disease had a RR of death of 4.3 (95% CI, 1.8–10.5) compared to those within situ or localized disease, and patients with a high fat intake had a RR of 3.2 (95% CI, 1.2–8.6) compared to subjects with a low fat intake. Menopausal status (pre- or postmenopausal) and replacement estrogen use were not related to survival from breast cancer in either ethnic group. When Japanese and Caucasian patients were compared with each other, there was no significant difference in survival between them.