Family history and breast cancer hormone receptor status in a Spanish cohort.
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ABSTRACT:
SUBMITTER: Jiang X
PROVIDER: S-EPMC3253097 | biostudies-other | 2012
REPOSITORIES: biostudies-other
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Project description:We examined whether differences in tumor DNA methylation were associated with more aggressive hormone receptor-negative breast cancer in an ethnically diverse group of patients in the Breast Cancer Care in Chicago (BCCC) study and using data from The Cancer Genome Atlas (TCGA).DNA was extracted from formalin-fixed, paraffin-embedded samples on 75 patients (21 White, 31 African-American, and 23 Hispanic) (training dataset) enrolled in the BCCC. Hormone receptor status was defined as negative if tumors were negative for both estrogen and progesterone (ER/PR) receptors (N?=?22/75). DNA methylation was analyzed at 1505 CpG sites within 807 gene promoters using the Illumina GoldenGate assay. Differential DNA methylation as a predictor of hormone receptor status was tested while controlling for false discovery rate and assigned to the gene closest to the respective CpG site. Next, those genes that predicted ER/PR status were validated using TCGA data with respect to DNA methylation (validation dataset), and correlations between CpG methylation and gene expression were examined. In the training dataset, 5.7 % of promoter mean methylation values (46/807) were associated with receptor status at P?<?0.05; for 88 % of these (38/46), hypermethylation was associated with receptor-positive disease. Hypermethylation for FZD9, MME, BCAP31, HDAC9, PAX6, SCGB3A1, PDGFRA, IGFBP3, and PTGS2 genes most strongly predicted receptor-positive disease. Twenty-one of 24 predictor genes from the training dataset were confirmed in the validation dataset. The level of DNA methylation at 19 out 22 genes, for which gene expression data were available, was associated with gene activity.Higher levels of promoter methylation strongly correlate with hormone receptor positive status of breast tumors. For most of the genes identified in our training dataset as ER/PR receptor status predictors, DNA methylation correlated with stable gene expression level. The predictors performed well when evaluated on independent set of samples, with different racioethnic distribution, thus providing evidence that this set of DNA methylation biomarkers will likely generalize to prospective patient samples.
| S-EPMC4754852 | biostudies-literature
Project description:IntroductionAssociations of hormone-receptor positive breast cancer with excess adiposity are reasonably well characterized; however, uncertainty remains regarding the association of body mass index (BMI) with hormone-receptor negative malignancies, and possible interactions by hormone replacement therapy (HRT) use.MethodsWithin the European EPIC cohort, Cox proportional hazards models were used to describe the relationship of BMI, waist and hip circumferences with risk of estrogen-receptor (ER) negative and progesterone-receptor (PR) negative (n = 1,021) and ER+PR+ (n = 3,586) breast tumors within five-year age bands. Among postmenopausal women, the joint effects of BMI and HRT use were analyzed.ResultsFor risk of ER-PR- tumors, there was no association of BMI across the age bands. However, when analyses were restricted to postmenopausal HRT never users, a positive risk association with BMI (third versus first tertile HR = 1.47 (1.01 to 2.15)) was observed. BMI was inversely associated with ER+PR+ tumors among women aged ?49 years (per 5 kg/m2 increase, HR = 0.79 (95%CI 0.68 to 0.91)), and positively associated with risk among women ?65 years (HR = 1.25 (1.16 to 1.34)). Adjusting for BMI, waist and hip circumferences showed no further associations with risks of breast cancer subtypes. Current use of HRT was significantly associated with an increased risk of receptor-negative (HRT current use compared to HRT never use HR: 1.30 (1.05 to 1.62)) and positive tumors (HR: 1.74 (1.56 to 1.95)), although this risk increase was weaker for ER-PR- disease (Phet = 0.035). The association of HRT was significantly stronger in the leaner women (BMI ?22.5 kg/m2) than for more overweight women (BMI ?25.9 kg/m2) for, both, ER-PR- (HR: 1.74 (1.15 to 2.63)) and ER+PR+ (HR: 2.33 (1.84 to 2.92)) breast cancer and was not restricted to any particular HRT regime.ConclusionsAn elevated BMI may be positively associated with risk of ER-PR- tumors among postmenopausal women who never used HRT. Furthermore, postmenopausal HRT users were at an increased risk of ER-PR- as well as ER+PR+ tumors, especially among leaner women. For hormone-receptor positive tumors, but not for hormone-receptor negative tumors, our study confirms an inverse association of risk with BMI among young women of premenopausal age. Our data provide evidence for a possible role of sex hormones in the etiology of hormone-receptor negative tumors.
| S-EPMC3446339 | biostudies-literature
Project description:Importance:First-degree family history is a strong risk factor for breast cancer, but controversy exists about the magnitude of the association among older women. Objective:To determine whether first-degree family history is associated with increased risk of breast cancer among older women, and identify whether the association varies by breast density. Design, Setting, and Participants:Prospective cohort study between 1996 and 2012 from 7 Breast Cancer Surveillance Consortium (BCSC) registries located in New Hampshire, North Carolina, San Francisco Bay area, western Washington state, New Mexico, Colorado, and Vermont. During a mean (SD) follow-up of 6.3 (3.2) years, 10?929 invasive breast cancers were diagnosed in a cohort of 403?268 women 65 years and older with data from 472?220 mammography examinations. We estimated the 5-year cumulative incidence of invasive breast cancer by first-degree family history, breast density, and age groups. Cox proportional hazards models were fit to estimate the association of first-degree family history with risk of invasive breast cancer (after adjustment for breast density, BCSC registry, race/ethnicity, body mass index, postmenopausal hormone therapy use, and benign breast disease for age groups 65 to 74 years and 75 years and older, separately). Data analyses were performed between June 2016 and June 2017. Exposure:First-degree family history of breast cancer. Main Outcomes and Measures:Incident breast cancer. Results:In 403 268 women 65 years and older, first-degree family history was associated with an increased risk of breast cancer among women ages 65 to 74 years (hazard ratio [HR],?1.48; 95% CI, 1.35-1.61) and 75 years and older (HR, 1.44; 95% CI, 1.28-1.62). Estimates were similar for women 65 to 74 years with first-degree relative's diagnosis age younger than 50 years (HR, 1.47; 95% CI, 1.25-1.73) vs 50 years and older (HR, 1.33; 95% CI, 1.17-1.51) and for women ages 75 years and older with the relative's diagnosis age younger than 50 years (HR, 1.31; 95% CI, 1.05-1.63) vs 50 years and older (HR, 1.55; 95% CI, 1.33-1.81). Among women ages 65 to 74 years, the risk associated with first-degree family history was highest among those with fatty breasts (HR, 1.67; 95% CI, 1.27-2.21), whereas in women 75 years and older the risk associated with family history was highest among those with dense breasts (HR, 1.55; 95% CI, 1.29-1.87). Conclusions and Relevance:First-degree family history was associated with increased risk of invasive breast cancer in all subgroups of older women irrespective of a relative's age at diagnosis.
| S-EPMC5876845 | biostudies-other
Project description:Genome wide DNA methylation profiling of invasive breast cancer samples isolated from an ethnically diverse group of 80 patients in the Breast Cancer Care in Chicago (BCCC) study. DNA was extracted from formalin fixed, paraffin-embedded samples on 80 patients (21 White, 31 African-American, 23 Hispanic and 5 not reported) (training dataset) enrolled in the BCCC. Hormone receptor status was defined as negative if tumors were negative for both estrogen and progesterone (ER/PR) receptors (N=22/75). Formalin-fixed, paraffin-embedded (FFPE) tumor samples came from the Breast Cancer Care in Chicago (BCCC) study (Dookeran KA, Silva A, Warnecke RB, Rauscher GH: Race/ethnicity and disparities in mastectomy practice in the Breast Cancer Care in Chicago study. Ann Surg Oncol 2015, 22:66â74). Copies of pathology reports and the corresponding set of Hematoxylin and Eosin (H&E) stained slides were requested from the pathology department at each diagnosing institution, and a single pathologist selected tumor blocks representative of the tumor. Two recuts (at 4 µm each) were made from each selected block for H&E staining. The recuts were then examined in order to identify invasive components of the sample, and areas were marked according to tissue component. Cores of invasive tissue (2 mm in diameter) were obtained from the marked areas and DNA was extracted for the DNA methylation study. Bisulphite converted DNA from the 80 samples were hybridised to the Illumina GoldenGate Methylation Cancer Panel I
2016-02-12 | E-GEOD-72110 | biostudies-arrayexpress
Project description:Genome wide DNA methylation profiling of invasive breast cancer samples isolated from an ethnically diverse group of 80 patients in the Breast Cancer Care in Chicago (BCCC) study. DNA was extracted from formalin fixed, paraffin-embedded samples on 80 patients (21 White, 31 African-American, 23 Hispanic and 5 not reported) (training dataset) enrolled in the BCCC. Hormone receptor status was defined as negative if tumors were negative for both estrogen and progesterone (ER/PR) receptors (N=22/75). Formalin-fixed, paraffin-embedded (FFPE) tumor samples came from the Breast Cancer Care in Chicago (BCCC) study (Dookeran KA, Silva A, Warnecke RB, Rauscher GH: Race/ethnicity and disparities in mastectomy practice in the Breast Cancer Care in Chicago study. Ann Surg Oncol 2015, 22:66–74). Copies of pathology reports and the corresponding set of Hematoxylin and Eosin (H&E) stained slides were requested from the pathology department at each diagnosing institution, and a single pathologist selected tumor blocks representative of the tumor. Two recuts (at 4 µm each) were made from each selected block for H&E staining. The recuts were then examined in order to identify invasive components of the sample, and areas were marked according to tissue component. Cores of invasive tissue (2 mm in diameter) were obtained from the marked areas and DNA was extracted for the DNA methylation study.
2016-02-12 | GSE72110 | GEO
Project description:Laboratory studies have observed chemopreventive effects of black and green tea on breast cancer development, but few epidemiologic studies have identified such effects. We investigated the association between tea consumption and breast cancer risk using data from 45,744?U.S. and Puerto Rican women participating in the Sister Study. Frequency and serving size of black and green tea consumption were measured at cohort enrollment. Breast cancer diagnoses were reported during follow-up and confirmed by medical record review. Multivariable Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI). We further investigated potential variation according to estrogen receptor (ER) status, menopausal status and body mass index (BMI). Overall, 81.6 and 56.0% of women drank black or green tea, respectively. A total of 2,809 breast cancer cases were identified in the cohort. The multivariable model suggested an inverse association between black (?5 vs. 0 cups/week: HR = 0.88, 95% CI 0.78, 1.00, p-trend = 0.08) and green tea (?5 vs. 0 cups/week: HR = 0.82, 95% CI 0.70, 0.95, p-trend?<?0.01) consumption and breast cancer risk. We did not observe differences by ER characteristics, menopausal status or BMI. In conclusion, our study suggests drinking at least five cups of green or black tea per week may be associated with decreased breast cancer risk.
| S-EPMC7283004 | biostudies-literature
Project description:BackgroundPubertal milestones, such as onset of breast development and menstruation, play an important role in breast cancer etiology. It is unclear if these milestones are different in girls with a first- or second-degree breast cancer family history (BCFH).MethodsIn the LEGACY Girls Study (n?=?1040), we examined whether three mother/guardian-reported pubertal milestones (having reached Tanner Stage 2 or higher (T2+) for breast and pubic hair development, and having started menstruation) differed by BCFH. We also examined whether associations between body size and race/ethnicity and pubertal milestones were modified by BCFH. We used mother/guardian reports as the primary measure of pubertal milestones, but also conducted sensitivity analyses using clinical Tanner measurements available for a subcohort (n?=?204). We analyzed cross-sectional baseline data with logistic regression models for the entire cohort, and longitudinal data with Weibull survival models for the subcohort of girls that were aged 5-7 years at baseline (n?=?258).ResultsBCFH was modestly, but not statistically significantly, associated with Breast T2+ (odds ratio (OR)?=?1.36, 95% confidence interval (CI)?=?0.88-2.10), with a stronger association seen in the subcohort of girls with clinical breast Tanner staging (OR?=?2.20, 95% CI?=?0.91-5.32). In a longitudinal analysis of girls who were aged 5-7 years at baseline, BCFH was associated with a 50% increased rate of having early breast development (hazard ratio (HR)?=?1.49, 95% CI?=?1.0-2.21). This association increased to twofold in girls who were not overweight at baseline (HR?=?2.04, 95% CI?=?1.29-3.21). BCFH was not associated with pubic hair development and post-menarche status. The median interval between onset of breast development and menarche was longer for BCFH+ than BCFH- girls (2.3 versus 1.7 years), suggesting a slower developmental tempo for BCFH+ girls. Associations between pubertal milestones and body size and race/ethnicity were similar in girls with or without a BCFH. For example, weight was positively associated with Breast T2+ in both girls with (OR?=?1.06 per 1 kg, 95% CI?=?1.03-1.10) and without (OR?=?1.14 per 1 kg, 95% CI?=?1.04-1.24) a BCFH.ConclusionsThese results suggest that BCFH may be related to earlier breast development and slower pubertal tempo independent of body size and race/ethnicity.
| S-EPMC5465536 | biostudies-literature
Project description:BackgroundEstrogen receptor-negative (ER(-)) breast cancer has few known or modifiable risk factors. Because ER(-) tumors account for only 15% to 20% of breast cancers, large pooled analyses are necessary to evaluate precisely the suspected inverse association between fruit and vegetable intake and risk of ER(-) breast cancer.MethodsAmong 993 466 women followed for 11 to 20 years in 20 cohort studies, we documented 19 869 estrogen receptor positive (ER(+)) and 4821 ER(-) breast cancers. We calculated study-specific multivariable relative risks (RRs) and 95% confidence intervals (CIs) using Cox proportional hazards regression analyses and then combined them using a random-effects model. All statistical tests were two-sided.ResultsTotal fruit and vegetable intake was statistically significantly inversely associated with risk of ER(-) breast cancer but not with risk of breast cancer overall or of ER(+) tumors. The inverse association for ER(-) tumors was observed primarily for vegetable consumption. The pooled relative risks comparing the highest vs lowest quintile of total vegetable consumption were 0.82 (95% CI = 0.74 to 0.90) for ER(-) breast cancer and 1.04 (95% CI = 0.97 to 1.11) for ER(+) breast cancer (P (common-effects) by ER status < .001). Total fruit consumption was non-statistically significantly associated with risk of ER(-) breast cancer (pooled multivariable RR comparing the highest vs lowest quintile = 0.94, 95% CI = 0.85 to 1.04).ConclusionsWe observed no association between total fruit and vegetable intake and risk of overall breast cancer. However, vegetable consumption was inversely associated with risk of ER(-) breast cancer in our large pooled analyses.
| S-EPMC3593764 | biostudies-literature
Project description:Single estrogen receptor (ER)+ and progesterone receptor (PR)+ tumors account for about10% of all breast cancers. However, the prognosis of these single hormone receptor-positive (HR+) tumor remains unclear. We aimed to investigate the characteristics of single HR+ breast tumors according to HER2 status in order to improve the treatment of patients with single HR+. Patients from the SEER program (2010-2016) were divided into ER+PR-, ER-PR+, ER+PR+ and ER-PR- molecular subtypes stratified by HER2 status. Overall survival (OS) and breast cancer-specific survival (BCSS) were compared by Kaplan-Meier curves after propensity score matching (PSM). A total of 203,406 patients were enrolled. Single ER+ and PR+ tumors account for 11.9% of the total population. For HER2- subtype, patients with ER+PR- (n = 16906 pairs) and ER-PR+ (n = 1395 pairs) had worse prognoses than those with ER+PR+ with hazard ratio (HR) and 95% confidence interval (CI) of 1.52 (1.41-1.64) and 2.25 (1.76-2.88) for OS; and 1.94 (1.76-2.14) and 2.57 (1.94-3.40) for BCSS, respectively; ER+PR- showed a better prognosis than ER-PR+ (n = 1394 pairs) and ER-PR- (n = 9626 pairs) with HR (95% CI) of 1.32 (1.06-1.65) and 1.44 (1.33-1.55) for OS, and 1.32 (1.03-1.69) and 1.46 (1.34-1.60) for BCSS, respectively; ER-PR+ had a similar prognosis relative to ER-PR- (n = 1395 pairs) after PSM. For HER2+ subtype, patients with ER-PR+, ER+PR-, and ER-PR- had similar OS and BCSS; ER+PR+ showed a similar prognosis compare with ER-PR+ (n = 535 pairs), but had better OS and BCSS than ER+PR- (n = 5376 pairs) and ER-PR- (n = 8143 pairs) after PSM. In addition, ER+PR+HER2+ showed similar OS and better BCSS compared with ER+PR+HER2- after PSM. In conclusion, single PR+ patients experienced poorer prognoses than single ER+ patients, and may be treated as ER-PR- patients in HER2- subtype. In HER2+ patients, both single ER+ and single PR+ cases showed similar prognoses compared with ER-PR- cases, and may be treated as ER-PR- patients.
| S-EPMC8165305 | biostudies-literature
Project description:Etiologic differences between subtypes of breast cancer defined by estrogen receptor (ER) and progesterone receptor (PR) status are not well understood. The authors evaluated associations of hormone-related factors with breast cancer subtypes in a population-based case-control study involving 1,409 ER-positive (ER+)/PR-positive (PR+) cases, 712 ER-negative (ER-)/PR-negative (PR-) cases, 301 ER+/PR- cases, 254 ER-/PR+ cases, and 3,474 controls aged 20-70 years in Shanghai, China (phase I, 1996-1998; phase II, 2002-2005). Polytomous logistic regression and Wald tests for heterogeneity across subtypes were conducted. Breast cancer risks associated with age at menarche, age at menopause, breastfeeding, age at first livebirth, waist-to-hip ratio, and oral contraceptive use did not differ by hormone receptor status. Among postmenopausal women, higher parity (?2 children vs. 1) was associated with reduced risk (odds ratio (OR) = 0.69, 95% confidence interval (CI): 0.52, 0.91) and higher body mass index (BMI; weight (kg)/height (m)(2)) with increased risk (highest quartile: OR = 2.40, 95% CI: 1.65, 3.47) of the ER+/PR+ subtype but was unrelated to the ER-/PR- subtype (for parity, P(heterogeneity) = 0.02; for BMI, P(heterogeneity) < 0.01). Hormone replacement therapy (OR = 2.25, 95% CI: 1.40, 3.62) and alcohol consumption (OR = 1.59, 95% CI: 1.01, 2.51) appeared to be preferentially associated with the ER+/PR- subtype. These findings indicate that BMI, parity, hormone replacement therapy, and alcohol consumption may play different roles in subtypes of breast cancer. More research is needed to better understand the etiology of 2 relatively rare subtypes, ER+/PR- tumors and ER-/PR+ tumors.
| S-EPMC3166707 | biostudies-literature