Menstrual and reproductive characteristics and breast cancer risk by hormone receptor status and ethnicity: The Breast Cancer Etiology in Minorities study.
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SUBMITTER: John EM
PROVIDER: S-EPMC8784189 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Few risk factors have been identified for triple negative breast cancer (TNBC) which lacks expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). This more aggressive subtype disproportionately affects some racial/ethnic minorities and is associated with lower survival. We pooled data from three population-based studies (558 TNBC and 5,111 controls) and examined associations of TNBC risk with reproductive history and breast-feeding. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using multivariable logistic regression. For younger women, aged <50 years, TNBC risk was increased two-fold for parous women who never breast-fed compared to nulliparous women (OR?=?2.02, 95% CI?=?1.12-3.63). For younger parous women, longer duration of lifetime breast-feeding was associated with a borderline reduced risk (?24 vs. 0 months: OR?=?0.52, 95% CI?=?0.26-1.04, Ptrend ?=?0.06). Considering the joint effect of parity and breast-feeding, risk was increased two-fold for women with ?3 full-term pregnancies (FTPs) and no or short-term (<12 months) breast-feeding compared to women with 1-2 FTPs and breast-feeding ?12 months (OR?=?2.56, 95% CI?=?1.22-5.35). None of these associations were observed among older women (?50 years). Differences in reproductive patterns possibly contribute to the ethnic differences in TNBC incidence. Among controls aged <50 years, the prevalence of no or short-term breast-feeding and ?3 FTPs was highest for Hispanics (22%), followed by African Americans (18%), Asian Americans (15%) and non-Hispanic whites (6%). Breast-feeding is a modifiable behavioral factor that may lower TNBC risk and mitigate the effect of FTPs in women under age 50 years.
| S-EPMC5893409 | biostudies-literature
Project description:PURPOSE:There are no published data from specific regions of sub-Saharan Africa describing the clinical and pathological characteristics and molecular subtypes of invasive breast cancer by ethnic group. The purpose of this study was to investigate these characteristics among the three major ethno-cultural groupings in Kenya. METHODS:The study included women with pathologically confirmed breast cancer diagnosed between March 2012 and May 2015 at 11 hospitals throughout Kenya. Sociodemographic, clinical, and reproductive data were collected by questionnaire, and pathology review and immunohistochemistry were performed centrally. RESULTS:The 846 cases included 661 Bantus (78.1%), 143 Nilotes (16.9%), 19 Cushites (2.3%), and 23 patients of mixed ethnicity (2.7%). In analyses comparing the two major ethnic groups, Bantus were more educated, more overweight, had an older age at first birth, and had a younger age at menopause than Nilotes (p < 0.05 for all comparisons). In analyses restricted to definitive surgery specimens, there were no statistically significant differences in tumor characteristics or molecular subtypes by ethnicity, although the Nilote tumors tended to be larger (OR for ? 5 cm vs. < 2 cm: 3.86, 95% CI 0.77, 19.30) and were somewhat more likely to be HER2 enriched (OR for HER2 enriched vs. Luminal A/B: 1.41, 95% CI 0.79, 2.49). CONCLUSION:This case series showed no significant differences in breast cancer tumor characteristics or molecular subtypes, but significant differences in sociodemographic characteristics and reproductive factors, among the three major ethnic groups in Kenya. We suggest further evaluation of ethnic differences in breast cancer throughout the genetically and culturally diverse populations of sub-Saharan Africa.
| S-EPMC5792313 | biostudies-literature
Project description:BackgroundReproductive characteristics are well-established risk factors for breast cancer, but the underlying mechanisms are not fully resolved. We hypothesized that altered DNA methylation, measured in tumor tissue, could act in concert with reproductive factors to impact breast carcinogenesis.MethodsAmong a population-based sample of women newly diagnosed with first primary breast cancer, reproductive history was assessed using a life-course calendar approach in an interviewer-administered questionnaire. Methylation-specific polymerase chain reaction and Methyl Light assays were used to assess gene promotor methylation status (methylated vs. unmethylated) for 13 breast cancer-related genes in archived breast tumor tissue. We used case-case unconditional logistic regression to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for associations with age at menarche and parity (among 855 women), and age at first birth and lactation (among a subset of 736 parous women) in association with methylation status.ResultsAge at first birth >?27?years, compared with <?23?years, was associated with lower odds of methylation of CDH1 (OR?=?0.44, 95% CI?=?0.20-0.99) and TWIST1 (OR?=?0.48, 95% CI?=?0.28-0.82), and higher odds of methylation of BRCA1 (OR?=?1.63, 95% CI?=?1.14-2.35). Any vs. no lactation was associated with higher odds of methylation of the PGR gene promoter (OR?=?1.59, 95% CI?=?1.01-2.49). No associations were noted for parity and methylation in any of the genes assayed.ConclusionsOur findings indicate that age at first birth, lactation and, perhaps age at menarche, are associated with gene promoter methylation in breast cancer, and should be confirmed in larger studies with robust gene coverage.
| S-EPMC6749688 | biostudies-literature
Project description:ObjectivesWomen report greater sleep disturbance during the premenstrual phase of the menstrual cycle and during menses. However, the putative hormonal basis of perceived menstrual cycle-related sleep disturbance has not been investigated directly. We examined associations of objective measures of sleep fragmentation with reproductive hormone levels in healthy, premenopausal women.MethodsTwenty-seven women with monthly menses had hormone levels measured at two time points during a single menstrual cycle: the follicular phase and the peri-ovulatory to mid-luteal phase. A single night of home polysomnography (PSG) was recorded on the day of the peri-ovulatory/mid-luteal-phase blood draw. Serum progesterone, estradiol, and estrone levels concurrent with PSG and rate of change in progesterone (PROGslope) from the follicular blood draw to PSG were correlated with log-transformed wake after sleep onset (lnWASO%) and number of wakes/hour of sleep (lnWake-Index) using linear regression.ResultsSleep was more fragmented in association with a steeper PROGslope (lnWASO% p=0.016; lnWake-Index p=0.08) and higher concurrent estrone level (lnWASO% p=0.03; lnWake-Index p=0.01), but the effect of estrone on WASO was lost after accounting for PROGslope. WASO% and Wake-Index were not associated with concomitant progesterone or estradiol levels.ConclusionsA steeper rate of rise in progesterone levels from the follicular phase through the mid-luteal phase was associated with significantly greater WASO, establishing a link between reproductive hormone dynamics and sleep fragmentation in the luteal phase of the menstrual cycle.
| S-EPMC4098663 | 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
Project description:BackgroundScant research has analyzed contemporary US cancer incidence rates in relation to historical redlining (ie, 1930s US federally imposed residential segregation), implemented via the color-coded federal Home Owners' Loan Corporation (HOLC) maps.MethodsWe analyzed Massachusetts Cancer Registry data for all patients with primary invasive breast cancer (BC) diagnosed in 2005-2015 among women in the 28 Massachusetts municipalities with digitized 1930s HOLC maps. Multilevel Poisson regression estimated BC incidence rate ratios (IRR), overall and by tumor estrogen receptor (ER-positive, ER-negative) and progesterone receptor (PR-positive, PR-negative) status, in relation to HOLC grade and contemporary census tract (CT) social characteristics.ResultsNet of age and racialized group, the extremes of BC incidence were detected by combinations of HOLC grade and contemporary CT racialized economic segregation. Compared with CTs with the best HOLC grade (A + B) and most privileged contemporary characteristics (T1), for all, ER-positive and PR-positive BC, incidence was highest in T1 and mixed HOLC grade CTs (eg, IRRER+; Mixed-T1 = 1.10, 95% confidence interval [CI] = 1.01 to 1.21) and lowest in CTs with most concentrated racialized economic deprivation (T3) and no HOLC grade (eg, IRRER+; No Grade-T3 = 0.85, 95% CI = 0.75 to 0.95). For ER-negative and PR-negative BC, incidence was highest in CTs with the most contemporary deprivation, but the best HOLC grade (eg, IRRER-; A+B-T3 = 1.27, 95% CI = 0.93 to 1.75) and lowest in T1 and worst HOLC-graded CTs (eg, IRRER-; D-T1 = 0.84, 95% CI = 0.56 to 1.25).ConclusionBreast cancer risk may be shaped by combined histories of redlining and present-day CT characteristics.
| S-EPMC8953461 | biostudies-literature
Project description:INTRODUCTION:Reproductive history has been associated with breast cancer risk, but more knowledge of the underlying biological mechanisms is needed. Because of limited data on normal breast tissue from healthy women, we examined associations of reproductive history and established breast cancer risk factors with breast tissue composition and markers of hormone receptors and proliferation in a nested study within the Karolinska Mammography project for risk prediction for breast cancer (Karma). MATERIALS AND METHODS:Tissues from 153 women were obtained by ultrasound-guided core needle biopsy as part of the Karma project. Immunohistochemical staining was used to assessed histological composition of epithelial, stromal and adipose tissue, epithelial and stromal oestrogen receptor (ER) and progesterone receptor (PR) status, and Ki-67 proliferation status. An individualised reproductive score including parity, number of pregnancies without birth, number of births, age at first birth, and duration of breastfeeding, was calculated based on self-reported reproductive history at the time of the Karma study entry. All analyses were adjusted for age and BMI. RESULTS:Cumulated reproductive score was associated with increased total epithelial content and greater expression of epithelial ER. Parity was associated with greater epithelial area, increased epithelial-stromal ratio, greater epithelial ER expression and a lower extent of stromal proliferation. Increasing numbers of pregnancies and births were associated with a greater epithelial area in the entire study set, which remained significant among postmenopausal women. Increasing numbers of pregnancies and births were also associated with a greater expression of epithelial ER among postmenopausal women. Longer duration of breastfeeding was associated with greater epithelial area and greater expression of epithelial PR both in the entire study set and among postmenopausal women. Breastfeeding was also positively associated with greater epithelial ER expression among postmenopausal women. Prior use of oral contraceptives was associated with lower epithelial-stromal ratio amongst all participants and among pre- and postmenopausal women separately. CONCLUSION:Reproductive risk factors significantly influence the epithelial tissue compartment and expression of hormone receptors in later life. These changes remain after menopause. This study provides deeper insights of the biological mechanisms by which reproductive history influences epithelial area and expression of hormone receptors, and as a consequence the risk of breast cancer.
| S-EPMC6022521 | biostudies-literature
Project description:ObjectiveTo estimate the effect of daily 81 mg low-dose aspirin (LDA) on menstrual cycle length and hormone profiles.DesignSecondary analysis of a trial evaluating the effect of daily LDA or placebo on live birth among women with one or two previous pregnancy losses.SettingUniversity medical centers.Patient(s)A total of 915 regularly menstruating women who had at least one menstrual cycle (3,190 total cycles) in which pregnancy did not occur.Intervention(s)Randomized allocation to LDA versus placebo.Main outcome measure(s)Menstrual cycle length and follicular and luteal phases were measured. Urinary pregnanediol glucuronide, follicle-stimulating hormone, luteinizing hormone, and estrone-3-glucuronide were assessed up to six times during the first two cycles. Generalized estimating equations estimated relative risk of short (<25th percentile: <27 days) and long (>75th percentile: ≥32 days) versus normal cycle length. Linear mixed models estimated mean hormone level differences with weights used to account for multiple cycles contributed per participant.Result(s)There were no significant differences in total menstrual cycle, follicular phase, or luteal phase length between LDA and placebo groups. LDA posed no greater risk of having a short versus normal-length or long versus normal-length follicular phase, or having a short versus normal-length or long versus normal-length luteal phase. There were no significant differences in hormone levels across the menstrual cycle between the LDA and placebo groups.Conclusion(s)Daily LDA use did not result in any changes to menstrual cycle, follicular phase, or luteal phase length or hormone levels across the menstrual cycle compared with placebo.Clinical trial registration numberNCT00467363.
| S-EPMC7722096 | biostudies-literature
Project description:In analyses combining estrogen with or without progestin, some observational studies describe minimal breast cancer risk in obese and black women. Therefore, we examined these suggested interactions in the two Women's Health Initiative (WHI) randomized hormone therapy trials. The estrogen plus progestin trial entered 16 608 postmenopausal women with a uterus, while the estrogen trial entered 10 736 postmenopausal women with prior hysterectomy. Hazard ratios (HRs), 95% confidence intervals (CIs), and P values from log-rank x(2) statistics were estimated from Cox proportional hazards models with subgroup analyses based on tests of interaction. All statistical tests were two-sided. Estrogen plus progestin statistically significantly increased breast cancer incidence (HR = 1.28, 95% CI = 1.11 to 1.48, P < .001), with hazard ratios greater than 1 in all body mass index (BMI) subgroups (P interaction = .58) and hazard ratios greater than 1 in black and white women (P interaction = .96). In contrast, estrogen alone statistically significantly decreased breast cancer incidence (HR = 0.79, 95% CI = 0.65 to 0.90, P = .02), with hazard ratios lower than 1 in all BMI subgroups (P interaction = .86) and hazard ratios lower than 1 in black and white women, where analyses with limited numbers suggest somewhat greater reduction in black women (P interaction = .09). In summary, estrogen plus progestin and estrogen alone have opposite effects on breast cancer incidence, with no statistically significant interactions by race/ethnicity or BMI. Therefore, observational studies should not combine these two regimens when examining breast cancer risk.
| S-EPMC5943827 | biostudies-literature
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