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Background: We examined associations of CD44, CD24 and ALDH1A1 breast stem cell markers with mammographic breast density (MBD), a well-established breast cancer (BCa) risk factor. Methods: We included 218 cancer-free women with biopsy-confirmed benign breast disease within the Nurses' Health Study (NHS) and NHSII. The data on BCa risk factors were obtained from biennial questionnaires. Immunohistochemistry (IHC) was done on tissue microarrays. For each core, the IHC expression was assessed using a semi-automated platform and expressed as percent of positively stained cells for each marker out of the total cell count. MBD was assessed with computer-assisted techniques. Generalised linear regression was used to examine the associations of each marker with square root-transformed percent density (PD), absolute dense and non-dense areas (NDA), adjusted for BCa risk factors. Results: Stromal CD44 and ALDH1A1 expression was positively associated with PD (≥ 10% vs. <10% β = 0.56, 95% confidence interval [CI] [0.06; 1.07] and β = 0.81 [0.27; 1.34], respectively) and inversely associated with NDA (β per 10% increase = −0.17 [−0.34; −0.01] and β for ≥10% vs. <10% = −1.17 [−2.07; −0.28], respectively). Epithelial CD24 expression was inversely associated with PD (β per 10% increase = −0.14 [−0.28; −0.01]. Stromal and epithelial CD24 expression was positively associated with NDA (β per 10% increase = 0.35 [0.2 × 10−2; 0.70] and β per 10% increase = 0.34 [0.11; 0.57], respectively). Conclusion: Expression of stem cell markers is associated with MBD. [ABSTRACT FROM AUTHOR]

Purpose: The gut microbiome is a potentially important contributor to endogenous estrogen levels after menopause. In healthy postmenopausal women, we examined associations of fecal microbiome composition with levels of urinary estrogens, their metabolites, and relevant metabolic pathway ratios implicated in breast cancer risk. Methods: Eligible postmenopausal women (n = 164) had a body mass index (BMI) ≤ 35 kg/m2 and no history of hormone use (previous 6 months) or cancer/metabolic disorders. Estrogens were quantified in spot urine samples with liquid chromatography-high resolution mass spectrometry (corrected for creatinine). Bacterial DNA was isolated from fecal samples and the V1–V2 hypervariable regions of 16S rRNA were sequenced on the Illumina MiSeq platform. We examined associations of gut microbiome's indices of within-sample (alpha) diversity (i.e., Shannon, Chao1, and Inverse Simpson), phylogenetic diversity, and the ratio of the two main phyla (Firmicutes and Bacteroidetes; F/B ratio) with individual estrogens and metabolic ratios, adjusted for age and BMI. Results: In this sample of 164 healthy postmenopausal women, the mean age was 62.9 years (range 47.0–86.0). We found significant inverse associations of observed species with 4-pathway:total estrogens (p = 0.04) and 4-pathway:2-pathway (p = 0.01). Shannon index was positively associated with 2-catechols: methylated 2-catechols (p = 0.04). Chao1 was inversely associated with E1:total estrogens (p = 0.04), and 4-pathway:2-pathway (p = 0.02) and positively associated with 2-pathway:parent estrogens (p = 0.01). Phylogenetic diversity was inversely associated with 4-pathway:total estrogens (p = 0.02), 4-pathway:parent estrogens (p = 0.03), 4-pathway:2-pathway (p = 0.01), and 4-pathway:16-pathway (p = 0.03) and positively associated with 2-pathway:parent estrogens (p = 0.01). F/B ratio was not associated with any of the estrogen measures. Conclusion: Microbial diversity was associated with several estrogen metabolism ratios implicated in breast cancer risk. Further studies are warranted to confirm these findings in a larger and more representative sample of postmenopausal women, particularly with enrichment of minority participants. [ABSTRACT FROM AUTHOR]

Background: Excessive energy intake has been shown to affect the mammalian target of the rapamycin (mTOR) signaling pathway and breast cancer risk. It is not well understood whether there are gene-environment interactions between mTOR pathway genes and energy intake in relation to breast cancer risk. Methods: The study included 1642 Black women (809 incident breast cancer cases and 833 controls) from the Women's Circle of Health Study (WCHS). We examined interactions between 43 candidate single-nucleotide polymorphisms (SNPs) in 20 mTOR pathway genes and quartiles of energy intake in relation to breast cancer risk overall and by ER− defined subtypes using Wald test with a 2-way interaction term. Results: AKT1 rs10138227 (C > T) was only associated with a decreased overall breast cancer risk among women in quartile (Q)2 of energy intake, odds ratio (OR) = 0.60, 95% confidence interval (CI) 0.40, 0.91 (p-interaction = 0.042). Similar results were found in ER− tumors. AKT rs1130214 (C > A) was associated with decreased overall breast cancer risk in Q2 (OR = 0.63, 95% CI 0.44, 0.91) and Q3 (OR = 0.65, 95% CI 0.48, 0.89) (p-interaction = 0.026). HIF-1α C1772T rs11549465 (C > T) was associated with decreased overall breast cancer risk in Q4 (OR = 0.29, 95% CI 0.14, 0.59, p-interaction = 0.007); the results were similar in ER+ tumors. These interactions became non-significant after correction for multiple comparisons. Conclusion: Our findings suggest that mTOR genetic variants may interact with energy intake in relation to breast cancer risk, including the ER− subtype, in Black women. Future studies should confirm these findings. [ABSTRACT FROM AUTHOR]

Background: Obesity is known to stimulate the mammalian target of rapamycin (mTOR) signaling pathway and both obesity and the mTOR signaling pathway are implicated in breast carcinogenesis. We investigated potential gene-environment interactions between mTOR pathway genes and obesity in relation to breast cancer risk among Black women. Methods: The study included 1,655 Black women (821 incident breast cancer cases and 834 controls) from the Women's Circle of Health Study (WCHS). Obesity measures including body mass index (BMI); central obesity i.e., waist circumference (WC) and waist/hip ratio (WHR); and body fat distribution (fat mass, fat mass index and percent body fat) were obtained by trained research staff. We examined the associations of 43 candidate single-nucleotide polymorphisms (SNPs) in 20 mTOR pathway genes with breast cancer risk using multivariable logistic regression. We next examined interactions between these SNPs and measures of obesity using Wald test with 2-way interaction term. Results: The variant allele of BRAF (rs114729114 C > T) was associated with an increase in overall breast cancer risk [odds ratio (OR) = 1.81, 95% confidence interval (CI) 1.10–2.99, for each copy of the T allele] and the risk of estrogen receptor (ER)-defined subtypes (ER+ tumors: OR = 1.83, 95% CI 1.04,3.29, for each copy of the T allele; ER- tumors OR = 2.14, 95% CI 1.03,4.45, for each copy of the T allele). Genetic variants in AKT, AKT1, PGF, PRKAG2, RAPTOR, TSC2 showed suggestive associations with overall breast cancer risk and the risk of, ER+ and ER– tumors (range of p-values = 0.040–0.097). We also found interactions of several of the SNPs with BMI, WHR, WC, fat mass, fat mass index and percent body fat in relation to breast cancer risk. These associations and interactions, however, became nonsignificant after correction for multiple testing (FDR-adjusted p-value > 0.05). Conclusion: We found associations between mTOR genetic variants and breast cancer risk as well as gene and body fatness interactions in relation to breast cancer risk. However, these associations and interactions became nonsignificant after correction for multiple testing. Future studies with larger sample sizes are required to confirm and validate these findings. [ABSTRACT FROM AUTHOR]

Background: Physical activity has been shown to affect the mammalian target of rapamycin (mTOR) signaling pathway and consequently breast carcinogenesis. Given that Black women in the USA are less physically active, it is not well understood whether there are gene–environment interactions between mTOR pathway genes and physical activity in relation to breast cancer risk in Black women. Methods: The study included 1398 Black women (567 incident breast cancer cases and 831 controls) from the Women's Circle of Health Study (WCHS). We examined interactions between 43 candidate single-nucleotide polymorphisms (SNPs) in 20 mTOR pathway genes with levels of vigorous physical activity in relation to breast cancer risk overall and by ER-defined subtypes using Wald test with 2-way interaction term and multivariable logistic regression. Results: AKT1 rs10138227 (C > T) and AKT1 rs1130214 (C > A) were only associated with a decreased risk of ER + breast cancer among women with vigorous physical activity (odds ratio [OR] = 0.15, 95% confidence interval (CI) 0.04, 0.56, for each copy of the T allele, p-interaction = 0.007 and OR = 0.51, 95% CI 0.27, 0.96, for each copy of the A allele, p-interaction = 0.045, respectively). MTOR rs2295080 (G > T) was only associated with an increased risk of ER + breast cancer among women with vigorous physical activity (OR = 2.24, 95% CI 1.16, 4.34, for each copy of the G allele; p-interaction = 0.043). EIF4E rs141689493 (G > A) was only associated with an increased risk of ER- breast cancer among women with vigorous physical activity (OR = 20.54, 95% CI 2.29, 184.17, for each copy of the A allele; p-interaction = 0.003). These interactions became non-significant after correction for multiple testing (FDR-adjusted p-value > 0.05). Conclusion: Our findings suggest that mTOR genetic variants may interact with physical activity in relation to breast cancer risk in Black women. Future studies should confirm these findings. [ABSTRACT FROM AUTHOR]

Purpose: We investigated the association of coffee and caffeine with breast cancer (BCa) risk, overall and by ER/PR status. We also examined potential interactions of coffee and caffeine with postmenopausal hormone use. Methods: Our study included 77,688 postmenopausal participants from the Women's Health Initiative observational study cohort without a history of any cancer at baseline (except non-melanoma skin) and with valid Food Frequency Questionnaire data and complete data on dietary caffeine. Regular coffee (none, 1, 2–3, 4–5, and ≥ 6 cups/day) and caffeine (tertiles) were assessed at baseline. Information on BCa risk factors was collected at baseline. The associations were examined using survival analysis, accounting for death as a competing risk. Results: The median follow-up time for our cohort was 18.3 years. During the follow-up, 5005 women developed invasive breast cancer. In multivariable analysis, coffee was not associated with the overall invasive BCa risk. Higher caffeine intake was mildly associated with increased BCa risk (2nd vs. 1st tertile SHR = 1.10, 95% CI 1.03–1.18, 3rd vs. 1st tertile SHR–1.05, 95% CI 0.98–1.13, overall p = 0.03). We found no interaction of coffee/caffeine with postmenopausal hormone use (p interaction = 0.44 and 0.42, respectively). In the exploratory analysis by ER/PR status, we found a positive association of caffeine with ER+ /PR+ BCa (2nd vs. 1st tertile SHR = 1.17, 95% CI 1.07–1.28, 3rd vs. 1st tertile SHR = 1.13, 95% CI 1.03–1.24, overall p = 0.002); no associations were observed for ER−/PR− tumors. Coffee was not associated with the risk of ER+ /PR+ or ER−/PR− tumors. Conclusion: We found no associations of coffee with BCa risk, overall and for ER/PR-defined tumor subtypes. The higher caffeine consumption was mildly and positively associated with the overall BCa risk and with ER+ /PR+ tumors. [ABSTRACT FROM AUTHOR]

Purpose: Circulating estrogens are an established risk factor for postmenopausal breast cancer (BCa). We describe the distribution of urinary estrogens, their metabolites, and relevant metabolic pathway ratios among healthy postmenopausal women and examine associations of several known BCa factors with these estrogen measures.Methods: Eligible postmenopausal women (n = 167) had no history of hormone use (previous 6 months) and cancer/metabolic disorders and had a body mass index (BMI) ≤ 35 kg/m2. Estrogens were quantified in spot urine samples with liquid chromatography-high-resolution mass spectrometry and corrected for creatinine. We assessed overall distributions of estrogens and associations of age, BMI, race/ethnicity, parity/age at first birth, age at menarche, alcohol, and smoking with log-transformed estrogen measures using multivariate regression.Results: BMI was positively associated with estrone (β per unit = 0.04, 95% Confidence Interval [CI] 0.00; 0.07), combined parent estrogens (β = 0.04, 95% CI 0.01; 0.07), and E2:total estrogens (β = 0.04, 95% CI 0.02; 0.06), and inversely associated with 4-MeOE1 (β = - 0.17, 95% CI - 0.33; - 0.02), E3:parent estrogens (β = - 0.04, 95% CI - 0.07; - 0.00), and 16-pathway:parent (β = - 0.04, 95% CI - 0.07; - 0.01). Being African American vs. white was associated with higher levels of 4-MeOE1 (β = 3.41, 95% CI 0.74; 6.08), 17-epiE3 (β = 1.19, 95% CI 0.07; 2.31), 2-pathway:parent (β = 0.54, 95% CI 0.04; 1.04), and lower levels of E2:total estrogens (β = - 0.48, 95% CI - 0.83; - 0.13). Having < 7 alcohol drinks/week vs. none was associated with higher levels of 16-ketoE2 (β = 1.32, 95% CI 0.36; 2.27), 16-epiE3 (β = 1.02, 95% CI 0.24; 1.79), and 17-epiE3 (β = 0.55, 95% CI 0.02; 1.08). Smoking was positively associated with E3:parent (β = 0.29, 95% CI 0.01; 0.57), 16-pathway:parent (β = 0.25, 95% CI 0.01; 0.49), and inversely associated with estradiol (β = - 0.52, 95% CI - 0.93; - 0.10). As compared to nulliparous, parous women with age at first birth ≥ 25 years had lower levels of estrone, combined parent estrogens, 2-OHE1, and 2-OHE2.Conclusion: Our findings suggest that BMI, race/ethnicity, and some reproductive and lifestyle factors may contribute to postmenopausal BCa through their effects on circulating estrogens. [ABSTRACT FROM AUTHOR]

Purpose: We examined gut microbiome (GM) profiles in relation to mammographic breast density (BD) and body mass index (BMI) in healthy postmenopausal women.Methods: Eligible women were postmenopausal, had a BMI ≤ 35 kg/m2, and had not recently taken oral/IV antibiotics. All women provided a fecal sample and information on breast cancer risk factors. Mammographic BD was classified with the American College of Radiology's BI-RADS BD classification system. Bacterial DNA was isolated from fecal samples and the V1-V2 hypervariable regions of 16S rRNA were sequenced on the Illumina MiSeq platform. We examined associations of GM with indices of within-sample (alpha) diversity and the ratio of the two main phyla (Firmicutes and Bacteroidetes; F/B ratio) with BD and BMI.Results: Among 69 women with BD data, 39 had low BD (BI-RADS I/II) and 30 had high BD (BI-RADS III/IV). BMI was inversely associated with BD (mean BMI = 23.8 and 28.0 in women with high and low BD, respectively, p = 1.07 × 10-5). Similar levels of GM diversity were found across weight groups according to Shannon (p = 0.83); Inverse Simpson (p = 0.97); and Chao1 (p = 0.31) indices. F/B ratio and microbiota diversity were suggestively greater in women with high vs. low BD (p = 0.35, 0.14, 0.15, and 0.17 for F/B ratio, Shannon, Inverse Simpson and Chao1, respectively).Conclusion: Suggestive differences observed in women with high and low BD with respect to GM alpha diversity and prevalence of specific GM taxa need to be confirmed in larger studies. [ABSTRACT FROM AUTHOR]

Purpose: Previous reports suggest that a complex microbiome exists within the female human breast that might contribute to breast cancer etiology. The purpose of this pilot study was to assess the variation in microbiota composition by breast side (left versus right) within individual women and compare the microbiota of normal and breast tumor tissue between women. We aimed to determine whether microbiota composition differs between these groups and whether certain bacterial taxa may be associated with breast tumors. Methods: Bilateral normal breast tissue samples (n = 36) were collected from ten women who received routine mammoplasty procedures. Archived breast tumor samples (n = 10) were obtained from a biorepository. DNA was extracted, amplified, and sequenced. Microbiota data were analyzed using QIIME and RStudio. Results: The most abundant phyla in both tumor and normal tissues were Bacteroidetes, Firmicutes, Proteobacteria, and Actinobacteria. There were statistically significant differences in the relative abundance of various bacterial taxa between groups. Alpha diversity (Simpson's index) was significantly higher in normal compared to tumor samples (0.968 vs. 0.957, p = 0.022). Based on unweighted UniFrac measures, breast tumor samples clustered distinctly from normal samples (R2 = 0.130; p = 0.01). Microbiota composition in normal samples clustered within women (R2 = 0.394; p = 0.01) and by breast side (left or right) within a woman (R2 = 0.189; p = 0.03). Conclusion: Significant differences in diversity between tumor and normal tissue and in composition between women and between breasts of the same woman were identified. These results warrant further research to investigate the relationship between microbiota and breast cancer. [ABSTRACT FROM AUTHOR]

Purpose: We investigated the associations of aspirin and other non-steroid anti-inflammatory drugs with mammographic breast density (MBD) and their interactions in relation to breast cancer risk. Methods: This study included 3,675 cancer-free women within the Nurses' Health Study (NHS) and Nurses' Health Study II (NHSII) cohorts. Percent breast density (PD), absolute dense area (DA), and non-dense area (NDA) were measured from digitized film mammograms using a computer-assisted thresholding technique; all measures were square root-transformed. Information on medication use was collected in 1980 (NHS) and 1989 (NHSII) and updated biennially. Medication use was defined as none, past or current; average cumulative dose and frequency were calculated for all past or current users from all bi-annual questionnaires preceding the mammogram date. We used generalized linear regression to quantify associations of medications with MBD. Two-way interactions were examined in logistic regression models. Results: In multivariate analysis, none of the anti-inflammatory medications were associated with PD, DA, and NDA. We found no interactions of any of the medications with PD with respect to breast cancer risk (all p-interactions > 0.05). However, some of the aspirin variables appeared to have positive associations with breast cancer risk limited only to women with PD 10–24% (past aspirin OR 1.56, 95% CI 1.03–2.35; current aspirin with < 5 years of use OR 1.82, 95% CI 1.01–3.28; current aspirin with ≥ 5 years of use OR 1.89, 95% CI 1.26–2.82). Conclusions: Aspirin and NSAIDs are not associated with breast density measures. We found no interactions of aspirin with MBD in relation to breast cancer risk. [ABSTRACT FROM AUTHOR]

Purpose: Previous studies suggest that coffee and caffeine intake may be associated with reduced breast cancer risk. To date, there is limited and inconsistent epidemiologic evidence for associations of adolescent diet with mammographic breast density, a strong and consistent predictor of breast cancer. We investigated the association of adolescent caffeine intake with mammographic density in premenopausal women. Methods: This study included 751 cancer-free women within the Nurses' Health Study II cohort. Percent breast density (PD), absolute dense (DA) and non-dense areas (NDA) were measured from digitized film mammograms using a computer-assisted thresholding technique; all measures were square root-transformed. Energy-adjusted adolescent caffeine intake was estimated using the data from a food frequency questionnaire. Information regarding breast cancer risk factors was obtained from questionnaires closest to the mammogram date. We used generalized linear regression to quantify associations of caffeine intake with breast density measures. Results: In multivariable analyses, adolescent caffeine intake was not associated with any of the density phenotypes (caffeine 4th vs. 1st quartile: β = − 1.27, 95% CI − 4.62; 2.09, p-trend = 0.55 for percent density; β = − 0.21, 95% CI − 0.76, 0.34, p-trend = 0.65 for absolute dense area, and β = 0.23, 95% CI − 0.28, 0.74, p-trend = 0.50 for non-dense area). Additional adjustment of the models for body mass index at age 18 resulted in attenuation of the risk estimates. Conclusions: Our findings do not support the hypothesis that adolescent caffeine intake is associated with premenopausal mammographic breast density. [ABSTRACT FROM AUTHOR]

Purpose: Epidemiological evidence on the risk factors for uterine/endometrial cancer in breast cancer (BCa) survivors is limited and inconsistent. Therefore, we critically reviewed and summarized available evidence related to the risk factors for uterine/endometrial cancer in BCa survivors. Methods: We conducted a literature search through PubMed, Web of Science Core Collection/Cited Reference Search, as well as through manual searches of the bibliographies of the articles identified in electronic searches. We included in this review studies that were published up to November 30, 2018 that were accessible in full-text format and were published in English. Results: Of the 27 eligible studies, 96% had > 700 participants, 74% were prospective cohorts, 70% originated outside of the US, 44% reported as having pre-/postmenopausal women, and 26% reported having racially heterogeneous populations. Risk factors positively associated with uterine/endometrial cancer risk among BCa survivors included age at BCa diagnosis > 50 years, African American race, greater BMI/weight gain, and Tamoxifen treatment. For other lifestyle, reproductive and clinical factors, associations were either not significant (parity) or inconsistent (HRT use, menopausal status, smoking status) or had limited evidence (alcohol intake, family history of cancer, age at first birth, oral contraceptive use, age at menopause, comorbidities). Conclusion: We identified several methodological concerns and limitations across epidemiological studies on potential risk factors for uterine/endometrial cancer in BCa survivors, including lack of details on uterine/endometrial cancer case ascertainment, varying and imprecise definitions of important covariates, insufficient adjustment for potential confounders, and small numbers of uterine/endometrial cancer cases in the overall as well as stratified analyses. Based on the available evidence, older age and higher body weight measures appear to be a shared risk factor for uterine/endometrial cancer in the general population as well as in BCa survivors. In addition, there is suggestive evidence that African American BCa survivors have a higher risk of uterine/endometrial cancer as compared to their White counterparts. There is also evidence that Tamoxifen contributes to uterine/endometrial cancer in BCa survivors. Given limitations of existing studies, more thorough investigation of these associations is warranted to identify additional preventive strategies needed for BCa survivors to reduce uterine/endometrial cancer risk and improve overall survival. [ABSTRACT FROM AUTHOR]

Purpose: High mammographic breast density is a strong, well-established breast cancer risk factor. Whether stem cells may explain high breast cancer risk in dense breasts is unknown. We investigated the association between breast density and breast cancer risk by the status of stem cell markers CD44, CD24, and ALDH1A1 in the tumor.Methods: We included 223 women with primary invasive or in situ breast cancer and 399 age-matched controls from Mayo Clinic Mammography Study. Percent breast density (PD), absolute dense area (DA), and non-dense area (NDA) were assessed using computer-assisted thresholding technique. Immunohistochemical analysis of the markers was performed on tumor tissue microarrays according to a standard protocol. We used polytomous logistic regression to quantify the associations of breast density measures with breast cancer risk across marker-defined tumor subtypes.Results: Of the 223 cancers in the study, 182 were positive for CD44, 83 for CD24 and 52 for ALDH1A1. Associations of PD were not significantly different across t marker-defined subtypes (51% + vs. 11-25%: OR 2.83, 95% CI 1.49-5.37 for CD44+ vs. OR 1.87, 95% CI 0.47-7.51 for CD44-, p-heterogeneity = 0.66; OR 2.80, 95% CI 1.27-6.18 for CD24+ vs. OR 2.44, 95% CI 1.14-5.22 for CD24-, p-heterogeneity = 0.61; OR 3.04, 95% CI 1.14-8.10 for ALDH1A1+ vs. OR 2.57. 95% CI 1.30-5.08 for ALDH1A1-, p-heterogeneity = 0.94). Positive associations of DA and inverse associations of NDA with breast cancer risk were similar across marker-defined subtypes.Conclusions: We found no evidence of differential associations of breast density with breast cancer risk by the status of stem cell markers. Further studies in larger study populations are warranted to confirm these associations. [ABSTRACT FROM AUTHOR]

Purpose: The prevalence of non-AIDS-related malignancies is on the rise among people aging with HIV population, but the evidence on healthy behaviors including cancer screening practices in this population subgroup is extremely limited. Therefore, we investigated the prevalence of healthy behaviors and sex-specific cancer screening among persons living with HIV, by sex and time since HIV diagnosis.Methods: We included 517 persons living with HIV from the Florida Cohort. Data were obtained from the baseline and follow-up questionnaires, electronic medical records, and Enhanced HIV/AIDS Reporting System. The prevalence of self-reported, age-appropriate cancer screening (anal, colorectal, prostate, breast, and cervical), and healthy behaviors (sustaining healthy body weight, refraining from smoking and alcohol and engaging in physical activity) was compared by sex and years since HIV diagnosis (≤ 13 vs. > 13 years).Results: In the analyses by sex, females were more likely to be obese than males (56.5% vs. 22.2%, p < 0.0001). Distribution of healthy behaviors did not differ by time since diagnosis among males and females. In the analysis of age-appropriate screening among males, 64.8% never had an anal Pap-smear, 36.2% never had a colonoscopy, and 38.9% never had prostate cancer screening. In the analysis of age-appropriate screening among females, 50.0% never had an anal Pap-smear, 46.5% never had a colonoscopy, 7.9% never had a cervical Pap-smear, and 12.7% never had a mammogram. The difference in anal Pap-smear by sex was statistically significant (p < 0.0001). Among males, the age-adjusted prevalence of never having a colonoscopy was higher in those who had HIV for ≤ 13 years (50.8% vs. 30.6%, p = 0.03).Conclusion: The prevalence of selected healthy behaviors and cancer screening differed by sex and/or years since HIV diagnosis suggesting a need for tailored cancer prevention efforts among persons living with HIV via long-term sex-specific interventions. [ABSTRACT FROM AUTHOR]

Purpose: We investigated the association of alcohol intake with mammographic breast density in postmenopausal women by their hormone therapy (HT) status.Methods: This study included 2,100 cancer-free postmenopausal women within the Nurses' Health Study and Nurses' Health Study II cohorts. Percent breast density (PD), absolute dense (DA), and non-dense areas (NDA) were measured from digitized film mammograms using a computer-assisted thresholding technique; all measures were square root transformed. Alcohol consumption was assessed with a food frequency questionnaire (0, < 5, and ≥ 5 g/day). Information regarding breast cancer risk factors was obtained from baseline or biennial questionnaires closest to the mammogram date. We used generalized linear regression to examine associations between alcohol and breast density measures in women with no HT history, current, and past HT users.Results: In multivariable analyses, we found no associations of alcohol consumption with PD (p trend = 0.32) and DA (p trend = 0.53) and an inverse association with NDA (β = - 0.41, 95% CI - 0.73, - 0.09 for ≥ 5 g/day, p trend < 0.01). In the stratified analysis by HT status, alcohol was not associated with PD in any of the strata. We found a significant inverse association of alcohol with NDA among past HT users (β = - 0.79, 95% CI - 1.51, - 0.07 for ≥ 5 g/day, p trend = 0.02). There were no significant interactions between alcohol and HT in relation to PD, DA, and NDA (p interaction = 0.19, 0.42, and 0.43, respectively).Conclusions: Our findings suggest that associations of alcohol with breast density do not vary by HT status. [ABSTRACT FROM AUTHOR]

Purpose: We investigated the association of coffee consumption with postmenopausal breast cancer risk, overall and by the status of postmenopausal hormone therapy (PMH).Methods: This study included 126,182 postmenopausal women (2,636 with breast cancer and 123,546 without) from UK Biobank. Cancer diagnoses were ascertained through the linkage to the UK National Health Service Central Registers. Information on breast cancer risk factors and coffee consumption was collected at baseline and updated during follow-up. We used Cox proportional hazards regression to evaluate associations between coffee consumption and breast cancer, overall and in stratified analyses by woman's PMH status (none, past, current).Results: In the overall analysis, coffee consumption was not associated with breast cancer risk (Hazard Ratio [HR] 1.00, 95% CI 0.91-1.11 for 2-3 cups/day, and HR 0.98, 95% CI 0.87-1.10 for ≥ 4 cups/day, p-trend = 0.69). Women with no PMH history who consumed ≥ 4 cups/day had a 16% reduced risk of breast cancer as compared to women who consumed < 7 cups/week (HR 0.84, 95% CI 0.71-1.00). Among women with past PMH, those consuming ≥ 4 cups/day had a 22% greater risk of breast cancer than women consuming < 7 cups/week (HR 1.22, 95% CI 1.01-1.47). No association was found among current PMH users. We found no significant interaction between PMH and coffee consumption (p = 0.24).Conclusions: Coffee consumption might be associated with increased breast cancer risk in women who used hormones in the past. Further studies are warranted to confirm these findings and elucidate potential biological mechanisms underlying the observed associations. [ABSTRACT FROM AUTHOR]

Purpose: Previous studies suggest that coffee and caffeine intake may be associated with reduced breast cancer risk. We investigated the association of coffee and caffeine intake with mammographic breast density by woman’s menopausal status and, in postmenopausal women, by hormone therapy (HT).Methods: This study included 4130 cancer-free women within the Nurses’ Health Study and Nurses’ Health Study II cohorts. Percent breast density (PD) was measured from digitized film mammograms using a computer-assisted thresholding technique and square root-transformed for the analysis. Average cumulative coffee/caffeine consumption was calculated using data from all food frequency questionnaires preceding the mammogram date. Information regarding breast cancer risk factors was obtained from questionnaires closest to the mammogram date. We used generalized linear regression to quantify associations of regular, decaffeinated, and total coffee, and energy-adjusted caffeine intake with percent density.Results: In multivariable analyses, decaffeinated coffee was positively associated with PD in premenopausal women (2+ cups/day: β = 0.23, p trend = 0.03). In postmenopausal women, decaffeinated and total coffee were inversely associated with PD (decaffeinated 2+ cups/day: β = − 0.24, p trend = 0.04; total 4+ cups/day: β = − 0.16, p trend = 0.02). Interaction of decaffeinated coffee with menopausal status was significant (p-interaction < 0.001). Among current HT users, regular coffee and caffeine were inversely associated with PD (regular coffee 4+ cups/day: β = − 0.29, p trend = 0.01; caffeine 4th vs. 1st quartile: β = − 0.32, p trend = 0.01). Among past users, decaffeinated coffee was inversely associated with PD (2+ cups/day β = − 0.70, p trend = 0.02).Conclusions: Associations of decaffeinated coffee with percent density differ by woman’s menopausal status. Associations of regular coffee and caffeine with percent density may differ by HT status. [ABSTRACT FROM AUTHOR]

A correction is presented to the article "Associations of Coffee/Caffeine Consumption With Postmenopausal Breast Cancer Risk and Their Interactions With Postmenopausal Hormone Use," which appeared in the 2022 issue of the magazine.

Purpose: We examined the associations of mammographic breast density with breast cancer risk by tumor aggressiveness and by menopausal status and current postmenopausal hormone therapy. Methods: This study included 2596 invasive breast cancer cases and 4059 controls selected from participants of four nested case-control studies within four established cohorts: the Mayo Mammography Health Study, the Nurses' Health Study, Nurses' Health Study II, and San Francisco Mammography Registry. Percent breast density (PD), absolute dense (DA), and non-dense areas (NDA) were assessed from digitized film-screen mammograms using a computer-assisted threshold technique and standardized across studies. We used polytomous logistic regression to quantify the associations of breast density with breast cancer risk by tumor aggressiveness (defined as presence of at least two of the following tumor characteristics: size ≥2 cm, grade 2/3, ER-negative status, or positive nodes), stratified by menopausal status and current hormone therapy. Results: Overall, the positive association of PD and borderline inverse association of NDA with breast cancer risk was stronger in aggressive vs. non-aggressive tumors (≥51 vs. 11-25% OR 2.50, 95% CI 1.94-3.22 vs. OR 2.03, 95% CI 1.70-2.43, p-heterogeneity = 0.03; NDA 4th vs. 2nd quartile OR 0.54, 95% CI 0.41-0.70 vs. OR 0.71, 95% CI 0.59-0.85, p-heterogeneity = 0.07). However, there were no differences in the association of DA with breast cancer by aggressive status. In the stratified analysis, there was also evidence of a stronger association of PD and NDA with aggressive tumors among postmenopausal women and, in particular, current estrogen+progesterone users (≥51 vs. 11-25% OR 3.24, 95% CI 1.75-6.00 vs. OR 1.93, 95% CI 1.25-2.98, p-heterogeneity = 0.01; NDA 4th vs. 2nd quartile OR 0.43, 95% CI 0.21-0.85 vs. OR 0.56, 95% CI 0.35-0.89, p-heterogeneity = 0.01), even though the interaction was not significant. Conclusion: Our findings suggest that associations of mammographic density with breast cancer risk differ by tumor aggressiveness. While there was no strong evidence that these associations differed by menopausal status or hormone therapy, they did appear more prominent among current estrogen+progesterone users. [ABSTRACT FROM AUTHOR]

We investigated the associations of reproductive factors related to childbearing with percent breast density, absolute dense and nondense areas, by menopausal status. This study included 4110 cancer-free women within the Nurses' Health Study and Nurses' Health Study II cohorts. Percent breast density, absolute dense and nondense areas were measured from digitized mammography film images with computerized techniques. All density measures were square root-transformed in all the analyses to improve normality. The data on reproductive variables and other breast cancer risk factors were obtained from biennial questionnaires, at the time of the mammogram date. As compared to nulliparous women, parous postmenopausal women had lower percent density ( β = −0.60, 95 % CI −0.84; −0.37), smaller absolute dense area ( β = −0.66, 95 % CI −1.03; −0.29), and greater nondense area ( β = 0.72, 95 % CI 0.27; 1.16). Among parous women, number of children was inversely associated with percent density in pre- ( β per one child = −0.12, 95 % CI −0.20; −0.05) and postmenopausal women ( β per one child = −0.07, 95 % CI −0.12; −0.02). The positive associations of breastfeeding with absolute dense and nondense areas were limited to premenopausal women, while the positive association of the age at first child's birth with percent density and the inverse association with nondense area were limited to postmenopausal women. Women with greater number of children and younger age at first child's birth have more favorable breast density patterns that could explain subsequent breast cancer risk reduction. [ABSTRACT FROM AUTHOR]

Background: This study aimed to determine if associations of pre-diagnostic percent breast density, absolute dense area, and non-dense area with subsequent breast cancer risk differ by the tumour's molecular marker status.Methods: We included 1010 postmenopausal women with breast cancer and 2077 matched controls from the Nurses' Health Study (NHS) and the Nurses' Health Study II (NHS II) cohorts. Breast density was estimated from digitised film mammograms using computer-assisted thresholding techniques. Information on breast cancer risk factors was obtained prospectively from biennial questionnaires. Polychotomous logistic regression was used to assess associations of breast density measures with tumour subtypes by the status of selected tissue markers. All tests of statistical significance were two sided.Results: The association of percent density with breast cancer risk appeared to be stronger in ER- as compared with ER+ tumours, but the difference did not reach statistical significance (density ⩾50% vs <10% odds ratio (OR)=3.06, 95% confidence interval (CI) 2.17-4.32 for ER+; OR=4.61, 95% CI 2.36-9.03 for ER-, Pheterogeneity=0.08). Stronger positive associations were found for absolute dense area and CK5/6- and EGFR- as compared with respective marker-positive tumours (Pheterogeneity=0.002 and 0.001, respectively). Stronger inverse associations of non-dense area with breast cancer risk were found for ER- as compared with ER+ tumours (Pheterogeneity=0.0001) and for AR+, CK5/6+, and EGFR+ as compared with respective marker-negative tumours (Pheterogeneity=0.03, 0.005, and 0.009, respectively). The associations of density measures with breast cancer did not differ by progesterone receptor and human epidermal growth factor receptor 2 status.Conclusions: Breast density influences the risk of breast cancer subtypes by potentially different mechanisms. [ABSTRACT FROM AUTHOR]

We investigated if associations of breast density and breast cancer differ according to the level of other known breast cancer risk factors, including body mass index (BMI), age at menarche, parity, age at first child's birth, age at menopause, alcohol consumption, a family history of breast cancer, a history of benign breast disease, and physical activity. This study included 1,044 postmenopausal incident breast cancer cases diagnosed within the Nurses' Health Study cohort and 1,794 matched controls. Percent breast density, absolute dense, and non-dense areas were measured from digitized film images with computerized techniques. Information on breast cancer risk factors was obtained prospectively from biennial questionnaires. Percent breast density was more strongly associated with breast cancer risk in current postmenopausal hormone users (≥50 vs. 10 %: OR 5.34, 95 % CI 3.36-8.49) as compared to women with past (OR 2.69, 95 % CI 1.32-5.49) or no hormone history (OR 2.57, 95 % CI 1.18-5.60, p-interaction = 0.03). Non-dense area was inversely associated with breast cancer risk in parous women, but not in women without children ( p-interaction = 0.03). Associations of density with breast cancer risk did not differ by the levels of BMI, age at menarche, parity, age at first child's birth, age at menopause, alcohol consumption, a family history of breast cancer, a history of benign breast disease, and physical activity. Women with dense breasts, who currently use menopausal hormone therapy are at a particularly high risk of breast cancer. Most breast cancer risk factors do not modify the association between mammographic breast density and breast cancer risk. [ABSTRACT FROM AUTHOR]

Purpose: We investigated racial disparities in healthy behaviors and cancer screening in a large sample from the US population. Methods: This analysis used the data from 2005 National Health Interview Survey and included women at age ≥ 40 years who completed the cancer questionnaires (2,427,075 breast cancer survivors and 57,978,043 women without cancer). Self-reported information on cancer history, healthy behaviors (body mass index, smoking, alcohol use, physical activity, fruit/vegetable consumption, sunscreen use) was collected. We compared distributions of each factor among Caucasian, African American, and Hispanic women with and without breast cancer history. Results: Caucasian breast cancer survivors as compared to their cancer-free counterparts were less likely to be current smokers (8.3 vs. 16.9 %, p < 0.001) and to have regular mammograms (51.5 vs. 36.9 %, p < 0.05). Differences in associations between cancer survivors and respondents without cancer among African American and Hispanic women did not reach statistical significance. Conclusions: Certain breast cancer survivor groups can benefit from tailored preventive services that would address concerns related to selected healthy behaviors and screening practices. However, most of the differences are suggestive and do not differ by race. [ABSTRACT FROM AUTHOR]

Studies show a protective relationship between physical activity and breast cancer risk across the life course from menarche to postmenopausal years. Mammographic breast density is a known and strong breast cancer risk factor. Whether the association of physical activity with breast cancer risk is mediated through mammographic breast density is poorly understood. This systematic review summarizes published studies that investigated the association between physical activity and mammographic breast density and discusses the methodological issues that need to be addressed. We included in this review studies that were published before October 31, 2011 that were accessible in full-text format and were published in English. We identified 20 studies through the PubMed Central, BioMed Central, Embase, and Scopus and using the search terms 'physical activity and breast density' and 'exercise and breast density' as well as through manual searches of the bibliographies of the articles identified in electronic searches. We found no evidence of association between physical activity and breast density across the studies by grouping them first by the timing of physical activity assessment (in adolescence, current/recent, past, and lifetime) and then by women's menopausal status (premenopausal and postmenopausal). Given the strength of the relationship between physical activity and breast cancer and the null findings of this review, it is unlikely that the effect of physical activity is mediated through an effect on breast density. [ABSTRACT FROM AUTHOR]

Purpose: Few studies have investigated the association between breast density and breast cancer by a family history of breast cancer, menopausal status, and postmenopausal hormone use (PMH). We investigated if associations of breast density and breast cancer differ according to the status of these risk factors. Methods: This study included 1,481 incident breast cancer cases diagnosed within the Nurses' Health Study I and II cohorts and 2,779 matched controls. Breast density was measured from digitized film images with computerized techniques. Information on breast cancer risk factors was obtained prospectively from the biennial questionnaires before the date of the cancer diagnosis for cancer cases and their matched controls. The data were analyzed with logistic regression. Results: Breast cancer risk increased with increasing percent breast density in all strata ( p for trend in all subsets <0.0001). The density-related risk of breast cancer was similar in women with and without a family history (OR = 4.00 [95 % CI 2.01-7.94] vs. 3.71 [95 % CI 2.79-4.94] for density ≥50 % vs. <10 %, p for interaction = 0.53). The magnitude of the association between density and breast cancer risk, however, appeared to be stronger in premenopausal women than in postmenopausal women without PMH history (OR = 5.49 [95 % CI 2.44-12.39] vs. 3.02 [95 % CI 1.62-5.63] for density ≥50 % vs. <10 %, p-heterogeneity = 0.17) and appeared to be stronger in postmenopausal women currently using hormones compared with postmenopausal women who never used PMH (OR = 4.50 [95 % CI 2.99-6.78] vs. 3.02, p-heterogeneity = 0.20) or with past hormone use (OR = 4.50 vs. 3.71 [95 % CI 1.90-7.23], p-heterogeneity = 0.23). Conclusions: Findings on associations by menopausal status/hormone use are suggestive and should be examined in additional larger studies. [ABSTRACT FROM AUTHOR]

Studies suggest a protective relationship between Vitamin D and breast cancer risk. Several studies assessed the association of Vitamin D with mammographic breast density, a known and strong breast cancer risk factor. Understanding the potential role of Vitamin D in the modification of breast density might open new avenues in breast cancer prevention. This systematic review summarizes published studies that investigated the association between Vitamin D and mammographic breast density and offers suggestions for strategies to advance our scientific knowledge. [ABSTRACT FROM AUTHOR]

The role of estrogens in breast carcinogenesis has been investigated at the level of whole body (plasma) and cell (molecular, receptors, etc.). Growing attention focused on the breast tissue being an intracrine organ, with potentially important local estrogen production in the breast. However, very little is known about the local breast tissue estrogen levels. Understanding the role of the tissue estrogens in breast carcinogenesis might open new avenues in breast cancer prevention. This systematic review summarizes published studies that measured local estrogen levels in the breast and offers suggestions for strategies to fill gaps in our existing scientific knowledge. [ABSTRACT FROM AUTHOR]