Metformin and other anti-diabetic medication use and breast cancer incidence in the Nurses' Health Studies.

We aimed to examine the association between the use of metformin and other anti-diabetic medications and breast cancer incidence within two large prospective cohort studies. We followed 185,181 women who participated in the Nurses' Health Study (NHS; 1994-2016) and the NHSII (1995-2017), with baseline corresponding to the date metformin was approved for type 2 diabetes (T2D) treatment in the US Information on T2D diagnosis, anti-diabetes medications, and other covariates was self-reported at baseline and repeatedly assessed by follow-up questionnaires every 2 years. Breast cancer cases were self-reported and confirmed by medical record review. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between medication use and breast cancer were estimated using Cox proportional hazards regression models, adjusting for breast cancer risk factors. During 3,324,881 person-years of follow-up, we ascertained 9,192 incident invasive breast cancer cases, of which 451 were among women with T2D. Compared with women without T2D (n = 169,263), neither metformin use (HR = 0.97; 95% CI = 0.81-1.15) nor other anti-diabetic medications use (HR = 1.11; 95% CI = 0.90-1.36) associated with significantly lower breast cancer incidence. Among women with T2D (n = 15,918), compared with metformin never users, metformin ever use was not significantly inversely associated with breast cancer (HR = 0.92; 95% CI = 0.74-1.15). Although we observed that past use of metformin was inversely associated with breast cancer in the T2D population (HR = 0.67; 95% CI = 0.48-0.94), current use (HR = 1.01; 95% CI = 0.80-1.27) and longer duration of metformin use were not associated with breast cancer (each 2-year interval: HR = 1.01; 95% CI = 0.95-1.07). Overall, metformin use was not associated with the risk of developing breast cancer among the overall cohort population or among women with T2D.

The role of breast cancer-related arm lymphedema in physical functioning and physical activity participation among long-term African American breast cancer survivors.

PURPOSE: Breast cancer-related arm lymphedema (BCRL) is a common chronic and debilitating condition that involves accumulation of lymphatic fluid in the arm or hand. Limited data are available on BCRL in African American women. Lack of physical activity (PA) and poor physical functioning (PF) are both associated with increased morbidity and mortality among breast cancer survivors. We examined the association of BCRL with PA and PF among African American breast cancer survivors. METHODS: 323 African American women who previously participated in a case-only study in three states (TN, GA, SC) completed a survivorship-focused questionnaire (mean: 4.2 years post-diagnosis) in 2015-2016. Validated measures were used to determine BCRL, PF, and PA. Adjusted binary logistic regression models estimated ORs and 95% CIs for the association of BCRL and meeting PA guidelines (≥ 150 min/week), while multinomial logistic regression was used for PF and PA (minutes/week) categorized based on tertiles. RESULTS: Approximately 32% reported BCRL since diagnosis; 25.4% reported BCRL in the last 12-months. About 26% and 50% reported that BCRL interfered with exercise and ability to do daily activities, respectively. The mean PF among those with BCRL was 51.0(SD:29.0) vs. 68.5(SD:30.1) among those without BCRL. BCRL was associated with lower PF (adjusted-OR for tertile 2: 2.12(95% CI:1.03-4.36) and adjusted-OR for tertile 1: 2.93(95% CI:1.44-5.96)). CONCLUSIONS: BCRL was associated with lower PF among long-term African American breast cancer survivors. Continued monitoring by health care professionals and increased education and behavioral interventions to support PA and improved PF among survivors living with BCRL are warranted.

Aspirin vs Placebo as Adjuvant Therapy for Breast Cancer: The Alliance A011502 Randomized Trial.

Importance: Observational studies of survivors of breast cancer and prospective trials of aspirin for cardiovascular disease suggest improved breast cancer survival among aspirin users, but prospective studies of aspirin to prevent breast cancer recurrence are lacking. Objective: To determine whether aspirin decreases the risk of invasive cancer events among survivors of breast cancer. Design, Setting, and Participants: A011502, a phase 3, randomized, placebo-controlled, double-blind trial conducted in the United States and Canada with 3020 participants who had high-risk nonmetastatic breast cancer, enrolled participants from 534 sites from January 6, 2017, through December 4, 2020, with follow-up to March 4, 2023. Interventions: Participants were randomized (stratified for hormone receptor status [positive vs negative], body mass index [≤30 vs >30], stage II vs III, and time since diagnosis [<18 vs ≥18 months]) to receive 300 mg of aspirin (n = 1510) or placebo once daily (n = 1510) for 5 years. Main Outcomes and Measures: The primary outcome was invasive disease-free survival. Overall survival was a key secondary outcome. Results: A total of 3020 participants were randomized when the data and safety monitoring committee recommended suspending the study at the first interim analysis because the hazard ratio had crossed the prespecified futility bound. By median follow-up of 33.8 months (range, 0.1-72.6 months), 253 invasive disease-free survival events were observed (141 in the aspirin group and 112 in the placebo group), yielding a hazard ratio of 1.27 (95% CI, 0.99-1.63; P = .06). All invasive disease-free survival events, including death, invasive progression (both distant and locoregional), and new primary events, were numerically higher in the aspirin group, although the differences were not statistically significant. There was no difference in overall survival (hazard ratio, 1.19; 95% CI, 0.82-1.72). Rates of grades 3 and 4 adverse events were similar in both groups. Conclusion and Relevance: Among participants with high-risk nonmetastatic breast cancer, daily aspirin therapy did not improve risk of breast cancer recurrence or survival in early follow-up. Despite its promise and wide availability, aspirin should not be recommended as an adjuvant breast cancer treatment. Trial Registration: ClinicalTrials.gov Identifier: NCT02927249.

Monitoring tree canopy dynamics across heterogeneous urban habitats: A longitudinal study using multi-source remote sensing data.

Urban trees have attracted increasing attention to serve as a green prescription for addressing various challenges facing human society like climate change and environmental deterioration. However, without healthy growth of urban trees, they cannot service any environmental, social, and economic benefits in a sustainable manner. By monitoring the canopy development, the tree growth dynamics in different urban habitats can be detected and appropriate management approaches can be executed. Using the Kowloon Peninsula, Hong Kong, as a case, this study explores how remote sensing data can help monitor and understand the impacts of heterogeneous urban habitats on tree canopy dynamics. Four algorithms based on WorldView-2 satellite image are compared to optimize the canopy segmentation. Then the individual tree canopy is integrated with Sentinel-2 satellite data to obtain canopy growth dynamics for each season from 2016 to 2020. Three indicators are applied to reflect tree canopy status, including the fluorescence correction vegetation index (FCVI, tracking leaf chlorophyll density), the soil adjusted total vegetation index (SATVI, measuring the density of woody branches and twigs), and the normalised difference phenology index (NDPI, capturing canopy water content). And four heterogeneous habitats where urban trees stand are specified. The results revealed that urban trees show varying canopy growth status, in a descending order from natural terrains, parks, residential lands, to road verges, suggesting that urban habitats curtail trees' growth significantly. Additionally, two super-typhoons in 2017 and 2018, respectively, caused serious damages to tree canopy. Relevant resiliency of tree varies, echoing the sequence of canopy growth status with those in road verges the least resilient. This study shows how remote sensing data can be used to provide a better understanding of long-term tree canopy dynamics across large-scale heterogeneous urban habitats, which is key to monitoring and maintaining the health and growth of urban trees.

Consumption of olive oil and risk of breast cancer in U.S. women: results from the Nurses' Health Studies.

BACKGROUND: Olive oil consumption may reduce breast cancer risk, but it is unclear whether olive oil is beneficial for breast cancer prevention in populations outside of Mediterranean regions, namely in the U.S., where the average consumption of olive oil is low compared with Mediterranean populations. We examined whether olive oil intake was associated with breast cancer risk in two prospective cohorts of U.S. women. METHODS: We used multivariable-adjusted time-varying Cox proportional hazards models to estimate hazard ratios (HR) and 95% confidence interval (CI) for breast cancer among 71,330 (Nurses' Health Study, 1990-2016) and 93,295 women (Nurses' Health Study II, 1991-2017) who were free of cancer at baseline. Diet was assessed by a validated semi-quantitative food frequency questionnaire every 4 years. RESULTS: During 3,744,068 person-years of follow-up, 9,638 women developed invasive breast cancer. The multivariable-adjusted HR (95% CI) for breast cancer among women who had the highest consumption of olive oil (>1/2 tablespoon/d or >7 g/d) compared with those who never or rarely consumed olive oil, was 1.01 (0.93, 1.09). Higher olive oil consumption was not associated with any subtype of breast cancer. CONCLUSION: We did not observe an association between higher olive oil intake and breast cancer risk in two large prospective cohorts of U.S. women, whose average olive oil consumption was low. Prospective studies are needed to confirm these findings and to further investigate whether different varieties of olive oil (e.g., virgin and extra virgin olive oil) may play a role in breast cancer risk.

Physical activity in association with mortality among Black women diagnosed with breast cancer in the Southern Community Cohort Study.

PURPOSE: Physical activity (PA) is associated with many health benefits. While PA has been associated with reduced mortality after breast cancer diagnosis in many studies, few studies have examined the role of PA in breast cancer survival among underserved and minority populations, including Black women. We investigated PA in association with mortality among Black predominantly low-income breast cancer survivors in the Southern Community Cohort Study (SCCS). METHODS: Study participants were women diagnosed with incident breast cancer (n = 949) in the SCCS, which is a prospective cohort study of predominantly low-income adults aged 40-79 years recruited from 12 Southeastern states between 2002 and 2009. Participants completed a detailed baseline questionnaire, with annual follow-up for mortality via registry linkages. Cox regression models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for associations of pre-diagnosis PA (measured via a validated questionnaire) with all-cause and breast cancer-specific mortality. RESULTS: Breast cancer survivors had a mean age of 61.1 years and most (79.3%) had a household income of < $25,000. In adjusted models, higher levels of total PA (MET-hours/day) were inversely associated with all-cause mortality with HRs (95% CIs): 0.79 (0.59-1.06), 0.66 (0.49-0.90), and 0.60 (0.43-0.84), for Q2, Q3, and Q4 (reference: Q1), respectively, ptrend ≤ 0.01. A similar inverse association was found for breast cancer-specific mortality. CONCLUSION: Higher levels of pre-diagnosis PA were associated with improved survival among low-income Black breast cancer survivors. Resources to reduce barriers to PA participation and increase support for education and intervention efforts to promote PA among Black women are needed.

Outcomes after treatment of breast cancer during pregnancy including taxanes and/or granulocyte colony-stimulating factor use: findings from a multi-institutional retrospective analysis.

BACKGROUND: Guidelines support comparable treatment for women diagnosed with breast cancer during pregnancy (PrBC) and nonpregnant women with limited case-specific modifications to ensure maternal-fetal safety. Experience during pregnancy with modern agents, such as taxanes or granulocyte colony-stimulating factors (GCSF), is limited. PATIENTS AND METHODS: We retrospectively identified a multi-institutional cohort of PrBC between 1996 and 2020. Propensity score analyses with multiple imputation for missing variables were applied to determine the associations between chemotherapy exposures during pregnancy, with or without taxanes or GCSF, and a compound maternal-fetal outcome including spontaneous preterm birth, preterm premature rupture of membranes, chorioamnionitis, small for gestational age newborns, congenital malformation, or 5-min Apgar score < 7. RESULTS: Among 139 PrBC pregnancies, 82 (59.0%) were exposed to chemotherapy, including 26 (31.7%) to taxane and 18 (22.0%) to GCSF. Chemotherapy use, in general, and inclusion of taxane and/or GCSF, specifically, increased over time. Pregnancies resulting in live singleton births (n = 123) and exposed to chemotherapy were as likely to reach term as those that were not (59.5% vs. 63.6%, respectively, punadjusted = 0.85). Among women treated with chemotherapy, propensity score-matched odds ratios (OR) for the composite maternal-fetal outcome were not significantly increased with taxane (OR 1.24, 95% CI 0.27-5.72) or GCSF (OR 2.11, 95% confidence interval (CI) 0.48-9.22) with similar effects in multiple imputation and sensitivity models. CONCLUSION: The judicious increased use of taxane chemotherapy and/or growth factor support during pregnancy was not associated with unfavorable short-term maternal-fetal outcomes. While these findings are reassuring, case numbers remain limited and continued surveillance of these patients and progeny is warranted.

Metabolic abnormalities and survival among patients with non-metastatic breast cancer.

BACKGROUND: Research on the impact of metabolic abnormalities on breast cancer prognosis is limited by small samples and assessment of laboratory values at a single time point, often prior to cancer diagnosis and treatment. In this population-based cohort, time-updated laboratory values were adjusted for cancer treatment to assess the association between metabolic risk factors (glucose, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides) and breast cancer survival. METHODS: 13,434 women diagnosed with stage I-III breast cancer from 2005-15 at Kaiser Permanente were included. All outpatient fasting glucose, HDL-C, LDL-C, and triglyceride values from diagnosis through 2019 or death were extracted from electronic medical records. Risk of breast cancer-specific mortality was evaluated with Cox proportional hazards models adjusted for metabolic labs, demographics, body mass index, diabetes, dyslipidemia and anti-hypertensive medications, tumor characteristics (stage, ER and HER2 receptor status) and cancer treatment (use of chemotherapy, tamoxifen, and aromatase inhibitors). RESULTS: Mean (SD) age at diagnosis was 62.3 (11.8) years. Over a median follow-up of 8.6 years, 2,876 patients died; 1,080 of breast cancer. Patients with low HDL-C (≤ 45 vs. > 45 mg/dL) had higher breast cancer-specific mortality (HR, 1.77; 95% CI, 1.53-2.05), as did those with elevated fasting glucose (> 99 vs. 60-99 mg/dL) (HR, 1.19; 95% CI, 1.03-1.37). Elevated levels of triglycerides and LDL-C were not associated with breast cancer-specific mortality. CONCLUSIONS: High fasting glucose and low HDL-C evaluated over time after cancer diagnosis were associated with higher breast cancer mortality independent of cancer treatments and changes in other metabolic risk factors. Future studies should address whether pharmacologic or lifestyle treatment of glucose and lipids after breast cancer diagnosis can optimize survival outcomes.

Environmental information disclosure and public choice decisions for urban river restoration: A comparative study between Brussels (Belgium) and Guangzhou (China).

Worldwide environmental information disclosure (EID) has been widely promoted as a policy approach to establish transparent governments, enhance public environmental awareness, and foster participatory environmental governance. While information disclosure and transparency are inherently incentivised within democratic regimes, how and through what pathways an increased flow of environmental information in the absence of democracy could lead to favourable public support for environmental/ecological projects remain under-investigated. Particularly, there exists very limited literature which compares how EID is associated with public environmental choices between different sociopolitical contexts. Taking Brussels (Belgium) and Guangzhou (China) as a comparative case, this study examines the association between citizens' perceived trustworthiness of various environmental information sources and their choice decisions regarding urban river restoration initiatives in contrasting socialpolitical contexts. Latent class modelling of two paralleled discrete choice experiments unveils a consistent classification of three distinctive groups for each city and also the combined sample, including Enthusiastic Supporters (Class 1, who are cost-insensitive and supportive of all proposed changes), Pragmatic Supporters (Class 2, who are cost-sensitive, prefer some changes they favour), and Non-Supporters (Class 3, who are unwilling to support the proposed initiatives). Incorporating respondents' trustworthiness in information sources as covariates in class membership likelihood function, respondents' membership is found to be associated solely with the most trusted information source, i.e., social contacts in Guangzhou, third parties in Brussels, and social contacts for the whole sample. Holding trust toward the most-trusted information source can increase the probability of being a member of Class 1, otherwise, more likely being a member of Class 3. Taken together with the insignificance of the variable denoting a respondent's city in explaining class membership, this study reveals that the variations in the EID levels (matured vs. emerging) and sociopolitical contexts (democratic vs. non-democratic) cannot significantly shape citizens' environmental decisions. Instead, it is respondents' perceived trustworthiness of information outlets that plays a positive role in their supportive decisions. These analytical results offer new insights about the role of EID in environmental governance and call for instilling institutional trust in China and relational trust in Belgium for facilitating effective communication and pro-environmental behaviours across the whole community.

Consumption of sugar-sweetened and artificially sweetened beverages and breast cancer survival.

BACKGROUND: The activation of insulin pathways is hypothesized to promote tumor growth and worsen breast cancer survival. Sugar-sweetened beverages (SSBs) can lead to a higher risk of insulin resistance and may affect survival. The authors prospectively evaluated the relation of postdiagnostic SSB and artificially sweetened beverage (ASB) consumption with mortality among women with breast cancer. METHODS: In total, 8863 women with stage I through III breast cancer were identified during follow-up of the Nurses' Health Study (NHS; 1980-2010) and Nurses' Health Study II (NHSII; 1991-2011). Women completed a validated food frequency questionnaire every 4 years after diagnosis and were followed until death or the end of follow-up (2014 for the NHS and 2015 for the NHSII). Multivariable Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of breast cancer-specific and all-cause mortality after adjusting for measures of adiposity and other potential predictors of cancer survival. RESULTS: With a median follow-up of 11.5 years, 2482 deaths were prospectively documented, including 1050 deaths from breast cancer. Compared with women who had no consumption, women who had SSB consumption after diagnosis had higher breast cancer-specific mortality (>1 to 3 servings per week: HR, 1.31 [95% CI, 1.09-1.58]; >3 servings per week: HR, 1.35 [95% CI, 1.12-1.62]; Ptrend = .001) and all-cause mortality (>1 to 3 servings per week: HR, 1.21 [95% CI, 1.07-1.37]; >3 servings per week: HR, 1.28 [95% CI, 1.13-1.45]; Ptrend = .0001). In contrast, ASB consumption was not associated with higher breast cancer-specific or all-cause mortality. Furthermore, replacing 1 serving per day of SSB consumption with 1 serving per day of ASB consumption was not associated with a lower risk of mortality. CONCLUSIONS: Higher postdiagnostic SSB consumption among breast cancer survivors was associated with higher breast cancer-specific mortality and death from all causes.

Partial attribute attendance in environmental choice experiments: A comparative case study between Guangzhou (China) and Brussels (Belgium).

Attribute non-attendance (ANA) in discrete choice experiment (DCE) exercises has attracted increasing, yet limited, scholarly attention. This paper attempts to investigate ANA in a comparative case study, with a focus on its patterns and their association with socioeconomic, behavioral and perceptual factors, as well as its impacts on willingness-to-pay (WTP) estimates. We deploy a four-level polytomous scale (always, often, seldom, and never considered) for respondents to state their various degrees of attribute attendance (SANA) in an identical DCE questionnaire about urban river restoration initiatives in two global cities with contrast socioeconomic contexts, yet similar request for restoring polluted and modified urban rivers, Guangzhou (south China) and Brussels (Belgium). The survey results reveal the existence of large proportions of partial attendance in two sampled cities. We use an extended mixed logit model, which incorporates separate parameters delineating each attribute's different attendance groups, to estimate respondents' average WTP values. We find that accounting for SANA could improve the goodness-of-fit of the model and affect the magnitude of mean WTP estimates. Respondents' attribute attendance level pertaining to various attributes is mainly associated with their perceived importance of urban rivers' ecosystem services, but may not be necessarily correlated with the strength of their preference for corresponding attributes as indicated by the mean WTP estimates. Whether this discontinuity between respondents' stated ANA levels and WTP estimates within Guangzhou sample questions the ability of DCEs to generate unbiased welfare estimation and policy guidance in developing countries calls for further studies.

Fruit and vegetable consumption and breast cancer incidence: Repeated measures over 30 years of follow-up.

We evaluated the relation of fruit and vegetable consumption, including specific fruits and vegetables, with incident breast cancer characterized by menopausal status, hormone receptor status and molecular subtypes. Fruit and vegetable consumption, cumulatively averaged across repeated, validated questionnaires, was examined in relation to risk of invasive breast cancer among 182,145 women initially aged 27-59 years in the Nurses' Health Study (NHS, 1980-2012) and NHSII (1991-2013). Cox proportional hazards regression, adjusted for known risk factors, was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) and assessed tumors by hormone receptor status and molecular subtypes. We prospectively documented 10,911 invasive breast cancer cases. Greater intake of total fruits and vegetables, especially cruciferous and yellow/orange vegetables, was associated with significantly lower breast cancer risk (>5.5 vs. ≤2.5 servings/day HR = 0.89, 95% CI = 0.83-0.96; ptrend = 0.006). Intake of total vegetables was especially associated with lower risk of estrogen receptor negative tumors (HR per 2 additional servings/day as a continuous variable = 0.84, 95%CI = 0.77-0.93; pheterogeneity = 0.02). Among molecular subtypes, higher intake of total fruits and vegetables (HR per 2 additional servings/day as a continuous variable) was most strongly associated with lower risk of human epidermal growth factor receptor 2 (HER2)-enriched (HR = 0.79, 95%CI = 0.67-0.93), basal-like (HR = 0.84, 95%CI = 0.72-0.97) and luminal A (HR = 0.94, 95%CI = 0.89-0.99), but not with luminal B tumors (pheterogeneity = 0.03). In conclusion, our findings support that higher intake of fruits and vegetables, and specifically cruciferous and yellow/orange vegetables, may reduce the risk of breast cancer, especially those that are more likely to be aggressive tumors.

Representing genetic variation with synthetic DNA standards.

The identification of genetic variation with next-generation sequencing is confounded by the complexity of the human genome sequence and by biases that arise during library preparation, sequencing and analysis. We have developed a set of synthetic DNA standards, termed 'sequins', that emulate human genetic features and constitute qualitative and quantitative spike-in controls for genome sequencing. Sequencing reads derived from sequins align exclusively to an artificial in silico reference chromosome, rather than the human reference genome, which allows them them to be partitioned for parallel analysis. Here we use this approach to represent common and clinically relevant genetic variation, ranging from single nucleotide variants to large structural rearrangements and copy-number variation. We validate the design and performance of sequin standards by comparison to examples in the NA12878 reference genome, and we demonstrate their utility during the detection and quantification of variants. We provide sequins as a standardized, quantitative resource against which human genetic variation can be measured and diagnostic performance assessed.

Spliced synthetic genes as internal controls in RNA sequencing experiments.

RNA sequencing (RNA-seq) can be used to assemble spliced isoforms, quantify expressed genes and provide a global profile of the transcriptome. However, the size and diversity of the transcriptome, the wide dynamic range in gene expression and inherent technical biases confound RNA-seq analysis. We have developed a set of spike-in RNA standards, termed 'sequins' (sequencing spike-ins), that represent full-length spliced mRNA isoforms. Sequins have an entirely artificial sequence with no homology to natural reference genomes, but they align to gene loci encoded on an artificial in silico chromosome. The combination of multiple sequins across a range of concentrations emulates alternative splicing and differential gene expression, and it provides scaling factors for normalization between samples. We demonstrate the use of sequins in RNA-seq experiments to measure sample-specific biases and determine the limits of reliable transcript assembly and quantification in accompanying human RNA samples. In addition, we have designed a complementary set of sequins that represent fusion genes arising from rearrangements of the in silico chromosome to aid in cancer diagnosis. RNA sequins provide a qualitative and quantitative reference with which to navigate the complexity of the human transcriptome.

Sleep and survival among women with breast cancer: 30 years of follow-up within the Nurses' Health Study.

This corrects the article DOI: 10.1038/bjc.2017.85.

Quantitative gene profiling of long noncoding RNAs with targeted RNA sequencing.

We compared quantitative RT-PCR (qRT-PCR), RNA-seq and capture sequencing (CaptureSeq) in terms of their ability to assemble and quantify long noncoding RNAs and novel coding exons across 20 human tissues. CaptureSeq was superior for the detection and quantification of genes with low expression, showed little technical variation and accurately measured differential expression. This approach expands and refines previous annotations and simultaneously generates an expression atlas.

Weight and weight changes in early adulthood and later breast cancer risk.

Obesity is a well-established cause of postmenopausal breast cancer. However, early life adiposity is inversely associated with breast cancer incidence. To understand these conflicting relations, we use validated measures to assess adiposity in childhood and late adolescence, as well as weight change, in relation to total invasive breast cancer incidence and receptor subtypes. We conducted a prospective observational study among 74,177 women from the Nurses' Health Study from 1980-2012, with updated risk factors every 2 years during which 4,965 incident invasive breast cancers occurred. Overall, weight at age 18 was inversely associated with both premenopausal (HR per 30 kg = 0.52, 95% CI = 0.39-0.71) and postmenopausal (HR per 30 kg = 0.81, 95% CI = 0.72-0.92) breast cancer which was largely explained by adiposity at age 10. Long-term weight gain from age 18 both during premenopause and postmenopause were positively associated with postmenopausal breast cancer risk. However, premenopausal weight gain was not related to premenopausal breast cancer risk. Furthermore, weight gain since age 18 was positively associated with ER+/PR+ postmenopausal breast cancer (HR per 30 kg = 1.50, 95% CI = 1.36-1.65) but not ER+/PR- (HR per 30 kg = 0.96, 95% CI = 0.78-1.19) or ER-/PR- (HR per 30 kg = 1.16, 95% CI = 0.95-1.42) postmenopausal breast cancer. Overall, 17% of ER+/PR+ postmenopausal breast cancer and 14% of total postmenopausal breast cancer are attributable to weight gain of > 5 kg since age 18.

Alcohol Consumption and Breast Cancer Risk in Younger Women According to Family History of Breast Cancer and Folate Intake.

To evaluate the association between alcohol consumption and breast cancer risk in younger women, overall and by family history of breast cancer and folate intake, we prospectively followed 93,835 US women aged 27-44 years in Nurses' Health Study II who had alcohol consumption data in 1991. Alcohol consumption and folate intake were measured by food frequency questionnaire every 4 years. We documented 2,866 incident cases of invasive breast cancer between 1991 and 2011. Alcohol consumption was not associated with breast cancer risk overall (for intake of ≥10 g/day vs. nondrinking, multivariate hazard ratio = 1.07, 95% confidence interval: 0.94, 1.22). When the association was stratified by family history and folate intake, a positive association between alcohol consumption and breast cancer was found among women with a family history and folate intake less than 400 µg/day (multivariate hazard ratio = 1.82, 95% confidence interval: 1.06, 3.12; P-trend = 0.08). Alcohol consumption was not associated with breast cancer in other categories of family history and folate intake (P-interaction = 0.55). In conclusion, in this population of younger women, higher alcohol consumption was associated with increased risk of breast cancer among those with both a family history of breast cancer and lower folate intake.

Body mass index, PAM50 subtype, recurrence, and survival among patients with nonmetastatic breast cancer.

BACKGROUND: Studies of obesity and survival among patients with breast cancer produce conflicting results, possibly because of heterogeneity by molecular subtype. METHODS: This study examined whether the association of body mass index (BMI) at diagnosis with breast cancer recurrence and survival varied across subtypes defined by PAM50 (Prediction Analysis of Microarray 50) gene expression. Included were 1559 Kaiser Permanente Northern California members ages 18 to 79 years who had PAM50 assays and were diagnosed with American Joint Committee on Cancer stage I through III breast cancer from 1996 to 2013. Patients reported weight and height. Cox regression models were adjusted for age, menopause, race/ethnicity, stage, and chemotherapy. RESULTS: Over a median of 9 years (maximum, 19 years), 378 women developed recurrent disease, and 312 died from breast cancer. Overall, BMI was not associated with breast cancer recurrence or survival when controlling for subtype (eg, the hazard ratio per 5 kg/m2 of BMI was 1.05 [95% confidence interval, 0.95-1.15] for breast cancer-specific death). However, associations varied by subtype. Among women with luminal A cancers, those who had class II/III obesity, but not class I obesity or overweight, had worse outcomes. When women who had a BMI ≥35 kg/m2 were compared with those who had a BMI from 18.5 to <25 kg/m2 , the hazard ratio was 2.24 (95% confidence interval,1.22-4.11) for breast cancer-specific death and 1.24 (95% confidence interval, 1.00-1.54) for recurrence. There was no association within luminal B, basal-like or human epidermal growth factor over-expressing subtypes. CONCLUSIONS: Among patients who had accurately classified breast cancer subtypes based on gene expression, a BMI ≥35 kg/m2 was adversely associated with outcomes only among those who had luminal A cancers. Research is needed into whether tailoring recommendations for weight management to tumor characteristics will improve outcomes. Cancer 2017;123:2535-42. © 2017 American Cancer Society.

Postdiagnosis social networks and breast cancer mortality in the After Breast Cancer Pooling Project.

BACKGROUND: Large social networks have been associated with better overall survival, though not consistently with breast cancer (BC)-specific outcomes. This study evaluated associations of postdiagnosis social networks and BC outcomes in a large cohort. METHODS: Women from the After Breast Cancer Pooling Project (n = 9267) provided data on social networks within approximately 2 years of their diagnosis. A social network index was derived from information about the presence of a spouse/partner, religious ties, community ties, friendship ties, and numbers of living first-degree relatives. Cox models were used to evaluate associations, and a meta-analysis was used to determine whether effect estimates differed by cohort. Stratification by demographic, social, tumor, and treatment factors was performed. RESULTS: There were 1448 recurrences and 1521 deaths (990 due to BC). Associations were similar in 3 of 4 cohorts. After covariate adjustments, socially isolated women (small networks) had higher risks of recurrence (hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.15-1.77), BC-specific mortality (HR, 1.64; 95% CI, 1.33-2.03), and total mortality (HR, 1.69; 95% CI, 1.43-1.99) than socially integrated women; associations were stronger in those with stage I/II cancer. In the fourth cohort, there were no significant associations with BC-specific outcomes. A lack of a spouse/partner (P = .02) and community ties (P = .04) predicted higher BC-specific mortality in older white women but not in other women. However, a lack of relatives (P = .02) and friendship ties (P = .01) predicted higher BC-specific mortality in nonwhite women only. CONCLUSIONS: In a large pooled cohort, larger social networks were associated with better BC-specific and overall survival. Clinicians should assess social network information as a marker of prognosis because critical supports may differ with sociodemographic factors. Cancer 2017;123:1228-1237. © 2016 American Cancer Society.