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For patients with breast cancer, delays in chemotherapy initiation have been adversely associated with recurrence and survival. We evaluated patient-level factors associated with delayed chemotherapy initiation, from both diagnosis and surgery, in a community-based cohort of women with early-stage breast cancer. For the Optimal Breast Cancer Chemotherapy Dosing study, we identified a cohort of 34,109 women diagnosed with stage I-IIIA breast cancer at two U.S. integrated healthcare delivery systems between 2004 and 2019. We used logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI) to identify patient factors associated with delays in chemotherapy initiation after diagnosis (≥90 days) and surgery (≥60 days). Among 10,968 women receiving adjuvant chemotherapy, 21.1% experienced delays in chemotherapy initiation after diagnosis and 21.3% after surgery. Older age, non-Hispanic Black and Hispanic race and ethnicity, and ER+ and/or PR+ disease were associated with increased likelihood of delays to chemotherapy initiation after diagnosis and surgery. People diagnosed in 2012-2019 (vs. 2005-2011), with a higher grade and larger tumor size were less likely to experience delays. Other factors were associated with a higher likelihood of delays specifically from diagnosis (earlier stage, mastectomy vs. breast-conserving surgery), or surgery (higher comorbidity, increased nodal number). Women diagnosed with breast cancer who were at highest risk of progression and recurrence were less likely to experience delays in chemotherapy initiation after diagnosis and surgery. Understanding reasons for chemotherapy delays beyond patient factors may be potentially important to reduce risk of breast cancer recurrence and progression., (© 2024 UICC.)

Purpose: The National Comprehensive Cancer Network (NCCN) guidelines recommend a variety of drug combinations with specific administration schedules for the treatment of early-stage breast cancer, allowing physicians to deliver treatments recognizing individual patient complexities, including comorbidities, and patient-physician preference. While use of guideline regimens has shifted over time, there is little data to describe changes in how treatment for early-stage breast cancer has evolved over time., Methods: In a cohort of 34,109 women treated for stage I-IIIA breast cancer between 2006-2019 at Kaiser Permanente Northern California and Kaiser Permanente Washington, we present the changes in chemotherapy regimens over time, and explore use of NCCN-guideline regimens (GR), guideline regimens used when said regimens were not included in guidelines, referred to as time-discordant regimens (TDR), and non-guideline regimens (NGR). Results are presented by drug combination and over time., Results: Among 12,506 women receiving chemotherapy, 77.4% (n = 9681) received GRs, 9.1% (n = 1140) received TDRs, and 13.5% (n = 1685) received NGRs. In 2006, AC-T (cyclophosphamide-doxorubicin, paclitaxel) was the most common regimen, with TC (cyclophosphamide-docetaxel) becoming the most prevalent by 2019. NGRs were more common in cyclophosphamide-methotrexate-5-fluorouracil (CMF); cyclophosphamide-doxorubicin-paclitaxel-trastuzumab (ACTH); and paclitaxel-trastuzumab (TH). The use of GR has increased over time (p-trend < 0.001), while use of NGR (both in terms of administration schedule and drug combination) and TDR have decreased, although patterns vary by drug combination., Conclusion: Chemotherapy delivery has changed markedly over time, with a move toward more use of GR. These data are important for understanding the landscape of chemotherapy delivery in community healthcare settings., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Vitamin D is critical to bone health by regulating intestinal absorption of calcium, whereas proinflammatory cytokines, including IL-1, IL-6, IL-12, and TNF-α, are known to increase bone resorption. We hypothesized that vitamin D and these cytokines at the time of breast cancer diagnosis were predictive for fragility fractures in women receiving aromatase inhibitors (AIs)., Methods: In a prospective cohort of 1,709 breast cancer patients treated with AIs, we measured the levels of 25-hydroxyvitamin D (25OHD), IL-1β, IL-6, IL-12, and TNF-α from baseline blood samples. The associations of these biomarkers were analyzed with bone turnover markers (BALP and TRACP), bone regulatory markers (OPG and RANKL), bone mineral density (BMD) close to cancer diagnosis, and risk of fragility fractures during a median of 7.5 years of follow up., Results: Compared to patients with vitamin D deficiency, patients with sufficient levels had higher bone turnover, lower BMD, and higher fracture risk; the latter became non-significant after controlling for covariates including BMD and no longer existed when patients taking vitamin D supplement or bisphosphonates or with history of fracture or osteoporosis were excluded. There was a non-significant trend of higher levels of IL-1β and TNF-α associated with higher risk of fracture (highest vs. lowest tertile, IL-1β: adjusted HR=1.37, 95% CI=0.94-1.99; TNF-α: adjusted HR=1.38, 95% CI=0.96-1.98)., Conclusions: Our results do not support proinflammatory cytokines or vitamin D levels as predictors for risk of fragility fractures in women receiving AIs for breast cancer., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Guidelines informing chemotherapy regimen selection are based on clinical trials with participants who do not necessarily represent general populations with breast cancer. Understanding who receives nonguideline regimens is important for understanding real-world chemotherapy administration and how it relates to patient outcomes., Methods: Using data from the Optimal Breast Cancer Chemotherapy Dosing (OBCD) study, based at Kaiser Permanente Northern California (2006-2019) and Kaiser Permanente Washington (2004-2015), we use logistic regression to examine the associations between patient characteristics and receipt of nonguideline chemotherapy regimens among 11,293 women with primary stage I to IIIA breast cancer receiving chemotherapy., Results: The use of nonguideline regimens was strongly associated with several factors, including older age [≥80 vs. 18-39 years: OR, 5.25; 95% confidence interval (CI), 3.06-9.00; P-trend = 0.002] and HER2 status (HER2+ vs. HER2-: OR, 3.44; 95% CI, 3.06-3.87) and was less likely in women with larger tumor size (>5 cm vs. 0.1 to ≤0.5 cm: OR, 0.56; 95% CI, 0.36-0.87; P-trend = 0.01) and diagnosed in later years (2012-2019 vs. 2005-2011: OR, 0.80; 95% CI, 0.71-0.90). Factors associated varied by type of nonguideline regimens. For example, women with comorbidity and older age were more likely to receive nonguideline drug combinations in particular, whereas women with larger tumor size were less likely to receive nonguideline administration schedules., Conclusions: Nonguideline chemotherapy regimens are more likely in certain patient populations., Impact: These associations highlight that vulnerable patient populations may be less likely to receive guideline care, and thus, real-world studies are essential for understanding how the use of nonguideline regimens impacts patient outcomes in these groups., (©2024 American Association for Cancer Research.)

Background: Relatively little is known about the differences in prognostic factors for early vs late recurrence among women with early stage estrogen receptor-positive breast cancer., Methods: We analyzed factors related to early (<5 years) vs late (≥5 years) recurrence in 2992 women with stage I-IIB estrogen receptor-positive breast cancer in the Pathways Study, a prospective cohort of women with breast cancer enrolled between 2006 and 2013, with ascertainment of recurrence and death through December 2021., Results: After a median follow-up of 13.3 years, 341 (13.8%) women had recurrences, including 181 (53.7%) with late recurrence. Higher stage and grade were associated with recurrence regardless of timing, whereas progesterone receptor negativity was associated with early but not late recurrence. Receipt of endocrine therapy was associated with reduced risk of overall recurrence, but the length of endocrine therapy was not statistically significant in multivariable models. Minoritized racial and ethnic groups, including Asian, Black, and Hispanic women, had higher risk of early but not late recurrence compared to non-Hispanic White women. The trend of higher risk of early recurrence among these groups remained after adjustment for clinical, demographic, and socioeconomic factors but was statistically significant only in Asian women., Conclusions: Our study revealed potentially important distinctions for early vs late recurrence, including the associations with progesterone receptor negativity and self-identified race and ethnicity. Possible higher risk of early recurrence among Asian, Black, and Hispanic women provides novel evidence for the existence of disparities in cancer outcomes, even within the breast cancer subtype indicative of generally good prognosis., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Purpose: Women with breast cancer (BC) are at high risk of developing cardiovascular disease (CVD). We examined adherence to CVD medications and their association with major CVD events over 14 years of follow-up in the Pathways Heart Study, a prospective study of 4,776 stage I-III BC patients diagnosed from 2005-2013., Methods: Eligibility included being alive 6 months post-BC diagnosis, with dyslipidemia, hypertension, or diabetes at diagnosis along with ≥1 prior outpatient order or dispensing for a statin, anti-hypertensive, or diabetes medication, respectively, in the 30 months prior. Medication adherence was measured from pharmacy data to calculate cumulative average adherence (CAA). Incident heart failure (HF), ischemic heart disease (IHD), and stroke were determined via validated diagnosis and procedure codes. Working marginal structural models (MSM) fitted with inverse probability weighting evaluated the effect of adherence regimens on the hazards for each CVD event, while controlling for baseline and time-varying confounders. MSM parameterizations included: 1) CAA<100% versus CAA = 100% (ref), 2) CAA<80% versus CAA≥80% (ref) and 3) CAA<80% versus 80%≤CAA<100% versus CAA = 100%., Results: Poor statin adherence (CAA<80%) was associated with higher risk of composite CVD (HR = 2.54; 95% CI: 1.09, 5.94) versus CAA≥80%. Poor statin adherence was also associated with a higher risk of stroke (HR = 8.13; 95% CI: 2.03, 32.51) but not risk of IHD and HF. Further, compared with perfect adherence (CAA = 100%), good adherence (80%≤CAA<100%) was associated with lower risk (HR = 0.35; 95% CI: 0.13, 0.92) while poor adherence (CAA<80%) was associated with higher risk of composite CVD (HR = 2.45; 95% CI: 1.05, 5.70). Levels of adherence to anti-hypertensives and diabetes medications had mixed or null associations with risk of CVD., Conclusions: Maintaining good adherence (≥80%) to statins after BC treatment is beneficial for cardiovascular health in patients with dyslipidemia. Future studies should determine factors associated with lower adherence to statins and ways to improve adherence., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Kwan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: Nonmuscle-invasive bladder cancer (NMIBC) has high recurrence rates and is often treated with mitomycin C (MMC) and bacillus Calmette-Guérin (BCG). Their efficacy relies on phase 2 enzyme metabolism and immune response activation, respectively. Dietary isothiocyanates, phytochemicals in cruciferous vegetables, are phase 2 enzyme inducers and immunomodulators, and may impact treatment outcomes. We investigated the modifying effects of cruciferous vegetable and isothiocyanate intake on recurrence risk following MMC or BCG treatment., Materials and Methods: Self-reported cruciferous vegetable intake, estimated isothiocyanate intake, and urinary isothiocyanate metabolites were collected from 1158 patients with incident NMIBC in the prospective Be-Well Study. Hazard ratios (HRs) and 95% CIs were calculated from Cox proportional hazards regression models for risk of first recurrences, and random effects Cox shared frailty models for multiple recurrences., Results: Over median follow-up of 23 months, 343 (30%) recurrences occurred. Receipt of MMC and BCG was associated with decreased risks of first recurrence (MMC: HR = 0.58; 95% CI: 0.46-0.73; BCG: HR = 0.66; 95% CI: 0.49-0.88) and multiple recurrences (MMC: HR = 0.55; 95% CI: 0.44-0.68; BCG: HR = 0.72; 95% CI: 0.55-0.95). Patients receiving BCG and having high intake (>2.4 servings/mo), but not low intake, of raw cruciferous vegetables had reduced risk of recurrence (HR: 0.56; 95% CI: 0.36-0.86; P for interaction = .02) and multiple recurrences (HR: 0.51; 95% CI: 0.34-0.77; P for interaction < .001). The inverse association between MMC receipt and recurrence risk was not modified., Conclusions: For NMIBC patients who receive induction BCG, increasing consumption of raw cruciferous vegetables could be a promising strategy to attenuate recurrence risk.

Background: Hypertension is an important contributor to cardiovascular disease (CVD) in breast cancer (BC) survivors; however, research on blood pressure (BP) and CVD outcomes in BC survivors is limited., Objectives: The purpose of this study was to better characterize the association between BP and CVD in a large, longitudinal cohort of BC patients., Methods: Women with invasive BC diagnosed from 2005 to 2013 at Kaiser Permanente Northern California were matched 1:5 to women without BC. Patient data were obtained from electronic health records. Multivariable Cox regression and penalized spline models were used to explore the linear and nonlinear relationship of systolic blood pressure (SBP) and diastolic blood pressure (DBP) on CVD outcomes., Results: BC cases (n = 12,713) and controls (n = 55,886) had median follow-up of 9.6 years (IQR: 5.0-11.9 years). Women with BC had a mean age of 60.6 years; 64.8% were non-Hispanic White. For ischemic heart disease (IHD), every 10 mmHg increase in SBP and DBP was associated with 1.23 (95% CI: 1.14-1.33) and 1.10 (95% CI: 0.98-1.24) risk, respectively, in women with BC. For stroke, every 10 mmHg increase in SBP and DBP was associated with a 1.45 (95% CI: 1.34-1.58) and 1.91 (95% CI: 1.68-2.18) risk, respectively. A U-shaped relationship was observed between heart failure/cardiomyopathy and BP. The associations between BP and risk of IHD, stroke, and any primary CVD were not statistically different comparing women with BC to controls, but risks varied by BC status for heart failure/cardiomyopathy ( P for interaction = 0.01)., Conclusions: Women with and without BC showed similar risks for IHD, stroke, and any primary CVD suggesting similar BP targets should be pursued regardless of BC survivorship status., Competing Interests: The Pathways Heart Study is supported by the National Cancer Institute (R01 CA214057, U01CA195565). This publication was partially supported by a grant from Alpha Phi. The contents are solely the responsibility of the authors and do not necessarily represent the official views of the funding agency. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Allostatic load (AL) is an intermediary outcome through which neighborhood drivers of health may impact cancer survivorship outcomes. We examined associations of neighborhood stressors and AL in 2,553 women with breast cancer recruited into the Pathways Study in 2006-2013. AL score was derived from biomarkers in the cardiovascular, metabolic, and immune domains of physiological stress measured within 3 years after baseline. Neighborhood data were appended to participants' geocoded baseline addresses. Odds ratios (OR) and 95% confidence intervals (CI) were used to estimate associations between neighborhood stressors and risk of higher AL score. Adjusting for age and stage, high AL was positively associated with low versus high neighborhood socioeconomic status (nSES; OR=2.24, 95% CI=1.61-3.12) and green space (OR=1.55, 95% CI=1.18-2.03); high versus low traffic (OR=1.32, 95% CI=1.01-1.72), crime (OR=1.32, 95% CI=1.05-1.67), and household crowding (OR=1.57, 95% CI=1.22-2.01); and more versus no fast-food restaurants (OR=1.50, 95% CI=1.21-1.84). Associations remained for nSES and fast-food restaurants after co-adjustment with other neighborhood stressors, and for fast-food restaurants after additional adjustment with individual sociodemographic and lifestyle factors. Our preliminary findings can inform further studies of the physiological effects of neighborhood stressors, which collectively may help improve survivorship outcomes for the growing population of breast cancer survivors., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Little is known about how use of chemotherapy has evolved in breast cancer patients. We therefore describe chemotherapy patterns for women with stage I-IIIA breast cancer in the Optimal Breast Cancer Chemotherapy Dosing (OBCD) Study using data from KPNC (Kaiser Permanente Northern California) and KPWA (Kaiser Permanente Washington)., Findings: Among 33,670 women, aged 18 + y, diagnosed with primary stage I-IIIA breast cancer at KPNC and KPWA from 2006 to 2019, we explored patterns of intravenous chemotherapy use, defined here as receipt of intravenous cytotoxic drugs and/or anti-HER2 therapies. We evaluated trends in chemotherapy receipt, duration over which chemotherapy was received, and number of associated infusion visits. In secondary analyses, we stratified by receipt of anti-HER2 therapies (trastuzumab and/or pertuzumab), given their longer duration. 38.9% received chemotherapy intravenously, declining from 40.2% in 2006 to 35.6% in 2019 (p-trend < 0.001). Among 13,089 women receiving chemotherapy, neoadjuvant treatment increased (4.1-14.7%; p-trend < 0.001), as did receipt of anti-HER2 therapies (20.8-30.9%) (p-trend < 0.001). The average treatment duration increased (5.3 to 6.0 months; p-trend < 0.001), as did the number of infusion visits (10.8 to 12.5; p-trend < 0.001). For those receiving anti-HER2 therapies, treatment duration and average number of visits decreased; among those not receiving anti-HER2 therapies, number of visits increased, with no change in duration., Conclusions: While the prevalence of chemotherapy receipt has decreased over time, the use of neoadjuvant chemotherapy has increased, as has use of anti-HER2 therapies; duration and number of administration visits have also increased. Understanding these trends is useful to inform clinical and administrative planning., (© 2024. The Author(s).)

Bladder cancer is primarily diagnosed as non-muscle-invasive bladder cancer (NMIBC), with high recurrence and progression rates. Environmental and occupational exposures to carcinogens are well-known risk factors for developing bladder cancer, yet their effects on prognosis remain unknown. In the Be-Well Study, a population-based prospective cohort study of 1472 Kaiser Permanente patients newly diagnosed with NMIBC in California from 2015 to 2019, we examined history of environmental and occupational exposures in relation to tumor stage and grade at initial diagnosis by multivariable logistic regression, and subsequent recurrence and progression by Cox proportional hazards regression. Exposure to environmental and occupational carcinogens was significantly associated with increased risk of progression (hazard ratio (HR) = 1.79; 95% CI, 1.04-3.09), specifically with increased progression to muscle-invasive disease (HR = 2.28; 95% CI, 1.16-4.50). Exposures to asbestos and arsenic were associated with increased odds of advanced stage at diagnosis (asbestos: odds ratio (OR) = 1.43 [95% CI, 1.11-1.84]; arsenic: OR = 1.27 [95% CI, 1.01-1.63]), and formaldehyde exposure was associated with increased risk of recurrence (HR = 1.38; 95% CI, 1.12-1.69). Our findings suggest that considering a patient's history of these exposures may benefit current risk stratification systems in better tailoring clinical care and improving prognosis among patients with NMIBC., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: Identification of patients' intended chemotherapy regimens is critical to most research questions conducted in the real-world setting of cancer care. Yet, these data are not routinely available in electronic health records (EHRs) at the specificity required to address these questions. We developed a methodology to identify patients' intended regimens from EHR data in the Optimal Breast Cancer Chemotherapy Dosing (OBCD) study., Methods: In women older than 18 years, diagnosed with primary stage I-IIIA breast cancer at Kaiser Permanente Northern California (2006-2019), we categorized participants into 24 drug combinations described in National Comprehensive Cancer Network guidelines for breast cancer treatment. Participants were categorized into 50 guideline chemotherapy administration schedules within these combinations using an iterative algorithm process, followed by chart abstraction where necessary. We also identified patients intended to receive nonguideline administration schedules within guideline drug combinations and nonguideline drug combinations. This process was adapted at Kaiser Permanente Washington using abstracted data (2004-2015)., Results: In the OBCD cohort, 13,231 women received adjuvant or neoadjuvant chemotherapy, of whom 10,213 (77%) had their intended regimen identified via the algorithm, 2,416 (18%) had their intended regimen identified via abstraction, and 602 (4.5%) could not be identified. Across guideline drug combinations, 111 nonguideline dosing schedules were used, alongside 61 nonguideline drug combinations. A number of factors were associated with requiring abstraction for regimen determination, including: decreasing neighborhood household income, earlier diagnosis year, later stage, nodal status, and human epidermal growth factor receptor 2 (HER2)+ status., Conclusion: We describe the challenges and approaches to operationalize complex, real-world data to identify intended chemotherapy regimens in large, observational studies. This methodology can improve efficiency of use of large-scale clinical data in real-world populations, helping answer critical questions to improve care delivery and patient outcomes.

Scope: Dietary isothiocyanate (ITC) exposure from cruciferous vegetable (CV) intake may improve non-muscle invasive bladder cancer (NMIBC) prognosis. This study aims to investigate whether genetic variations in key ITC-metabolizing/functioning genes modify the associations between dietary ITC exposure and NMIBC prognosis outcomes., Methods and Results: In the Bladder Cancer Epidemiology, Wellness, and Lifestyle Study (Be-Well Study), a prospective cohort of 1472 incident NMIBC patients, dietary ITC exposure is assessed by self-reported CV intake and measured in plasma ITC-albumin adducts. Using Cox proportional hazards regression models, stratified by single nucleotide polymorphisms (SNPs) in nine key ITC-metabolizing/functioning genes, it is calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for recurrence and progression. The rs15561 in N-acetyltransferase 1 (NAT1) is alter the association between CV intake and progression risk. Multiple SNPs in nuclear factor E2-related factor 2 (NRF2) and nuclear factor kappa B (NFκB) are modify the associations between plasma ITC-albumin adduct level and progression risk (p int < 0.05). No significant association is observed with recurrence risk. Overall, >80% study participants are present with at least one protective genotype per gene, showing an average 65% reduction in progression risk with high dietary ITC exposure., Conclusion: Despite that genetic variations in ITC-metabolizing/functioning genes may modify the effect of dietary ITCs on NMIBC prognosis, dietary recommendation of CV consumption may help improve NMIBC survivorship., (© 2024 Wiley‐VCH GmbH.)

Importance: It is unclear whether breast cancer (BC) with low ERBB2 expression (ERBB2-low) is a distinct clinical, pathological, and epidemiological entity from BC classified as no ERBB2 expression (ERBB2-negative)., Objective: To evaluate the clinical, pathological, and epidemiologic features of BC with ERBB2-low expression compared with ERBB2-negative BC in a large population study., Design, Setting, and Participants: This cohort study was conducted as part of the Pathways Study, a prospective, racially and ethnically diverse cohort study of women with BC enrolled between 2006 and 2013 in Kaiser Permanente Northern California (KPNC). The hematoxylin and eosin slides underwent centralized pathology review, including the percentage of tumor infiltrating lymphocytes (TILs). Breast biomarker results were extracted from pathology reports, and women were included if they had a documented ERBB2 value that was not classified ERBB2-positive. Data were analyzed from February 2023 through January 2024., Exposure: Clinical and tumor characteristics associated with BC and ERBB2-low or ERBB2-negative status., Main Outcome and Measures: ERBB2-low was defined as immunohistochemistry score of 1+ or 2+ (negative by in situ hybridization); ERBB2-negative was defined as immunohistochemistry score of 0+. Other data were collected by self-report or extraction from electronic health records, including BC risk factors, tumor characteristics, treatment modality, and survival outcomes, with recurrence-free survival (RFS) as the primary outcome and overall survival (OS) and BC-specific mortality (BCSM) as secondary outcomes. The clinical, pathological, and epidemiological variables were compared between ERBB2-low and ERBB2-negative BC., Results: Of 2200 eligible patients (all female; with mean [SD] age, 60.4 [11.9] years), 1295 (57.2%) had tumors that were ERBB2-low. Hormone receptors were positive in 1956 patients (88.9%). The sample included 291 Asian patients (13.2%), 166 Black patients (7.5%), 253 Hispanic patients (11.5%), 1439 White patients (65.4%), and 51 patients (2.3%) who identified as other race or ethnicity (eg, American Indian or Alaska Native and Pacific Islander). Within the hormone receptor-negative group, patients whose tumors had ERBB2-low staining, compared with those with ERBB2-negative tumors, had better OS (hazard ratio [HR], 0.54; 95% CI, 0.33-0.91; P = .02), RFS (HR, 0.53; 95% CI, 0.30-0.95; P = .03), and BCSM (HR, 0.43; 95% CI, 0.22-0.84; P = .01). In multivariable survival analysis stratified by hormone receptor status and adjusted for key covariates, patients with ERBB2-low and hormone receptor-negative tumors had lower overall mortality (HR, 0.48; 95% CI, 0.27-0.83; P = .009), RFS (HR, 0.45; 95% CI, 0.24-0.86; P = .02), and BCSM (subdistribution HR, 0.21; 95% CI, 0.10-0.46; P < .001) compared with patients with ERBB2-negative and hormone receptor-negative tumors. Within the hormone receptor-negative subtype, patients with ERBB2-low and high TILs tumors had better survival across all 3 outcomes compared with patients with ERBB2-negative and low TILs tumors. Additionally, patients with ERBB2-low and low TILs tumors had better BCSM (subdistribution HR, 0.36; 95% CI, 0.14-0.92; P = .03)., Conclusions and Relevance: These findings suggest that there were clinical, pathological, and epidemiological differences between ERBB2-low and ERBB2-negative BC, raising the possibility that ERBB2-low might be a unique biologic entity.

Background: We updated algorithms to identify breast cancer recurrences from administrative data, extending previously developed methods., Methods: In this validation study, we evaluated pairs of breast cancer recurrence algorithms (vs. individual algorithms) to identify recurrences. We generated algorithm combinations that categorized discordant algorithm results as no recurrence [High Specificity and PPV (positive predictive value) Combination] or recurrence (High Sensitivity Combination). We compared individual and combined algorithm results to manually abstracted recurrence outcomes from a sample of 600 people with incident stage I-IIIA breast cancer diagnosed between 2004 and 2015. We used Cox regression to evaluate risk factors associated with age- and stage-adjusted recurrence rates using different recurrence definitions, weighted by inverse sampling probabilities., Results: Among 600 people, we identified 117 recurrences using the High Specificity and PPV Combination, 505 using the High Sensitivity Combination, and 118 using manual abstraction. The High Specificity and PPV Combination had good specificity [98%, 95% confidence interval (CI): 97-99] and PPV (72%, 95% CI: 63-80) but modest sensitivity (64%, 95% CI: 44-80). The High Sensitivity Combination had good sensitivity (80%, 95% CI: 49-94) and specificity (83%, 95% CI: 80-86) but low PPV (29%, 95% CI: 25-34). Recurrence rates using combined algorithms were similar in magnitude for most risk factors., Conclusions: By combining algorithms, we identified breast cancer recurrences with greater PPV than individual algorithms, without additional review of discordant records., Impact: Researchers should consider tradeoffs between accuracy and manual chart abstraction resources when using previously developed algorithms. We provided guidance for future studies that use breast cancer recurrence algorithms with or without supplemental manual chart abstraction., (©2023 American Association for Cancer Research.)

Background: Women with breast cancer are at higher risk of cardiovascular disease (CVD) compared with women without breast cancer. Whether higher diet quality at breast cancer diagnosis lowers this risk remains unknown. We set out to determine if higher diet quality at breast cancer diagnosis was related to lower risk of CVD and CVD-related death., Methods: This analysis included 3415 participants from the Pathway Study, a prospective cohort of women diagnosed with invasive breast cancer at Kaiser Permanente Northern California between 2005 and 2013 and followed through December 31, 2021. Scores from 5 diet quality indices consistent with healthy eating were obtained at the time of breast cancer diagnosis. Scores were categorized into ascending quartiles of concordance for each diet quality index, and multivariable adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated. P values were 2-sided., Results: The Dietary Approaches to Stop Hypertension diet quality index was associated with lower risk of heart failure (HR = 0.53, 95% CI = 0.33 to 0.87; Ptrend = .03), arrhythmia (HR = 0.77, 95% CI = 0.62 to 0.94; Ptrend = .008), cardiac arrest (HR = 0.77, 95% CI = 0.61 to 0.96; Ptrend = .02), valvular heart disease (HR = 0.79, 95% CI = 0.64 to 0.98; Ptrend = .046), venous thromboembolic disease (HR = 0.75, 95% CI = 0.60 to 0.93; Ptrend = .01), and CVD-related death (HR = 0.70, 95% CI = 0.50 to 0.99; Ptrend = .04), when comparing the highest with lowest quartiles. Inverse associations were also found between the healthy plant-based dietary index and heart failure (HR = 0.60, 95% CI = 0.39 to 0.94; Ptrend = .02), as well as the alternate Mediterranean dietary index and arrhythmia (HR = 0.74, 95% CI = 0.60 to 0.93; Ptrend = .02)., Conclusion: Among newly diagnosed breast cancer patients, higher diet quality at diagnosis was associated with lower risk of CVD events and death., (© The Author(s) 2024. Published by Oxford University Press.)

Purpose: Most cytotoxic drugs are dosed using body surface area (BSA), yet not all cancer patients receive the full BSA-determined dose. Prior work suggests that breast cancer patients who are obese are more likely to experience dose reduction than normal weight patients. However, the factors driving dose reduction remain unclear., Methods: In 452 women diagnosed with stage I-IIIA primary breast cancer at Kaiser Permanente Northern California, we evaluated the association between obesity and dose reduction, and further explored other factors in relation to dose reduction, including various sociodemographic characteristics, tumor characteristics, and comorbidities. Study participants were a part of the Pathways Study, diagnosed between 2006 and 2013 and treated with cyclophosphamide + doxorubicin, followed by paclitaxel (ACT). Dose reduction was assessed using first cycle dose proportion (FCDP) and average relative dose intensity (ARDI), a metric of dose intensity over the course of chemotherapy., Results: Overall, 8% of participants received a FCDP < 90% and 21.2% had an ARDI < 90%, with dose reduction increasing with body mass index. In adjusted logistic regression models, obese women had 4.1-fold higher odds of receiving an ARDI < 90% than normal weight women (95% CI: 1.9-8.9; p-trend = 0.0006). Increasing age was positively associated with an ADRI < 90%, as was the presence of comorbidity. Dose reduction was less common in later calendar years., Conclusion: Results offer insight on factors associated with chemotherapy dosing for a common breast cancer regimen. Larger studies are required to evaluate relevance to other regimens, and further work will be needed to determine whether dose reductions impact outcomes in obese women., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Identifying women at high risk of osteoporotic fracture from aromatase inhibitor (AI) therapy for breast cancer is largely based on known risk factors for healthy postmenopausal women, which might not accurately reflect the risk in breast cancer patients post-AI therapy. To determine whether a polygenic score associated with fracture in healthy women is also significant in women treated with AIs for breast cancer, we used data from a prospective observational cohort of 2152 women diagnosed with hormonal receptor positive breast cancer treated with AIs as the initial endocrine therapy and examined a polygenic score of heel quantitative ultrasound speed of sound (gSOS) in relation to incident osteoporotic fracture after AI therapy during a median 6.1 years of follow up after AI initiation. In multivariable models, patients with the second and third highest tertiles (T) versus the lowest tertile of gSOS had significantly lower risk of fracture (T2: adjusted HR = 0.61, 95% CI: 0.46-0.80; T3: adjusted HR = 0.53, 95% CI: 0.40-0.70). The lower risk of fracture in patients with the highest tertile of gSOS remained significant after further adjustment for BMD at the hip (T3: adjusted HR = 0.62, 95% CI: 0.42-0.91). In conclusion, our analysis showed gSOS as a novel genetic predictor for fracture risk independent of BMD among breast cancer patients treated with AIs. Future studies are warranted to evaluate the performance of incorporating gSOS in prediction models for the risk of AI-related fracture in breast cancer patients., (© 2024. The Author(s).)

Background: The impact of alcohol consumption on breast cancer (BC) prognosis remains unclear., Methods: The authors examined short-term alcohol intake in relation to recurrence and mortality in 3659 women who were diagnosed with stage I-IV BC from 2003 to 2013 in the Pathways Study. Alcohol drinking in the past 6 months was assessed at cohort entry (mean, 2 months postdiagnosis) and 6 months later using a food-frequency questionnaire. Study end points were recurrence and death from BC, cardiovascular disease, and all causes. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox proportional hazards models., Results: Over an average follow-up of 11.2 years, 524 recurrences and 834 deaths (369 BC-specific and 314 cardiovascular disease-specific) occurred. Compared with nondrinkers (36.9%), drinkers were more likely younger, more educated, and current or past smokers. Overall, alcohol consumption was not associated with recurrence or mortality. However, women with higher body mass index (BMI ≥ 30 kg/m 2 ) had lower risk of overall mortality with increasing alcohol consumption for occasional drinking (HR, 0.71; 95% CI, 0.54-0.94) and regular drinking (HR, 0.77; 95% CI, 0.56-1.08) around the time of diagnosis, along with 6 months later, in a dose-response manner (p < .05). Women with lower BMI (<30 kg/m 2 ) were not at higher risk of mortality but were at possibly higher, yet nonsignificant, risk of recurrence for occasional drinking (HR, 1.29; 95% CI, 0.97-1.71) and regular drinking (HR, 1.19; 95% CI, 0.88-1.62)., Conclusions: Alcohol drinking around the time of and up to 6 months after BC diagnosis was associated with lower risk of all-cause mortality in obese women. A possible higher risk of recurrence was observed in nonobese women., (© 2023 American Cancer Society.)

Background: The number of breast cancer survivors is increasing, yet evidence to inform dietary and lifestyle guidelines is limited., Methods: This analysis included 3,658 participants from the Pathways Study, a prospective cohort of women diagnosed with invasive breast cancer. A healthy plant-based dietary index score (hPDI), an American Cancer Society (ACS) nutrition guidelines score, a 2015 Healthy Eating Index score (HEI), hours per week of moderate to vigorous physical activity (PA), and lifetime cumulative pack-years of cigarette smoking (SM) were each measured at diagnosis, 6, 24, and 72 months. Using g-computation, 5- and 10-year risk ratios (RR), risk differences, and 95% confidence intervals (CI) for all-cause mortality under hypothetical interventions on diet quality, PA, and SM, compared with the natural course (no intervention) were calculated., Results: Hypothetical moderate to extreme interventions on hPDI, ACS, and HEI, each in combination with PA and SM, showed 11% to 56%, 9% to 38%, and 9% to 49% decreases in 5-year risks of all-cause mortality compared with no intervention, respectively [(hPDI: RRmoderate = 0.89, 95% CI: 0.82-0.94; RRextreme = 0.44, 95% CI: 0.26-0.67), (ACS: RRmoderate = 0.91, 95% CI: 0.85-0.96; RRextreme = 0.62, 95% CI: 0.43-0.82), (HEI: RRmoderate = 0.91, 95% CI: 0.84-0.95; RRextreme = 0.51, 95% CI: 0.33-0.72)]. While 10-year relative risks were slightly attenuated, absolute risk reductions were more pronounced., Conclusions: Interventions to improve diet quality, increase PA, or reduce SM at the time of diagnosis may improve survival among breast cancer survivors., Impact: We estimate that over 10% of deaths could be delayed by even moderate adoption of these behaviors., (©2023 American Association for Cancer Research.)

Purpose: Studies comparing the effect of aromatase inhibitor (AI) and tamoxifen use on cardiovascular disease (CVD) risk factors in hormone receptor-positive breast cancer (BC) survivors report conflicting results. We examined associations of endocrine therapy use with incident diabetes, dyslipidemia, and hypertension., Methods: The Pathways Heart Study examines cancer treatment exposures with CVD-related outcomes in Kaiser Permanente Northern California members with BC. Electronic health records provided sociodemographic and health characteristics, BC treatment, and CVD risk factor data. Hazard ratios (HR) and 95% confidence intervals (CI) of incident diabetes, dyslipidemia, and hypertension in hormone receptor-positive BC survivors using AIs or tamoxifen compared with survivors not using endocrine therapy were estimated using Cox proportional hazards regression models adjusted for known confounders., Results: In 8985 BC survivors, mean baseline age and follow-up time was 63.3 and 7.8 years, respectively; 83.6% were postmenopausal. By treatment, 77.0% used AIs, 19.6% used tamoxifen, and 16.0% used neither. Postmenopausal women who used tamoxifen had an increased rate (HR 1.43, 95% CI 1.06-1.92) of developing hypertension relative to those who did not use endocrine therapy. Tamoxifen use was not associated with incident diabetes, dyslipidemia, or hypertension in premenopausal BC survivors. Postmenopausal AI users had higher hazard rates of developing diabetes (HR 1.37, 95% CI 1.05-1.80), dyslipidemia (HR 1.58, 95% CI 1.29-1.92), and hypertension (HR 1.50, 95% CI 1.24-1.82) compared with non-endocrine therapy users., Conclusion: Hormone receptor-positive BC survivors treated with AIs may have higher rates of developing diabetes, dyslipidemia, and hypertension over an average 7.8 years post-diagnosis., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Breast cancer survivors are at a higher risk of cardiovascular disease (CVD) morbidity and mortality compared with the general population. The impact of objective social and built neighborhood attributes on CVD risk in a cohort of female breast cancer survivors was examined., Methods: The 3975 participants came from the Pathways Study, a prospective cohort of women with invasive breast cancer from an integrated health care system in northern California. Women diagnosed with breast cancer from 2006 through 2013 were enrolled on average approximately 2 months after diagnosis. Their baseline addresses were geocoded and appended to neighborhood attributes for racial/ethnic composition, socioeconomic status (SES), population density, urbanization, crime, traffic density, street connectivity, parks, recreational facilities, and retail food environment. Incident CVD events included ischemic heart disease, heart failure, cardiomyopathy, or stroke. Cox proportional hazards models estimated associations of neighborhood attributes with CVD risk, which accounted for clustering by block groups. Fully adjusted models included sociodemographic, clinical, and behavioral factors., Results: During follow-up through December 31, 2018, 340 participants (8.6%) had CVD events. A neighborhood racial/ethnic composition measure, percent of Asian American/Pacific Islander residents (lowest quintile hazard ratio [HR], 1.85; 95% CI, 1.03-3.33), and crime index (highest quartile HR, 1.48; 95% CI, 1.08-2.03) were associated with the risk of CVD events independent of individual SES, hormone receptor status, treatment, cardiometabolic comorbidities, body mass index, and physical activity., Conclusions: With the application of a socio-ecological framework, how residential environments shape health outcomes in women with breast cancer and affect CVD risk in this growing population can be understood., (© 2023 American Cancer Society.)

Background: Lifestyle habits can impact breast cancer development, but its impact on breast cancer prognosis remains unclear. We investigated associations of post-diagnosis lifestyle with mortality and recurrence in 1,964 women with invasive breast cancer enrolled in the Kaiser Permanente Northern California Pathways Study shortly after diagnosis with lifestyle information at baseline (2005-2013) and the 2-year follow-up., Methods: We calculated a post-diagnosis lifestyle score (range, 0-18) based on 9 diet, physical activity, and body weight recommendations from the American Cancer Society/American Society of Clinical Oncology (ACS/ASCO) using follow-up data (body weight also included baseline data); higher scores indicate greater guideline concordance. Similarly, we calculated a pre-diagnosis lifestyle score using baseline data to investigate pre- to post-diagnosis changes. We estimated hazard ratios (HR) and 95% confidence intervals (CI) using Cox proportional hazard models, with follow-up through December 2018 (observing 290 deaths and 176 recurrences)., Results: The 2-year post-diagnosis lifestyle score was inversely associated with all-cause mortality (ACM; HR per 2-point increase = 0.90; 95% CI, 0.82-0.98), and breast cancer-related mortality (HR, 0.79; 95% CI, 0.67-0.95), but not recurrence. Relative to women who maintained low concordance with recommendations at both time points, women who maintained high concordance had a lower risk of ACM (HR, 0.61, 95% CI, 0.37-1.03). Improved concordance with some specific recommendations (particularly PA) may be associated with a lower hazard of ACM (HRPA, 0.52; 95% CI, 0.35-0.78)., Conclusions: Results suggest that women with breast cancer may benefit from a post-diagnosis lifestyle aligned with ACS/ASCO guidelines., Impact: This information may potentially guide lifestyle recommendations for breast cancer survivors to reduce mortality risk., (©2023 American Association for Cancer Research.)

Previous studies suggest associations of metabolic syndromes with breast cancer prognosis, yet the evidence is mixed. In recent years, the maturation of genome-wide association study findings has led to the development of polygenic scores (PGS) for many common traits, making it feasible to use Mendelian randomization to examine associations between metabolic traits and breast cancer outcomes. In the Pathways Study of 3,902 patients and a median follow-up time of 10.5 years, we adapted a Mendelian randomization approach to calculate PGS for 55 metabolic traits and tested their associations with seven survival outcomes. Multivariable Cox proportional hazards models were used to derive HRs and 95% confidence intervals (CI) with adjustment for covariates. The highest tertile (T3) of PGS for cardiovascular disease was associated with shorter overall survival (HR = 1.34, 95% CI = 1.11-1.61) and second primary cancer-free survival (HR = 1.31, 95% CI = 1.12-1.53). PGS for hypertension (T3) was associated with shorter overall survival (HR = 1.20, 95% CI = 1.00-1.43), second primary cancer-free survival (HR = 1.24, 95% CI = 1.06-1.45), invasive disease-free survival (HR = 1.18, 95% CI = 1.01-1.38), and disease-free survival (HR = 1.21, 95% CI = 1.04-1.39). PGS for serum cystatin C levels (T3) was associated with longer disease-free survival (HR = 0.82, 95% CI = 0.71-0.95), breast event-free survival (HR = 0.74, 95% CI = 0.61-0.91), and breast cancer-specific survival (HR = 0.72, 95% CI = 0.54-0.95). The above associations were significant at a nominal P < 0.05 level but not after correcting for multiple testing (Bonferroni P < 0.0009). Our analyses revealed notable associations of PGS for cardiovascular disease, hypertension, and cystatin C levels with breast cancer survival outcomes. These findings implicate metabolic traits in breast cancer prognosis., Significance: To our knowledge, this is the largest study of PGS for metabolic traits with breast cancer prognosis. The findings revealed significant associations of PGS for cardiovascular disease, hypertension, and cystatin C levels with several breast cancer survival outcomes. These findings implicate an underappreciated role of metabolic traits in breast cancer prognosis that would warrant further exploration., (© 2023 The Authors; Published by the American Association for Cancer Research.)

Background: High recurrence and progression rates are major clinical challenges for non-muscle-invasive bladder cancer (NMIBC). Dietary isothiocyanates (ITCs), phytochemicals primarily from cruciferous vegetables (CV), show strong anticancer activities in preclinical BC models, yet their effect on NMIBC prognosis remains unknown., Objectives: This study aimed to investigate the associations of dietary ITC exposure at diagnosis with NMIBC recurrence and progression., Methods: The study analyzed 1143 participants from the Be-Well study, a prospective cohort of newly diagnosed NMIBC cases in 2015-2019 with no prior history of BC. Dietary ITC exposure was indicated by self-reported CV intake, estimated ITC intake, urinary metabolites, and plasma ITC-albumin adducts. Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for recurrence and progression, and unconditional logistic regression models were used to calculate odds ratios (ORs) and 95% CIs for delayed and multiple recurrence., Results: Over a mean follow-up of 25 mo, 347 (30%) developed recurrence and 77 (6.7%) had disease progression. Despite no significant associations with the overall risk of recurrence, urinary ITC metabolites (OR: 1.96; 95% CI: 1.01, 4.43) and dietary ITC intake (OR: 2.13; 95% CI: 1.03, 4.50) were associated with late recurrence after 12-mo postdiagnosis compared with before 12-mo postdiagnosis. Raw CV intake was associated with reduced odds of having ≥2 recurrences compared with having one (OR: 0.34; 95% CI: 0.16, 0.68). Higher plasma concentrations of ITC-albumin adducts were associated with a reduced risk of progression, including progression to muscle-invasive disease (for benzyl ITC, HR: 0.40; 95% CI: 0.17, 0.93; for phenethyl ITC, HR: 0.40; 95% CI: 0.19, 0.86)., Conclusions: Our findings indicate the possible beneficial role of dietary ITCs in NMIBC prognosis. Given the compelling preclinical evidence, increasing dietary ITC exposure with CV intake could be a promising strategy to attenuate recurrence and progression risks in patients with NMIBC., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Although racial/ethnic disparities in health-care access, treatment, and cancer outcomes are well documented, the impact of racial/ethnic discrimination on cancer survivorship is unclear. We examined associations between quality of life (QoL) and self-reported discrimination among 3,991 women with breast cancer recruited during 2006-2013 from the Pathways Study in the Kaiser Permanente Northern California integrated health-care system, using linear regression models. Overall, 31% of women reported experiencing racial/ethnic discrimination, with differences by race/ethnicity (82% among non-Hispanic Black women vs. 19% among non-Hispanic White women) and nativity (40% among foreign-born Hispanic women vs. 76% among US-born Asian-American women). Experiencing racial/ethnic discrimination was associated with lower QoL in fully adjusted models. The mean QoL score was 119.6 (95% confidence interval (CI): 102.0, 137.1) for women who did not report discrimination, 115.5 (95% CI: 98.0, 133.0) for those who reported some discrimination/less than the median level, and 110.2 (95% CI: 92.7, 127.7) for those who reported more discrimination/greater than or equal to the median level. Discrimination was associated with lower QoL among women who used passive coping strategies or lived in neighborhoods with high neighborhood socioeconomic status, neighborhoods with high levels of segregation, or non-ethnic enclaves. Among breast cancer survivors, clinically meaningful differences in QoL scores were associated with racial/ethnic discrimination. Additional studies are needed to understand potential pathways through which these social factors affect survivorship outcomes., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: Fracture and osteoporosis are known side effects of aromatase inhibitors (AIs) for postmenopausal hormone receptor positive (HR+) breast cancer (BC) patients. How modifiable lifestyle factors impact fracture risk in these patients is relatively unknown., Methods: We conducted a prospective cohort study to examine the association of lifestyle factors, focusing on physical activity, with risk of incident major osteoporotic fracture and osteoporosis in 2152 HR+ BC patients diagnosed from 2006 to 2013 at Kaiser Permanente Northern California and who received AIs. Patients self-reported lifestyle factors at study entry and at 6-month follow-up. Fracture and osteoporosis outcomes were prospectively ascertained by physician-adjudication and bone mineral density (BMD) values, respectively. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated from multivariable proportional hazards regression. Models were adjusted for age, menopausal status, race/ethnicity, body mass index (BMI), AJCC stage, breast cancer treatment, prior osteoporosis, and prior major fracture., Results: Over a median 6.1 years of follow-up after AI initiation, 165 women experienced an incident osteoporotic fracture and 243 women had osteoporosis. No associations were found between overall moderate-vigorous physical activity and fracture risk, although < 150 min/week of aerobic exercise in the 6 months after BC diagnosis was associated with increased fracture risk (HR=2.42; 95% CI: 1.34, 4.37) compared with ≥ 150 min/week (meeting physical activity guidelines). Risk was also higher for never or infrequently engaging in aerobic exercise (HR=1.90; 95% CI: 1.05, 3.44). None or infrequent overall moderate-vigorous physical activity in the 6 months before BC diagnosis was associated with increased risk of osteoporosis (HR=1.94; 95% CI: 1.11; 3.37)., Conclusions: Moderate-vigorous physical activity during the immediate period after BC diagnosis, particularly aerobic exercise, was associated with lower risk of major osteoporotic fractures in women on AI therapy., Implications for Cancer Survivors: Findings may inform fracture prevention in women on AI therapy through non-pharmacologic lifestyle-based strategies., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

Importance: Tobacco smoking is an established risk factor associated with bladder cancer, yet its impact on bladder cancer prognosis is unclear., Objective: To examine associations of use of tobacco (cigarettes, pipes, and cigars), e-cigarettes, and marijuana with risk of recurrence and progression of non-muscle-invasive bladder cancer (NMIBC) and to explore use of smoking cessation interventions., Design, Setting, and Participants: The Be-Well Study is a prospective cohort study of patients with NMIBC diagnosed from 2015 to 2019 and followed-up for 26.4 months in the Kaiser Permanente Northern and Southern California integrated health care system. Eligibility criteria were age at least 21 years, first NMIBC diagnosis (stages Ta, Tis, or T1), alive, and not in hospice care. Exclusion criteria were previous diagnosis of bladder cancer or other cancer diagnoses within 1 year prior to or concurrent with NMIBC diagnosis. Data were analyzed from April 1 to October 4, 2022., Exposures: Use of cigarettes, pipes, cigars, e-cigarettes, and marijuana was reported in the baseline interview. Use of smoking cessation interventions (counseling and medications) was derived from electronic health records., Main Outcomes and Measures: Hazard ratios (HRs) and 95% CIs of recurrence and progression of bladder cancer were estimated by multivariable Cox proportional hazards regression., Results: A total of 1472 patients (mean [SD] age at diagnosis, 70.2 [10.8%] years; 1129 [76.7%] male patients) with NMIBC were enrolled at a mean (SD) of 2.3 (1.3) months after diagnosis, including 874 patients (59.4%) who were former smokers and 111 patients (7.5%) who were current cigarette smokers; 67 patients (13.7%) smoked pipes and/or cigars only, 65 patients (4.4%) used e-cigarettes, 363 patients (24.7%) used marijuana. Longer cigarette smoking duration and more pack-years were associated with higher risk of recurrence in a dose-dependent manner, with the highest risks for patients who had smoked for 40 or more years (HR, 2.36; 95% CI, 1.43-3.91) or 40 or more pack-years (HR, 1.97; 95% CI, 1.32-2.95). There was no association of having ever smoked, being a former or current cigarette smoker, and years since quit smoking with recurrence risk. No associations with pipes, cigars, e-cigarettes, or marijuana were found. Of 102 patients offered a smoking cessation intervention, 57 (53.8%) received an interventions after diagnosis, with female patients more likely than male patients to engage in such interventions (23 of 30 female patients [76.7%] vs 34 of 76 male patients [44.7%]; P = .003)., Conclusions and Relevance: These findings suggest that longer duration and more pack-years of cigarette smoking were associated with higher risk of NMIBC recurrence. Cigarette smoking remains a critical exposure before and after diagnosis in survivors of NMIBC.

Background: The use of archived formalin-fixed paraffin-embedded (FFPE) tumor tissues has become a common practice in clinical and epidemiologic genetic research. Simultaneous extraction of DNA and RNA from FFPE tissues is appealing but can be practically challenging. Here we report our results and lessons learned from processing FFPE breast tumor tissues for a large epidemiologic study., Methods: Qiagen AllPrep DNA/RNA FFPE kit was adapted for dual extraction using tissue punches or sections from breast tumor tissues. The yield was quantified using Qubit and fragmentation analysis by Agilent Bioanalyzer. A subset of the DNA samples were used for genome-wide DNA methylation assays and RNA samples for sequencing. The QC metrices and performance of the assays were analyzed with pre-analytical variables., Results: A total of 1859 FFPE breast tumor tissues were processed. We found it critical to adjust proteinase K digestion time based on tissue volume to achieve balanced yields of DNA and RNA. Tissue punches taken from tumor-enriched regions provided the most reliable output. A median of 1475 ng DNA and 1786 ng RNA per sample was generated. The median DNA integrity number (DIN) was 3.8 and median DV200 for RNA was 33.2. Of 1294 DNA samples used in DNA methylation assays, 97% passed quality check by qPCR and 92% generated data deemed high quality. Of the 130 RNA samples with DV200 ≥ 20% used in RNA-sequencing, all but 5 generated usable transcriptomic data with a mapping rate ≥ 60%., Conclusions: Dual DNA/RNA purification using Qiagen AllPrep FFPE extraction protocol is feasible for clinical and epidemiologic studies. We recommend tissue punches as a reliable source material and fine tuning of proteinase K digestion time based on tissue volume., Impact: Our protocol and recommendations may be adapted by future studies for successful extraction of archived tumor tissues., (© 2022. The Author(s).)

Purpose: While clinical heart failure (HF) is recognized as an adverse effect from breast cancer (BC) treatment, sparse data exist on specific HF phenotypes in affected BC survivors. We examined risk of HF by left ventricular ejection fraction (LVEF) status in women with a history of BC., Methods: 14,804 women diagnosed with all stages of invasive BC from 2005 to 2013 and with no history of HF were matched 1:5 to 74,034 women without BC on birth year, race, and ethnicity. LVEF values were extracted from echocardiography studies within 30 days before through 90 days after the HF clinical encounter. HF was stratified into HF with preserved ejection fraction (HFpEF, LVEF ≥ 45%) and HF with reduced ejection fraction (HFrEF, LVEF < 45%). Cumulative incidence rates (CIRs) were estimated with competing risk of overall death. Hazard ratios (HR) were calculated by multivariable Cox proportional hazards regression., Results: Mean time to HF diagnosis was 5.31 years (range 0.03-13.03) in cases and 5.25 years (range 0.01-12.94) in controls. 10-year CIRs were 1.2% and 0.9% for overall HF, 0.8% and 0.7% for HFpEF, and 0.4% and 0.2% for HFrEF in cases and controls, respectively. In fully adjusted models, an overall significant increased risk of HF in cases versus controls was observed (HR: 1.31, 95% CI 1.14, 1.51). The increased risk was seen for both HFrEF (HR: 1.59, 95% CI 1.22, 2.08) and HFpEF (HR: 1.22; 95% CI 1.03, 1.45)., Conclusion: BC survivors experienced higher risk of HF compared with women without BC, and the risk persisted across LVEF phenotypes. Systematic cardio-oncology surveillance should be considered to mitigate this risk in BC patients., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: To examine cardiovascular disease (CVD) and mortality risk in women with breast cancer (BC) by cancer therapy received relative to women without BC., Methods: The study population comprised Kaiser Permanente Northern California members. Cases with invasive BC diagnosed from 2005 to 2013 were matched 1:5 to controls without BC on birth year and race/ethnicity. Cancer treatment, CVD outcomes, and covariate data were from electronic health records. Multivariable Cox proportional hazards models estimated hazard ratios (HRs) and 95% CIs of CVD incidence and mortality by receipt of chemotherapy treatment combinations, radiation therapy, and endocrine therapy., Results: A total of 13,642 women with BC were matched to 68,202 controls without BC. Over a 7-year average follow-up (range < 1-14 years), women who received anthracyclines and/or trastuzumab had high risk of heart failure/cardiomyopathy relative to controls, with the highest risk seen in women who received both anthracyclines and trastuzumab (HR, 3.68; 95% CI, 1.79 to 7.59). High risk of heart failure and/or cardiomyopathy was also observed in women with BC with a history of radiation therapy (HR, 1.38; 95% CI, 1.13 to 1.69) and aromatase inhibitor use (HR, 1.31; 95% CI, 1.07 to 1.60), relative to their controls. Elevated risks for stroke, arrhythmia, cardiac arrest, venous thromboembolic disease, CVD-related death, and death from any cause were also observed in women with BC on the basis of cancer treatment received., Conclusion: Women with BC had increased incidence of CVD events, CVD-related mortality, and all-cause mortality compared with women without BC, and risks varied according to the history of cancer treatment received. Studies are needed to determine how women who received BC treatment should be cared for to improve cardiovascular outcomes., Competing Interests: Carlos IribarrenConsulting or Advisory Role: Gen in CODE, LLCResearch Funding: Genentech/Roche Dawn L. HershmanConsulting or Advisory Role: AIM Specialty Health Romain NeugebauerEmployment: Kaiser PermanenteNo other potential conflicts of interest were reported.

Purpose: The incidence of cardiometabolic risk factors in breast cancer (BC) survivors has not been well described. Thus, we compared risk of hypertension, diabetes, and dyslipidemia in women with and without BC., Methods: Women with invasive BC diagnosed from 2005 to 2013 at Kaiser Permanente Northern California (KPNC) were identified and matched 1:5 to noncancer controls on birth year, race, and ethnicity. Cumulative incidence rates of hypertension, diabetes, and dyslipidemia were estimated with competing risk of overall death. Subdistribution hazard ratios (sHRs) were estimated by Fine and Gray regression, adjusted for cardiovascular disease-related risk factors, and stratified by treatment and body mass index (BMI)., Results: A total of 14,942 BC cases and 74,702 matched controls were identified with mean age 61.2 years and 65% non-Hispanic White. Compared with controls, BC cases had higher cumulative incidence rates of hypertension (10.9% v 8.9%) and diabetes (2.1% v 1.7%) after 2 years, with higher diabetes incidence persisting after 10 years (9.3% v 8.8%). In multivariable models, cases had higher risk of diabetes (sHR, 1.16; 95% CI, 1.07 to 1.26) versus controls. Cases treated with chemotherapy (sHR, 1.23; 95% CI, 1.11 to 1.38), left-sided radiation (sHR, 1.29; 95% CI, 1.13 to 1.48), or endocrine therapy (sHR, 1.23; 95% CI, 1.12 to 1.34) continued to have higher diabetes risk. Hypertension risk was higher for cases receiving left-sided radiation (sHR, 1.11; 95% CI, 1.02 to 1.21) or endocrine therapy (sHR, 1.10; 95% CI, 1.03 to 1.16). Normal-weight (BMI < 24.9 kg/m 2 ) cases had higher risks overall and within treatment subgroups versus controls., Conclusion: BC survivors at KPNC experienced elevated risks of diabetes and hypertension compared with women without BC depending on treatments received and BMI. Future studies should examine strategies for cardiometabolic risk factor prevention in BC survivors., Competing Interests: Carlos IribarrenConsulting or Advisory Role: Gen in CODE, LLCResearch Funding: Genentech/Roche Dawn L. HershmanConsulting or Advisory Role: AIM Specialty HealthNo other potential conflicts of interest were reported.

Few germline genetic variants have been robustly linked with breast cancer outcomes. We conducted trans-ethnic meta genome-wide association study (GWAS) of overall survival (OS) in 3973 breast cancer patients from the Pathways Study, one of the largest prospective breast cancer survivor cohorts. A locus spanning the UACA gene, a key regulator of tumor suppressor Par-4, was associated with OS in patients taking Par-4 dependent chemotherapies, including anthracyclines and anti-HER2 therapy, at a genome-wide significance level ([Formula: see text]). This association was confirmed in meta-analysis across four independent prospective breast cancer cohorts (combined hazard ratio = 1.84, [Formula: see text]). Transcriptome-wide association study revealed higher UACA gene expression was significantly associated with worse OS ([Formula: see text]). Our study identified the UACA locus as a genetic predictor of patient outcome following treatment with anthracyclines and/or anti-HER2 therapy, which may have clinical utility in formulating appropriate treatment strategies for breast cancer patients based on their genetic makeup., (© 2022. The Author(s).)

Background: Many women with breast cancer also have a high likelihood of cardiovascular mortality, and while there are several cardiovascular risk prediction models, none have been validated in a cohort of breast cancer patients. We first compared the performance of commonly-used cardiovascular models, and then derived a new model where breast cancer and cardiovascular mortality were modeled simultaneously, to account for the competing risk endpoints and commonality of risk factors between the two events., Methods: We included 20,462 women diagnosed with stage I-III breast cancer between 2000 and 2010 in Kaiser Permanente Northern California (KPNC) with follow-up through April 30, 2015, and examined the performance of the Framingham, CORE and SCOREOP cardiovascular risk models by area under the receiver operating characteristic curve (AUC), and observed-to -expected (O/E) ratio. We developed a multi-state model based on cause-specific hazards (CSH) to jointly model the causes of mortality., Results: The extended models including breast cancer characteristics (grade, tumor size, nodal involvement) with CVD risk factors had better discrimination at 5-years with AUCs of 0.85 (95% CI 0.83, 0.86) for cardiovascular death and 0.80 (95% CI 0.78, 0.87) for breast cancer death compared with the existing cardiovascular models evaluated at 5 years AUCs ranging 0.71-0.78. Five-year calibration for breast and cardiovascular mortality from our multi-state model was also excellent (O/E = 1.01, 95% CI 0.91-1.11)., Conclusion: A model incorporating cardiovascular risk factors, breast cancer characteristics, and competing events, outperformed traditional models of cardiovascular disease by simultaneously estimating cancer and cardiovascular mortality risks., (© 2021. The Author(s).)

Plant-based diets are recommended for cancer survivors, but their relationship with breast cancer outcomes has not been examined. We evaluated whether long-term concordance with plant-based diets reduced the risk of recurrence and mortality among a prospective cohort of 3646 women diagnosed with breast cancer from 2005 to 2013. Participants completed food frequency questionnaires at diagnosis and 6-, 25-, and 72-month follow-up, from which we derived plant-based diet indices, including overall (PDI), healthful (hPDI), and unhealthful (uPDI). We observed 461 recurrences and 653 deaths over a median follow-up of 9.51 years. Using multivariable-adjusted Cox proportional hazards models, we estimated hazard ratios (HR) and 95% confidence intervals for breast cancer recurrence and all-cause, breast-cancer-specific, and non-breast-cancer mortality. Increased concordance with hPDI was associated with a reduced hazard of all-cause (HR 0.93, 95% CI: 0.83-1.05) and non-breast-cancer mortality (HR 0.83, 95% CI: 0.71-0.98), whereas increased concordance with uPDI was associated with increased hazards (HR 1.07, 95% CI: 0.96-1.2 and HR 1.20, 95% CI: 1.02-1.41, respectively). No associations with recurrence or breast-cancer-specific mortality were observed. In conclusion, healthful vs. unhealthful plant-based dietary patterns had differing associations with mortality. To enhance overall survival, dietary recommendations for breast cancer patients should emphasize healthful plant foods.

Background: Prior research suggests a relationship between overall diet quality and breast cancer survival, although few studies have reported on this topic. We evaluated whether 4 dietary quality indices consistent with healthy eating recommendations around the time of breast cancer diagnosis were associated with risk of recurrence, cause-specific, and all-cause mortality., Methods: A total of 3660 women diagnosed with invasive breast cancer were included. Diet was assessed an average of 2.3 (range = 0.7-18.7) months after diagnosis, from which 4 dietary quality indices were derived: the American Cancer Society guidelines (ACS), the alternate Mediterranean Diet Index (aMED), the Dietary Approaches to Stop Hypertension (DASH), and the 2015 Healthy Eating Index (HEI). Over 40 888 person-years of follow-up, 461 breast cancer recurrences, and 655 deaths were ascertained. Cox models were used to estimate hazards ratios (HRs) and 95% confidence intervals (CIs)., Results: Adjusted comparisons between extreme quintiles showed all 4 dietary quality indices to be inversely associated with all-cause mortality, suggesting a 21%-27% lower risk (ACS HR = 0.73, 95% CI = 0.56 to 0.95; aMED HR = 0.79, 95% CI = 0.61 to 1.03; DASH HR = 0.76, 95% CI = 0.58 to 1.00; HEI HR = 0.77, 95% CI = 0.60 to 1.01). Similar patterns were noted for non-breast cancer mortality (ACS HR = 0.69, 95% CI = 0.48 to 0.98; aMED HR = 0.73, 95% CI = 0.50 to 1.05; DASH HR = 0.55, 95% CI = 0.38 to 0.79; HEI HR = 0.67, 95% CI = 0.48 to 0.94). None of the dietary quality indices were associated with recurrence or breast cancer-specific mortality., Conclusion: Food intake patterns concordant with dietary quality indices consistent with recommendations for healthy eating may be beneficial for women with breast cancer., (© The Author(s) 2021. Published by Oxford University Press.)

Cruciferous vegetables are primary sources of dietary isothiocyanates (ITCs), a group of phytochemicals showing promising cancer-chemopreventive activities in multiple cancer models. However, no study has thoroughly examined how cooking affects the yields of ITCs from cruciferous vegetables. In this study, a high-performance liquid chromatography (HPLC)-based cyclocondensation assay was performed to examine the ITC yields from four major cruciferous vegetables (broccoli, cabbage, cauliflower, and kale) under six cooking conditions (stir-frying, steaming, microwaving, boiling, stewing, and chip-baking for kale only) and measured the level of ITCs under the raw condition for a comprehensive list of cruciferous vegetables and ITC-containing condiments. A wide range of ITC yields was found across vegetables and condiments. Cooking significantly altered the ITC yields, showing an averagely four-fold increase by lightly cooking (stir-frying, steaming, and microwaving) and a 58% decrease by heavily cooking (boiling, stewing, and chip-baking). These findings will provide the evidence-based cooking guidance on cruciferous vegetable consumption and help better estimate dietary ITC exposure in epidemiologic studies., Competing Interests: The authors report no conflict of interest., (© 2020 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC.)

Rubbery polymer membranes prepared from CO 2 -philic PEO and/or highly permeable PDMS are desired for efficient CO 2 separation from light gases (CH 4 and N 2 ). Poor mechanical properties and size-sieving ability, however, limit their application in gas separation applications. Cross-linked rubbery polymer-based gas separation membranes with a low T g based on both PEG/PPG and PDMS units with various compositions between these two units are prepared for the first time in this work by ring-opening metathesis polymerization type cross-linking and in situ membrane casting. The developed membranes display excellent CO 2 separation performance with CO 2 permeability ranging from 301 to 561 Barrer with excellent CO 2 /N 2 selectivity ranging from 50 to 59, overcoming the Robeson upper bound (2008). The key finding underlying the excellent performance of the newly developed cross-linked x (PEG/PPG:PDMS) membranes is the formation of a well-connected interlocked network structure, which endows the rubbery materials with the properties of rigid polymers, e.g., size-sieving ability and high thermomechanical stability. Moreover, the membrane shows long-term antiaging performance of up to eight months and antiplasticization behavior up to 25 atm pressure.

Purpose: To identify distinct trajectories of total moderate-to-vigorous physical activity (MVPA) and sedentary behavior following a breast cancer diagnosis and their correlates., Methods: The analysis examined 3000 female breast cancer survivors within Kaiser Permanente Northern California between 2006 and 2013. Self-reported time spent on total MVPA and sedentary behaviors were assessed at baseline (mean = 1.8 months post-diagnosis) and at 6 and 24 months follow up. Trajectory groups were identified using group-based trajectory modeling and K-means for longitudinal data analysis. Trajectory groups were named by baseline activity level (high, medium, or low) and direction of change (increaser, decreaser, or maintainer)., Results: Trajectory analyses identified three MVPA trajectories [high decreaser (7%), medium decreaser (35%), low maintainer (58%)] and four sedentary behavior trajectories [high maintainer (18%), high decreaser (27%), low increaser (24%), and low maintainer (31%)]. Women with higher education (ORs: 1.63-4.37), income (OR: 1.37), dispositional optimism (ORs: 1.60-1.86), and social support (OR: 1.33) were more likely to be high or medium decreasers of MVPA (all P < 0.05). High maintainers and high decreasers of sedentary behavior were more likely to have higher education (OR: 1.84) and social support (ORs: 1.42-1.86), but lower income (OR: 0.66; all P < 0.05)., Conclusions: In the 24 months following breast cancer diagnosis, 42% of survivors decreased MVPA and 73% maintained or increased time on sedentary behavior. Socioeconomic status and stress coping at diagnosis predicted subsequent PA trajectory., Implications for Cancer Survivors: It is important to prioritize exercise intervention and counseling during early stage of breast cancer survivorship, especially in survivors who are at high risk of becoming physically inactive post-diagnosis.

Purpose: Osteoporosis and fragility fracture are major bone toxicities of aromatase inhibitors (AIs) for postmenopausal hormone receptor-positive breast cancer. Except for a few small studies on bone turnover markers and reduced bone mineral density after AI treatment, data on the associations of bone markers and risk of osteoporosis or fracture from prospective studies are lacking., Methods: In a prospective study of 1709 women on AIs, two bone turnover markers, BALP and TRACP, and two bone regulatory markers, RANKL and OPG, were measured and examined in relation to risk of osteoporosis and fragility fractures during a median follow-up time of 6.1 years., Results: Higher levels of BALP and TRACP were both associated with increased risk of osteoporosis and higher BALP/TRACP ratios were associated with lower risk of osteoporosis, but no associations were observed for fracture risk. Higher levels of OPG were associated with increased risk of fracture, whereas higher levels of RANKL were associated with lower risk. As a result, OPG/RANKL ratios were positively associated with fracture risk [hazard ratio (HR) = 2.49, 95% confidence interval (CI) 1.34-4.61]. After controlling for age and fracture history, the associations became non-significant but a suggestive trend remained (HR = 1.80, 95% CI 0.96-3.37)., Conclusion: Our study provides suggestive evidence for the potential utility of OPG/RANKL ratios in predicting risk of fracture in women treated with AIs for breast cancer. Further validation may be warranted.

Purpose: To identify distinct diet trajectories after breast cancer (BC) diagnosis, and to examine the characteristics associated with diet trajectories., Methods: We analyzed 2865 Pathways Study participants who completed ≥ 2 food frequency questionnaires at the time of BC diagnosis (baseline), and at 6 and 24 months after baseline. Trajectory groups of fruit and vegetable (F/V) intake, % calories from dietary fat, and alcohol intake over 24 months were identified using group-based trajectory modeling. Associations between diet trajectories and sociodemographic, psychosocial, and clinical factors were analyzed using multinomial logistic regression., Results: Analyses identified 3 F/V trajectory groups, 4 dietary fat groups, and 3 alcohol groups. All 3 F/V trajectory groups reported slightly increased F/V intake post-diagnosis (mean increase = 0.2-0.5 serving/day), while 2 groups (48% of participants) persistently consumed < 4 servings/day of F/V. Dietary fat intake did not change post-diagnosis, with 45% of survivors maintaining a high-fat diet (> 40% of calories from fat). While most survivors consumed < 1 drink/day of alcohol at all times, 21% of survivors had 1.4-3.0 drinks/day at baseline and temporarily decreased to 0.1-0.5 drinks/day at 6 months. In multivariable analysis, diet trajectory groups were significantly associated with education (ORs: 1.93-2.49), income (ORs: 1.32-2.57), optimism (ORs: 1.93-2.49), social support (OR = 1.82), and changes in physical well-being (ORs: 0.58-0.61) and neuropathy symptoms after diagnosis (ORs: 1.29-1.66)., Conclusions: Pathways Study participants reported slightly increasing F/V and decreasing alcohol intake after BC diagnosis. Nearly half of survivors consumed insufficient F/V and excessive dietary fat. It is important to prioritize nutrition counseling and education in BC survivors.

Introduction: GATA3 is a critical transcription factor in maintaining the differentiated state of luminal mammary epithelial cells. We sought to determine the prognostic and predictive roles of GATA3 genotypes for breast cancer., Patients and Methods: Twelve single nucleotide polymorphisms (SNPs) were genotyped in 2 breast cancer cohorts, including the SWOG S8897 trial where patients were treated with adjuvant chemotherapy (CAF [cyclophosphamide, doxorubicin, 5-fluorouracil] vs. CMF [cyclophosphamide, methotrexate, 5-fluorouracil]) or untreated, and the observational Pathways Study., Results: In the S8897 trial, rs3802604 and rs568727 were associated with disease-free survival and overall survival in the treated group, regardless of chemotherapy regimen. The GG genotype of rs3802604 conferred poorer overall survival (adjusted hazard ratio, 2.45; 95% confidence interval, 1.48-4.05) and disease-free survival (adjusted hazard ratio, 1.95; 95% confidence interval, 1.27-2.99) compared with the AA genotype. Similar associations were found for rs568727. In contrast, no association with either SNP was found in the untreated group. Subgroup analyses indicated that these 2 SNPs more strongly influenced outcomes in the patients who also received tamoxifen. However, the associations in the subgroup with tamoxifen treatment were not replicated in the Pathways Study, possibly owing to substantial differences between the 2 patient cohorts, such as chemotherapy regimen and length of follow-up. Results from joint analyses across these 2 cohorts were marginally significant, driven by the results in S8897. Bioinformatic analyses support potential functional disruption of the GATA3 SNPs in breast tissue., Conclusions: The present study provides some evidence for the predictive value of GATA3 genotypes for breast cancer adjuvant therapies. Future replication studies in appropriate patient populations are warranted., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Young black women are at higher risk of triple-negative breast cancer (TNBC); however, a majority of the genetic studies on cancer predisposition were carried out in White populations. The underrepresentation of minority racial/ethnic populations in cancer genetic studies may have led to disproportionate gaps in our knowledge of cancer predisposition genes in these populations. We surveyed the protein-truncating mutations at the exome-wide scale and in known breast cancer predisposition genes among 170 patients of multiple racial/ethnic groups with early-onset (≤age 50) TNBC from two independent cohorts. Black patients, on average, had a higher number of truncating mutations than Whites at the exome-wide level, but fewer truncating mutations in the panel of known breast cancer genes. White TNBC patients showed a strong enrichment of truncating variants in known breast cancer genes, whereas no such enrichment was found among Black patients. Our findings indicate likely more breast cancer disposition genes yet to be discovered in minority racial/ethnic groups, and the current multigene panels may result in unequal benefits from cancer genetic testing., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

As next-generation sequencing (NGS) technology has become widely used to identify genetic causal variants for various diseases and traits, a number of packages for checking NGS data quality have sprung up in public domains. In addition to the quality of sequencing data, sample quality issues, such as gender mismatch, abnormal inbreeding coefficient, cryptic relatedness, and population outliers, can also have fundamental impact on downstream analysis. However, there is a lack of tools specialized in identifying problematic samples from NGS data, often due to the limitation of sample size and variant counts. We developed SeqSQC, a Bioconductor package, to automate and accelerate sample cleaning in NGS data of any scale. SeqSQC is designed for efficient data storage and access, and equipped with interactive plots for intuitive data visualization to expedite the identification of problematic samples. SeqSQC is available at http://bioconductor.org/packages/SeqSQC., (Copyright © 2019 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

Context: Patients with cancer commonly experience depression. If not addressed, depression can lead to reduced quality of life and survival., Objective: Given the introduction of national initiatives to improve management of psychiatric symptoms among patients with cancer, we examined patterns of depression detection and treatment over time, and with respect to patient characteristics., Methods: This cross-sectional study linked data from the Pathways Study, a prospective cohort study of women diagnosed with breast cancer at Kaiser Permanente Northern California between 2005 and 2013, with data from Kaiser Permanente Northern California's electronic medical record. Pathways participants eligible for this analysis had no known prior depression but reported depressive symptoms at baseline. We used modified Poisson regression to assess the association of cancer diagnosis year and other patient characteristics with receipt of a documented clinician response to depressive symptoms (depression diagnosis, mental health referral, or antidepressant prescription)., Results: Of the 725 women in our sample, 34% received a clinician response to depression. We observed no statistically significant association of breast cancer diagnosis year with clinician response. Characteristics associated with clinician response included Asian race (adjusted risk ratio, Asian vs. white: 0.44, 95% CI: 0.29-0.68) and depression severity (adjusted risk ratio, mild-moderate vs. severe depression: 1.45, 95% CI: 1.11-1.88)., Conclusion: Most patients in our sample did not receive a clinician response to their study-reported depression, and rates of response do not appear to have improved over time. Asian women, and those with less severe depression, appeared to be at increased risk of having unmet mental health care needs., (Copyright © 2018 American Academy of Hospice and Palliative Medicine. All rights reserved.)