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Cumulative incidence of all-cause mortality, breast cancer-specific mortality, and breast cancer recurrence among women diagnosed with invasive breast cancer in the Pathways Study, according to tertiles of the 2-year post-diagnosis lifestyle score, 2006–2018

Hazard ratios (HR) and 95% confidence intervals (95% CI) for the association of 2-year post-diagnosis lifestyle with all-cause mortality, breast cancer-mortality, and breast cancer recurrence among women diagnosed with stage I–III breast cancer.

Supplementary text providing additional information regarding methods.

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.

Supplementary tables 1s-4s. Supplementary Table 1s. Concordance of variant calls. Supplementary Table 2s. Breast cancer-related genes from the Cancer Gene Consensus database. Supplementary Table 3s. Concordance of variant calls in known breast cancer genes. Supplementary Table 4s. Discordant variant calls in breast cancer-related genes.

Background: Whole-exome sequencing (WES) has recently emerged as an appealing approach to systematically study coding variants. However, the requirement for a large amount of high-quality DNA poses a barrier that may limit its application in large cancer epidemiologic studies. We evaluated the performance of WES with low input amount and saliva DNA as an alternative source material.Methods: Five breast cancer patients were randomly selected from the Pathways Study. From each patient, four samples, including 3 μg, 1 μg, and 0.2 μg blood DNA and 1 μg saliva DNA, were aliquoted for library preparation using the Agilent SureSelect Kit and sequencing using Illumina HiSeq2500. Quality metrics of sequencing and variant calling, as well as concordance of variant calls from the whole exome and 21 known breast cancer genes, were assessed by input amount and DNA source.Results: There was little difference by input amount or DNA source on the quality of sequencing and variant calling. The concordance rate was about 98% for single-nucleotide variant calls and 83% to 86% for short insertion/deletion calls. For the 21 known breast cancer genes, WES based on low input amount and saliva DNA identified the same set variants in samples from a same patient.Conclusions: Low DNA input amount, as well as saliva DNA, can be used to generate WES data of satisfactory quality.Impact: Our findings support the expansion of WES applications in cancer epidemiologic studies where only low DNA amount or saliva samples are available. Cancer Epidemiol Biomarkers Prev; 24(8); 1207–13. ©2015 AACR.

Supplementary Figure 2s. Comparisons of quality metrics between concordant and discordant short insertion/deletions (indel).

Supplementary Figure 1s. Comparisons of quality metrics between concordant and discordant single nucleotide variants (SNVs).

ImportanceTobacco smoking is an established risk factor associated with bladder cancer, yet its impact on bladder cancer prognosis is unclear.ObjectiveTo 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 ParticipantsThe 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.ExposuresUse 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 MeasuresHazard ratios (HRs) and 95% CIs of recurrence and progression of bladder cancer were estimated by multivariable Cox proportional hazards regression.ResultsA 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 RelevanceThese 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.

A whole-food plant-based (WFPB) diet in combination with healthful lifestyle modifications has been shown to be an effective approach to managing and reversing the progression of coronary artery disease and type 2 diabetes mellitus (T2DM). The Health Achieved Through Lifestyle Transformation Program (HALT) is a 20-week real-world healthful diet and lifestyle intervention program implemented at Kaiser Permanente South Sacramento Medical Center (KPSSC), whose goal is to treat, and where possible, reverse CAD and T2DM. Here, our objective is to describe HALT, including enrollment, the intervention, adherence, and data collection activities during a 2-year period from October 15th, 2016, through October 9th, 2018. There were 204 KPSSC members enrolled, of which, 19 (9.3%) had CAD only, 166 (81.4%) had T2DM only, and 19 (9.3%) had both CAD and T2DM. Among the enrolled, 196 (96.1%) completed self-administered questionnaires, and 88.2 to 97.5% completed blood tests, depending on the test. The enrolled were predominantly female (63.2%), ≥50 years old at program entry (83.3%), and white (32.8%) or black (25.5%). HALT has the potential to become a valuable resource for examining the impact of dietary and lifestyle modifications on patients diagnosed with CAD and/or T2DM.

Introduction Chemotherapy administration in real-world cancer care can differ extensively from clinical trials. It is important to understand real-world practice to identify dose reductions, delays, regimen changes and early discontinuations that impact cancer outcomes. Such variables require knowledge of intended regimens, which may not be well-documented in structured data in electronic health records (EHRs). We examined EHR data from the Kaiser Permanente Northern California (KPNC) site of the Optimal Breast Cancer Chemotherapy Dosing (OBCD) study to develop a process to identify each patient’s intended regimen. Methods In this study of women diagnosed and treated with primary stage I-IIIA breast cancer at KPNC from 2006-2019, and ages 18+y at diagnosis, we analyzed treatment patterns using structured EHR data on the drugs, dosages, and dates at which they were administered (from which intervals and total length can be derived). Chemotherapy agents were identified using the NCI’s CANMED database augmented with other sources. We used these data to categorize patients into the 22 drug combinations described in the National Cancer Care Network (NCCN) guidelines for breast cancer treatment. Within these 22 drug combinations, women were then subcategorized into 45 distinct chemotherapy administration schedules, defined as NCCN guideline regimens (NGRs). For this step, algorithms were developed that categorized patients into NGRs if they received the exact regimen described in the guidelines. For the second step, we conducted a manual review of the EHR data for patients who were unable to be categorized. This enabled us to gradually loosen the criteria (in terms of cycle intervals or number of cycles) so patients whose chemotherapy administration aligned closely with NGRs were categorized into each of the 45 NGRs. Clear patterns emerged of regimens that were administered to multiple patients, despite being outside of the NCCN guidelines, which we have defined as non-standard NGRs. For example, in the drug combination TC (cyclophosphamide and docetaxel) the NGR was TC every 21 days for 4 cycles. We found approximately 1 in 10 patients received 6 cycles, which we defined as a non-NGR. For the remaining uncategorized patients, medical chart abstraction was undertaken as a third step, at which point patients were categorized into either existing regimens or new non-NGRs if their intended regimen had not been previously described in the guidelines. Results Among 31,418 women with breast cancer, 12,427 (39.6%) received chemotherapy. We determined the intended chemotherapy regimens for 6,559 (52.8%) receiving the 45 NGRs using EHR data. We further expanded the algorithms through a manual review of the EHR data, which enabled us to categorize 2,977 (24.0%) additional women into their intended regimens. Abstracted medical notes were reviewed for the remaining patients for whom we had not been able to identify the intended regimen. Across both the manual review and abstraction processes, we were able to identify additional non-standard NGR regimens. In total, 9,536 (76.7%) of women were categorized into their intended regimen through the algorithm/manual review process, while 2891 (23.3%) of women underwent medical chart abstraction to identify the intended regimen. Conclusion Here, we describe the challenges and approaches to operationalize complex, real-world data to identify intended chemotherapy regimens at a granularity and scale not seen previously. We are adapting this method at a second OBCD study site, Kaiser Permanente Washington, where all women have undergone medical chart abstraction. We hope this methodology leads to increased feasibility and efficiency of use of large-scale clinical data, in turn improving cancer care delivery, patient outcome evaluation, and other real-world questions. Citation Format: Jenna Bhimani, Kelli O’Connell, Rachael P. Burganowski, Isaac J. Ergas, Marilyn J. Foley, Grace B. Gallagher, Jennifer J. Griggs, Narre Heon, Tatjana Kolevska, Yuriy Kotsurovskyy, Candyce H. Kroenke, Kanichi G. Nakata, Sonia Persaud, Donna R. Rivera, Janise M. Roh, Sara Tabatabai, Emily Valice, Erin J. Bowles, Elisa V. Bandera, Lawrence H. Kushi, Elizabeth D. Kantor. A methodology for using real-world data from electronic health records to assess chemotherapy administration in women with breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-03-16.

Background: Most cytotoxic drugs are dosed according to body surface area (BSA), yet not all patients receive the full BSA-determined dose. Prior work suggests that dose reduction may occur more frequently in obese patients, likely due to concern about inducing toxicity at high doses. Other factors, such as race/ethnicity, have been suggested to be associated with dosing, yet the factors associated with dose reduction remain poorly understood, with little known about dosing patterns in integrated healthcare delivery systems and how such patterns have changed over time. Methods: We examined chemotherapy dosing in 452 women diagnosed with stage I-IIIA primary breast cancer at Kaiser Permanente Northern California. All study participants were a part of the Pathways Study, diagnosed between 2006-2013, and treated with the common breast cancer regimen, ACT (cyclophosphamide and doxorubicin, followed by paclitaxel). We explored 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. We assessed dosing using first cycle dose proportion (< 90% expected dose) and average relative dose intensity (ARDI, a metric of dose intensity over the entire course of chemotherapy). Results: Overall, 8% of women received a dose reduction >10% in the first cycle of chemotherapy and 21.2% of patients had an ARDI < 90%. Obesity was a strong predictor of dose reduction, both in the first cycle and across all cycles. In the first cycle, 21.9% of severely obese patients (body mass index, BMI: 35+ kg/m2) were dose reduced, whereas no normal weight patients (BMI: 18.5-< 25 kg/m2) experienced a first cycle dose reduction. Across all cycles, 38.4% of severely obese women had an ARDI < 90%, as compared 12.8% of normal weight women. In logistic regression models adjusted for age, race/ethnicity, and white blood cell count, obese women had 4.1-fold higher odds of receiving a dose reduction of 10% or more over the course of chemotherapy than their normal weight counterparts (95% CI: 1.9, 8.9; p-trend: 0.006). Increasing age was positively associated with dose reduction across the course of chemotherapy, as was the presence of comorbidity. Importantly, dose reduction was less common in later calendar years. Sensitivity analyses revealed that the positive association between obesity and dosing was robust to further adjustment for these other significantly associated factors. Impact: These results offer insight on factors associated with variation in chemotherapy dosing for a common breast cancer treatment regimen. Larger studies are required to evaluate relevance of these findings to other treatment regimens. Further work will be needed to determine whether dose reductions impact breast cancer outcomes. Citation Format: Elizabeth D. Kantor, Kelli O’Connell, Isaac J. Ergas, Emily Valice, Janise M. Roh, Jenna Bhimani, Narre Heon, Jennifer J. Griggs, Jean Lee, Erin J. Bowles, Donna R. Rivera, Tatjana Kolevska, Elisa Bandera, Lawrence H. Kushi. Assessment of Breast Cancer Chemotherapy Dose Reduction in an Integrated Healthcare Delivery System [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-03-09.

Prior studies suggest a strong genetic influence on breast cancer prognosis. Six genome-wide association studies (GWAS) on breast cancer prognosis have been published to date. However, none of the reported loci was replicated across studies and only two passed genome-wide significance (P < 5 x 10-8). In the Pathways Study, a prospective cohort of breast cancer survivors begun in Kaiser Permanente Northern California (KPNC) in 2006, we carried out a GWAS of overall survival (OS) in 3,973 patients. Trans-ethnic meta-GWAS identified an association with OS of a locus on chromosome 15 that almost reached genome-wide significance (P = 9.42 x 10-8). This locus spanned the UACA gene, a key regulator of tumor suppressor Par-4. We found that receipt of chemotherapy modified the effect of the UACA locus on OS (Pinteraction = 2.4 x 10-4). This observation led us to hypothesize that the UACA locus effect on OS may be specific to Par-4 dependent chemotherapies, which include anti-HER2 therapy and doxorubicin. We stratified patients into two groups, those who received Par-4 dependent chemotherapy agents versus other patients. In separate trans-ethnic meta-GWAS, the UACA locus was significantly associated with OS in patients taking Par-4 dependent chemotherapies (P = 1.27 x 10-9), while no association was observed in the other patients (P = 0.21). To evaluate whether the UACA gene may be responsible for this association, we performed a transcriptome-wide association study (TWAS) of OS in White patients taking Par-4 dependent chemotherapies. Higher UACA gene expression was significantly associated with OS (P = 4.68 x 10-7), the only gene reaching transcriptome-wide significance (P < 4.34 x 10-6). These results suggest that higher UACA expression may inhibit Par-4 induced apoptosis and lead to stronger chemoresistance and worse survival. We attempted to validate our findings in the independent KPNC Genetic Epidemiology Research on Aging (GERA) cohort. The GERA cohort included only 168 White patients with incident breast cancer after DNA collection who received Par-4 dependent chemotherapies. We found a non-significant association (hazard ratio (HR) = 1.46, P = 0.66) consistent with Pathways Study findings. However, the GERA cohort also included 1,983 prevalent breast cancer patients with biospecimen collection after diagnosis. In this group, the risk allele frequency in breast cancer survivors receiving Par-4 dependent chemotherapies was significantly lower than that in the White population (P = 5.50 x 10-3) while the risk allele frequency in the those not receiving these chemotherapies was similar to the population (P = 0.07). This is consistent with Pathways Study observations that the UACA locus risk allele significantly increased risk of mortality in patients taking Par-4 dependent chemotherapies. A higher mortality in breast cancer survivors carrying the risk allele would result in decreased risk allele frequency. We further validated our findings in Shanghai Breast Cancer Survival Study (SBCSS)and Shanghai Breast Cancer Study, which were conducted from 1996 to 2006 in urban Shanghai and recruited 5,575 breast cancer patients. In this independent Asian breast cancer population, the UACA locus was modestly associated with OS in the overall population (HR = 1.18, P = 0.012), and more significantly in 1,289 SBCSS patients who received anthracyclines (HR = 1.66, P = 1.55 x 10-4). This is the first human study suggesting the Par-4 pathway affects breast cancer patient survival with UACA a key modulator of treatment outcomes by anti-Her2 therapy and doxorubicin. Our findings suggest a path toward new predictive pharmacogenetic markers for personalized medicine targeting the Par-4 pathway for breast cancer treatment. Citation Format: Lawrence H Kushi, Qianqian Zhu, Emily Schultz, Jirong Long, Janise M Roh, Emily Valice, Cecile A Laurent, Li Yan, Isaac J Ergas, Warren Davis, Dilrini K Ranatunga, Marilyn L Kwan, Ping-Ping Bao, Wei Zheng, Xiao-Ou Shu, Christine B Ambrosone, Song Yao. Genome-wide association study identifies UACA as a modulator of breast cancer chemoresistance and survival [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr GS2-05.

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 ($$P = 1.27 \times 10^{ - 9}$$ P = 1.27 × 1 0 − 9 ). This association was confirmed in meta-analysis across four independent prospective breast cancer cohorts (combined hazard ratio = 1.84, $$P = 1.28 \times 10^{ - 11}$$ P = 1.28 × 1 0 − 11 ). Transcriptome-wide association study revealed higher UACA gene expression was significantly associated with worse OS ($$P = 4.68 \times 10^{ - 7}$$ P = 4.68 × 1 0 − 7 ). 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.

INTRODUCTION AND OBJECTIVE:Even though non-muscle invasive bladder cancer (NMIBC) has high costs care, the patient-level impact of this cost (“financial toxicity”) has been understudied. We describ...

PURPOSE: To identify distinct diet trajectories after breast cancer (BC) diagnosis, and to examine characteristics associated with diet trajectories. METHODS: We analyzed 2,865 Pathways Study participants who completed ≥2 food frequency questionnaires at the time of BC diagnosis (baseline), and 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 40% of calories from fat). While most survivors consumed

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.

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.

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 3,000 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

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: The U.S. Hispanic/Latino population is heterogeneous both socioculturally and by the proportion of European, Indigenous American, and African ancestry of the regions from which individuals originate. A previous study reported that genetic ancestry was associated with breast cancer survival among Latinas, independent of sociodemographic and tumor characteristics, suggesting that a genetic factor associated with ancestry may affect breast cancer survival. Methods: We evaluated the association of genetic ancestry with breast cancer outcomes among 506 Latina women with invasive breast cancer in the Pathways Study, a cohort study within Kaiser Permanente, an integrated health care delivery system. Proportional hazards models were used to assess the effect of ancestry on breast cancer recurrence (53 events), breast cancer–specific mortality (31 events) and all-cause mortality (54 events), with a mean follow-up time of 6 years. Results: Indigenous American ancestry was not associated with breast cancer recurrence [HR = 1.00 per 10% increase; 95% confidence interval (CI), 0.86–1.16], breast cancer mortality (HR = 0.95; 95% CI, 0.77–1.17), or all-cause mortality (HR = 0.93; 95% CI, 0.80–1.08). Adjustment for sociodemographic variables, tumor characteristics, and treatment did not alter the associations. Conclusions: Our results suggest that previously reported differences in breast cancer survival by genetic ancestry may be overcome by improving health care access and/or quality. Impact: Improving health care access and quality may reduce breast cancer disparities among U.S. Latinas. Cancer Epidemiol Biomarkers Prev; 26(9); 1466–9. ©2017 AACR.

PURPOSE: Bladder cancer is one of the top five cancers diagnosed in the U.S. with a high recurrence rate, and also one of the most expensive cancers to treat over the life-course. However, there are few observational, prospective studies of bladder cancer survivors. METHODS: The Bladder Cancer Epidemiology, Wellness, and Lifestyle Study (Be-Well Study) is a National Cancer Institute-funded, multi-center prospective cohort study of non-muscle invasive bladder cancer (NMIBC) patients (Stage Ta, T1, Tis) enrolled from the Kaiser Permanente Northern California (KPNC) and Southern California (KPSC) health care systems, with genotyping and biomarker assays performed at Roswell Park Comprehensive Cancer Center. The goal is to investigate diet and lifestyle factors in recurrence and progression of NMIBC, with genetic profiles considered, and to build a resource for future NMIBC studies. RESULTS: Recruitment began in February 2015. As of June 30, 2018, 1,281 patients completed the baseline interview (774 KPNC, 511 KPSC) with a recruitment rate of 54%, of whom 77% were male and 23% female, and 80% White, 6% Black, 8% Hispanic, 5% Asian, and 2% other race/ethnicity. Most patients were diagnosed with Ta (69%) or T1 (27%) tumors. Urine and blood specimens were collected from 67% and 73% of consented patients at baseline, respectively. To date, 599 and 261 patients have completed the 12- and 24-month follow-up questionnaires, respectively, with additional urine and saliva collection. CONCLUSIONS: The Be-Well Study will be able to answer novel questions related to diet, other lifestyle, and genetic factors and their relationship to recurrence and progression among early-stage bladder cancer patients.

Breast cancer-related lymphedema (BCRL) is a serious chronic condition after breast cancer (BC) surgery and treatment. It is unclear if BCRL risk varies by race/ethnicity. In a multiethnic prospective cohort study of 2953 BC patients, we examined the association of self-reported BCRL status with self-reported race/ethnicity and estimated genetic ancestry. Hazard ratios (HR) and 95 % confidence intervals (CI) were calculated by multivariable Cox proportional hazards models, with follow-up starting 6 months post-BC diagnosis. Estimates were further stratified by body mass index (BMI). By 48 months of follow-up, 342 (11.6 %) women reported having BCRL. Younger age at BC diagnosis, higher BMI at baseline, and lower physical activity were associated with greater BCRL risk. African American (AA) women had a 2-fold increased risk of BCRL compared with White women (HR = 2.04; 95 % CI 1.35–3.08). African genetic ancestry was also associated with an increased risk (HR = 2.50; 95 % CI 1.43, 4.36). Both risks were attenuated but remained elevated after adjusting for known risk factors and became more pronounced when restricted to the nonobese women (adjusted HR = 2.31 for AA and HR = 3.70 for African ancestry, both p < 0.05). There was also evidence of increased BCRL risk with Hispanic ethnicity in the nonobese women. Nonobese AA women had a higher risk of BCRL than White women, which cannot be fully explained by known risk factors. This is the first large-scale, prospective study demonstrating differences in BCRL risk according to race/ethnicity as assessed by both self-report and genetic ancestry data, with a potential ancestry–obesity interaction.

Objective To examine intravesical chemotherapy (IVC) use according to non–muscle-invasive bladder cancer patient disease risk, and the contributions of multilevel factors to variation in proficient use among patients with low-intermediate disease. Methods This study included 988 patients diagnosed with non–muscle-invasive bladder cancer in an integrated health system in Northern California from 2015-2017. We calculated IVC receipt by disease risk, and among patients with low-intermediate risk disease, assessed the relationship between multilevel factors and IVC receipt using a logistic regression model with random intercepts for provider and service area, and patient-, provider-, and service area-level fixed effects. We further assessed the association of provider- and service area-level factors with IVC use by examining intraclass correlation coefficients. Results Similar proportions of low-intermediate (36%) and high-risk (34%) patients received IVC. In the multivariate analysis, including low-intermediate risk patients, service area volume was strongly and statistically significantly associated with IVC use (adjusted odds ratio, high- vs low-volume: 0.08, 95% Confidence Interval: 0.01-0.58). Provider- and service area-level intraclass correlation coefficients were large, (38%, P = .0009 and 39% P = .03, respectively) indicating that much of the variance in IVC use was explained by factors at these levels. Conclusion Our findings highlight opportunities to improve proficient use of IVC. Future research should assess provider- and practice-level barriers to IVC use among low-intermediate risk patients.

PurposeRacial/ethnic differences in cancer symptom burden are well documented, but limited research has evaluated modifiable factors underlying these differences. Our objective was to examine the role of patient-provider interactions to help explain the relationship between race/ethnicity and cancer-specific physical well-being (PWB) among women with breast cancer.MethodsThe Pathways Study is a prospective cohort study of 4505 women diagnosed with breast cancer at Kaiser Permanente Northern California between 2006 and 2013. Our analysis included white, black, Hispanic, and Asian participants who completed baseline assessments of PWB, measured using the Functional Assessment of Cancer Therapy for Breast Cancer, and patient-provider interactions, measured by the Interpersonal Processes of Care Survey (IPC) (N = 4002). Using step-wise linear regression, we examined associations of race/ethnicity with PWB, and changes in associations when IPC domains were added.ResultsWe observed racial/ethnic differences in PWB, with minorities reporting lower scores than whites (beta, black: - 1.79; beta, Hispanic: - 1.92; beta, Asian: - 1.68; p

PURPOSE: We evaluated associations between personal and clinical social support and nonadherence to adjuvant endocrine therapy (AET) in a large, Northern California breast cancer (BC) cohort from an integrated healthcare network. METHODS: This study included 3,382 women from the Pathways Study diagnosed from 2005–2013 with stages I–III hormone receptor-positive BC and who responded to the Medical Outcomes Study Social Support and Interpersonal Processes of Care surveys, approximately two months post-diagnosis. We used logistic regression to evaluate associations between tertiles of social support and noninitiation (

Background: Whole-exome sequencing (WES) has recently emerged as an appealing approach to systematically study coding variants. However, the requirement for a large amount of high-quality DNA poses a barrier that may limit its application in large cancer epidemiologic studies. We evaluated the performance of WES with low input amount and saliva DNA as an alternative source material. Methods: Five breast cancer patients were randomly selected from the Pathways Study. From each patient, four samples, including 3 μg, 1 μg, and 0.2 μg blood DNA and 1 μg saliva DNA, were aliquoted for library preparation using the Agilent SureSelect Kit and sequencing using Illumina HiSeq2500. Quality metrics of sequencing and variant calling, as well as concordance of variant calls from the whole exome and 21 known breast cancer genes, were assessed by input amount and DNA source. Results: There was little difference by input amount or DNA source on the quality of sequencing and variant calling. The concordance rate was about 98% for single-nucleotide variant calls and 83% to 86% for short insertion/deletion calls. For the 21 known breast cancer genes, WES based on low input amount and saliva DNA identified the same set variants in samples from a same patient. Conclusions: Low DNA input amount, as well as saliva DNA, can be used to generate WES data of satisfactory quality. Impact: Our findings support the expansion of WES applications in cancer epidemiologic studies where only low DNA amount or saliva samples are available. Cancer Epidemiol Biomarkers Prev; 24(8); 1207–13. ©2015 AACR.

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.

We examined mechanisms through which social relationships influence quality of life (QOL) in breast cancer survivors. This study included 3,139 women from the Pathways Study who were diagnosed with breast cancer from 2006 to 2011 and provided data on social networks (the presence of a spouse or intimate partner, religious/social ties, volunteering, and numbers of close friends and relatives), social support (tangible support, emotional/informational support, affection, positive social interaction), and QOL, measured by the FACT-B, approximately 2 months post diagnosis. We used logistic models to evaluate associations between social network size, social support, and lower versus higher than median QOL scores. We further stratified by stage at diagnosis and treatment. In multivariate-adjusted analyses, women who were characterized as socially isolated had significantly lower FACT-B (OR = 2.18, 95 % CI: 1.72-2.77), physical well-being (WB) (OR = 1.61, 95 % CI: 1.27-2.03), functional WB (OR = 2.08, 95 % CI: 1.65-2.63), social WB (OR = 3.46, 95 % CI: 2.73-4.39), and emotional WB (OR = 1.67, 95 % CI: 1.33-2.11) scores and higher breast cancer symptoms (OR = 1.48, 95 % CI: 1.18-1.87) compared with socially integrated women. Each social network member independently predicted higher QOL. Simultaneous adjustment for social networks and social support partially attenuated associations between social networks and QOL. The strongest mediator and type of social support that was most predictive of QOL outcomes was "positive social interaction." However, each type of support was important depending on outcome, stage, and treatment status. Larger social networks and greater social support were related to higher QOL after a diagnosis of breast cancer. Effective social support interventions need to evolve beyond social-emotional interventions and need to account for disease severity and treatment status.

Background Breast cancer survivors are less likely to be employed than similar healthy women, yet effects of employment on the well being of survivors are largely unknown. In a prospective cohort study of 2013 women diagnosed from 2006 to 2011 with invasive breast cancer in Kaiser Permanente Northern California, we describe associations between hours worked per week and change in employment with quality of life (QOL) from diagnosis through active treatment. Methods Participants completed information on employment status and QOL approximately 2 and 8 months post-diagnosis. QOL was assessed by the Functional Assessment of Cancer Therapy—Breast Cancer. Multivariable linear regression models were adjusted for potential confounders including demographic, diagnostic, and medical care factors to examine associations between employment and QOL. Results At baseline, overall well being was higher for women who worked at least some hours per week compared with women who were not working. Women working 1–19 h/week at baseline also had higher functional well being compared with women who were not working. There was a significant, positive association between hours worked per week and physical and social well being. At the 6-month follow-up, women working at least 20 h/week had higher physical and functional well being than those who were not working. Lower scores for physical and functional well being were observed among women who stopped working during the 6-month follow-up period. Conclusions Continuing to work after a breast cancer diagnosis may be beneficial to multiple areas of QOL. Strategies to help women continue working through treatment should be explored. Copyright © 2012 John Wiley & Sons, Ltd.

Physical activity offers many benefits to breast cancer survivors, yet research on physical activity during the immediate period following a breast cancer diagnosis is limited. In a prospective cohort study of 1,696 women diagnosed with invasive breast cancer in the Kaiser Permanente Northern California Medical Care Program from 2006–2009, we describe change in self-reported physical activity levels from around diagnosis to six months post-diagnosis and determine factors associated with change. Participants completed a comprehensive physical activity questionnaire at baseline (2 months post-diagnosis) and at follow-up (8 months post-diagnosis). Predictors of physical activity change were determined by multivariable linear regression. Reductions in all physical activity levels were observed (P

In the U.S., women of European ancestry have historically had the highest incidence of breast cancer compared to other major race/ethnicity groups. In recent years, the incidence rate for black women has approached that of white women, while rates for Asian and Hispanic women are about 25% lower than for white or black women. However, once diagnosed with breast cancer, black women have poorer survival rates than white women. The most recent “Annual Report to the Nation on the Status of Cancer” using nationwide cancer-registry data from 2006-2013 (Jemal et al., JNCI, 2017) reported a higher age- and stage-adjusted relative mortality risk after breast cancer of 1.71 (95% confidence interval (CI), 1.66-1.76) for non-Hispanic blacks compared to non-Hispanic whites. Hispanic women also experienced a slightly increased relative mortality risk of 1.14 (95% CI, 1.10-1.18) compared to white women, while Asians experienced a lower relative mortality risk of 0.84 (95% CI, 0.80-0.88). The reasons for such disparities in outcomes after breast cancer are complex. One suggested contributing factor is differences in access to care, as blacks and Hispanics tend to be of lower socioeconomic status than whites or Asians. It is possible to minimize the effects of access to health care by examining outcomes after breast cancer diagnosis in an integrated health care setting such as Kaiser Permanente Northern California (KPNC), in which all patients have health insurance coverage with access to the same health care providers. We are currently conducting the Pathways Study, a prospective cohort study of 4,505 women diagnosed with breast cancer with enrollment from 2006-2013. This diverse cohort includes 557 Hispanics, 578 Asians, and 358 blacks. Preliminary analyses in the larger population of 11,176 women who were diagnosed with invasive breast cancer in KPNC and eligible for the Pathways Study found that, despite the uniform health care access, racial disparities in mortality after breast cancer were qualitatively similar to those observed nationally. With 1,738 total deaths as of September 20, 2016, and adjusted for age and stage at diagnosis, compared to white women, black women had an increased relative mortality risk of 1.59 (95% CI, 1.24-2.03). For Hispanic women, the relative risk was 0.92 (95% CI, 0.72-1.19), and for Asians it was 0.70 (95% CI, 0.51-0.97). Among the subset of women enrolled in the Pathways Study (n=538 total deaths), comparable relative risks were 1.74 (95% CI, 1.35-2.24) for black women, 0.99 (95% CI, 0.75-1.29) for Hispanic women, and 0.73 (95% CI, 0.52-1.02) for Asians. Similar black-white differences were also seen for breast cancer-specific mortality and recurrence in the Pathways Study cohort in which recurrences are being documented. These observations indicate that health care access is unlikely to explain racial/ethnic disparities in breast cancer outcomes. As the Pathways Study, we will be able to explore aspects of health care utilization, such as treatment-related factors such as treatment delay, adherence, and early discontinuation. We will also be able to explore presence of comorbid conditions or use of non-cancer medications that may influence mortality and breast cancer outcomes. In the Pathways Study, we are collecting data on lifestyle and psychosocial factors (e.g., food intake, physical activity, social support, doctor-patient communications, and quality of life); linking to geospatial databases to characterize the social and built environment of cohort members; and conducting genome-wide assays. For example, in preliminary analyses that adjusted additionally for estrogen receptor status, body mass index, educational attainment, and physical activity, black-white differences in mortality persisted even though they were somewhat attenuated (relative risk of 1.43; 95% CI, 1.09-1.86). Along with other studies that are examining breast cancer outcomes in different populations, the Pathways Study is poised to contribute to better understanding of the persistent black-white differences in mortality after breast cancer, and thus identify avenues to improve outcomes for all women with breast cancer. Citation Format: Lawrence H. Kushi, Isaac J. Ergas, Janise M. Roh, Scarlett Lin Gomez, Marilyn L. Kwan, Catherine Thomsen, Song Yao, Christine B. Ambrosone. Disparities in breast cancer survivorship and outcomes [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr IA27.

Few studies have assessed quality of life (QOL) of women diagnosed with breast cancer within the first few weeks of their initial diagnosis. We describe QOL among 950 women recently diagnosed with invasive breast cancer. Starting in January 2006, we invited women agedor =21 years who were diagnosed with first primary invasive breast cancer within Kaiser Permanente Northern California (KPNC) to enroll in the Pathways Study, a prospective study of breast cancer survivorship. QOL was measured using the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B), along with sociodemographic and social support information. Clinical characteristics were obtained from the KPNC cancer registry and electronic medical record. We used multivariable linear regression models to identify factors associated with QOL scores calculated from the FACT-B. The mean age +/- SD of the sample was 59.6 years (+/-11.9 years), and the mean time +/-SD from diagnosis until interview was 8.0 weeks (+/-3.2 weeks). Younger age at diagnosis was associated with lower scores in all QOL domains (P0.01), and later stage at diagnosis was associated with lower scores in all domains (P0.05) except for social well-being. Higher levels of social support were associated with higher QOL except for physical well-being (P0.05). These associations were stronger within 2 months of breast cancer diagnosis. Quality of life as influenced by a diagnosis of breast cancer is an important factor in cancer survivorship. Age, stage at diagnosis, and social support are key factors in this important variable.

Many women use complementary and alternative medicine (CAM) to maintain or improve their health. We describe CAM use among the first 1,000 participants enrolled in the Pathways Study, an ongoing prospective cohort study of women diagnosed with breast cancer (BC). Participants, identified by rapid case ascertainment in Kaiser Permanente Northern California, are women > or = 21 years diagnosed with first invasive BC. Comprehensive baseline data are collected on CAM use through in-person interviews. Study participants include 70.9% non-Hispanic whites, 10.2% Hispanics, 9.0% Asians, 6.5% African-Americans, and 3.4% others. Most women (82.2%) were diagnosed with AJCC stage I/II BC at average (+/-SD) age 59.5 (+/-12.0) years and reported prior use of at least one form of CAM (96.5% of participants). In the 5 years before diagnosis, CAM therapies used at least weekly by >20% of women included green tea, glucosamine, omega-3 fatty acids, prayer and religion. CAM use was high (86.1% of participants) in the period immediately following diagnosis; 47.5% used botanical supplements, 47.2% used other natural products, 28.8% used special diets, 64.2% used mind-body healing, and 26.5% used body/energy/other treatments. In multivariable analyses, frequent use of each CAM modality before and after diagnosis was associated with use of other CAM modalities and other health behaviors (i.e., high fruit/vegetable intake, lower BMI). CAM use before and after BC diagnosis is common in this diverse group of women. Our results emphasize the need for clinicians to discuss CAM use with all BC patients.

With 2.3 million breast cancer survivors in the US today, identification of modifiable factors associated with breast cancer recurrence and survival is increasingly important. Only recently new studies have been designed to examine the impact of lifestyle factors on prognosis, including Pathways, a prospective study of women with breast cancer in Kaiser Permanente Northern California (KPNC). Pathways aims to examine the effect on recurrence and survival of (1) lifestyle factors such as diet, physical activity, quality of life, and use of alternative therapies and (2) molecular factors such as genetic polymorphisms involved in metabolism of chemotherapeutic agents. Eligibility includes any woman diagnosed with invasive breast cancer within KPNC, no previous diagnosis of other invasive cancer, age 21 years or older, and ability to speak English, Spanish, Cantonese, or Mandarin. Newly diagnosed patients are identified daily from electronic pathology records and are enrolled within two months of diagnosis. An extensive baseline interview is conducted, blood and saliva samples are collected, and body measurements are taken. Women are followed for lifestyle updates, treatment, and outcomes by self-report and query of KPNC databases. Recruitment began in 9 January, 2006, and as of 16 January, 2008, 1,539 women have been enrolled along with collection of 1,323 blood samples (86%) and 1,398 saliva samples (91%). The Pathways Study will become a rich resource to examine behavioral and molecular factors and breast cancer prognosis.

PURPOSE: Adjuvant therapy is associated with improved survival for women with breast cancer, but not all women who could benefit initiate treatment. Women's belief systems are related to treatment initiation. It has been hypothesized that complementary and alternative (CAM) use is associated with decreased initiation of standard oncology treatments because patients may be exploring alternative treatment approaches. However, there are limited data on the association between CAM use and cancer treatment initiation. We examined the association between CAM use and initiation of adjuvant breast cancer chemotherapy in a prospective cohort of early stage breast cancer patients. PATIENTS AND METHODS: Subjects participated in a multi-center prospective cohort study of women with early stage invasive breast cancer (n=1,156). National Comprehensive Cancer Network guidelines were used to define groups based on whether chemotherapy was indicated. Three subgroups were created: chemotherapy indicated for subjects RESULTS: Current CAM use was reported by 87% of women and 38% reporting current use of ≥3 modalities. The most commonly used CAM modalities were mind body therapies (63%) and other natural products (41%). In bivariate analyses, among women CONCLUSIONS: High use of CAM was associated with decreased chemotherapy initiation among women with breast cancer for whom chemotherapy was indicated. It is important for oncologists to discuss CAM use with their patients, especially since high CAM use is associated with negative expectations and beliefs about chemotherapy. Citation Format: Greenlee H, Neugut AI, Falci L, Hillyer GC, Buono D, Roh JM, Ergas IJ, Kwan ML, Lee M, Tsai WY, Shi Z, Lamerato L, Mandelblatt JS, Kushi LH, Hershman DL. Complementary and alternative medicine use and breast cancer chemotherapy initiation: The BQUAL study. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr PD4-05.

48 Background: Prior research suggests that black patients with cancer report a greater burden of symptoms compared to white patients. Differences in patient-provider relationships may be an underlying and modifiable factor in these observed disparities. We examined differences in side effect burden by race/ethnicity and tested the hypothesis that patient-provider communication and trust may partly explain differences in symptom burden among women with breast cancer (BC). Methods: We conducted a cross-sectional analysis of data collected from 4,505 women diagnosed with BC from 2005-2013 at Kaiser Permanente Northern California. Women were asked two months post-diagnosis how much they were bothered by treatment side effects (FACT-B). Using modified Poisson regression, we assessed the association of race/ethnicity with side effect bother, adjusting for clinical characteristics, socioeconomic status (SES), and patient-provider communication and patients’ trust in providers in a step-wise fashion. Provider communication and trust were measured using the Interpersonal Processes of Care survey and a one-item assessment of patients’ trust in providers, respectively. Results: Before adjustment, Black, Hispanic, and Asian patients were at least 75% more likely than white patients to report high (vs. low) side effect bother (p < 0.0001). Bivariate associations of communication and trust with side effect bother and race/ethnicity were statistically significant. For example, patients with high (vs. low) scores for shared decision-making were more likely to be white than black (46% vs. 39%) and less likely to experience high vs. low side effect bother (10% vs. 14%, p < 0.0001 for both comparisons). However, after adjusting for clinical and SES characteristics in a multivariable analysis, the addition of patient-provider communication and trust to the model did not substantially alter disparity estimates. Conclusions: In our sample, patient-provider communication did not modify racial disparities in side effect bother. Further research is needed to explore additional modifiable factors underlying potential disparities in side effect management.

e13097 Background: Use of complementary and alternative medicine (CAM) has been associated with initiation of breast cancer chemotherapy.We examined the association of CAM use with initiation of hormonal therapy in women with hormone receptor-positive (HR+) breast cancer. Methods: In aprospective cohort study designed to examine predictors of breast cancer treatment initiation and adherence, 699 women with non-metastatic stage I-III breast cancer and aged < 70 years were recruited from Kaiser Permanente Northern California during 2006-2010. Baseline interviews assessed current use of five CAM modalities (dietary supplements: vitamins/minerals, herbs/botanicals, other natural products; mind/body therapies: mind-body self-practice, mind-body practitioner-based). Based on electronic pharmacy records, hormonal therapy initiation was defined as ≥2 prescriptions of ≥30 pills of any hormonal therapy drug within 1 year after diagnosis. Multivariable logistic regression analysis examined a priori hypotheses testing whether current CAM use was associated with hormonal therapy initiation, adjusted for demographic, tumor characteristics, and cancer treatment. Results: Of the 699 participants,552 were diagnosed with HR+ breast cancer. Among the 552 women with HR+ breast cancer, 494 (89%) used at least 1 modality of CAM, 414 (76%) used dietary supplements, and 391 (71%) used mind/body therapies. Within 1 year after diagnosis, 481 (87%) participants initiated hormonal therapy. The rate of initiation was comparable between CAM users and non-users (87% vs. 86%). In multivariable analyses, baseline overall CAM use was not associated with initiation of hormonal therapy. However, vitamins/minerals users were more likely to initiate hormonal therapy compared to non-users (OR = 1.87, 95% CI: 1.04, 3.51). Conclusions: CAM use was high among early stage HR+ breast cancer patients. Overall, use of CAM was not associated with hormonal therapy initiation. Current use of vitamins/minerals was associated with higher initiation rate of hormonal chemotherapy.

Importance There are long-standing interests in the potential benefits of vitamin D for preventing breast cancer recurrence and mortality, yet data from prospective cohort studies are limited. Objective To investigate a serum biomarker of vitamin D status, 25-hydroxyvitamin D (25OHD) measured at the time of breast cancer diagnosis, to determine the association with prognosis. Design, Setting, and Participants The Pathways Study is a prospective cohort study of breast cancer survivors established in 2006. Enrollment was completed in 2013; follow-up is ongoing. The cohort was established in Kaiser Permanente Northern California, a large integrated health care delivery system in northern California. Women with a diagnosis of incident invasive breast cancer were typically consented and enrolled within 2 months of diagnosis. The overall enrollment rate was 46% (4505 of 9820). Participants are followed for health outcomes and comorbidities at 12, 24, 48, 72, and 96 months after baseline interview. A case-cohort design was used for efficiency assay of 25OHD, selecting 1666 cohort members with serum samples and ensuring representation in the subcohort of races and clinical subtypes. The data analysis was performed from January 5, 2014, to March 15, 2015. Main Outcomes and Measures Primary outcomes are breast cancer recurrence, second primary cancer, and death. Results Mean (SD) age was 58.7 (12.4) years. Serum 25OHD concentrations were lower in women with advanced-stage tumors, and the lowest in premenopausal women with triple-negative cancer. Levels were also inversely associated with hazards of disease progression and death. Compared with the lowest tertile, women with the highest tertile of 25OHD levels had superior overall survival (OS). This association remained after adjustment for clinical prognostic factors (hazard ratio [HR], 0.72; 95% CI, 0.54-0.98). Among premenopausal women, the association with OS was stronger, and there were also associations with breast cancer–specific survival and invasive disease–free survival (OS: HR, 0.45; 95% CI, 0.21-0.96; breast cancer–specific survival: HR, 0.37; 95% CI, 0.15-0.93; invasive disease–free survival: HR, 0.58; 95% CI, 0.34-1.01; all after full adjustment). Conclusions and Relevance Serum 25OHD levels were independently associated with breast cancer prognostic characteristics and patient prognosis, most prominently among premenopausal women. Our findings from a large, well-characterized prospective cohort provide compelling observational evidence on associations of vitamin D with lower risk of breast cancer morbidity and mortality.

Background/Aims With over 2.5 million breast cancer survivors in the U.S. today, identification of modifiable factors associated with recurrence and survival is imperative. The Pathways Study, a prospective study of breast cancer survivors in Kaiser Permanente Northern California (KPNC) is examining the effects of lifestyle (e.g., diet, physical activity, complementary and alternative medicine [CAM]), contextual (e.g., social and built environment characteristics), medical care, and genetic and molecular factors on breast cancer prognosis.

Few studies have explored how patient-physician interactions influence patients' quality of life (QOL). In a prospective cohort study of 1,855 women diagnosed with invasive breast cancer in the Kaiser Permanente Northern California Medical Care Program from 2006 to 2011, we examined associations between patient-physician interactions during cancer treatment and QOL, overall and by racial/ethnic group. Participants completed the interpersonal processes of care (IPC) survey at approximately 8 months post-diagnosis to assess specific domains of the patient-physician interaction during the months after cancer diagnosis. Domains included: compassion, elicited concerns, explained results, decided together, lack of clarity, discrimination due to race/ethnicity, and disrespectful office staff. The functional assessment of cancer therapy-breast cancer was completed concurrently to measure QOL. Linear regression models examined the association of IPC with QOL, first adjusting for patient covariates including age, race, clinical factors, and psychosocial measures and then for physician characteristics such as age, sex, race/ethnicity, and specialty. For all participants (n = 1,855), IPC scores suggesting greater lack of clarity, discrimination due to race/ethnicity, and disrespectful office staff in patient-physician interactions were associated with lower QOL (P< 0.01). IPC scores suggesting physicians demonstrating compassion, eliciting concerns, or explaining results were associated with higher QOL (P< 0.01). Among Whites (n = 1,306), only the associations with higher QOL remained. African Americans (n = 110) who reported higher scores on physician compassion and elicited concerns had higher QOL, whereas higher scores for disrespectful office staff had lower QOL. No associations were observed among Asians (n = 201) and Hispanics (n = 186). After further adjustment for physician factors, the associations among Whites remained, whereas those among African Americans disappeared. In the breast cancer treatment setting, characteristics of the patient-physician interaction as perceived by the patient are associated with QOL, yet were not specific to patient race/ethnicity.

Background Lifestyle factors may be associated with chemotherapy-induced peripheral neuropathy (CIPN). We examined associations between body mass index (BMI) and lifestyle factors with CIPN in the Pathways Study, a prospective cohort of women with invasive breast cancer. Methods Analyses included 1237 women who received taxane treatment and provided data on neurotoxicity symptoms. Baseline interviews assessed BMI (normal: 5 hours/week) and fruit/vegetable intake (low

Importance Not all women initiate clinically indicated breast cancer adjuvant treatment. It is important for clinicians to identify women at risk for noninitiation. Objective To determine whether complementary and alternative medicine (CAM) use is associated with decreased breast cancer chemotherapy initiation. Design, Setting, and Participants In this multisite prospective cohort study (the Breast Cancer Quality of Care [BQUAL] study) designed to examine predictors of breast cancer treatment initiation and adherence, 685 women younger than 70 years with nonmetastatic invasive breast cancer were recruited from Columbia University Medical Center, Kaiser Permanente Northern California, and Henry Ford Health System and enrolled between May 2006 and July 31, 2010. Overall, 306 patients (45%) were clinically indicated to receive chemotherapy per National Comprehensive Cancer Network guidelines. Participants were followed for up to 12 months. Exposures Baseline interviews assessed current use of 5 CAM modalities (vitamins and/or minerals, herbs and/or botanicals, other natural products, mind-body self-practice, mind-body practitioner-based practice). CAM use definitions included any use, dietary supplement use, mind-body use, and a CAM index summing the 5 modalities. Main Outcomes and Measures Chemotherapy initiation was assessed via self-report up to 12 months after baseline. Multivariable logistic regression models examined a priori hypotheses testing whether CAM use was associated with chemotherapy initiation, adjusting for demographic and clinical covariates, and delineating groups by age and chemotherapy indication. Results A cohort of 685 women younger than 70 years (mean age, 59 years; median age, 59 years) with nonmetastatic invasive breast cancer were recruited and followed for up to 12 months to examine predictors of breast cancer treatment initiation. Baseline CAM use was reported by 598 women (87%). Chemotherapy was initiated by 272 women (89%) for whom chemotherapy was indicated, compared with 135 women (36%) for whom chemotherapy was discretionary. Among women for whom chemotherapy was indicated, dietary supplement users and women with high CAM index scores were less likely than nonusers to initiate chemotherapy (odds ratio [OR], 0.16; 95% CI, 0.03-0.51; and OR per unit, 0.64; 95% CI, 0.46-0.87, respectively). Use of mind-body practices was not related to chemotherapy initiation (OR, 1.45; 95% CI, 0.57-3.59). There was no association between CAM use and chemotherapy initiation among women for whom chemotherapy was discretionary. Conclusions and Relevance CAM use was high among patients with early-stage breast cancer enrolled in a multisite prospective cohort study. Current dietary supplement use and higher number of CAM modalities used but not mind-body practices were associated with decreased initiation of clinically indicated chemotherapy. Oncologists should consider discussing CAM with their patients during the chemotherapy decision-making process.

Background: Bladder cancer is one of the top 10 incident cancers. Most cases (75%) are diagnosed as non-muscle invasive disease (NMID), yet NMID typically recurs (70%) and a subset (25%) progresses to muscle-invasive disease. The Be-Well Study is an NCI-funded collaborative, multi-center prospective cohort study, with NMID bladder cancer patients enrolled at Kaiser Permanente Northern (KPNC) and Southern California (KPSC) and bioassays performed at Roswell Park Cancer Institute (RPCI). The goal is to examine diet and lifestyle factors and prognosis, with an emphasis on cruciferous vegetable (CV) intake and their unique isothiocyanate (ITC) content, the modifying effect of polymorphisms of ITC-metabolizing genes, and interactions with treatment. Our prior work suggests that dietary ITCs may prevent disease recurrence and progression in NMID patients. Methods: Newly-diagnosed patients with NMID (Ta, Tis, T1), who are English-speaking, KP members, and ≥21 years of age, are ascertained rapidly from electronic pathology reports and enrolled on average 2.6 months post-diagnosis. Baseline participation consists of a telephone interview including a food frequency questionnaire focused on CV intake, and providing blood and urine samples. Patients will be contacted for follow-up interviews and urine samples at 12 and 24 months. Smoking, medication use, occupational exposures, physical activity, quality of life, and urinary function are also queried. Biospecimens are processed and assayed at RPCI. Strong support for Be-Well by KP urologists will promote dissemination of study results in patient care and recommendations. Results: Recruitment began in February 2015. To date, 222 patients have completed the baseline interview, representing 78% male and 22% female, and 81% White, 7% Black, 5% Hispanic, 3% Asian, and 4% Other. Urine specimens have been collected from 82% of consented patients. Blood specimens have been collected from 85% of KPNC patients, and collection at KPSC began in November 2015. The 12-month follow-up interview and outcome ascertainment for disease recurrence and progression are scheduled to begin in February 2016. Conclusions: The Be-Well Study is poised to be the largest and most comprehensive study to answer critical questions related to prognosis, quality of life, and care in patients diagnosed with early-stage bladder cancer. Citation Format: Marilyn L. Kwan, Lawrence H. Kushi, Virginia P. Quinn, Nirupa R. Ghai, Janise M. Roh, Tracy Becerra, Adriana Martinez, Kimberly L. Cannavale, Alexander S. Carruth, Valerie S. Lee, Isaac J. Ergas, Ronald K. Loo, David S. Aaronson, Yuesheng Zhang, Christine B. Ambrosone, Li Tang. Identifying lifestyle and genetic factors to prevent recurrence of non-muscle invasive bladder cancer in a prospective cohort study at Kaiser Permanente (The Be-Well Study). [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3415.

10002Background: We examined associations of body mass index (BMI) and lifestyle factors with chemotherapy-induced peripheral neuropathy (CIPN) in the Pathways Study, a prospective cohort study of ...

e296 Background: Bladder cancer is one of the top 10 incident cancers. Most cases (75%) are diagnosed as non-muscle invasive disease (NMID), yet NMID typically recurs (70%) and a subset (25%) progresses to muscle-invasive disease. Be-Well is a 5-year, NCI-funded prospective cohort study of NMID bladder cancer patients at Kaiser Permanente Northern (KPNC) and Southern California (KPSC). The goal is to examine diet and lifestyle factors and prognosis, with an emphasis on cruciferous vegetable (CV) intake and their unique isothiocyanate (ITC) content, the modifying effect of polymorphisms of ITC-metabolizing genes, and interactions with treatment. Our prior work suggests that dietary ITCs may prevent disease recurrence and progression in NMID patients. Methods: Newly-diagnosed patients with NMID (Ta, Tis, T1), who are English-speaking, KP members, and ≥ 21 years of age, are rapidly ascertained from electronic pathology reports and enrolled on average 2.6 months post-diagnosis. Baseline participation consists of a telephone interview including a food frequency questionnaire focused on CV intake, and providing blood and urine samples. Patients will be contacted for follow-up interviews and urine samples at 12 and 24 months. Smoking, medication use, occupational exposures, physical activity, quality of life, and urinary function are also queried. Biospecimens are processed and assayed at Roswell Park Cancer Institute. Strong support for Be-Well by KP urologists will promote dissemination of study results in patient care and recommendations. Results: Recruitment began in February 2015. To date, 159 patients have completed the baseline interview, representing 76% male and 24% female, and 80% White, 8% Black, 6% Hispanic, 3% Asian, and 3% Other. Urine specimens have been collected from 87% of consented patients. Blood specimens have been collected from 87% of KPNC patients, with collection at KPSC to begin in Fall 2015. Conclusions: The Be-Well Study is poised to be the largest and most comprehensive study to answer critical questions related to prognosis, quality of life, and care in patients diagnosed with early-stage bladder cancer.

Physical activity can improve quality of life (QOL) in breast cancer survivors but little is known about associations of physical activity and QOL during active cancer therapy. We examine associations between activity levels and QOL in a large cohort of breast cancer patients. Women with invasive, non-metastatic breast cancer (n = 2,279) were enrolled between 2006 and 2009 from a managed care organization; assessment were done during active therapy. A physical activity frequency questionnaire was used to calculate the average weekly metabolic equivalent task (MET) hours spent in moderate and vigorous activity during active treatment. QOL was measured by the Functional Assessment of Cancer Therapy-Breast Cancer. Linear regression models tested cross-sectional associations of QOL and functional well-being with physical activity and covariates [socio-demographics, comorbidity, body mass index (BMI), clinical variables, social support, and assessment timing]. Physical activity had a significant positive unadjusted association with all QOL sub-scales (except emotional well-being) (all P values < 0.01). Overall QOL was 4.6 points higher for women in the highest quartile of moderate and vigorous activity versus women in the lowest quartile (P < 0.001). In regression models, higher activity was associated with better overall QOL and functional well-being, controlling for covariates (P < 0.05). Increasing BMI was also independently but inversely associated with overall QOL (P < 0.001) but did not explain the relationship of activity and QOL. White women reported the higher levels of activity than minority women and activity was associated with QOL for Whites but not for minority women. Greater physical activity is associated with small but clinically meaningful increases in QOL during active breast cancer care therapy for Whites but this effect is not seen for minority women. If confirmed in longitudinal analyses, these differences may have implications for disparities research.