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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: 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.)

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.)

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.)

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 30 June 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.

Purpose: We assessed bone mineral density (BMD) change with aromatase inhibitor (AI) treatment in a contemporary cohort of women with breast cancer treated in Kaiser Permanente Northern California., Methods: Percent and estimated annual percent changes in BMD at the total hip and lumbar spine were examined in 676 women receiving AI therapy who had two serial BMD reports available (at least 1 year apart) before and after AI initiation (N = 317) or during continued AI therapy (N = 359). BMD changes were examined at the total hip and lumbar spine and compared by age and clinical subgroups., Results: Women experienced BMD declines after AI initiation or continued therapy, with median annual percent change - 1.2% (interquartile range, IQR - 2.4 to - 0.1%) at the hip and - 1.0% (IQR - 2.3 to 0.1%) at the spine after AI initiation, and - 1.1% (IQR - 2.4 to 0.1%) at the hip and - 0.9% (IQR - 2.4 to 0.5%) at the spine during continued therapy. Higher levels of bone loss were observed among younger (< 55 years) compared with older (≥ 75 years) women at the hip (- 1.6% vs. - 0.8%) and at the spine (- 1.5% vs. - 0.5%) after AI initiation, and at the hip (- 1.4% vs. - 1.2%) and at the spine (- 2.4% vs. - 0.001%) during continued therapy., Conclusions: Small but consistent declines in total hip and lumbar spine BMD were present in breast cancer patients following AI therapy initiation or continued AI therapy. Although the overall rates of osteoporosis were low, greater estimated levels of annual bone loss were evident among women < 55 years.

Purpose: National guidelines encourage counseling high-risk women about pharmacologic breast cancer risk reduction. We evaluated the use of integrated health care data to identify and characterize breast cancer chemoprevention use. Chemoprevention included US Food and Drug Administration-approved use of tamoxifen and raloxifene and off-label use of aromatase inhibitors (AIs)., Patients and Methods: Using electronic medical and pharmacy records (EMRs) in the Kaiser Permanente Northern California health care system, we sampled cancer-free women age 35 to 69 years who used tamoxifen, raloxifene, exemestane, anastrozole, or letrozole from 2005 to 2013. Risk-benefit profiles were calculated for tamoxifen and raloxifene using published indices. The proportion of days covered was calculated from pharmacy records to assess adherence., Results: Among 90 chemoprevention users (confirmed with EMR review from a sample of 371 women), 74% used tamoxifen, 11% used raloxifene, and 13% used an AI. For tamoxifen and raloxifene users, the risk-benefit index indicated 23% of women had insufficient evidence that benefits would outweigh risks. For all agents, adherence decreased from an average proportion of days covered of 75% at 1 year to 67% at 5 years. Automated EMR searches identified breast cancer chemoprevention users with 60% positive predictive value overall and 75% for tamoxifen after post hoc modifications., Conclusion: Our study contributes to an emerging picture of breast cancer chemoprevention use in real-world settings, where evidence of net benefit is not uniform and nonadherence is common. Among breast cancer chemoprevention agents, our automated selection best performed for tamoxifen use. We also identified off-label use of AIs for chemoprevention, suggesting that expansion of risk-benefit indices to include AIs is warranted.

Purpose: To compare information from self-report and electronic medical records for four common comorbidities (diabetes, hypertension, myocardial infarction, and other heart diseases)., Methods: We pooled data from two multiethnic studies (one case-control and one survivor cohort) enrolling 1,936 women diagnosed with breast cancer, who were members of Kaiser Permanente Northern California., Results: Concordance varied by comorbidity; kappa values ranged from 0.50 for other heart diseases to 0.87 for diabetes. Sensitivities for comorbidities from self-report versus medical record were similar for racial/ethnic minorities and non-Hispanic Whites, and did not vary by age, neighborhood socioeconomic status, or education. Women with a longer history of comorbidity or who took medications for the comorbidity were more likely to report the condition. Hazard ratios for all-cause mortality were not consistently affected by source of comorbidity information; the hazard ratio was lower for diabetes, but higher for the other comorbidities when medical record versus self-report was used. Model fit was better when the medical record versus self-reported data were used., Conclusions: Comorbidities are increasingly recognized to influence the survival of patients with breast or other cancers. Potential effects of misclassification of comorbidity status should be considered in the interpretation of research results.

Recent epidemiologic evidence suggests that prediagnosis physical activity is associated with survival in women diagnosed with breast cancer. However, few data exist for racial/ethnic groups other than non-Latina whites. To examine the association between prediagnosis recreational physical activity and mortality by race/ethnicity, we pooled data from the California Breast Cancer Survivorship Consortium for 3 population-based case-control studies of breast cancer patients (n=4,608) diagnosed from 1994 to 2002 and followed up through 2010. Cox proportional hazards models provided estimates of the relative hazard ratio for mortality from all causes, breast cancer, and causes other than breast cancer associated with recent recreational physical activity (i.e., in the 10 years before diagnosis). Among 1,347 ascertained deaths, 826 (61%) were from breast cancer. Compared with women with the lowest level of recent recreational physical activity, those with the highest level had a marginally decreased risk of all-cause mortality (hazard ratio=0.88, 95% confidence interval: 0.76, 1.01) and a statistically significant decreased risk of mortality from causes other than breast cancer (hazard ratio=0.63, 95% confidence interval: 0.49, 0.80), and particularly from cardiovascular disease. No association was observed for breast cancer-specific mortality. These risk patterns did not differ by race/ethnicity (non-Latina white, African American, Latina, and Asian American). Our findings suggest that physical activity is beneficial for overall survival regardless of race/ethnicity., (© The Author 2015. 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: Breast cancer chemotherapy toxicity is not well documented outside of randomized trials. We developed and conducted preliminary evaluation of an algorithm to detect grade 3 and 4 toxicities using electronic data from a large integrated managed care organization., Methods: The algorithm used administrative, pharmacy, and electronic data from outpatient, emergency room, and inpatient records of 99 women diagnosed with breast cancer from 2006 to 2009 who underwent chemotherapy. Data were abstracted for 12 months post-treatment initiation (24 months for trastuzumab recipients). An oncology nurse independently blindly reviewed records; these results were the "gold standard." Sensitivity and specificity were calculated for overall toxicity, categories of toxicities, and toxicity by age or regimen. The algorithm was applied to an independent sample of 1,575 patients with breast cancer diagnosed during the study period to estimate prevalence rates., Results: The overall sensitivity for detecting chemotherapy-related toxicity was 89% (95% CI, 77% to 95%). The highest sensitivity was for identification of hematologic toxicities (97%; 95% CI, 84% to 99%). There were good sensitivities for infectious toxicity, but rates dropped for GI and neurological toxicities. Specificity was high within each category (89% to 99%), but when combined to measure any toxicity, it was lower (70%; 95% CI, 57% to 81%). When applied to an independent chemotherapy sample, the algorithm estimates a 26% rate of hematologic toxicity; rates were higher among patients age ≥ 65 years versus less than 65 years., Conclusions: If validated in other samples and health care settings, algorithms to capture toxicity could be useful in comparative and cost-effectiveness evaluations of community practice-delivered treatment., (Copyright © 2015 by American Society of Clinical Oncology.)

Background: Vitamin and mineral supplement use after a breast cancer diagnosis is common and controversial. Dosages used and the timing of initiation and/or discontinuation of supplements have not been clearly described., Methods: We prospectively examined changes in use of 17 vitamin/mineral supplements in the first six months following breast cancer diagnosis among 2,596 members (28% non-white) of Kaiser Permanente Northern California. We used multivariable logistic regression to examine demographic, clinical, and lifestyle predictors of initiation and discontinuation., Results: Most women used vitamin/mineral supplements before (84%) and after (82%) diagnosis, with average doses far in excess of Institute of Medicine reference intakes. Over half (60.2%) reported initiating a vitamin/mineral following diagnosis, 46.3% discontinuing a vitamin/mineral, 65.6% using a vitamin/mineral continuously, and only 7.2% not using any vitamin/mineral supplement before or after diagnosis. The most commonly initiated supplements were calcium (38.2%), vitamin D (32.01%), vitamin B6 (12.3%) and magnesium (11.31%); the most commonly discontinued supplements were multivitamins (17.14%), vitamin C (15.97%) and vitamin E (45.62%). Higher education, higher intake of fruits/vegetables, and receipt of chemotherapy were associated with initiation (p-values <0.05). Younger age and breast-conserving surgery were associated with discontinuation (p-values <0.05)., Conclusions: In this large cohort of ethnically diverse breast cancer patients, high numbers of women used vitamin/mineral supplements in the 6 months following breast cancer diagnosis, often at high doses and in combination with other supplements. The immediate period after diagnosis is a critical time for clinicians to counsel women on supplement use.

We investigated body size and survival by race/ethnicity in 11,351 breast cancer patients diagnosed from 1993 to 2007 with follow-up through 2009 by using data from questionnaires and the California Cancer Registry. We calculated hazard ratios and 95% confidence intervals from multivariable Cox proportional hazard model-estimated associations of body size (body mass index (BMI) (weight (kg)/height (m)(2)) and waist-hip ratio (WHR)) with breast cancer-specific and all-cause mortality. Among 2,744 ascertained deaths, 1,445 were related to breast cancer. Being underweight (BMI <18.5) was associated with increased risk of breast cancer mortality compared with being normal weight in non-Latina whites (hazard ratio (HR) = 1.91, 95% confidence interval (CI): 1.14, 3.20), whereas morbid obesity (BMI ≥ 40) was suggestive of increased risk (HR = 1.43, 95% CI: 0.84, 2.43). In Latinas, only the morbidly obese were at high risk of death (HR = 2.26, 95% CI: 1.23, 4.15). No BMI-mortality associations were apparent in African Americans and Asian Americans. High WHR (quartile 4 vs. quartile 1) was associated with breast cancer mortality in Asian Americans (HR = 2.21, 95% CI: 1.21, 4.03; P for trend = 0.01), whereas no associations were found in African Americans, Latinas, or non-Latina whites. For all-cause mortality, even stronger BMI and WHR associations were observed. The impact of obesity and body fat distribution on breast cancer patients' risk of death may vary across racial/ethnic groups.

Racial/ethnic disparities in mortality among US breast cancer patients are well documented. Our knowledge of the contribution of lifestyle factors to disease prognosis is based primarily on non-Latina Whites and is limited for Latina, African American, and Asian American women. To address this knowledge gap, the California Breast Cancer Survivorship Consortium (CBCSC) harmonized and pooled interview information (e.g., demographics, family history of breast cancer, parity, smoking, alcohol consumption) from six California-based breast cancer studies and assembled corresponding cancer registry data (clinical characteristics, mortality), resulting in 12,210 patients (6,501 non-Latina Whites, 2,060 African Americans, 2,032 Latinas, 1,505 Asian Americans, 112 other race/ethnicity) diagnosed with primary invasive breast cancer between 1993 and 2007. In total, 3,047 deaths (1,570 breast cancer specific) were observed with a mean (SD) follow-up of 8.3 (3.5) years. Cox proportional hazards regression models were fit to data to estimate hazards ratios (HRs) and 95 % confidence intervals (CIs) for overall and breast cancer-specific mortality. Compared with non-Latina Whites, the HR of breast cancer-specific mortality was 1.13 (95 % CI 0.97-1.33) for African Americans, 0.84 (95 % CI 0.70-1.00) for Latinas, and 0.60 (95 % CI 0.37-0.97) for Asian Americans after adjustment for age, tumor characteristics, and select lifestyle factors. The CBCSC represents a large and racially/ethnically diverse cohort of breast cancer patients from California. This cohort will enable analyses to jointly consider a variety of clinical, lifestyle, and contextual factors in attempting to explain the long-standing disparities in breast cancer outcomes.

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 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.