Lawrence H. Kushi's research while affiliated with Kaiser Permanente and other places

Publications (416)

Article
Introduction The COVID-19 pandemic drove rapid, widespread adoption of telehealth (TH). We evaluated surgical telehealth utilization and outcomes for newly diagnosed breast cancer patients during the initial pandemic period. Methods We identified patients with breast cancer diagnosed March 17, 2020 through May 17, 2020 who underwent surgery as the...
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Background: The incidence of and risk factors for severe clinical outcomes with the Omicron (B.1.1.529) SARS-CoV-2 variant have not been well-defined. Methods: We conducted a retrospective cohort study to assess risks of severe clinical outcomes within 21 days after SARS-CoV-2 diagnosis in a large, diverse, integrated health system. Findings:...
Article
Purpose: Chemotherapy drugs to treat breast cancer (BC) are cardiotoxic, but few studies have examined the effects of specific chemotherapy combinations on cardiovascular disease (CVD). We examined the additive effects of combinations of BC chemotherapy drugs associated with incident CVD events among women with a history of BC compared to those wit...
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Background: Genetic susceptibility to breast cancer has been studied extensively in European ancestry populations, but few studies have addressed genetic susceptibility in non-European women. Latinas are a genetically diverse group with contributions from European, African, and Indigenous American ancestries. Genome-wide association studies (GWAS)...
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Purpose While clinical heart failure (HF) is recognized as an adverse effect from breast cancer (BC) treatment, sparse data exist on specific HF phenotypes in affected BC survivors. We examined risk of HF by left ventricular ejection fraction (LVEF) status in women with a history of BC. Methods 14,804 women diagnosed with all stages of invasive BC...
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Purpose The Risk of Pediatric and Adolescent Cancer Associated with Medical Imaging (RIC) Study is quantifying the association between cumulative radiation exposure from fetal and/or childhood medical imaging and subsequent cancer risk. This manuscript describes the study cohorts and research methods. Methods The RIC Study is a longitudinal study...
Article
Background: Global efforts are needed to elucidate the epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the underlying cause of coronavirus disease 2019 (COVID-19), including seroprevalence, risk factors, and long-term sequelae, as well as immune responses after vaccination across populations and the social dimensions...
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PURPOSE To examine cardiovascular disease (CVD) and mortality risk in women with breast cancer (BC) by cancer therapy received relative to women without BC. METHODS The study population comprised Kaiser Permanente Northern California members. Cases with invasive BC diagnosed from 2005 to 2013 were matched 1:5 to controls without BC on birth year a...
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Background: Early puberty increases risk of adverse health conditions throughout the life course. US girls are experiencing earlier puberty without clear reasons. Studies suggest early life factors, such as infant growth, may influence pubertal timing. We assessed the associations between infant growth and onset of breast development (thelarche),...
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Background Financial hardship among adolescents and young adults (AYA) with cancer who receive gonadotoxic treatments may be exacerbated by the use of fertility services. This study examined whether AYA women with cancer who used fertility preservation had increased financial hardship. Methods AYA women with cancer in North Carolina and California...
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The overall 5‐year relative survival rate for all cancers combined is now 68%, and there are over 16.9 million survivors in the United States. Evidence from laboratory and observational studies suggests that factors such as diet, physical activity, and obesity may affect risk for recurrence and overall survival after a cancer diagnosis. The purpose...
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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 tu...
Article
There are >1.9 million survivors of adolescent and young adult cancers (AYA, diagnosed at ages 15–39) living in the U.S. today. Epidemiologic studies to address the cancer burden in this group have been a relatively recent focus of the research community. In this article, we discuss approaches and data resources for cancer epidemiology and health s...
Preprint
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Up to one of every six individuals diagnosed with one cancer will be diagnosed with a second primary cancer in their lifetime. Genetic factors contributing to the development of multiple primary cancers, beyond known cancer syndromes, have been underexplored. To characterize genetic susceptibility to multiple cancers, we conducted a pan-cancer, who...
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Purpose: Studies on long-term cardiovascular disease (CVD) risk in breast cancer (BC) survivors are limited. We examined CVD risk associated with exposure to specific BC therapies and explored whether body mass index (BMI) or prevalent CVD risk factors at BC diagnosis modified these associations. Methods: The Pathways Heart Study is a prospective c...
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Purposes To delineate operational changes in Kaiser Permanente Northern California breast care and evaluate the impact of these changes during the initial COVID-19 Shelter-in-Place period (SiP, 3/17/20–5/17/20). Methods By extracting data from institutional databases and reviewing electronic medical charts, we compared clinical and treatment chara...
Article
PURPOSE The incidence of cardiometabolic risk factors in breast cancer (BC) survivors has not been well described. Thus, we compared risk of hypertension, diabetes, and dyslipidemia in women with and without BC. METHODS Women with invasive BC diagnosed from 2005 to 2013 at Kaiser Permanente Northern California (KPNC) were identified and matched 1:...
Preprint
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PURPOSE: To examine the ability of 5 artificial intelligence (AI)-based computer vision algorithms, most trained to detect visible breast cancer on mammograms, to predict future risk relative to the Breast Cancer Surveillance Consortium clinical risk prediction model (BCSC v2). PATIENTS AND METHODS: In this case-cohort study, women who had a screen...
Article
Purpose: Investigate whether disparities and other factors influence referral to genetic counseling and testing for hereditary breast and ovarian cancer syndrome (HBOC) in a large health care system. Methods: Examination of clinical, demographic, and socioeconomic factors from electronic health records associated with genetic referral and testin...
Article
Background To facilitate community-based epidemiologic studies of pediatric leukemia, we validated use of ICD-9-CM diagnosis codes to identify pediatric leukemia cases in electronic medical records of six U.S. integrated health plans from 1996–2015 and evaluated the additional contributions of procedure codes for diagnosis/treatment. Procedures Su...
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Introduction The Patient Protection and Affordable Care Act eliminated cost sharing for preventive services, including colorectal cancer screening for individuals aged 50–75 years with private health insurance. This study examines the impact of the Affordable Care Act's removal of cost sharing for colorectal cancer screening on colorectal cancer in...
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The purpose of this study was to evaluate the potential collective opportunities and challenges of transforming real‐world data (RWD) to real‐world evidence (RWE) for clinical effectiveness by focusing on aligning analytic definitions of oncology endpoints. Patients treated with a qualifying therapy for advanced non‐small cell lung cancer (aNSCLC)...
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Background Many women with breast cancer also have a high likelihood of cardiovascular mortality, and while there are several cardiovascular risk prediction models, none have been validated in a cohort of breast cancer patients. We first compared the performance of commonly-used cardiovascular models, and then derived a new model where breast cance...
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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 complet...
Article
Background: Low socioeconomic status (SES) has been associated with a higher risk of aggressive breast cancer (BC) subtypes, but few studies have examined the independent effects of both neighborhood-level socioeconomic status (nSES) and individual-level SES measures. Methods: This study included 5547 women from the Pathways and Life After Cance...
Article
Objectives CHEK2 mutations are associated with increased risk of breast, colon, and prostate cancer but not ovarian cancer. Our study investigated if women with CHEK2 mutations underwent risk reducing salpingo-oophorectomies (RRSO), despite no known risk of ovarian cancer associated with CHEK2, and if personal or family history of ovarian cancer wa...
Article
Objectives To identify racial and health factors associated with referral, assessment and genetic testing patterns for women with ovarian cancer. Methods Women were identified with a new diagnosis of ovarian cancer in a large integrated health care system in Northern California between 8/1/2013 and 12/31/2018. Women were excluded if they had under...
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PURPOSE There is a need for industry-independent decision tools that integrate clinicopathologic features, comorbidities, and genomic information for women with node-negative, invasive, hormone receptor–positive, human epidermal growth factor receptor-2–negative (early-stage) breast cancer. METHODS We adapted an extant Cancer Intervention and Surv...
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Our study describes breast cancer risk loci using a cross-ancestry GWAS approach. We first identify variants that are associated with breast cancer at P < 0.05 from African ancestry GWAS meta-analysis (9241 cases and 10193 controls), then meta-analyze with European ancestry GWAS data (122977 cases and 105974 controls) from the Breast Cancer Associa...
Article
Purpose: The relationship between socioeconomic status (SES) and menarche has implications for understanding social level influences on early life development and adult disease, including breast cancer, but remains ill defined. We report here results from the Breast Cancer and the Environment Research Program, which permitted a longitudinal study...
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10510 Background: There have been suggestive findings for better cancer survival with vitamin D supplementation in the recent VITAL trial. The findings are consistent with meta-analyses based on earlier randomized trials testing daily supplement vitamin D intake. As there is no ongoing or planned randomized trial of vitamin D supplementation in sig...
Article
e12507 Background: There is a need for web-based decision tools that integrate clinicopathologic features and genomic information to guide breast cancer therapy for women with node-negative, hormone receptor positive, HER2 negative (“early-stage”) breast cancer. We developed a novel simulation model-based clinical decision tool that provides progno...
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Background Prior research suggests a relationship between overall diet quality and breast cancer survival, though few studies have reported on this topic. We evaluated whether four dietary quality indices consistent with healthy eating recommendations around the time of breast cancer diagnosis were associated with risk of recurrence, cause-specific...
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Background Prior research suggests a relationship between overall diet quality and breast cancer survival, though few studies have reported on this topic. We evaluated whether four dietary quality indices consistent with healthy eating recommendations around the time of breast cancer diagnosis were associated with risk of recurrence, cause-specific...
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Social scientific studies of social support predominantly focus on the positive associations between social support and emotional well-being. The negative aspects of social support have received much less attention. We conducted semi-structured interviews of women with breast cancer (n = 47) to examine the emotional strain associated with social su...
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Background: In the United States (U.S.), >45,000 adolescent and young adult (AYA) women are diagnosed with cancer annually. Reproductive issues are critically important to AYA cancer survivors, but insufficient information is available to address their concerns. The AYA Horizon Study was initiated to contribute high-quality, contemporary evidence...
Conference Paper
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 b...
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Even distinct cancer types share biological hallmarks. Here, we investigate polygenic risk score (PRS)-specific pleiotropy across 16 cancers in European ancestry individuals from the Genetic Epidemiology Research on Adult Health and Aging cohort (16,012 cases, 50,552 controls) and UK Biobank (48,969 cases, 359,802 controls). Within cohorts, each PR...
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Purpose Fracture and osteoporosis are known side effects of aromatase inhibitors (AIs) for postmenopausal hormone receptor positive (HR+) breast cancer (BC) patients. How modifiable lifestyle factors impact fracture risk in these patients is relatively unknown. Methods We conducted a prospective cohort study to examine the association of lifestyle...
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Purpose Earlier timing and faster tempo of puberty have been linked to adolescents' poor mental health. Previous research rarely adjusted for childhood mental health, did not use physical examination to assess puberty, and excluded Latinas and Asian Americans. This study addressed these limitations. Methods We followed 822 girls, recruited at ages...
Article
Objective: Social pain and physical pain are related bidirectionally, but how these variables cluster in the population is unknown. Methods: This study included 2833 women from the Study of Women's Health Across the Nation (SWAN), a community-based cohort of middle-aged women, and 3972 women from the Pathways Study, a population-based cohort of...
Article
Introduction: Incidence of heart failure (HF), specifically with preserved ejection fraction (HFpEF), is rising in the general population, yet is understudied. To provide a population-based estimate of HF in breast cancer (BC) survivors, we compared risk of HF in women with and without BC history in the Kaiser Permanente Northern California (KPNC)...
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Background Girls who experience early-life familial stress may have heightened risk of early puberty, which has adverse implications for adolescent and adult health. We assessed the association between household intactness and pubertal onset using a racially/ethnically diverse cohort of girls from Northern California. Methods A prospective cohort...
Preprint
Background The Patient Protection and Affordable Care Act (ACA) eliminated cost sharing for preventive services, including colorectal cancer (CRC) screening for individuals aged 50 to 75 with private health insurance. The present study is the first to examine the impact of the no-cost CRC screening due to the ACA on CRC incidence and mortality. Me...
Article
Background: The importance of addressing adverse financial effects of cancer among adolescents and young adults (AYAs) is paramount as survival improves. In the current study, the authors examined whether cancer-related employment disruption was associated with financial hardship among female AYA cancer survivors in North Carolina and California....
Article
Objective: To develop a longitudinal algorithm combining two biomarkers, CA125 and HE4, for early detection of ovarian cancer in women with BRCA mutations. Methods: Women with BRCA mutations and intact ovaries were invited to participate in a novel ovarian cancer early detection prospective study. The Risk of Ovarian Cancer Algorithm (ROCA) iden...
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Deciphering the shared genetic basis of distinct cancers has the potential to elucidate carcinogenic mechanisms and inform broadly applicable risk assessment efforts. Here, we undertake genome-wide association studies (GWAS) and comprehensive evaluations of heritability and pleiotropy across 18 cancer types in two large, population-based cohorts: t...
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PurposeInflammatory breast cancer (IBC) is a rare, poorly understood and aggressive tumor. We extended prior findings linking high body mass index (BMI) to substantial increased IBC risk by examining BMI associations before and after adjustment for well-characterized comorbidities using medical record data for diabetes, insulin resistance, and dist...
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Cruciferous vegetables are primary sources of dietary isothiocyanates (ITCs), a group of phytochemicals showing promising cancer‐chemopreventive activities in multiple cancer models. However, no study has thoroughly examined how cooking affects the yields of ITCs from cruciferous vegetables. In this study, a high‐performance liquid chromatography (...
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Using health care systems data for research and care improvement is of intense interest. The now widespread availability of electronic health records (EHRs) holds great promise for population sciences cancer research. Founded in 1999, the Cancer Research Network (CRN) is a consortium of a dozen research groups affiliated with US integrated health c...
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Objective Referral to Genetics for pre-testing counseling may be inefficient for women with ovarian cancer. This study assesses feasibility of gynecologic oncologists directly offering genetic testing. Methods A prospective pilot study was conducted at two gynecologic oncology hubs in an integrated healthcare system from May 1 to November 6, 2019....
Article
Background: Polycyclic aromatic hydrocarbons (PAHs) are a class of ubiquitous, environmental chemicals that may have endocrine disrupting capabilities. We investigated whether childhood exposure to PAHs was associated with adiposity and pubertal timing in a longitudinal study of 404 girls enrolled in the Northern California site of the Breast Canc...
Article
The American Cancer Society (ACS) publishes the Diet and Physical Activity Guideline to serve as a foundation for its communication, policy, and community strategies and, ultimately, to affect dietary and physical activity patterns among Americans. This guideline is developed by a national panel of experts in cancer research, prevention, epidemiolo...
Conference Paper
Background: Racial/ethnic disparities in access to care, receipt of treatment, and cancer outcomes are well documented. Racial/ethnic discrimination has been proposed as an important explanatory factor, with interpersonal and institutional discrimination shown to be associated with adverse outcomes. However, the impact of racial/ethnic discriminati...
Conference Paper
Background: Social factors and physical pain are related bidirectionally and as a function of temperament and disease processes, but the relevance of this to population research is unknown. We developed social-pain clusters, or groups that were similar with regard to social and pain characteristics, in a large, population-based cohort of women with...
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PurposeTo identify distinct trajectories of total moderate-to-vigorous physical activity (MVPA) and sedentary behavior following a breast cancer diagnosis and their correlates.Methods The analysis examined 3000 female breast cancer survivors within Kaiser Permanente Northern California between 2006 and 2013. Self-reported time spent on total MVPA a...
Conference Paper
Many breast cancer therapies have adverse effects on the cardiovascular health of patients. Breast cancer patients who are members of racial/ethnic minority and disadvantaged socioeconomic groups suffer disproportionately from cardiotoxicity during and after cancer treatment, leading to disparities in overall survival. These disparities may exist,...
Article
12017 Background: Women with a history of breast cancer (BC) are at increased long-term risk of dying from cardiovascular disease (CVD). However, the onset of CVD risk factors in women with BC has not been well-described. We compared risk of incident CVD risk factors in women with and without BC enrolled in the Kaiser Permanente Northern California...
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e19270 Background: Friends of Cancer Research convened 9 data partners to identify data elements and common definitions for real world (rw) endpoints to evaluate populations typically excluded from clinical trials. Here we report on rwOS by frontline treatment and comorbidities. Methods: A retrospective observational analysis of patients with aNSCL...
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e19311 Background: Leveraging data from a collaboration with 9 data partners, Friends of Cancer Research convened the Real-world Evidence Pilot 2.0, to examine trends and real world (rw) data endpoints in immunotherapy (IO) use for the front line treatment of aNSCLC. Methods: This study leveraged parallel analyses of rw data elements across heterog...
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12016 Background: Breast cancer (BC) survivors are at increased risk of cardiovascular disease (CVD) following diagnosis, as compared to women without BC. To provide a population-based estimate of CVD risk in BC survivors, we compared risk of CVD events in women with and without BC history enrolled in the Kaiser Permanente Northern California (KPNC...
Article
Objective We assessed the feasibility, patient acceptability of and compliance of a new surveillance strategy for ovarian cancer surveillance in women with BRCA mutations, based on assessments of serum CA125 and HE4 every 4 months (Risk of Ovarian Cancer Algorithm (ROCA) arm), compared to Standard of Care (SOC) surveillance with CA125 blood tests a...
Conference Paper
Background: Polygenic risk scores (PRS) integrate risk information from breast cancer associated SNPs (single nucleotide polymorphism). The risk scores have mostly been developed in populations of European ancestry, and have been shown to improve risk prediction over standard breast cancer risk models in these populations. The ability of the PRS to...
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Purpose: Osteoporosis and fragility fracture are major bone toxicities of aromatase inhibitors (AIs) for postmenopausal hormone receptor-positive breast cancer. Except for a few small studies on bone turnover markers and reduced bone mineral density after AI treatment, data on the associations of bone markers and risk of osteoporosis or fracture f...
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PurposeReports suggest that up to 50% of women with hormone receptor-positive (HR+) breast cancer (BC) do not complete the recommended 5 years of adjuvant endocrine therapy (AET). We examined the impact of an outreach program at Kaiser Permanente Northern California (KPNC) on adherence and discontinuation of AET among patients who initiated AET.Met...
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Context: The Patient Protection and Affordable Care Act increases healthcare access and includes provisions that