The unexplained protective effect of childhood adiposity on breast cancer risk may be mediated via mammographic density (MD). Here, we investigate a complex relationship between adiposity in childhood and adulthood, puberty onset, MD phenotypes (dense area (DA), non-dense area (NDA),…
To investigate the associations of longitudinal changes in sex hormone binding globulin (SHBG) and testosterone (T) over the menopause transition with the risk of diabetes. We followed 2,952 participants in the Study of Women's Health Across the Nation (SWAN) who…
To examine whether overall survival (OS) differs for male and female patients with advanced soft-tissue sarcoma (STS). The study included patients from Kaiser Permanente Northern California and Stanford Cancer Center with grade 2 and 3 locally advanced or metastatic STS…
The International Ki67 Working Group (IKWG) has developed training for immunohistochemistry (IHC) scoring reproducibility and recommends cut points of ≤ 5% and ≥ 30% for prognosis in ER+, HER2-, stage I/II breast cancer. We examined scoring reproducibility following IKWG training and evaluated these cut…
Understanding the relative contributions of SARS-CoV-2 infection-induced and vaccine-induced seroprevalence is key to measuring overall population-level seroprevalence and help guide policy decisions. Using a series of six population-based cross-sectional surveys conducted among persons aged ≥7 years in a large health…
For patients undergoing posttreatment surveillance after ductal carcinoma in situ (DCIS), the NCCN Guidelines for Breast Cancer recommend annual breast imaging and physical examination every 6 to 12 months for 5 years, and then annually. The aim of our study…
We compared the results of hereditary cancer multigene panel testing among patients ≤ 45 years of age diagnosed with ductal carcinoma in situ (DCIS) versus invasive breast cancer (IBC) in a large integrated health care system. A retrospective cohort study of hereditary cancer…
Breast density is strongly associated with breast cancer risk. Fully automated quantitative density assessment methods have recently been developed that could facilitate large-scale studies, although data on associations with long-term breast cancer risk are limited. We examined LIBRA assessments and…
With the increasing utilization of medications worldwide, coupled with the increasing availability of long-term data, there is a growing opportunity and need for robust studies evaluating drug-cancer associations. One methodology of importance in such studies is the application of lag…
Young breast cancer (YBC) patients are a unique subpopulation that are often underrepresented in randomized clinical trials. Furthermore, large national cancer databases lack detailed information on recurrence, a meaningful oncologic outcome for young patients. A retrospective review of YBC patients…
Background Although several clinical breast cancer risk models are used to guide screening and prevention, they have only moderate discrimination. Purpose To compare selected existing mammography artificial intelligence (AI) algorithms and the Breast Cancer Surveillance Consortium (BCSC) risk model for…
Whether sex and co-mutations impact prognosis of patients with SMARCA4-mutated (mutSMARCA4) malignancies is not clear. This cohort included patients from Northern California Kaiser Permanente with next-generation sequencing (NGS) performed from August 2020 to October 2022. We used Cox regression modeling…
To examine the impact of TP53 gain-of-function (GOF) and non-GOF mutations on prognosis of advanced pancreatic ductal adenocarcinoma (PDAC) among patients with KRAS, CDKN2A, and SMAD4 comutations. This cohort included patients with locally advanced, recurrent, and de novo metastatic PDAC…
Human bulk tissue samples comprise multiple cell types with diverse roles in disease etiology. Conventional transcriptome-wide association study approaches predict genetically regulated gene expression at the tissue level, without considering cell-type heterogeneity, and test associations of predicted tissue-level expression with…
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…
Creating more personalized breast cancer risk prediction models would enhance the benefits and limit the harms of routine breast cancer screening. This study aims to evaluate the performance of multi-feature image risk score (radiomics) models in a large population-based cohort;…
The relation of premenopausal anti-Müllerian hormone (AMH) levels with breast cancer risk has been evaluated in a few studies, but primarily in non-Hispanic White women. We evaluated the association of AMH levels with breast cancer risk in Study of Women's…
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…
The main tool in drug safety monitoring, spontaneous reporting of adverse effects, is unlikely to detect delayed adverse drug effects including cancer. Hypothesis-free screening studies based on administrative data could improve ongoing drug safety monitoring. Using Danish health registries, we…
Beta blockers (BB) have been associated with improved, worsened, or unchanged breast cancer outcomes in previous studies. This study examines the association between the post-diagnostic use of BBs and death from breast cancer in a large, representative sample of New…
Mammographic density (MD) phenotypes, including percent density (PMD), area of dense tissue (DA), and area of non-dense tissue (NDA), are associated with breast cancer risk. Twin studies suggest that MD phenotypes are highly heritable. However, only a small proportion of…
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). By extracting data from institutional databases and reviewing electronic medical charts, we compared clinical…
Identify KPNC patients with metastatic/incurable cancer for testing of tumors by next generation sequencing (NGS). NGS screening protocol is aligned to a portfolio of pharma-sponsored therapeutic protocols open now or theoretically open in the future, in addition to treatment off…
The overarching goal of the KP NCORP Community Site is to bring the benefits of medical advances to our racially and ethnically diverse membership and to the community at large by increasing clinical trial access/accrual and by conducting cancer care…
This study will combine functional data from gene expression and co-expression networks with GWAS data to elucidate the genetic determinants of mammographic density, an important risk factor for breast cancer.
The goal of this project is to identify the optimal IBIS model that maximizes screening benefits and minimizes harms. We hypothesize that the “full” model (with all breast cancer risk factors) has better calibration/discrimination compared to a reduced model that…
The goal of this project is to determine whether Ki-67 testing, using newer methods, could be used as a replacement for Oncotype DX testing in selected patients with HR+/HER2- breast cancer.
Improving breast cancer risk prediction models could enable more personalized screening. This would enhance the benefits of screening while limiting the harms. This study will evaluate the performance of multi-feature image risk score models in a large population-based cohort; determine…
To examine the association of gain-of-function (GOF) and non-gain-of-function (non-GOF) TP53 mutations with prognosis of metastatic right-sided (RCC) versus left-sided colorectal cancer (LCC). This cohort study included patients with metastatic colorectal cancer (CRC) who had next-generation sequencing performed from November…
Hydrochlorothiazide (HCTZ), a common diuretic known to be photosensitizing and previously associated with non-melanoma skin cancer, was recently reported to be associated with two melanoma subtypes, nodular and lentigo, among residents of Denmark. Our goal was to examine whether Danish…
It has been shown that racial/ethnic disparities exist with regard to initiation of and adherence to adjuvant endocrine therapy (AET). However, the relationship among American Indian/Alaska Native (AIAN) individuals is poorly understood, particularly among those who reside in urban areas.…
To examine the effects of prescription sleep medications on patient-reported sleep disturbances. Retrospective cohort. Longitudinal cohort of community-dwelling women in the USA. Racially and ethnically diverse middle-aged women who reported a sleep disturbance. New users of prescription sleep medications propensity…
To identify rare variants associated with prostate cancer susceptibility and better characterize the mechanisms and cumulative disease risk associated with common risk variants, we conducted an integrated study of prostate cancer genetic etiology in two cohorts using custom genotyping microarrays,…
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…
We examined whether the apparent association between renal cell carcinoma (RCC) and use of dihydropyridine calcium channel blockers (CCBs) was explained by confounding by indication since hypertension, the main indication for CCBs, is a risk factor for RCC. Using Danish…
Mammographic density (MD) phenotypes are strongly associated with breast cancer risk and highly heritable. In this GWAS meta-analysis of 24,192 women, we identify 31 MD loci at P
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…
Recent clinical trials have evaluated angiotensin-converting enzyme (ACE) inhibitors (ACEis), angiotensin receptor blockers (ARBs), and beta blockers (BBs) in relation to cardiotoxicity in patients with cancer, typically defined by ejection fraction declines. However, these trials have not examined long-term, hard…
Percent density (PD) is a strong risk factor for breast cancer that is potentially modifiable by lifestyle factors. PD is a composite of the dense (DA) and nondense (NDA) areas of a mammogram, representing predominantly fibroglandular or fatty tissues, respectively.…
Reports 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)…
Insulin-like growth factors (IGFs) and insulin-like growth factor binding proteins (IGFBPs) have been implicated in the aetiology of several cancers. To better understand whether anthropometric, behavioural and sociodemographic factors may play a role in cancer risk via IGF signalling, we…
The antipsychotic drug haloperidol has antiproliferative and growth-inhibiting properties on prostate cancer cell lines in vitro by binding the sigma 1 protein. Evidence is needed regarding a possible preventive association in men. To examine whether our epidemiologic data support an…
We examined the fracture risk after initiation of blood pressure-lowering drugs compared with initiation of antidepressants. Multivariable regression models demonstrated an increased risk of fracture among women initiating a blood pressure-lowering medication (HR 1.73, 95% CI 1.02-2.95). This is likely…
Breast density is a modifiable factor that is strongly associated with breast cancer risk. We sought to understand the influence of newer technologies of full-field digital mammography (FFDM) on breast density research and to determine whether results are comparable across…
There is no consensus regarding the management of benign papillary breast lesions diagnosed on image-guided core needle biopsy (IGCNB). This is a retrospective review of 407 patients within Kaiser Permanente Northern California diagnosed between 2012 and 2013. The study focused…
Epidemiologic analyses of gabapentin use and cancer risk in Kaiser Permanente Northern California were previously carried out in a collaborative study and independently evaluated in a UK database. To update these epidemiologic analyses with 7.5 more years of follow-up. Case-control…
To investigate the implications of a cancer diagnosis on medication adherence for pre-existing comorbid conditions, we explored statin adherence patterns prior to and following a new diagnosis of breast, colorectal, or prostate cancer among a multi-ethnic cohort. We identified adults…
To examine the role of uniform access to care in reducing racial/ethnic disparities in receipt of resection for early stage non-small cell lung cancer (NSCLC) by comparing integrated health system member patients to demographically similar non-member patients. Using data from…
Many antihypertensive drugs (ADs) are photosensitizing, heightening reactivity of the skin to sunlight. Photosensitizing ADs have been associated with lip cancer, but whether they impact the risk of cutaneous squamous cell carcinoma (cSCC) is unknown. To examine the association between…
Background: Several epidemiologic studies have reported strong inverse associations between metformin use and risk of colorectal cancer, although time-related biases, such as immortal time bias, may in part explain these findings. We reexamined this association using methods to minimize these…
The purpose of the study was to assess the feasibility of quantifying long-term trends in breast tumor DNA copy number variation (CNV) profiles. We evaluated CNV profiles in formalin-fixed paraffin-embedded (FFPE) tumor specimens from 30 randomly selected Kaiser Permanente Northern…
Many studies suggest a role for cholesterol in cancer development. Serum cholesterol levels have been observed to be low in newly diagnosed lymphoma cases. The objective of these analyses was to examine the time-varying relationship of cholesterol with lymphomagenesis in…
Use of oral chemotherapy agents for the treatment of many solid tumors has been increasing. This project aims to examine the use of oral chemotherapy over the last 10 years, the proportion of patients who are adherent to their oral…
Cancer is the second leading cause of death among American Indians and Alaskan Natives (AIAN), although cancer survival information in this population is limited, particularly among urban AIAN. In this retrospective cohort study, we compared all-cause and prostate, breast, lung,…
A majority of women with ductal carcinoma in situ (DCIS) receive breast-conserving surgery (BCS) but then face a risk of ipsilateral breast tumor recurrence (IBTR) which can be either recurrence of DCIS or invasive breast cancer. We developed a score…
The diuretic hydrochlorothiazide is amongst the most frequently prescribed drugs in the United States and Western Europe, but there is suggestive evidence that hydrochlorothiazide use increases the risk of lip cancer. To study the association between use of hydrochlorothiazide and…
Background: High mammographic density is strongly associated with increased breast cancer risk. Some, but not all, risk factors for breast cancer are also associated with higher mammographic density.Methods: The study cohort (N = 24,840) was drawn from the Research Program…
Animal and human data suggest statins may be protective against developing multiple myeloma; however, findings may be biased by the interrelationship with lipid levels. We investigated the association between statin use and risk of multiple myeloma in a large US…
Environmental exposures during pregnancy may increase breast cancer risk for mothers and female offspring. Tumor tissue assays may provide insight regarding the mechanisms. This study assessed the feasibility of obtaining tumor samples and pathology reports from mothers (F0) who were…
Half of US states mandate women be notified if they have dense breasts on their mammogram, yet guidelines and data on supplemental screening modalities are limited. Breast density (BD) refers to the extent that breast tissue appears radiographically dense on…
Antihypertensive medication use may vary by race and ethnicity. Longitudinal antihypertensive medication use patterns are not well described in women. Participants from the Study of Women's Health Across the Nation (SWAN), a prospective cohort of women (n=3302, aged 42-52), who…
This study continues surveillance of more than 200 of the most commonly prescribed drugs for carcinogenicity, and examines selected drug-cancer associations of potential importance.
Understanding similarities among phenotypically distinct cancers could provide insight into biological basis of disease and suggest treatment overlap among patients with seemingly distinct cancers. We will evaluate this by undertaking a genome-wide association study (GWAS) across all major cancers types…
This R03 study will add new assays for DNA copy number alteration, building on our R21, which has obtained tumor specimens on breast cancer patients from KPNC. Our aim has two parts: 1) Extract DNA from the 30 tumor blocks…
The goal of the project is to examine the impact of a recently implemented outreach and education program at KPNC on adherence and compliance of hormonal therapy among women diagnosed with hormone receptor positive breast cancer. The program was implemented…
We hypothesize that high tensile forces of activated stroma play a critical role in the survival and proliferation of cancerous epithelial cells through direct involvement of the YAP-TAZ and PI3-k pathways, and that disengaging pro-survival mechanosignaling emanating from the activated…
Prostate-specific antigen (PSA) levels have been used for detection and surveillance of prostate cancer (PCa). However, factors other than PCa-such as genetics-can impact PSA. Here we present findings from a genome-wide association study (GWAS) of PSA in 28,503 Kaiser Permanente…
The primary goal of this study is to determine whether mammographic density at diagnosis of invasive breast cancer predicts risk of subsequent breast cancer events among patients participating in two large and well-characterized population-based cohorts (LACE and Pathways) within the…
Mammographic density (MD) is one of the strongest known risk factors for breast cancer. Our primary goal is to identify novel genes for MD by conducting a genome-wide association study (GWAS) in 30,000 Caucasian women participating in KPNC's Research Program…
The aims of this study are to: 1) Estimate the age-specific incidence of HER2+ breast cancer in the Northern California Kaiser Permanente membership. 2) Among breast cancer patients diagnosed between 2000 and 2005, compare demographic (e.g., age, race) and tumor…
The objective of this project is to follow a large multi-ethnic sample of premenopausal women through the menopausal transition, in order to investigate the influence of biological and social and cultural factors on age at menopause, symptoms of menopause and…
Sex hormones have been implicated in the etiology of a number of diseases. To better understand disease etiology and the mechanisms of disease-risk factor associations, this analysis aimed to investigate the associations of anthropometric, sociodemographic and behavioural factors with a…
A negative association of statin use with liver cancer risk has been reported frequently. We added laboratory measurements, to our knowledge not included in previous investigations, to a case-control analysis of 2877 case patients and 142 850 matched control subjects…
Phosphodiesterase 5A inhibitors (PDEIs), a common treatment for erectile dysfunction, were recently linked to an increased risk of melanoma. We conducted two parallel case-control studies, using the Danish Nationwide Health Registries (DNHR) and the Kaiser Permanente Northern California (KPNC) electronic…
To investigate whether the impact of postdiagnosis exercise on breast cancer outcomes in women diagnosed with early-stage breast cancer differs on the basis of tumor clinicopathologic and molecular features. Using a prospective design, 6,211 patients with early-stage breast cancer from…
Cardiovascular disease (CVD) is a leading cause of death among women with nonmetastatic breast cancer. Whether exercise is associated with reductions in CVD risk in patients with breast cancer with an elevated CVD risk phenotype is not known. Using a…
Full-field digital mammography (FFDM) has largely replaced film-screen mammography in the US. Breast density assessed from film mammograms is strongly associated with breast cancer risk, but data are limited for processed FFDM images used for clinical care. We conducted a…
We present a systematic screening for identifying associations between prescribed drugs and cancer risk using the high quality Danish nationwide health registries. We identified all patients (cases) with incident cancer in Denmark during 2000-2012 (n=278,485) and matched each case to…
A 21-gene test that predicts recurrence risk among women with hormone receptor positive (HR+), localized breast cancer was nationally recommended in 2007, but we know little about its subsequent impact. We evaluated: a) patient characteristics associated with test use, b)…
The role of insulin-like growth factors (IGF) in prostate cancer development is not fully understood. To investigate the association between circulating concentrations of IGFs (IGF-I, IGF-II, IGFBP-1, IGFBP-2, and IGFBP-3) and prostate cancer risk, we pooled individual participant data from…
The effectiveness of bisphosphonates (BP) in reducing risk of second breast cancer and recurrence in observational studies has been minimally studied. We examined the association of oral BP use on risk of contralateral breast cancer (CBC) and recurrence in 16,781…
Controversy persists about whether certain antidepressants reduce tamoxifen's effectiveness on lowering breast cancer recurrence. We investigated whether taking tamoxifen and antidepressants (in particular, paroxetine) concomitantly is associated with an increased risk of recurrence or contralateral breast cancer. We examined 16…
We examined the clinical/pathologic features of ipsilateral second breast cancers (IP-SBCs) following breast-conserving surgery (BCS) for DCIS among community-treated patients and ascertained the degree of correlation between the features of index DCIS and IP-SBC events. From a Cancer Research Network…
Various patient, treatment, and pathologic factors have been associated with an increased risk of local recurrence (LR) following breast-conserving therapy (BCT) for ductal carcinoma in situ (DCIS). However, the strength and importance of individual factors has varied; whether combining factors…
The association between leisure-time physical activity (LTPA) and male breast cancer risk is unclear. In the Male Breast Cancer Pooling Project, with 449 cases and 13,855 matched controls, we used logistic regression with study stratification to generate adjusted ORs and…
A genome-wide association study (GWAS) of prostate cancer in Kaiser Permanente health plan members (7,783 cases, 38,595 controls; 80.3% non-Hispanic white, 4.9% African-American, 7.0% East Asian, and 7.8% Latino) revealed a new independent risk indel rs4646284 at the previously identified…
Studies suggest pioglitazone use may increase risk of cancers. To examine whether pioglitazone use for diabetes is associated with risk of bladder and 10 additional cancers. Cohort and nested case-control analyses among persons with diabetes. A bladder cancer cohort followed…
Although previous studies have implicated a variety of hormone-related risk factors in the etiology of male breast cancers, no previous studies have examined the effects of endogenous hormones. Within the Male Breast Cancer Pooling Project, an international consortium comprising 21…
We examined the combined influence of race/ethnicity and neighborhood socioeconomic status (SES) on short-term survival among women with uniform access to health care and treatment. Using electronic medical records data from Kaiser Permanente Northern California linked to data from the…
Many cancer registries do not capture recurrence; thus, outcome studies have often relied on time-intensive and costly manual chart reviews. Our goal was to build an effective and efficient method to reduce the numbers of chart reviews when identifying subsequent…
High mammographic density (MD) is a strong risk factor for breast cancer. Chronic inflammation may be related to breast cancer risk through a mechanism involving the percent of breast area that is dense (percent MD). Longitudinal assessments, however, are lacking…
Methodologic biases may explain why observational studies examining metformin use in relation to lung cancer risk have produced inconsistent results. We conducted a cohort study to further investigate this relationship, accounting for potential biases. For 47,351 patients with diabetes ages…
An efficient approach to characterizing the disease burden of rare genetic variants is to impute them into large well-phenotyped cohorts with existing genome-wide genotype data using large sequenced referenced panels. The success of this approach hinges on the accuracy of…
Considerable debate exists about the optimal treatment of ductal carcinoma in situ (DCIS). Using electronic data sources, we examined first course treatment patterns among women aged 18 years and older diagnosed with DCIS between 2000-2010 from six Kaiser Permanente (KP)…
Determining long-term trends in tumor biomarker expression is essential for understanding aspects of tumor biology amenable to change. Limiting the availability of such data, currently used assays for biomarkers are relatively new. For example, assays for the estrogen receptor (ER),…
Invasive breast cancers are now commonly classified using gene expression into biologically and clinically distinct tumor subtypes. However, the role of obesity in breast tumor gene expression and intrinsic subtype is unknown. Early-stage breast cancer (BC) patients (n?=?1,676) were sampled…
The optimal treatment strategy for ductal carcinoma in situ (DCIS) continues to evolve and should consider the consequences of initial treatment on the likelihood, type, and treatment of recurrences. We conducted a retrospective cohort study using two data sources of…
To determine the invasive recurrence (IR) risk among patients with small, node-negative human epidermal growth factor receptor 2 (HER2) -positive breast cancer. Among 16,975 consecutive patients with invasive breast cancer diagnosed from January 1, 2000, to December 31, 2006, in…
Cancer patients tend to have a higher incidence of herpes zoster (HZ), but little is known about their risk of HZ complications. We conducted a retrospective study of 424 newly diagnosed hematologic (HM, n = 140) and solid tumor malignancy…
The observed association between pioglitazone and bladder cancer could be causal or because of bias in the design of prior studies. We hypothesize that proteinuria testing may lead to detection bias if routine test results for proteinuria lead to a…
Data are lacking to describe gene expression-based breast cancer intrinsic subtype patterns for population-based patient groups. We studied a diverse cohort of women with breast cancer from the Life After Cancer Epidemiology and Pathways studies. RNA was extracted from 1…
The PAM50, a gene expression assay to categorize breast tumors into intrinsic subtypes, has not been previously used to examine short- and long-term prognostication in a population-based cohort where treatment patterns and time of initial follow-up vary. In a stratified…
Cardiotoxicity is a known complication of certain breast cancer therapies, but rates come from clinical trials with design features that limit external validity. The ability to accurately identify cardiotoxicity from administrative data would enhance safety information. To characterize the performance…
To evaluate whether differences in PAM50 breast cancer (BC) intrinsic (Luminal A, Luminal B, Basal-like, and HER2-enriched) subtypes help explain the Black-White BC survival disparity. Utilizing a stratified case-cohort design, this study included 1,635 women from the Pathways and Life…
Re-examine association of fluoxetine and paroxetine with risk of testicular cancer noted in drug screening, with 4 years more follow-up and expanded study of these and other antidepressant drugs. In the Kaiser Permanente Medical Care Program in Northern California, 906…
To estimate ovarian and peritoneal cancer rates after hysterectomy with and without salpingo-oophorectomy for benign conditions. All patients after hysterectomy for benign disease from 1988 to 2006 in Kaiser Permanente Northern California, an integrated health organization. Incidence rates per 100,000…
To examine whether use of insulin glargine, compared with another long-acting insulin, is associated with risk of breast, prostate, colorectal cancer, or all cancers combined. Computerized health records from Kaiser Permanente Northern and Southern California regions starting in 2001 and…
We aimed to identify clinicopathologic factors associated with local recurrence (LR) in a large population of DCIS patients treated with breast-conserving therapy between 1990-2001 in three health plans. Regression methods were used to estimate relative risks (RR) of LR. Among…
BACKGROUND: Five-year breast cancer survival rates are lower among Hispanic and African-American women than among Non-Hispanic White women. Differences in breast cancer treatment likely play a role. Adjuvant hormonal therapies increase overall survival among women with hormone receptor-positive breast cancer.…
Studies have shown that a two-gene ratio (HOXB13:IL17BR) and a five-gene (BUB1B, CENPA, NEK2, RACGAP1, RRM2) molecular grade index (MGI) are predictive of clinical outcomes among early-stage breast cancer patients. In an independent population of lymph node-negative breast cancer patients…
BACKGROUND: Given the limited literature, we conducted a study to examine the epidemiology of herpes zoster (HZ) among newly diagnosed cancer patients. METHODS: We identified adult health plan members of Kaiser Permanente Northern California diagnosed with invasive cancer from 2001…
Chemotherapy regimens for early stage breast cancer have been tested by randomized clinical trials, and specified by evidence-based practice guidelines. However, little is known about the translation of trial results and guidelines to clinical practice. We extracted individual-level data on…
Human epidermal growth factor receptor 2 (HER2) expression is amplified in about 20% of breast cancer tumors, and evaluation of HER2 status should influence therapy selection. A critical gap in our knowledge is the real-world implementation of HER2 testing and…
The association of smoking with outcomes following breast cancer prognosis is not well understood. In a cohort study called Life After Cancer Epidemiology (LACE), 2,265 women diagnosed with breast cancer were followed for a median of 12 years. We used…
BACKGROUND: In screening pharmaceuticals for possible carcinogenic effects we noted an association between lip cancer risk and the photosensitizing antihypertensive drugs hydrochlorothiazide and nifedipine. In this study, we further characterized the risk of lip cancer associated with these and other…
BACKGROUND: Clinical trials demonstrated that women treated for breast cancer with anthracycline or trastuzumab are at increased risk for heart failure and/or cardiomyopathy (HF/CM), but the generalizability of these findings is unknown. We estimated real-world adjuvant anthracycline and trastuzumab use…
BACKGROUND: In the United States, 5-year breast cancer survival is highest among Asian American women, followed by non-Hispanic white, Hispanic, and African American women. Breast cancer treatment disparities may play a role. We examined racial/ethnic differences in adjuvant hormonal therapy…
BACKGROUND: Breast-conserving surgery (BCS) is the most common treatment for ductal carcinoma in situ (DCIS); however, how often women experience subsequent diagnostic evaluations over time is not known. METHODS: We identified 2948 women with DCIS who were treated with BCS…
BACKGROUND: Cancer Research Network (CRN) sites use administrative data to populate their Virtual Data Warehouse (VDW). However, information on VDW chemotherapy data validity is limited. The purpose of this study was to assess the validity of VRN chemotherapy data.METHODS: This…
BACKGROUND: The frequent recurrence of early-stage non-small-cell lung cancer (NSCLC) is generally attributable to metastatic disease undetected at complete resection. Management of such patients depends on prognostic staging to identify the individuals most likely to have occult disease. We aimed…
PURPOSE: High doses of gabapentin were associated with pancreatic acinar cell tumors in male Wistar rats, but there is little published epidemiological data regarding gabapentin and carcinogenicity. We explored the association between gabapentin and cancer in a US medical care…
Mortality after breast cancer diagnosis is known to vary by race/ethnicity even after adjustment for differences in tumor characteristics. As adjuvant hormonal therapy decreases risk of recurrence and increases overall survival among women with hormone receptor-positive tumors, treatment disparities may…
CONTEXT: More than 1.5 million US adults use stimulants and other medications labeled for treatment of attention-deficit/hyperactivity disorder (ADHD). These agents can increase heart rate and blood pressure, raising concerns about their cardiovascular safety. OBJECTIVE: To examine whether current use…
BACKGROUND: Adverse-event reports from North America have raised concern that the use of drugs for attention deficit-hyperactivity disorder (ADHD) increases the risk of serious cardiovascular events. METHODS: We conducted a retrospective cohort study with automated data from four health plans…
Little is known about the relation of multivitamin use to breast cancer outcomes. 2,236 women diagnosed from 1997 to 2000 with early-stage breast cancer (Stage I >/= 1 cm, II, or IIIA) were enrolled about 2 years post-diagnosis, primarily from…
PURPOSE: The contribution of menstrual and reproductive factors to risk of ductal carcinoma (DCIS) of the breast is poorly understood. METHODS: The association between menstrual and reproductive factors and subsequent DCIS risk was examined in Women's Health Initiative (WHI) clinical…
The metabolic syndrome (MetS) is associated with an increase in breast cancer risk. In our study, we evaluated whether the MetS was associated with an increase in percent mammographic density (MD), a breast cancer risk factor. We used linear regression…
There is increasing interest in the relationship between host lifestyle factors and the outcomes of cancer treatment. Behavioral factors, comorbid conditions, and non-cancer-related pharmaceutical exposures may affect breast cancer (BC) outcomes. We used observational data from the LACE Study cohort…
PURPOSE: Data in epidemiological studies sometimes are collected off-schedule from planned study visits. In an ancillary study to the Study of Women's Health Across the Nation (SWAN), longitudinal breast density data were collected retrospectively from mammograms that were not acquired…
OBJECTIVE: To explore whether treatment with pioglitazone was associated with risk of incident cancer at the 10 most common sites (prostate, female breast, lung/bronchus, endometrial, colon, non-Hodgkin lymphoma [NHL], pancreas, kidney/renal pelvis, rectal, and melanoma). RESEARCH DESIGN AND METHODS: A…
BACKGROUND: Hyperglycemia may increase the risk of colorectal neoplasia by serving as an energy source for neoplastic growth. We sought to determine whether glycemic control measured by serial hemoglobin A1c (HbA1c) was associated with the risk of colorectal adenoma. METHODS:…
BACKGROUND/AIMS: Statins are widely used and of high interest as potential chemopreventive agents for cancer. Preclinical studies suggest that lipophilic statins have anticancer properties targeting hormone receptor (HR)-negative breast cancer. Few epidemiologic studies have investigated the relationship between lipophilic statin…
BACKGROUND: We examined whether mammographic density predicts risk of second breast cancers among patients with ductal carcinoma in situ (DCIS). METHODS: The study included DCIS patients diagnosed during 1990 to 1997 and treated with breast-conserving surgery at Kaiser Permanente Northern…
PURPOSE: The optimal method to assess human epidermal growth factor receptor 2 (HER2) status remains highly controversial. Before reporting patient HER2 results, American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines mandate that laboratories demonstrate >/= 95% concordance…
Epidemiologic evidence suggests that cancer incidence is associated with diabetes as well as certain diabetes risk factors and treatments. This consensus statement of experts assembled jointly by the American Diabetes Association and the American Cancer Society reviews the state of…
OBJECTIVE: To examine whether use of adjuvant therapy varies by race/ethnicity among patients with ductal carcinoma in situ (DCIS) at 3 integrated health plan delivery sites based in California and Massachusetts. STUDY DESIGN: Cross-sectional study nested within a cohort of…
One potential mechanism by which physical activity may protect against breast cancer is by decreasing mammographic density. Percent mammographic density, the proportion of dense breast tissue area to total breast area, declines with age and is a strong risk factor…
PURPOSE: The opposing carcinogenic and antiestrogenic properties of tobacco smoke may explain why epidemiologic studies have not consistently reported positive associations for active smoking and breast cancer risk. A negative relation between mammographic density, a strong breast cancer risk factor,…
Prior studies have shown that young patient age at diagnosis is associated with an increased risk of local recurrence among women with ductal carcinoma in situ (DCIS) treated with breast-conserving therapy. Whether this can be explained by differences in clinical…
OBJECTIVE: To screen commonly used prescription drugs for possible carcinogenic effects. METHODS: In a large health care program we identified 105 commonly used drugs, not previously screened. Recipients were followed for up to 12(1/2) years for incident cancer. Nested case-control…
Thorough review by the International Agency for Research on Cancer (IARC) has resulted in classifying many substances, including pharmaceuticals, as probably or possibly carcinogenic to humans, based on experiments on animals or limited data on humans. We evaluated 9 such…
BACKGROUND: Numerous modifiable factors have been associated with a reduced risk of colorectal cancer, including the chronic use of NSAIDs. Thus, it is biologically plausible that HMG-CoA reductase inhibitors (statins), therapeutic agents that also possess anti-inflammatory effects, are also associated…
PURPOSE Breast-conserving surgery (BCS) is an effective treatment for ductal carcinoma in situ (DCIS) but women who undergo BCS remain at risk for recurrences. Whether mammographic surveillance after BCS occurs and by whom is not known. METHODS We reviewed medical…
Risk of breast cancer in women was assessed for eight pharmaceuticals that produce mammary tumors in experimental animals, using nested case-control analyses in two cohorts with prescription records in a comprehensive medical care program. The two cohorts were: (1) earlier…
High percent mammographic breast density is strongly associated with increased breast cancer risk. Though body mass index (BMI) is positively associated with risk of postmenopausal breast cancer, BMI is negatively associated with percent breast density in cross-sectional studies. Few longitudinal…
OBJECTIVE: To evaluate the demographics and incidence of Barrett's oesophagus diagnosis using community-based data. DESIGN: Observational study. SETTING: Kaiser Permanente, Northern California healthcare membership, 1994-2006. PATIENTS: Members with an electronic diagnosis of Barrett's oesophagus. MAIN OUTCOME MEASURES: Incidence and prevalence…
INTRODUCTION: Randomized trials indicate that adjuvant radiotherapy plus tamoxifen decrease the five-year risk of recurrence among ductal carcinoma in situ patients treated with breast-conserving surgery from about 20% to 8%. The aims of this study were to examine the use…
BACKGROUND: Analyzing health conditions and medical utilization of mothers of children with attention-deficit/hyperactivity disorder (ADHD) can shed light on biologic, environmental, and psychosocial factors relating to ADHD. OBJECTIVE: To examine health conditions, health care utilization, and costs of mothers of…
Conditions causing high iron levels, such as hemochromatosis, are proposed risk factors for esophageal adenocarcinoma. Although this hypothesis is supported by animal models, no human data currently exist. We conducted a case-control study of persons with a new Barrett's esophagus…
OBJECTIVE: High iron stores are a proposed modifiable risk factor for esophageal adenocarcinoma, but minimal human data exist. We evaluated whether iron intake and iron stores were associated with Barrett's esophagus, a metaplastic change that is a strong risk factor…
BACKGROUND & AIMS: Thiazolidinedione ligands for peroxisome proliferator-activated receptor gamma (PPARgamma), are used to treat diabetes. PPARgamma is highly expressed in the colon, and exposure to thiazolidinediones has been proposed to affect the risk for colorectal neoplasia. In vitro models…
Menstrual and reproductive factors may increase breast cancer risk through a pathway that includes increased mammographic density. We assessed whether known or suspected menstrual and reproductive breast cancer risk factors were cross-sectionally associated with mammographic density, by measuring area of…
BACKGROUND: Gastric colonization with Helicobacter pylori is a proposed protective factor against gastroesophageal reflux disease (GERD), but little population-based data exist and other data conflict. METHODS: We conducted a case-control study within the membership of a large integrated health-care system…
PURPOSE: We examined the association between post-diagnosis statin use (3-hydroxy-3-methylglutaryl-coenzyme A [HMG-CoA] inhibitors) and risk of breast cancer recurrence. MATERIALS AND METHODS: The study included 1945 early stage breast cancer survivors participating in the Life After Cancer Epidemiology (LACE) Study.…
OBJECTIVE: Gastric colonisation with the Helicobacter pylori bacterium is a proposed protective factor against oesophageal adenocarcinoma, but its point of action is unknown. Its associations with Barrett's oesophagus, a metaplastic change that is a probable early event in the carcinogenesis…
PURPOSE: Physical activity (PA) is one of few modifiable breast cancer risk factors. There have been few studies of the relation between PA and mammographic density, especially in multiethnic populations. METHODS: In a cohort of pre- and early perimenopausal women…
BACKGROUND: To examine the risk of prostate cancer and glucose tolerance in a large, racially diverse cohort. METHODS: We conducted a cohort study of 47,209 male members of Kaiser Permanente Northern California who had completed at least one Multiphasic Health…
PURPOSE: Determine the risk of cancer in statin users. METHODS: Risk of cancer in up to 9.4 years after first recorded receipt of statins was evaluated in subscribers of an integrated health care program in northern California. Statin use and…
PURPOSE: A recent report linked methylphenidate (MPH) use in children to cytologic abnormalities in plasma lymphocytes, a possible cancer biomarker. The purpose of this study was to investigate the association of MPH use and childhood cancer risk. METHODS: Using automated…
Flat epithelial atypia is an alteration of mammary terminal duct lobular units that is considered to be a precursor to, or early stage in, the development of some forms of ductal carcinoma in situ. No prior study has systematically evaluated…
Statins have known anticarcinogenic effects, however, evidence for long-term statin use as effective chemoprevention for prostate cancer is inconsistent. We examined the association between statin use and risk of prostate cancer among 69,047 eligible participants in the California Men's Health…
BACKGROUND: Diabetes mellitus is associated with an increased risk of colorectal neoplasia and diabetes medications may further influence the risk. Observational studies of the effect of diabetes medications on colonic neoplasia may be biased if use of diabetes medications is…
OBJECTIVES: To compare mammographic density among premenopausal and early perimenopausal women from four racial/ethnic groups and to examine density and acculturation among Japanese and Chinese women. DESIGN: The study included 391 white, 60 African American, 171 Japanese, and 179 Chinese…
BACKGROUND: Bone mineral density and mammographic breast density are each associated with markers of lifetime estrogen exposure. The association between mammographic breast density and bone mineral density in early perimenopausal women is unknown. METHODS: We analyzed data from a cohort…
OBJECTIVE: We examined the association between NSAID use and breast cancer recurrence in a prospective cohort of 2,292 early-stage breast cancer survivors diagnosed from 1997 to 2000 participating in the Life After Cancer Epidemiology (LACE) Study. METHODS: From 2000 to…
BACKGROUND: As the majority of patients diagnosed with colorectal cancer have no known risk factors, regular screening is strongly recommended. The authors examined factors associated with screening sigmoidoscopy use among participants in the California Men's Health Study (CMHS). METHODS: The…
BACKGROUND: Barrett's esophagus is a strong risk factor for esophageal adenocarcinoma, but little is known about its associations with body mass index (BMI) or abdominal obesity. METHODS: We conducted a case-control study within the Kaiser Permanente Northern California population. Persons…
Antibiotic use has been associated with risk of breast cancer in previous reports. Using Cox proportional hazards analysis, we evaluated this association in 2,130,829 adult female subscribers of a health care program according to their receipt of prescriptions of antibiotics…
OBJECTIVES: To estimate the excess costs for children in the years surrounding initial diagnosis of attention-deficit/hyperactivity disorder (ADHD) and to estimate differences in treatment costs by ethnicity. DESIGN: We identified children diagnosed with ADHD and estimated their health service costs…
PURPOSE: To examine whether weight gain after diagnosis of breast cancer affects the risk of breast cancer recurrence. PATIENT AND METHODS: Patients included 3215 women diagnosed with early stage breast cancer (Stage I >1 cm., II, and IIIA) who were…
OBJECTIVES: Medications that may increase gastroesophageal reflux could be risk factors for esophageal adenocarcinoma; however, epidemiologic studies present conflicting results. We evaluated patients with a high-risk condition, Barrett's esophagus, to identify risk factors that may act early in the carcinogenic…
PURPOSE: To examine raloxifene use among women with a history of breast cancer. METHODS: Kaiser Permanente tumor registry and membership files were used to identify women diagnosed with breast cancer after 1994 who were health plan members in 1998 or…
INTRODUCTION: The Oncotype DX assay was recently reported to predict risk for distant recurrence among a clinical trial population of tamoxifen-treated patients with lymph node-negative, estrogen receptor (ER)-positive breast cancer. To confirm and extend these findings, we evaluated the performance…
BACKGROUND: We established a male, multiethnic cohort primarily to study prostate cancer etiology and secondarily to study the etiologies of other cancer and non-cancer conditions. METHODS/DESIGN: Eligible participants were 45-to-69 year old males who were members of a large, prepaid…
OBJECTIVE: The aim of this study was to examine the use of stimulants among youths in a large and diverse health plan in California from 1996-2000. METHODS: Computerized pharmacy, outpatient visit, and membership files were used to conduct a population-based…
Women with ductal carcinoma in situ (DCIS) are at substantially increased risk for a second breast cancer, but few strong predictors for these subsequent tumors have been identified. We used Cox regression modeling to examine the association between mammographic density…
PURPOSE: To determine the risk for malignant primary adult-onset glioma (MPAG) associated with cigarette smoking and other lifestyle behaviors in a large, multiethnic, managed-care cohort. METHODS: The study population included a cohort of 133,811 subscribers to the Kaiser Permanente Medical…
PURPOSE: Determine the risk of subsequent cancer following squamous cell skin cancer. METHODS: Using computerized surgical pathology records and membership data from a health maintenance organization, we retrospectively identified 822 individuals with primary squamous cell skin cancer (SCSC) and 3662…
OBJECTIVE: To examine the relationship between daily aspirin use and risk of prostate cancer in a large, racially diverse cohort of men followed for up to 32 years. METHODS: The study population included 90,100 male subscribers to the Kaiser Permanente…
BACKGROUND & AIMS: Guidelines recommend periodic endoscopic surveillance of Barrett's esophagus (BE) patients to detect and treat early esophageal adenocarcinomas; however, no trials or population-based studies exist. We evaluated the association between endoscopic surveillance of BE and survival among esophageal/gastric…
Infection with Helicobacter pylori (H. pylori) increases stomach cancer risk. Helicobacter pylori strains with the cag pathogenicity island (PAI) induce more severe inflammation in the gastric epithelium and are more strongly associated with stomach cancer risk than strains lacking the…
Epidemiology of gastric adenocarcinoma suggests that intestinal-type and diffuse-type cancers develop through distinct causal pathways. To examine the differences in risk factors and molecular changes between the histological types, reliable data on histological typing are essential. We evaluated the concordance…
BACKGROUND: The purpose of this study was to examine the potential relationship between body size, self-reported age at initiation of shaving, and subsequent risk of prostate cancer in a large, racially diverse cohort of men followed for up to 32…
Purpose - The study was conducted to examine whether use of cimetidine is associated with the risk of cancer, with special attention to cancers of the breast and prostate because cimetidine increases estradiol levels and interferes with androgen binding. Methods…
BACKGROUND: Barbiturates, particularly phenobarbital, have been shown to be a tumour promoter in animal experiments and were found to be associated with increased risk of lung cancer in our cohort follow-up study to screen pharmaceuticals for possible carcinogenic effects. Sixteen…
Phenobarbital treatment has been observed to be negatively associated with bladder cancer risk in a few studies. It has been suggested that phenobarbital may induce drug-metabolizing enzymes that detoxify the bladder carcinogens found in cigarette smoke. We examined the relationship…
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