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1.
Clin Breast Cancer ; 19(4): 225-235.e2, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30928413

RESUMO

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

2.
Genomics Proteomics Bioinformatics ; 17(2): 211-218, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30959223

RESUMO

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

3.
Cancer Med ; 8(4): 1845-1853, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30864286

RESUMO

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.

4.
Cancer Causes Control ; 30(2): 187-193, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30656539

RESUMO

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.


Assuntos
Recidiva Local de Neoplasia/epidemiologia , Neoplasias da Bexiga Urinária/epidemiologia , Idoso , Idoso de 80 Anos ou mais , California/epidemiologia , Sobreviventes de Câncer , Dieta , Progressão da Doença , Feminino , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/prevenção & controle , Estudos Prospectivos , Neoplasias da Bexiga Urinária/genética
5.
Artigo em Inglês | MEDLINE | ID: mdl-30508637

RESUMO

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

6.
Urology ; 2018 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-30359712

RESUMO

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

7.
Breast Cancer Res Treat ; 170(3): 593-603, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29623576

RESUMO

PURPOSE: Racial/ethnic differences in cancer symptom burden are well documented, but limited research has evaluated modifiable factors underlying these differences. Our objective was to examine the role of patient-provider interactions to help explain the relationship between race/ethnicity and cancer-specific physical well-being (PWB) among women with breast cancer. METHODS: The Pathways Study is a prospective cohort study of 4505 women diagnosed with breast cancer at Kaiser Permanente Northern California between 2006 and 2013. Our analysis included white, black, Hispanic, and Asian participants who completed baseline assessments of PWB, measured using the Functional Assessment of Cancer Therapy for Breast Cancer, and patient-provider interactions, measured by the Interpersonal Processes of Care Survey (IPC) (N = 4002). Using step-wise linear regression, we examined associations of race/ethnicity with PWB, and changes in associations when IPC domains were added. RESULTS: We observed racial/ethnic differences in PWB, with minorities reporting lower scores than whites (beta, black: - 1.79; beta, Hispanic: - 1.92; beta, Asian: - 1.68; p < 0.0001 for all comparisons). With the addition of health and demographic covariates to the model, associations between race/ethnicity and PWB score became attenuated for blacks and Asians (beta: - 0.63, p = 0.06; beta: - 0.68, p = 0.02, respectively) and, to a lesser extent, for Hispanic women (beta: - 1.06, p = 0.0003). Adjusting for IPC domains did not affect Hispanic-white differences (beta: - 1.08, p = 0.0002), and slightly attenuated black-white differences (beta: - 0.51, p = 0.14). Asian-white differences narrowed substantially (beta: - 0.31, p = 0.28). CONCLUSIONS: IPC domains, including those capturing perceived discrimination, respect, and clarity of communication, appeared to partly explain PWB differences for black and Asian women. Results highlight opportunities to improve providers' interactions with minority patients, and communication with minority patients about their supportive care needs.

8.
Breast Cancer Res Treat ; 168(2): 523-530, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29249058

RESUMO

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.

9.
Cancer Epidemiol Biomarkers Prev ; 26(9): 1466-1469, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28864455

RESUMO

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


Assuntos
Neoplasias da Mama/genética , Acesso aos Serviços de Saúde/tendências , Hispano-Americanos/genética , Recidiva Local de Neoplasia/genética , Adulto , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Estudos de Coortes , Feminino , Predisposição Genética para Doença , Humanos , Pessoa de Meia-Idade , Análise de Sobrevida , Estados Unidos
10.
Cancer Causes Control ; 28(6): 557-562, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28349440

RESUMO

PURPOSE: Breast cancer patients can switch hormonal therapy (HT) regimens due to treatment side effects or menopausal status change. We describe HT class switching from aromatase inhibitor (AI) to tamoxifen (TAM), and vice versa. METHODS: In a cohort of 3,265 women diagnosed with hormone-receptor-positive breast cancer at Kaiser Permanente Northern California from 2005 to 2013, we analyzed prescription records, switching reasons, and treatment adherence post-switch by chart review, through 31 December 2014. RESULTS: There were 290 women who switched from AI to TAM (AI switchers), including 130 (45%) switchers during the first year of treatment; and 446 women who switched from TAM to AI (TAM switchers), including 120 (27%) switchers within the first year. After the switch, 136 (47%) AI switchers and 260 (58%) TAM switchers finished or remained on the planned therapy; 69 (24%) AI switchers and 99 (22%) TAM switchers discontinued therapy. AI side effects (73%), specifically joint pain/arthralgia and bone health issues, were the most common reasons for switching from AI to TAM, whereas from TAM to AI, it was menopausal status change (42%). CONCLUSIONS: Study findings highlight the need for better ways to control patient symptoms from HT to prevent discontinuation, and thus ensure best prognosis.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Tamoxifeno/uso terapêutico , Idoso , Antineoplásicos Hormonais/efeitos adversos , Inibidores da Aromatase/efeitos adversos , California , Tomada de Decisões , Substituição de Medicamentos , Feminino , Humanos , Pessoa de Meia-Idade , Tamoxifeno/efeitos adversos
11.
Cancer Epidemiol Biomarkers Prev ; 26(4): 505-515, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28154107

RESUMO

Background: As social and built environment factors have been shown to be associated with physical activity, dietary patterns, and obesity in the general population, they likely also influence these health behaviors among cancer survivors and thereby impact survivorship outcomes.Methods: Enhancing the rich, individual-level survey and medical record data from 4,505 breast cancer survivors in the Pathways Study, a prospective cohort drawn from Kaiser Permanente Northern California, we geocoded baseline residential addresses and appended social and built environment data. With multinomial logistic models, we examined associations between neighborhood characteristics and body mass index and whether neighborhood factors explained racial/ethnic/nativity disparities in overweight/obesity.Results: Low neighborhood socioeconomic status, high minority composition, high traffic density, high prevalence of commuting by car, and a higher number of fast food restaurants were independently associated with higher odds of overweight or obesity. The higher odds of overweight among African Americans, U.S.-born Asian Americans/Pacific Islanders, and foreign-born Hispanics and the higher odds of obesity among African Americans and U.S.-born Hispanics, compared with non-Hispanic whites, remained significant, although somewhat attenuated, when accounting for social and built environment features.Conclusions: Addressing aspects of neighborhood environments may help breast cancer survivors maintain a healthy body weight.Impact: Further research in this area, such as incorporating data on individuals' perceptions and use of their neighborhood environments, is needed to ultimately inform multilevel interventions that would ameliorate such disparities and improve outcomes for breast cancer survivors, regardless of their social status (e.g., race/ethnicity, socioeconomic status, nativity). Cancer Epidemiol Biomarkers Prev; 26(4); 505-15. ©2017 AACRSee all the articles in this CEBP Focus section, "Geospatial Approaches to Cancer Control and Population Sciences."


Assuntos
Índice de Massa Corporal , Tamanho Corporal , Neoplasias da Mama/epidemiologia , Sobreviventes de Câncer/estatística & dados numéricos , Obesidade/epidemiologia , Características de Residência/estatística & dados numéricos , Adulto , Idoso , California , Estudos de Coortes , Fast Foods/provisão & distribução , Feminino , Disparidades nos Níveis de Saúde , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores Socioeconômicos
12.
J Natl Cancer Inst ; 109(2)2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27794123

RESUMO

Background: Lifestyle factors may be associated with chemotherapy-induced peripheral neuropathy (CIPN). We examined associations between body mass index (BMI) and lifestyle factors with CIPN in the Pathways Study, a prospective cohort of women with invasive breast cancer. Methods: Analyses included 1237 women who received taxane treatment and provided data on neurotoxicity symptoms. Baseline interviews assessed BMI (normal: <25 kg/m2; overweight: 25-29.9 kg/m2; obese: ≥30 kg/m2), moderate-to-vigorous physical activity (MVPA) (low: <2.5; medium: 2.5-5; high: >5 hours/week) and fruit/vegetable intake (low: <35 servings/week; high: ≥35 servings/week). Baseline and six-month interviews assessed antioxidant supplement use (nonuser, discontinued, continued user, initiator). CIPN was assessed at baseline, six months, and 24 months using the Functional Assessment of Cancer Therapy-Taxane Neurotoxicity (FACT-NTX); a 10% decrease was considered clinically meaningful. Results: At baseline, 65.6% of patients in the sample were overweight or obese, 29.9% had low MVPA, 57.5% had low fruit/vegetable intake, and 9.5% reported antioxidant supplement use during treatment. In multivariable analyses, increased CIPN was more likely to occur in overweight (odds ratio [OR] = 2.37, 95% confidence interval [CI] = 1.19 to 4.88) and obese patients (OR = 3.21, 95% CI = 1.52 to 7.02) compared with normal weight patients at 24 months and less likely to occur in patients with high MVPA compared with those with low MVPA at six (OR = 0.56, 95% CI = 0.34 to 0.94) and 24 months (OR = 0.43, 95% CI = 0.21 to 0.87). Compared with nonusers, patients who initiated antioxidant use during treatment were more likely to report increased CIPN at six months (OR = 3.81, 95% CI = 1.82 to 8.04). Conclusions: Obesity and low MVPA were associated with CIPN in breast cancer patients who received taxane treatment.


Assuntos
Antineoplásicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Hidrocarbonetos Aromáticos com Pontes/efeitos adversos , Carcinoma Ductal de Mama/tratamento farmacológico , Obesidade/complicações , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Taxoides/efeitos adversos , Adulto , Antioxidantes , Índice de Massa Corporal , Dieta , Suplementos Nutricionais , Exercício , Feminino , Frutas , Humanos , Estilo de Vida , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Proteção , Fatores de Risco , Verduras
13.
JAMA Oncol ; 3(3): 351-357, 2017 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-27832250

RESUMO

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


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias da Mama/diagnóstico , Vitamina D/análogos & derivados , Neoplasias da Mama/sangue , Neoplasias da Mama/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pré-Menopausa , Prognóstico , Estudos Prospectivos , Análise de Sobrevida , Sobreviventes , Vitamina D/sangue
14.
Breast Cancer Res Treat ; 161(3): 501-513, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27915435

RESUMO

PURPOSE: The majority of breast cancer patients receive endocrine therapy, including aromatase inhibitors known to cause increased bone resorption. Bone-related biomarkers at the time of breast cancer diagnosis may predict future risk of osteoporosis and fracture after endocrine therapy. METHODS: In a large population of 2,401 female breast cancer patients who later underwent endocrine therapy, we measured two bone remodeling biomarkers, TRAP5b and BAP, and two bone regulating biomarkers, RANKL and OPG, in serum samples collected at the time of breast cancer diagnosis. We analyzed these biomarkers and their ratios with patients' demographic, lifestyle, clinical tumor characteristics, as well as bone health history. RESULTS: The presence of bone metastases, prior bisphosphonate (BP) treatment, and blood collection after chemotherapy had a significant impact on biomarker levels. After excluding these cases and controlling for blood collection time, several factors, including age, race/ethnicity, body mass index, physical activity, alcohol consumption, smoking, and hormonal replacement therapy, were significantly associated with bone biomarkers, while vitamin D or calcium supplements and tumor characteristics were not. When prior BP users were included in, recent history of osteoporosis and fracture was also associated. CONCLUSIONS: Our findings support further investigation of these biomarkers with bone health outcomes after endocrine therapy initiation in women with breast cancer.


Assuntos
Doenças Ósseas/complicações , Doenças Ósseas/metabolismo , Remodelação Óssea , Neoplasias da Mama/complicações , Neoplasias da Mama/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Biomarcadores Tumorais , Densidade Óssea , Doenças Ósseas/epidemiologia , Doenças Ósseas/patologia , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/secundário , Neoplasias da Mama/diagnóstico , Exercício , Feminino , Fraturas Ósseas/epidemiologia , Fraturas Ósseas/etiologia , Fraturas Ósseas/metabolismo , Humanos , Estilo de Vida , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Osteoporose/epidemiologia , Osteoporose/etiologia , Osteoporose/metabolismo , Pós-Menopausa , Pré-Menopausa , Fatores de Risco
15.
JCO Clin Cancer Inform ; 1: 1-12, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-30657366

RESUMO

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.


Assuntos
Neoplasias da Mama/epidemiologia , Neoplasias da Mama/prevenção & controle , Quimioprevenção , Prestação Integrada de Cuidados de Saúde , Adulto , Idoso , Antineoplásicos Hormonais/uso terapêutico , California/epidemiologia , Quimioprevenção/métodos , Prestação Integrada de Cuidados de Saúde/métodos , Registros Eletrônicos de Saúde , Feminino , Humanos , Estilo de Vida , Adesão à Medicação , Pessoa de Meia-Idade , Vigilância em Saúde Pública , Medição de Risco , Tamoxifeno/uso terapêutico
16.
Breast Cancer Res Treat ; 159(1): 119-29, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27449493

RESUMO

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


Assuntos
Afro-Americanos/genética , Linfedema Relacionado a Câncer de Mama/etnologia , Linfedema Relacionado a Câncer de Mama/epidemiologia , Grupo com Ancestrais do Continente Europeu/genética , Hispano-Americanos/genética , Adulto , Idade de Início , Idoso , Índice de Massa Corporal , Linfedema Relacionado a Câncer de Mama/genética , Feminino , Humanos , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Autorrelato
17.
JAMA Oncol ; 2(9): 1170-6, 2016 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-27243607

RESUMO

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


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/terapia , Quimioterapia Adjuvante/estatística & dados numéricos , Terapias Complementares/estatística & dados numéricos , Terapia por Acupuntura/estatística & dados numéricos , Adulto , Idoso , Antioxidantes/uso terapêutico , Estudos de Coortes , Suplementos Nutricionais/estatística & dados numéricos , Feminino , Óleos de Peixe/uso terapêutico , Glucosamina/uso terapêutico , Comportamentos Relacionados com a Saúde , Humanos , Modelos Logísticos , Massagem/estatística & dados numéricos , Meditação , Melatonina/uso terapêutico , Pessoa de Meia-Idade , Terapias Mente-Corpo/estatística & dados numéricos , Análise Multivariada , Preparações de Plantas/uso terapêutico , Estudos Prospectivos , Autorrelato , Toque Terapêutico/estatística & dados numéricos , Vitaminas/uso terapêutico , Ioga
18.
Cancer Causes Control ; 27(3): 391-401, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26797455

RESUMO

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.


Assuntos
Neoplasias da Mama/epidemiologia , Registros Eletrônicos de Saúde , Autorrelato , California/epidemiologia , Comorbidade , Grupos de Populações Continentais , Grupos Étnicos , Grupo com Ancestrais do Continente Europeu , Feminino , Humanos , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Características de Residência , Taxa de Sobrevida , Sobreviventes
19.
Am J Epidemiol ; 181(12): 944-55, 2015 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-25925388

RESUMO

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.


Assuntos
Neoplasias da Mama/mortalidade , Grupos Étnicos , Exercício , Recreação , Adulto , Idoso , Neoplasias da Mama/etnologia , California/epidemiologia , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores de Risco , Taxa de Sobrevida
20.
Cancer Epidemiol Biomarkers Prev ; 24(8): 1207-13, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25990554

RESUMO

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


Assuntos
DNA/genética , Exoma/genética , Neoplasias/epidemiologia , Análise de Sequência de DNA/métodos , Genômica , Humanos
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