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Pathways: A Study of Breast Cancer Survivorship - Pathways Publications

Clustering of Social and Physical Pain Variables and Their Association With Mortality in Two Population-Based Cohorts

Social pain and physical pain are related bidirectionally, but how these variables cluster in the population is unknown. This study included 2833 women from the Study of Women’s Health Across the Nation (SWAN), a community-based cohort of middle-aged women, and 3972 women from the Pathways Study, a population-based cohort of women diagnosed with American Joint Committee on Cancer stages I-IV breast cancer diagnosed between 2005 and 2013. Women provided data on measures related to social pain (social network size, social support, loneliness, social well-being) and physical pain (sensitivity to pain, bodily pain) at study baseline. Analyzing each cohort separately, we used latent class analysis to evaluate social-physical pain clusters, logistic regression to evaluate predictors of categorization into clusters, and Cox proportional hazards models to evaluate associations of clusters with all-cause mortality. We also performed a meta-analysis to combine cohort mortality associations. Each cluster analysis produced a “low social-physical pain” cluster (SWAN, 48.6%; Pathways, 35.2%) characterized by low social and pain symptoms, a “high social-physical pain” cluster (SWAN, 17.9%; Pathways, 17.9%) characterized by high symptoms, and a “low social/high physical pain” cluster of women with high pain and compromised social functioning but otherwise low social symptoms (SWAN, 33.5%; Pathways, 46.9%). In meta-analysis, categorization into the high social-physical pain cluster was associated with elevated mortality (adjusted hazard ratio = 1.34, 95% confidence interval = 1.05-1.71, Q statistic = 0.782), compared with those in the low social-physical pain cluster. In two cohorts of women, latent class analysis produced similar sets of social-physical pain clusters, with the same proportion having both high social and pain symptoms; women in this cluster had elevated mortality.

Authors: Kroenke, Candyce H; Alexeeff, Stacey; Kushi, Lawrence H; Kwan, Marilyn L; Matthews, Karen A

Psychosom Med. 2021 04 01;83(3):228-238.

PubMed abstract

Impact of social and built environment factors on body size among breast cancer survivors: the Pathways Study

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 thisCEBP Focussection, “Geospatial Approaches to Cancer Control and Population Sciences.”

Authors: Shariff-Marco S; Roh JM; Ambrosone C; Gomez SL; Gomez SL; et al.

Cancer Epidemiol Biomarkers Prev. 2017 Apr;26(4):505-515. Epub 2017-02-02.

PubMed abstract

Adiposity, post-diagnosis weight change, and risk of cardiovascular events among early-stage breast cancer survivors

Little research examines whether adiposity or post-diagnosis weight changes influence Cardiovascular disease (CVD) among breast cancer patients for whom effects may differ due to treatment and recovery. We studied Stage I-III breast cancer survivors 18 to  <80 years, without pre-existing CVD, diagnosed from 1997 to 2013 at Kaiser Permanente. Women reported weight at diagnosis and weight and waist circumference (WC) around 24 months post diagnosis. Using Cox models for time to incident coronary artery disease, heart failure, valve abnormality, arrhythmia, stroke, or CVD death, we examined at-diagnosis body mass index (BMI, n = 3109) and post-diagnosis WC (n = 1898) and weight change (n = 1903, stable, ±5 to  <10-lbs or ±≥10-lbs). Mean (SD) age was 57 (11) years, and BMI was 28 (6) kg-m2. Post diagnosis, 25% of women gained and 14% lost ≥10-lbs; mean (SD) WC was 90 (15) cm. Over a median of 8.28 years, 915 women developed CVD. BMI 25-30-kg/m2 (vs. BMI < 25-kg/m2) was not associated with CVD, while BMI ≥ 35-kg/m2 increased risk by 33% (HR: 1.33; 95%CI 1.08-1.65), independent of lifestyle and tumor/treatment factors. The increased risk at BMI ≥ 35-kg/m2 attenuated with adjustment for pre-existing CVD risk factors to HR: 1.20; 95%CI 0.97-1.50. By contrast, even moderate elevations in WC increased risk of CVD, independent of pre-existing risk factors (HR: 1.93; 95%CI 1.31-2.84 comparing ≥100-cm vs. ≤80-cm). Post-diagnosis weight change had no association with CVD. Extreme adiposity and any elevation in WC increased risk of CVD among breast cancer survivors; however, changes in weight in the early post-diagnosis period were not associated with CVD. Survivors with high WC and existing CVD risk factors should be monitored.

Authors: Cespedes Feliciano EM; Kwan ML; Kushi LH; Weltzien EK; Castillo AL; Caan BJ

Breast Cancer Res Treat. 2017 04;162(3):549-557. Epub 2017-02-07.

PubMed abstract

BMI, Lifestyle Factors and Taxane-Induced Neuropathy in Breast Cancer Patients: The Pathways Study

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. Analyses included 1237 women who received taxane treatment and provided data on neurotoxicity symptoms. Baseline interviews assessed BMI (normal: <25?kg/m 2 ; overweight: 25-29.9?kg/m 2 ; obese: ?30?kg/m 2 ), 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. 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). Obesity and low MVPA were associated with CIPN in breast cancer patients who received taxane treatment.

Authors: Greenlee H; Hershman DL; Shi Z; Kwan ML; Ergas IJ; Roh JM; Kushi LH

J Natl Cancer Inst. 2017 Feb 01;109(2):1-8.

PubMed abstract

Bone remodeling and regulating biomarkers in women at the time of breast cancer diagnosis

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. 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. 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. Our findings support further investigation of these biomarkers with bone health outcomes after endocrine therapy initiation in women with breast cancer.

Authors: Yao S; Zhang Y; Tang L; Roh JM; Laurent CA; Hong CC; Hahn T; Lo JC; Ambrosone CB; Kushi LH; Kwan ML

Breast Cancer Res Treat. 2017 02;161(3):501-513. Epub 2016-12-03.

PubMed abstract

Exercise and Prognosis on the Basis of Clinicopathologic and Molecular Features in Early Stage Breast Cancer: The LACE and Pathways Studies

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 two large population-based cohort studies were studied. Age-adjusted and multivariable Cox regression models were performed to determine the relationship between exercise exposure (total MET-hours/week) and recurrence and breast cancer-related death for: (i) all patients (“unselected” cohort), and on the basis of (ii) classic clinicopathologic features, (iii) clinical subtypes, (iv) PAM50-based molecular intrinsic subtypes, and (v) individual PAM50 target genes. After a median follow-up of 7.2 years, in the unselected cohort (n = 6,211) increasing exercise exposure was not associated with a reduction in the risk of recurrence (adjusted Ptrend = 0.60) or breast cancer-related death (adjusted Ptrend = 0.39). On the basis of clinicopathologic features, an exercise-associated reduction in breast cancer-related death was apparent for tumors <2 cm [HR, 0.50; 95% confidence interval (CI), 0.34-0.72], well/moderately differentiated tumors (HR, 0.63; 95% CI, 0.43-0.91), and ER-positive tumors (HR, 0.72; 95% CI, 0.53-0.97). Stratification by clinical subtype indicated that the ER(+)/PR(+)/HER2(-)/low-grade clinical subtype was preferentially responsive to exercise (recurrence: adjusted HR, 0.63; 95% CI, 0.45-0.88; breast cancer-related death: adjusted HR, 0.57; 95% CI, 0.37-0.86). The impact of exercise on cancer outcomes appears to differ as a function of pathologic and molecular features in early-stage breast cancer. Cancer Res; 76(18); 5415-22. ©2016 AACR.

Authors: Jones LW; Kwan ML; Sternfeld B; Habel LA; Kroenke CH; Queensberry CP; Kushi LH; Caan BJ; et al.

Cancer Res. 2016 Sep 15;76(18):5415-22. Epub 2016-08-03.

PubMed abstract

A prospective cohort study of early discontinuation of adjuvant chemotherapy in women with breast cancer: the breast cancer quality of care study (BQUAL)

For many women with non-metastatic breast cancer, adjuvant chemotherapy prevents recurrence and extends survival. Women who discontinue chemotherapy early may reduce those benefits, but little is known about what predicts early discontinuation. We sought to determine prospectively the rate and reasons for early discontinuation of adjuvant chemotherapy in women with breast cancer. We conducted a prospective cohort study among three U.S. health care organizations. Of 1158 women with newly diagnosed non-metastatic breast cancer, 2006-2010, we analyzed 445 (38.4 %) patients who initiated standard adjuvant chemotherapy as defined by accepted guidelines. We interviewed patients at baseline and twice during treatment regarding sociodemographic/psychosocial factors and treatment decision-making and collected clinical data. They were categorized according to the number of cycles required by the chemotherapy regimen they had initiated. The outcome was early discontinuation (<80 % of planned cycles). Of patients analyzed, 392 (88.1 %) completed the prescribed therapy. The strongest predictor was receipt of a regimen entailing >4 cycles of therapy (18.1 % for longer regimens, 7.4 % for 4 cycles) (odds ratio [OR] 2.59, 95 % CI 1.32-5.08), controlling for race, age, stage, hormone receptor status, social support, optimism, spirituality, stress, and physical symptoms. Higher levels of psychological symptoms on the Memorial symptom assessment scale also increased the odds of early discontinuation (OR 1.92, 95 % CI 0.998-3.68). The large majority of patients who initiated adjuvant chemotherapy for breast cancer completed their prescribed regimens, but early discontinuation was associated with lengthier regimens and, with borderline statistical significance, for those with psychological side effects.

Authors: Neugut AI; Hillyer GC; Kushi LH; Lamerato L; Buono DL; Nathanson SD; Bovbjerg DH; Mandelblatt JS; Tsai WY; Jacobson JS; Hershman DL

Breast Cancer Res Treat. 2016 07;158(1):127-38. Epub 2016-06-10.

PubMed abstract

RE: Body Mass Index, PAM50 Subtype, and Outcomes in Node-Positive Breast Cancer: CALGB 9741

Authors: Kwan ML; Quesenberry CP; Caan BJ

J Natl Cancer Inst. 2016 Jan;108(1).

PubMed abstract

Preliminary Development and Evaluation of an Algorithm to Identify Breast Cancer Chemotherapy Toxicities Using Electronic Medical Records and Administrative Data

Breast cancer chemotherapy toxicity is not well documented outside of randomized trials. We developed and conducted preliminary evaluation of an algorithm to detect grade 3 and 4 toxicities using electronic data from a large integrated managed care organization. The algorithm used administrative, pharmacy, and electronic data from outpatient, emergency room, and inpatient records of 99 women diagnosed with breast cancer from 2006 to 2009 who underwent chemotherapy. Data were abstracted for 12 months post-treatment initiation (24 months for trastuzumab recipients). An oncology nurse independently blindly reviewed records; these results were the “gold standard.” Sensitivity and specificity were calculated for overall toxicity, categories of toxicities, and toxicity by age or regimen. The algorithm was applied to an independent sample of 1,575 patients with breast cancer diagnosed during the study period to estimate prevalence rates. The overall sensitivity for detecting chemotherapy-related toxicity was 89% (95% CI, 77% to 95%). The highest sensitivity was for identification of hematologic toxicities (97%; 95% CI, 84% to 99%). There were good sensitivities for infectious toxicity, but rates dropped for GI and neurological toxicities. Specificity was high within each category (89% to 99%), but when combined to measure any toxicity, it was lower (70%; 95% CI, 57% to 81%). When applied to an independent chemotherapy sample, the algorithm estimates a 26% rate of hematologic toxicity; rates were higher among patients age ≥ 65 years versus less than 65 years. If validated in other samples and health care settings, algorithms to capture toxicity could be useful in comparative and cost-effectiveness evaluations of community practice-delivered treatment.

Authors: Mandelblatt JS; Kushi L; et al.

J Oncol Pract. 2015 Jan;11(1):e1-8. Epub 2014-08-26.

PubMed abstract

Body Mass Index, PAM50 Subtype, and Outcomes in Node-Positive Breast Cancer

Authors: Kwan ML; Quesenberry CP; Caan BJ

J Natl Cancer Inst. 2015 Jan;108(1). Epub 2015-11-11.

PubMed abstract

Representativeness of breast cancer cases in an integrated health care delivery system

Integrated health care delivery systems, with their comprehensive and integrated electronic medical records (EMR), are well-poised to conduct research that leverages the detailed clinical data within the EMRs. However, information regarding the representativeness of these clinical populations is limited, and thus the generalizability of research findings is uncertain. Using data from the population-based California Cancer Registry, we compared age-adjusted distributions of patient and neighborhood characteristics for three groups of breast cancer patients: 1) those diagnosed within Kaiser Permanente Northern California (KPNC), 2) non-KPNC patients from NCI-designated cancer centers, and 3) those from all other hospitals. KPNC patients represented 32 % (N = 36,109); cancer center patients represented 7 % (N = 7805); and all other hospitals represented 61 % (N = 68,330) of the total breast cancer patients from this geographic area during 1996-2009. Compared with cases from all other hospitals, KPNC had slightly fewer non-Hispanic Whites (70.6 % versus 74.4 %) but more Blacks (8.1 % versus 5.0 %), slightly more patients in the 50-69 age range and fewer in the younger and older age groups, a slightly lower proportion of in situ but higher proportion of stage I disease (41.6 % versus 38.9 %), were slightly less likely to reside in the lowest (4.2 % versus 6.5 %) and highest (36.2 % versus 39.0 %) socioeconomic status neighborhoods, and more likely to live in suburban metropolitan areas and neighborhoods with more racial/ethnic minorities. Cancer center patients differed substantially from patients from KPNC and all other hospitals on all characteristics assessed. All differences were statistically significant (p

Authors: Gomez SL; Shariff-Marco S; Von Behren J; Kwan ML; Kroenke CH; Keegan TH; Reynolds P; Kushi LH

BMC Cancer. 2015;15:688. Epub 2015-10-14.

PubMed abstract

Non-initiation and early discontinuation of adjuvant trastuzumab in women with localized HER2-positive breast cancer

One year of trastuzumab therapy is recommended for women with HER2-positive breast cancer ? 1.0 cm in size to increase survival and is considered for women with tumors 0.5-0.9 cm in size. We analyzed compliance with trastuzumab among women with HER2-positive breast cancer in a prospective cohort study. Of 1145 recruited patients with breast cancer, 152 were HER2-positive (13.2 %), of whom 126 had tumors ? 1.0 cm; 110/126 (87.3 %) of these initiated trastuzumab. Non-receipt was associated with older age, better prognosis tumors, and with non-receipt of adjuvant chemotherapy. Of the 110 who initiated treatment, 18 (15 %) did not complete treatment, 15 (83 %) of them because of cardiotoxicity. Of 20 women with tumors 0.5-0.9 cm, 5 (25 %) initiated trastuzumab. Compliance with trastuzumab was very high among those with HER2-positive breast cancer, as was the completion of the recommended therapy.

Authors: Neugut AI; Hillyer GC; Kushi LH; Lamerato L; Leoce N; Ambrosone CB; Bovbjerg DH; Mandelblatt JS; Hershman DL

Breast Cancer. 2014 Nov;21(6):780-5. Epub 2014-06-06.

PubMed abstract

Intrinsic subtypes from PAM50 gene expression assay in a population-based breast cancer cohort: Differences by age, race, and tumor characteristics

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 mm punches from fixed tumor tissue. Quantitative reverse-transcriptase PCR was conducted for the 50 genes that comprise the PAM50 intrinsic subtype classifier. In a subcohort of 1,319 women, the overall subtype distribution based on PAM50 was 53.1% luminal A, 20.5% luminal B, 13.0% HER2-enriched, 9.8% basal-like, and 3.6% normal-like. Among low-risk endocrine-positive tumors (i.e., estrogen and progesterone receptor positive by immunohistochemistry, HER2 negative, and low histologic grade), only 76.5% were categorized as luminal A by PAM50. Continuous-scale luminal A, luminal B, HER2-enriched, and normal-like scores from PAM50 were mutually positively correlated. Basal-like score was inversely correlated with other subtypes. The proportion with non-luminal A subtype decreased with older age at diagnosis, P Trend < 0.0001. Compared with non-Hispanic Whites, African American women were more likely to have basal-like tumors, age-adjusted OR = 4.4 [95% confidence intervals (CI), 2.3-8.4], whereas Asian and Pacific Islander women had reduced odds of basal-like subtype, OR = 0.5 (95% CI, 0.3-0.9). Our data indicate that over 50% of breast cancers treated in the community have luminal A subtype. Gene expression-based classification shifted some tumors categorized as low risk by surrogate clinicopathologic criteria to higher-risk subtypes. Subtyping in a population-based cohort revealed distinct profiles by age and race.

Authors: Sweeney C; Kwan ML; Habel LA; Quesenberry CP; Kushi LH; Caan BJ; et al.

Cancer Epidemiol Biomarkers Prev. 2014 May;23(5):714-24. Epub 2014-02-12.

PubMed abstract

Intrinsic subtypes from the PAM50 gene expression assay in a population-based breast cancer survivor cohort: Prognostication of short and long term outcomes

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 case-cohort design of 1,691 women from the LACE and Pathways breast cancer survivor cohorts, we used PAM50 to categorize tumors into Luminal A (LumA), Luminal B (LumB), HER2-enriched (HER2-E), Basal-like and Normal-like, and to examine risk of early and late recurrence and mortality by Cox proportional hazards regression. Compared with LumA, cumulative risk of recurrence and breast cancer death was higher for LumB, HER2-E, and Basal-like tumors at 2, 5, and 10 years. However, HR of breast cancer death varied over time [<5 years (early) vs. > 5 years (late)] for both Basal-like (HR, 6.23 early vs. HR, 0.63 late) and HER2-E tumors (HR, 2.97 early vs. HR, 0.73 late) but not for LumB tumors where risk was elevated consistently (HR, 2.67 early vs. HR, 1.47 late). The contrast between LumB, HER2-E, and Basal-like compared with LumA on early recurrence was stronger when subtype was defined by PAM50 than by immunohistochemistry (IHC) markers. The PAM50 categorized intrinsic subtypes in a manner that more accurately predicts recurrence and survival, especially for luminal tumors, compared with commonly used methods that rely on traditional IHC clinical markers. The PAM50 is robust for use in epidemiologic studies and should be considered when archived tumor tissues are available.

Authors: Caan BJ; Sweeney C; Habel LA; Kwan ML; Kroenke CH; Weltzien EK; Quesenberry CP; Castillo A; Factor RE; Kushi LH; Bernard PS

Cancer Epidemiol Biomarkers Prev. 2014 May;23(5):725-34. Epub 2014-02-12.

PubMed abstract

Race and breast cancer survival by intrinsic subtype based on PAM50 gene expression

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 After Cancer Epidemiology cohorts, selecting women with tumors based upon IHC classification, recurrences, and deaths.One millimeter punches were obtained from tumor tissue, and expression of the PAM50 genes for molecular subtype was determined by RT-qPCR of extracted RNA. Cox proportional hazards models were used to analyze associations between race and BC outcomes, adjusted for PAM50 BC subtype. All tests of statistical significance were two-sided. Black women had a higher prevalence of the Basal-like BC subtype. Adjusted for potential confounding variables and disease characteristics at diagnosis, Black women had higher risks of recurrence (HR 1.65, 95 % CI 1.06-2.57) and breast cancer-specific mortality (HR 1.71, 95 % CI 1.02-2.86) than White women, but adjusting further for subtype did not attenuate survival disparities. By contrast, Hispanic women had a lower risk of recurrence (HR 0.54, 95 % CI 0.30-0.96) than Whites. Among those with the Basal-like subtype, Black women had a similar recurrence risk as women in other race groups but a higher recurrence risk for all other subtypes. Hispanic women had a lower recurrence risk within each subtype, though associations were not significant, given limited power. Although Black women had a higher risk of the Basal-like subtype, which has poor prognosis, this did not explain the Black-White BC survival disparity.

Authors: Kroenke CH; Sweeney C; Kwan ML; Quesenberry CP; Weltzien EK; Habel LA; Castillo A; Bernard PS; Factor RE; Kushi LH; Caan BJ

Breast Cancer Res Treat. 2014 Apr;144(3):689-99. Epub 2014-03-07.

PubMed abstract

Bone health history in breast cancer patients on aromatase inhibitors

A cross-sectional study was performed to assess bone health history among aromatase inhibitor (AI) users before breast cancer (BC) diagnosis, which may impact fracture risk after AI therapy and choice of initial hormonal therapy. A total of 2,157 invasive BC patients initially treated with an AI were identified from a prospective cohort study at Kaiser Permanente Northern California (KPNC). Data on demographic and lifestyle factors were obtained from in-person interviews, and bone health history and clinical data from KPNC clinical databases. The prevalence of osteoporosis and fractures in postmenopausal AI users was assessed, compared with 325 postmenopausal TAM users. The associations of bone health history with demographic and lifestyle factors in AI users were also examined. Among all initial AI users, 11.2% had a prior history of osteoporosis, 16.3% had a prior history of any fracture, and 4.6% had a prior history of major fracture. Postmenopausal women who were taking TAM as their initial hormonal therapy had significantly higher prevalence of prior osteoporosis than postmenopausal AI users (21.5% vs. 11.8%, p<0.0001). Among initial AI users, the associations of history of osteoporosis and fracture in BC patients with demographic and lifestyle factors were, in general, consistent with those known in healthy older women. This study is one of the first to characterize AI users and risk factors for bone morbidity before BC diagnosis. In the future, this study will examine lifestyle, molecular, and genetic risk factors for AI-induced fractures.

Authors: Kwan ML; Lo JC; Quesenberry CP; Kushi LH; Yao S; et al.

PLoS ONE. 2014;9(10):e111477. Epub 2014-10-29.

PubMed abstract

A survey of breast cancer physicians regarding patient involvement in breast cancer treatment decisions

Shared breast cancer treatment decision-making between patients and physicians increases patient treatment satisfaction and compliance and is influenced by physician-related factors. Attitudes and behaviors about patient involvement in breast cancer treatment decisions and treatment-related communication were assessed by specialty among breast cancer physicians of women enrolled in the Breast Cancer Quality of Care Study (BQUAL). Of 275 BQUAL physicians identified, 50.0% responded to the survey. Most physicians spend 46-60 min with the patient during the initial consult visit and 51.5% report that the treatment decision is made in one visit. Oncologists spend more time with new breast cancer patients during the initial consult (p = 0.021), and find it more difficult to handle their own feelings than breast surgeons (p = <0.001). Breast surgeons and oncologists share similar attitudes and behaviors related to patient involvement in treatment decision-making, yet oncologists report more difficulty managing their own feelings during the decision-making process.

Authors: Hillyer GC; Hershman DL; Kushi LH; Lamerato L; Ambrosone CB; Bovbjerg DH; Mandelblatt JS; Rana S; Neugut AI

Breast. 2013 Aug;22(4):548-54. Epub 2012-10-27.

PubMed abstract

Racial Disparities in Posttraumatic Stress After Diagnosis of Localized Breast Cancer; The BQUAL Study

BACKGROUND: Little is known about the development of posttraumatic stress disorder (PTSD) over time among women diagnosed with breast cancer. This study examines changes in PTSD symptoms in the first 6 months after diagnosis and assesses racial/ethnic differences in PTSD symptomatology over time. METHODS: We recruited women with newly diagnosed breast cancer, stages I to III, from three sites in the United States. Three telephone interviews were conducted: baseline at about 2 to 3 months after diagnosis, first follow-up at 4 months after diagnosis, and second follow-up at 6 months after diagnosis. We measured traumatic stress in each interview using the Impact of Events Scale; recorded sociodemographic, tumor, and treatment factors; and used generalized estimating equations and polytomous logistic regression modeling to examine the associations between variables of interest and PTSD. RESULTS: Of 1139 participants, 23% reported symptoms consistent with a diagnosis of PTSD at baseline, 16.5% at first follow-up, and 12.6% at the second follow-up. Persistent PTSD was observed among 12.1% participants, as defined by having PTSD at two consecutive interviews. Among participants without PTSD at baseline, 6.6% developed PTSD at the first follow-up interview. Younger age at diagnosis, being black (odds ratio [OR] = 1.48 vs white, 95% confidence interval [CI] =1.04 to 2.10), and being Asian (OR = 1.69 vs white, 95% CI = 1.10 to 2.59) were associated with PTSD. CONCLUSIONS: Nearly one-quarter of women newly diagnosed with breast cancer reported symptoms consistent with PTSD shortly after diagnosis, with increased risk among black and Asian women. Early identification of PTSD may present an opportunity to provide interventions to manage symptoms.

Authors: Vin-Raviv N; Hillyer GC; Hershman DL; Galea S; Leoce N; Bovbjerg DH; Kushi LH; Kroenke C; Lamerato L; Ambrosone CB; Valdimorsdottir H; Jandorf L; Mandelblatt JS; Tsai WY; Neugut AI

J Natl Cancer Inst. 2013 Apr 17;105(8):563-72. Epub 2013 Feb 21.

PubMed abstract

Interpersonal influences and attitudes about adjuvant therapy treatment decisions among non-metastatic breast cancer patients: an examination of differences by age and race/ethnicity in the BQUAL study

Patients are increasingly involved in cancer treatment decisions and yet little research has explored factors that may affect patient attitudes and beliefs about their therapeutic choices. This paper examines psychosocial factors (e.g., attitudes, social support), provider-related factors (e.g., communication, trust), and treatment considerations in a prospective study of a sample of non-metastatic breast cancer patients eligible for chemotherapy and/or hormonal therapy (BQUAL cohort). The data come from a multisite cohort study of white, black, Hispanic, and Asian non-metastatic breast cancer patients recruited in New York City, Northern California, and Detroit, Michigan. Baseline surveys were conducted over the telephone between 2006 and 2010 among a total of 1,145 women. Most participants were white (69 %), had more than a high school education (76 %), and were diagnosed with stage I disease (51 %). The majority of women reported discussing chemotherapy and hormonal therapy with their doctor (90 and 83 %, respectively); these discussions primarily took place with medical oncologists. Nearly a quarter of women reported that the treatment decision was difficult, and the majority were accompanied to the doctor (76 %) and involved a friend or family member in making the decision (54 %). Positive considerations (e.g., beliefs about treatment reducing risk of recurrence) were important in making treatment decisions. Participants preferred a shared decision-making style, but results suggested that there is room for improvement in terms of actual patient’s involvement in making the decision and provider communication, particularly among black patients. Patients 65 years and older reported fewer provider discussions of chemotherapy, poorer patient-provider communication, higher rates of being assisted by family members in making the decision, and more negative attitudes and beliefs toward treatment.

Authors: Shelton RC; Clarke Hillyer G; Hershman DL; Leoce N; Bovbjerg DH; Mandelblatt JS; Kushi LH; Lamerato L; Nathanson SD; Ambrosone CB; Neugut AI

Breast Cancer Res Treat. 2013 Feb;137(3):817-28. Epub 2012 Dec 22.

PubMed abstract

Patterns and predictors of breast cancer chemotherapy use in Kaiser Permanente Northern California, 2004-2007

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 chemotherapy administration from the electronic medical records of Kaiser Permanente Northern California (KPNC), a pre-paid integrated healthcare system serving 29 % of the local population. We linked data to the California Cancer Registry, incorporating socio-demographic and tumor factors, and performed multivariable logistic regression analyses on the receipt of specific chemotherapy regimens. We identified 6,004 women diagnosed with Stage I-III breast cancer at KPNC during 2004-2007; 2,669 (44.5 %) received at least one chemotherapy infusion at KPNC within 12 months of diagnosis. Factors associated with receiving chemotherapy included <50 years of age [odds ratio (OR) 2.27, 95 % confidence interval (CI) 1.81-2.86], tumor >2 cm (OR 2.14, 95 % CI 1.75-2.61), involved lymph nodes (OR 11.3, 95 % CI 9.29-13.6), hormone receptor-negative (OR 6.94, 95 % CI 4.89-9.86), Her2/neu-positive (OR 2.71, 95 % CI 2.10-3.51), or high grade (OR 3.53, 95 % CI 2.77-4.49) tumors; comorbidities associated inversely with chemotherapy use [heart disease for anthracyclines (OR 0.24, 95 % CI 0.14-0.41), neuropathy for taxanes (OR 0.45, 95 % CI 0.22-0.89)]. Relative to high-socioeconomic status (SES) non-Hispanic Whites, we observed less anthracycline and taxane use by SES non-Hispanic Whites (OR 0.63, 95 % CI 0.49-0.82) and American Indians (OR 0.23, 95 % CI 0.06-0.93), and more anthracycline use by high-SES Asians/Pacific Islanders (OR 1.72, 95 % CI 1.02-2.90). In this equal-access healthcare system, chemotherapy use followed practice guidelines, but varied by race and socio-demographic factors. These findings may inform efforts to optimize quality in breast cancer care.

Authors: Kurian AW; Lichtensztajn DY; Keegan TH; Leung RW; Shema SJ; Hershman DL; Kushi LH; Habel LA; Kolevska T; Caan BJ; Gomez SL

Breast Cancer Res Treat. 2013 Jan;137(1):247-60. Epub 2012 Nov 9.

PubMed abstract

Noninitiation of Adjuvant Chemotherapy in Women With Localized Breast Cancer: The Breast Cancer Quality of Care Study

PURPOSE: For some women, adjuvant chemotherapy for nonmetastatic breast cancer decreases recurrences and increases survival; however, patient-physician decisions regarding chemotherapy receipt can be influenced by medical and nonmedical factors. PATIENTS AND METHODS: We used a prospective cohort design and multivariate modeling to investigate factors related to noninitiation of chemotherapy among women with newly diagnosed breast cancer recruited from three US sites. We interviewed patients at baseline and during treatment on sociodemographic, tumor, and treatment decision-making factors. Patients were categorized according to National Comprehensive Cancer Network guidelines as those for whom chemotherapy was definitely indicated, clinically discretionary, or discretionary based on age greater than 70 years. RESULTS: Of 1,145 patients recruited, chemotherapy was clinically indicated for 392 patients, clinically discretionary for 459 patients, discretionary because of age for 169 patients, and not indicated for 93 patients; data were insufficient for 32 patients. Chemotherapy rates were 90% for those in whom chemotherapy was clinically indicated, 36% for those in whom it was discretionary because of clinical factors, and 19% for those in whom it was discretionary based on age greater than 70 years. Nonreceipt of chemotherapy was associated with older age, more negative beliefs about treatment efficacy, less positive beliefs about chemotherapy, and more concern about adverse effects. In the two discretionary groups, clinical predictors of worse outcome (greater tumor size, positive nodes, worse grade, and estrogen receptor- and progesterone receptor-negative status) were associated with increased chemotherapy initiation. CONCLUSION: Utilization of adjuvant chemotherapy was most common among patients who, based on clinical criteria, would most likely benefit from it, patients with more positive than negative beliefs regarding treatment efficacy, and patients with few concerns about adverse effects.

Authors: Neugut AI; Kushi LH; Hershman DL; et al.

J Clin Oncol. 2012 Nov 1;30(31):3800-9. Epub 2012 Sep 24.

PubMed abstract

Non-initiation of adjuvant hormonal therapy in women with hormone receptor-positive breast cancer: The Breast Cancer Quality of Care Study (BQUAL)

Adjuvant hormonal therapy for non-metastatic hormone receptor (HR)-positive breast cancer decreases risk of breast cancer recurrence and increases survival. However, some women do not initiate this life-saving treatment. We used a prospective cohort design to investigate factors related to non-initiation of hormonal therapy among women with newly diagnosed, non-metastatic HR-positive breast cancer recruited from three U.S. sites. Serial interviews were conducted at baseline and during treatment to examine sociodemographic factors, tumor characteristics, and treatment decision-making factors. Multivariate modeling assessed associations between variables of interest and hormonal therapy initiation. Of 1,050 breast cancer patients recruited, 725 (69 %) had HR-positive breast cancer, of whom 87 (12.0 %) based on self-report and 122 (16.8 %) based on medical record/pharmacy fill rates did not initiate hormonal therapy. In a multivariable analysis, non-initiation of hormonal therapy, defined by medical record/pharmacy, was associated with having greater negative beliefs about efficacy of treatment (OR 1.42, 95 % CI 1.18-1.70). Non-initiation was less likely in those who found the quality of patient/physician communication to be higher (OR 0.96, 95 % CI 0.93-0.99), the hormonal therapy treatment decision an easy one to make (OR 0.45, 95 % CI 0.23-0.90) or neither easy nor difficult (OR 0.34, 95 % CI 0.20-0.58); and had more positive beliefs about hormonal therapy efficacy (OR 0.40, 95 % CI 0.34-0.62). Factors influencing non-initiation of adjuvant hormonal therapy are complex and influenced by patient beliefs regarding treatment efficacy and side effects. Educational interventions to women about the benefits of hormonal therapy may decrease negative beliefs and increase hormone therapy initiation.

Authors: Neugut AI; Kushi LH; Hershman DL; et al.

Breast Cancer Res Treat. 2012 Jul;134(1):419-28. Epub 2012 Apr 22.

PubMed abstract

The Breast Cancer Quality of Care Study (BQUAL): A Multi-Center Study to Determine Causes for Noncompliance with Breast Cancer Adjuvant Therapy

In oncology, quality of care is a major issue for patients and providers. Significant variations in care, including nonreceipt of adjuvant systemic therapy, nonadherence to therapy, and/or early discontinuation of therapy, occur frequently and may impact survival. Reasons for these variations are not well understood, but may play a role in the prominent disparity in breast cancer survival between blacks and whites. Since May 2006, the Breast Cancer Quality of Care Study (BQUAL) has recruited 1158 women with nonmetastatic breast cancer from several centers across the country, with completed data on 1057 participants to date. Detailed information on demographic, behavioral, biomedical, and emotional factors related to chemotherapy use was collected on each participant at baseline and at two follow-up interviews during the first 6 months. In addition, for women with ER+ tumors, further questionnaires were completed every 6 months regarding hormonal therapy use. Each participant was also asked to provide a DNA sample, and to allow medical record review. We surveyed physicians providing care to the study participants regarding attitudes toward adjuvant treatment. The mean age of participants was 58 years (SD 11.6), and 15% (n = 160) were black. The majority had an annual household income <$90,000 (n = 683), had college education or higher (n = 802), 55.9% were married, and 57.9% were not currently employed. Seventy-six percent had hormone-receptor-positive tumors, 49.9% initiated chemotherapy and 82.7% started hormonal therapy. Blacks were more likely to have lower annual household income (p < 0001), less education (p = 0.0005), ER negative tumor status (p = 0.02), and poorly differentiated cancer (p = 0.0002). The main endpoints of the study are noninitiation of chemotherapy or hormonal therapy, nonadherence to therapy and early discontinuation of therapy. Treatment and outcomes will be compared on the 15% of participants who are black versus other participants. The BQUAL Study will be a rich ongoing source of information regarding reasons for differences in receipt of both adjuvant chemotherapy and hormonal therapy. This information may be useful in planning interventions to improve quality of care.

Authors: Neugut AI; Kushi LH; Hershman DL; et al.

Breast J. 2012 May-Jun;18(3):203-13. Epub 2012 Apr 5.

PubMed abstract

Racial/ethnic differences in initiation of adjuvant hormonal therapy among women with hormone receptor-positive breast cancer

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 play a role. We explored racial/ethnic differences in initiation of adjuvant hormonal therapy, defined as two or more prescriptions for tamoxifen or aromatase inhibitor filled within the first year after diagnosis of hormone receptor-positive localized or regional-stage breast cancer. The sample included women diagnosed with breast cancer enrolled in Kaiser Permanente Northern California (KPNC). Odds ratios [OR] and 95% confidence intervals [CI] compared initiation by race/ethnicity (Hispanic, African American, Chinese, Japanese, Filipino, and South Asian vs. non-Hispanic White [NHW]) using logistic regression. Covariates included age and year of diagnosis, area-level socioeconomic status, co-morbidities, tumor stage, histology, grade, breast cancer surgery, radiation and chemotherapy use. Our sample included 13,753 women aged 20-79 years, diagnosed between 1996 and 2007, and 70% initiated adjuvant hormonal therapy. In multivariable analysis, Hispanic and Chinese women were less likely than NHW women to initiate adjuvant hormonal therapy ([OR] = 0.82; [CI] 0.71-0.96 and [OR] = 0.78; [CI] 0.63-0.98, respectively). Within an equal access, insured population, lower levels of initiation of adjuvant hormonal therapy were found for Hispanic and Chinese women. Findings need to be confirmed in other insured populations and the reasons for under-initiation among these groups need to be explored.

Authors: Livaudais JC; Hershman DL; Habel L; Kushi L; Gomez SL; Li CI; Neugut AI; Fehrenbacher L; Thompson B; Coronado GD

Breast Cancer Res Treat. 2012 Jan;131(2):607-17. Epub 2011 Sep 16.

PubMed abstract

Early discontinuation and non-adherence to adjuvant hormonal therapy are associated with increased mortality in women with breast cancer

Despite the benefit of adjuvant hormonal therapy (HT) on mortality among women with breast cancer (BC), many women are non-adherent with its use. We investigated the effects of early discontinuation and non-adherence to HT on mortality in women enrolled in Kaiser Permanente of Northern California (KPNC). We identified women diagnosed with hormone-sensitive stage I-III BC, 1996-2007, and used automated pharmacy records to identify prescriptions and dates of refill. We categorized patients as having discontinued HT early if 180 days elapsed from the prior prescription. For those who continued, we categorized patients as adherent if the medication possession ratio was >/=80%. We used Cox proportional hazards models to estimate the association between discontinuation and non-adherence with all-cause mortality. Among 8,769 women who filled at least one prescription for HT, 2,761 (31%) discontinued therapy. Of those who continued HT, 1,684 (28%) were non-adherent. During a median follow-up of 4.4 years, 813 women died. Estimated survival at 10 years was 80.7% for women who continued HT versus 73.6% for those who discontinued (P < 0.001). Of those who continued, survival at 10 years was 81.7 and 77.8% in women who adhered and non-adhered, respectively (P < 0.001). Adjusting for clinical and demographic variables, both early discontinuation (HR 1.26, 95% CI 1.09-1.46) and non-adherence (HR 1.49, 95% CI 1.23-1.81), among those who continued, were independent predictors of mortality. Both early discontinuation and non-adherence to HT were common and associated with increased mortality. Interventions to improve continuation of and adherence to HT may be critical to improve BC survival.

Authors: Hershman DL; Shao T; Kushi LH; Buono D; Tsai WY; Fehrenbacher L; Kwan M; Gomez SL; Neugut AI

Breast Cancer Res Treat. 2011 Apr;126(2):529-37. Epub 2010 Aug 28.

PubMed abstract

A practical method for collecting food record data in a prospective cohort study of breast cancer survivors

Multiple-day diet records can be unsuitable for cohort studies because of high administrative and analytical costs. Costs could be reduced if a subsample of participants were analyzed in a nested case-control study. However, completed records are usually reviewed (‘documented’) with participants to correct errors and omissions before analysis. The authors evaluated the suitability of using undocumented 3-day food records in 2 samples of women in a Northern California cohort study of breast cancer survivorship (2006-2009). One group of participants (n = 130) received an introduction to the food record at enrollment, while another (n = 70) received more comprehensive instruction. Food records were mailed to participants 6 months later for follow-up and were analyzed as received and after phone documentation. Error rates for adequate completion were high in the first group but substantially lower among persons receiving instruction; prevalences of missing data on serving size and incomplete food descriptions changed from 30% to 4% and from 32% to 6%, respectively (P < 0.0001). Correlations between nutrient intakes calculated from undocumented and documented records were 0.72-0.93 in the first group and were significantly stronger (0.84-0.99) among persons receiving instruction. Documentation had little effect on intraclass correlation coefficients across days, but training increased the coefficients for many nutrients. When participants receive proper instruction, undocumented food records can be satisfactory for large epidemiologic studies.

Authors: Kwan ML; Kushi LH; Song J; Timperi AW; Boynton AM; Johnson KM; Standley J; Kristal AR

Am J Epidemiol. 2010 Dec 1;172(11):1315-23. Epub 2010 Oct 11.

PubMed abstract

Risk factors for lymphedema in a prospective breast cancer survivorship study: the Pathways Study

OBJECTIVE: To determine the incidence of breast cancer-related lymphedema (BCRL) during the early survivorship period as well as demographic, lifestyle, and clinical factors associated with BCRL development. DESIGN: The Pathways Study, a prospective cohort study of breast cancer survivors with a mean follow-up time of 20.9 months. SETTING: Kaiser Permanente Northern California medical care program. PARTICIPANTS: We studied 997 women diagnosed from January 9, 2006, through October 15, 2007, with primary invasive breast cancer and who were at least 21 years of age at diagnosis, had no history of any cancer, and spoke English, Spanish, Cantonese, or Mandarin. MAIN OUTCOME MEASURE: Clinical indication for BCRL as determined from outpatient or hospitalization diagnostic codes, outpatient procedural codes, and durable medical equipment orders. RESULTS: A clinical indication for BCRL was found in 133 women (13.3%), with a mean time to diagnosis of 8.3 months (range, 0.7-27.3 months). Being African American (hazard ratio, 1.93; 95% confidence interval, 1.00-3.72) or more educated (P for trend = .03) was associated with an increased risk of BCRL. Removal of at least 1 lymph node (hazard ratio, 1.04; 95% confidence interval, 1.02-1.07) was associated with an increased risk, yet no significant association was observed for type of lymph node surgery. Being obese at breast cancer diagnosis was suggestive of an elevated risk (hazard ratio, 1.43; 95% confidence interval, 0.88-2.31). CONCLUSIONS: In a large cohort study, BCRL occurs among a substantial proportion of early breast cancer survivors. Our findings agree with those of previous studies on the increased risk of BCRL with removal of lymph nodes and being obese, but they point to a differential risk according to race or ethnicity.

Authors: Kwan ML; Darbinian J; Schmitz KH; Citron R; Partee P; Kutner SE; Kushi LH

Arch Surg. 2010 Nov;145(11):1055-63.

PubMed abstract

Breast cancer DNA methylation profiles are associated with tumor size and alcohol and folate intake

Although tumor size and lymph node involvement are the current cornerstones of breast cancer prognosis, they have not been extensively explored in relation to tumor methylation attributes in conjunction with other tumor and patient dietary and hormonal characteristics. Using primary breast tumors from 162 (AJCC stage I-IV) women from the Kaiser Division of Research Pathways Study and the Illumina GoldenGate methylation bead-array platform, we measured 1,413 autosomal CpG loci associated with 773 cancer-related genes and validated select CpG loci with Sequenom EpiTYPER. Tumor grade, size, estrogen and progesterone receptor status, and triple negative status were significantly (Q-values <0.05) associated with altered methylation of 209, 74, 183, 69, and 130 loci, respectively. Unsupervised clustering, using a recursively partitioned mixture model (RPMM), of all autosomal CpG loci revealed eight distinct methylation classes. Methylation class membership was significantly associated with patient race (P<0.02) and tumor size (P<0.001) in univariate tests. Using multinomial logistic regression to adjust for potential confounders, patient age and tumor size, as well as known disease risk factors of alcohol intake and total dietary folate, were all significantly (P<0.0001) associated with methylation class membership. Breast cancer prognostic characteristics and risk-related exposures appear to be associated with gene-specific tumor methylation, as well as overall methylation patterns.

Authors: Christensen BC; Kushi LH; Kwan ML; Wiencke JK; et al.

PLoS Genet. 2010 Jul 29;6(7):e1001043.

PubMed abstract

Re: Declines in invasive breast cancer and use of postmenopausal hormone therapy in a screening mammography population

Authors: Caan B; Habel L; Quesenberry C; Kushi L; Herrinton L

J Natl Cancer Inst. 2008 Apr 16;100(8):597-8; author reply 599. Epub 2008 Apr 8.

PubMed abstract

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