Months Of Breast Cancer Diagnosis Research Articles

Left ventricular global longitudinal strain is worse in BRCA mutation positive breast cancer patients prior to cancer treatment and premature menopause.

Breast cancer patients with mutations in human tumor suppressor genes BRCA1 and BRCA2 are at higher risk of cardiovascular disease (CVD) than the general population, as they are frequently exposed to cardiotoxic chemotherapy, anti-estrogen therapy, radiation, and/or oophorectomy for cancer-related treatment and prophylaxis. Animal and cell culture models suggest that BRCA mutations may play an independent role in heart failure. We sought to evaluate cardiac structure and function in female BRCA1 and BRCA2 mutation carriers with breast cancer compared to BRCA wildtype women with breast cancer. We performed a 1:2 age- and hypertension-matched retrospective cohort study comparing BRCA1 and BRCA2 mutation carriers (n = 38) versus BRCA wildtype controls (n = 76) with a new diagnosis of breast cancer. Echocardiographic data were obtained within 6months of breast cancer diagnosis and prior to chemotherapy, anti-estrogen therapy, radiation, or oophorectomy. Left ventricular global longitudinal strain (LV-GLS), a highly sensitive marker of LV function, was measured using QLab 15 (Philips Healthcare). In the total cohort of 114 patients with a new diagnosis of breast cancer, the median age was 45 ± 11years and the prevalence of hypertension was 8%. There were no differences in traditional cardiovascular disease risk factors between cases and controls. BRCA carriers had lower LV-GLS (-18.1% ± 4.7% vs. -20.1% ± 3.8%, p = 0.02) and greater right atrial area (12.9cm2 ± 2.7cm2 vs. 11.8cm2 ± 2.0cm2, p = 0.04) compared to controls; however, both LV-GLS and right atrial area were within the normal range. Compared to controls, BRCA carriers had a trend toward worse LV posterior wall thickness (0.89cm ± 0.15cm vs. 0.83cm ± 0.16cm, p = 0.06) although not statistically significant. In women with newly diagnosed breast cancer and prior to treatment, LV-GLS was worse in BRCA1 and BRCA2 mutation carriers compared to those with BRCA wildtype. These findings suggest that BRCA mutations may be associated with subtle changes in cardiac function. Whether differences in GLS translate to increased cardiovascular risk in women with BRCA mutations needs to be further characterized.

Abstract 804: Temporal trends and disparities by race and ethnicity in treatment of women diagnosed with advanced hormone receptor-positive breast cancer: A SEER-Medicare analysis

Abstract Background: The clinical guidelines for management of advanced hormone receptor-positive (HR+) breast cancer (BC) have changed in the past decade with the addition of novel drug classes. We assessed temporal patterns of treatment initiation among women diagnosed with advanced HR+ BC and examined disparities in treatment initiation by race and ethnicity. Methods: Women aged ≥65 years diagnosed with stage IV or metastatic HR+ BC between 2010-2019 were identified in SEER-Medicare. Poisson models were used to estimate age-adjusted annual incidence rates (IR) and 95% confidence intervals (CIs) for treatment initiation within 12 months of BC diagnosis independently by human epidermal growth factor receptor 2 (HER2) status. Age-adjusted incidence rate ratios (IRR) and 95% CIs were estimated to compare rates of initiation among non-Hispanic Black (NHB) and Hispanic patients with non-Hispanic White (NHW) patients. Results: Among 3,476 eligible patients with a mean age of 76.7 (SD: 7.5) years at diagnosis, 79.6% were NHW, 9.5% were NHB, and 6.0% were Hispanic. Among 2,668 women with HR+/HER2- BC, most initiated on aromatase inhibitors (AIs) alone (56.7%), followed by AIs with palbociclib (12.6%). There was a temporal increase in rates of initiation of AIs with palbociclib (IR [95% CI] per 1000 person-years: 252.8 [240.8, 265.4] in 2015 and 343.9 [330.8, 357.7] in 2019. We did not observe significant differences in rates of initiation of AIs alone or with palbociclib by race and ethnicity. Among 537 HR+/HER2+ patients, 25.0% initiated on AIs alone, 24.6% on pertuzumab and trastuzumab with chemotherapy, 14.3% on trastuzumab with chemotherapy, and 9.1% on AIs and trastuzumab with chemotherapy. IRs (95% CI) for initiation of pertuzumab and trastuzumab with chemotherapy increased from 175.6 (146.3, 210.9) in 2013 to 756.5 (698.3, 819.5) in 2019, while rates for trastuzumab with chemotherapy declined from 963.1 (809.4, 1146.0) in 2010 to 88.4 (72.6, 107.5) in 2019. Rates of initiation of AIs and trastuzumab with chemotherapy remained constant over time. Compared to NHW, NHB and Hispanic women were less likely to initiate pertuzumab and trastuzumab with chemotherapy (IRR [95% CI]: 0.52 [0.27, 1.00] and 0.54 [0.24, 1.23] respectively) and more likely to initiate AIs alone (IRR [95% CI]: 2.23 [1.39, 3.55] and 2.98 [1.69, 5.24] respectively). Conclusions: We observed a temporal increase in the initiation of AIs with palbociclib among patients with advanced HR+/HER2- BC. Among patients with HR+/HER2+ BC, rates of initiating pertuzumab and trastuzumab with chemotherapy increased while rates of trastuzumab with chemotherapy declined. The observed differential management of NHB and Hispanic compared with NHW patients with HR+/HER2+ BC using pertuzumab and trastuzumab with chemotherapy and AIs alone requires further investigation. Citation Format: Kexin Zhu, Elisa Bandera, Farzin Khosrow-Khavar. Temporal trends and disparities by race and ethnicity in treatment of women diagnosed with advanced hormone receptor-positive breast cancer: A SEER-Medicare analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 804.

Abstract P2-02-05: Patterns of adjuvant bone modifying agent use in patients with early-stage breast cancer in the United States

Abstract Background: The bone modifying agents (BMAs), bisphosphonates, reduce risk of cancer recurrence after diagnosis of early-stage breast cancer (EBC), particularly in postmenopausal women, while another BMA, denosumab, has not been shown to improve EBC outcomes. The 2017 American Society of Clinical Oncology (ASCO) and Cancer Care Ontario (CCO) clinical guidelines recommended consideration of adjuvant bisphosphonates for postmenopausal women with EBC who are candidates for adjuvant systemic therapy. Despite this, small survey-based studies suggest that their prescribing is variable. The goal of this study was to evaluate prescribing of adjuvant BMAs in the United States before and after publication of the 2017 ASCO/CCO guidelines (ACGD). Methods: This retrospective cohort study used the nationwide Flatiron Health electronic health record (EHR)-derived de-identified database and included 11,740 patients diagnosed with stage I-III breast cancer from 2012 to 2019. We analyzed data on use of BMAs (bisphosphonates or denosumab) in the adjuvant setting, defined as receiving first dose of BMA within 24 months of breast cancer diagnosis and before diagnosis of metastatic disease. Any episodes of BMA use after a metastatic recurrence were excluded. We used Chi-squared test to compare the proportion of patients receiving adjuvant BMAs pre- and post-ACGD. We used univariable and multivariable logistic regression analyses with list-wise missing value deletions to identify predictors of adjuvant BMA prescribing. Results: Of 11,740 patients, 7,391 were diagnosed pre-ACGD and 4,349 post-ACGD. Of the pre-ACGD patients, 545 (7.4%) patients received adjuvant BMAs, and of the post-ACGD patients, 390 (9.0%) patients received adjuvant BMAs. Patients diagnosed post-ACGD were more likely to receive adjuvant BMAs compared with patients diagnosed pre-ACGD (OR 1.23; 95% confidence interval (CI) 1.08-1.42; p=0.002). Of patients age ≥ 50 (n=9,654), 522 of 6,027 (8.7%) and 360 of 3,627 (9.9%) received adjuvant BMAs pre- and post-ACGD, respectively (OR 1.146; 95% CI 0.996-1.319; p=0.0572). In multivariable analysis, age ≥ 50 years at diagnosis, post-menopausal status, having T2 or higher stage at diagnosis, adjuvant endocrine therapy, and coexisting bone loss diagnosis were significantly associated with receipt of adjuvant BMAs (Table 1). Of the 935 patients who received adjuvant BMAs, 615 (65.8%) had denosumab only, 305 (32.6%) had a bisphosphonate only, and 13 (1.4%) received both a bisphosphonate and denosumab during the course of adjuvant treatment. Two patients received an adjuvant BMA as part of a clinical trial. Conclusions: Adjuvant BMA prescribing in our cohort was overall low; there was a modest increase in uptake in patients with EBC diagnosed after the publication of the 2017 ACGD. Older age, higher T stage, endocrine therapy, and coexisting bone loss diagnoses were significantly associated with receipt of adjuvant BMAs. Despite the recommendations for bisphosphonates in the adjuvant setting in EBC, the majority of patients received denosumab only. Considering these findings, further research is required to determine barriers to BMA prescribing and factors that influence physician and patient decisions. There continues to be a need for improved implementation and dissemination of recent guidelines, including the updated 2021 ASCO/CCO recommendations which continue to endorse bisphosphonate use in the adjuvant setting. Table 1: Univariable and multivariable logistic regression analyses to identify predictors of receiving adjuvant BMAs sabs Citation Format: Nicole Odzer, Rachel Jaber Chehayeb, Maryam Lustberg, Cary P. Gross, Julia Foldi. Patterns of adjuvant bone modifying agent use in patients with early-stage breast cancer in the United States [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-02-05.

BRCA1/2 testing among young women with breast cancer in Massachusetts, 2010–2013: An observational study using state cancer registry and All‐Payer claims data

BackgroundTesting for BRCA1/2 pathogenic variants is recommended for women aged ≤45 years with breast cancer. Some studies have found racial/ethnic and socioeconomic disparities in testing. We linked Massachusetts' All‐Payer Claims Database with Massachusetts Cancer Registry data to assess factors associated with BRCA1/2 testing among young women with breast cancer in Massachusetts, a state with high levels of access to care and equitable insurance coverage of breast cancer gene (BRCA) testing.MethodsWe identified breast cancer diagnoses in the Massachusetts Cancer Registry from 2010 to 2013 and linked registry data with Massachusetts All‐Payer Claims Data from 2010 to 2014 among women aged ≤45 years with private insurance or Medicaid. We used multivariable logistic regression to examine factors associated with BRCA1/2 testing within 6 months of diagnosis.ResultsThe study population included 2424 women; 80.3% were identified as non‐Hispanic White, 6.4% non‐Hispanic Black, and 6.3% Hispanic. Overall, 54.9% received BRCA1/2 testing within 6 months of breast cancer diagnosis. In adjusted analyses, non‐Hispanic Black women had less than half the odds of testing compared with non‐Hispanic White women (adjusted odds ratio [OR] = 0.45, 95% CI = 0.31, 0.64). Medicaid‐insured women had half the odds of testing compared with privately‐insured women (OR = 0.51, 95% CI = 0.41, 0.63). Living in lower‐income areas was also associated with lower odds of testing. Having an academically‐affiliated oncology clinician was not associated with testing.ConclusionSocioeconomic and racial/ethnic disparities exist in BRCA1/2 testing among women with breast cancer in Massachusetts, despite equitable insurance coverage of testing. Further research should examine whether disparities have persisted with growing testing awareness and availability over time.

Mediterranean diet and quality of life in women treated for breast cancer: A baseline analysis of DEDiCa multicentre trial

Evidence suggests a beneficial role of the Mediterranean Diet (MedDiet) on health-related quality of life (HRQoL) in healthy subjects. HRQoL is relevant in cancer therapy and disease outcomes, therefore we investigated the association between adherence to the MedDiet and HRQoL in breast cancer survivors participating in the multicentre trial DEDiCa. Diet and HRQoL were assessed at baseline in a subgroup of 309 women enrolled within 12 months of breast cancer diagnosis without metastasis (stages I-III, mean age 52±1 yrs, BMI 27±7 kg/m2). The 14-item PREDIMED questionnaire was used to analyse adherence to the MedDiet. HRQoL was assessed with three validated questionnaires measuring physical, mental, emotional and social factors: EQ-5D-3L, EORTC QLQ-C30 and EORTC QLQ-BR23. Analysis of variance (ANOVA) and multivariate analyses were performed to assess the possible role of the MedDiet on HRQoL. Patients with higher adherence to MedDiet (PREDIMED score >7) showed significantly higher scores for physical functioning (p = 0.02) and lower scores on the symptomatic pain scale (p = 0.04) assessed by the EORTC QLQ-C30 questionnaire compared to patients with a lower adherence to MedDiet (PREDIMED score ≤7). Higher scores from the EQ-5D-3L indicating higher well-being were observed mainly in participants with higher MedDiet adherence (p = 0.05). In adjusted multivariate analyses significant positive associations were found between MedDiet, physical functioning (p = 0.001) and EQ 5D-3L score (p = 0.003) while inverse associations were found with pain and insomnia symptoms (p = 0.005 and p = 0.029, respectively). These results suggest that higher adherence to the MedDiet in breast cancer survivors is associated with better aspects of quality of life, specifically higher physical functioning, better sleep, lower pain and generally higher well-being confirming findings in healthy subjects.

Spirituality and physical health status: a longitudinal examination of reciprocal effects in breast cancer survivors.

This longitudinal study sought to examine the reciprocal relationship between spirituality and physical health status among breast cancer survivors. Breast cancer survivors (N = 634) completed baseline assessments (T1) within 8months of breast cancer diagnosis and 12 (T2) and 18months (T3) after their baseline assessment. Spirituality was assessed by the Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being (FACIT-Sp) scale which consists of three subscales: meaning, peace, and faith. Physical health status was measured with the SF-36 Physical Component Summary (PCS). A cross-lagged structural equation model (SEM) was used to analyze the three-wave data to examine the reciprocal relationships between the observed variable, PCS, and the three subscales of the FACIT-Sp, treated as latent variables. The cross-lagged SEM yielded an adequate fit to the data: RMSEA = .036, CFI = 0.97, TLI = 0.96. After controlling for relevant sociodemographic and cancer-related variables, only higher PCS at T2 predicted greater meaning at T3. PCS at T1 did not predict meaning at T2 and the reciprocal relationship of meaning predicting PCS was not significant. Neither peace nor faith was reciprocally related to PCS. Results provide evidence of a unidirectional relationship between self-reported physical health status and subsequent meaning among breast cancer survivors during the period of early to later survivorship. Additional studies are needed that examine the longitudinal and directional relationships between spirituality and physical health among diverse samples of cancer survivors.

Cancer-related coping processes as predictors of depressive symptoms, trajectories, and episodes.

Although numerous studies address the relationships of depression with coping processes directed toward approaching or avoiding stressful experiences, the large majority are cross-sectional in design, assess coping processes at only one timepoint, or solely include prediction of the linear slope of depressive symptoms. In this research, coping processes were investigated as predictors of depressive symptoms, symptom trajectory classes (consistently high, recovery, consistently low), and major depressive episodes (MDEs) over 12 months in the cancer context. Women (N = 460) within 4 months of breast cancer diagnosis completed assessments of cancer-related coping processes, depressive symptoms, and MDEs at 7 points across 1 year. Beyond sociodemographic and medical variables, coping through cancer-related avoidance an average of 2 months after diagnosis was associated with likelihood of being in the high depressive symptom trajectory class and occurrence of a MDE during the year. Less decline in avoidant coping over time also predicted poor outcomes. In contrast, high initial engagement in approach-oriented coping, as well as increases in coping through emotional expression and acceptance, were associated with lower depressive symptoms across assessments and higher likelihood of being in the recovery or low trajectory class. Greater engagement in cancer-related avoidant coping was associated with all three indicators of depression, and greater approach-oriented coping was related to more favorable outcomes (except MDE). Sustained or increasing coping through emotional expression or acceptance predicted recovery from initially high depressive symptoms. Approach- and avoidance-oriented coping processes constitute malleable targets for preventive and ameliorative approaches. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Characterization of bone only metastasis patients with respect to tumor subtypes

Metastatic breast cancer (MBC) patients with bone only metastasis (BOM) are a unique population with limited characterization. We identified patients followed at MD Anderson Cancer Center from 01/01/1997 to 12/31/2015 for at least 6 months with a BOM diagnosis as first site of metastasis. Tumor subtype (TS) was assessed by initial breast biopsy immunohistochemistry using hormonal receptor (HR) and HER2 status, with four subtypes identified: HR+/HER2−, HR+/HER2+, HR−/HER2−, HR−/HER2+. HR+ was defined as estrogen receptor or progesterone receptor ≥1%. We identified 1445 patients with BOM, 1048 with TS data available. Among these patients, the majority were HR+/HER2− (78%). Median time from breast cancer diagnosis to first bone metastasis was 2.3 years (95% CI 2.1, 2.5) and varied significantly by TS, with longer time to distant disease in HR+/HER2− patients relative to all other TS (p < .0001). Median overall survival (OS) from breast cancer diagnosis was 8.7 years (95% CI 8.0, 9.7) and varied significantly by TS with poorer OS for HR−/HER2− and HR-/HER2+ patients relative to HR+/HER2− TS (p < .0001). The 442 patients with de novo BOM disease, defined as bone metastasis diagnosis within 4 months of breast cancer diagnosis, had significantly shorter OS (p < .0001). Overall, several higher risk BOM subsets were identified in this analysis, most notably HR−/HER2+ and HR−/HER2− TS and de novo BOM patients.

Abstract P6-07-12: A physical activity and dietary counseling intervention in breast cancer survivors and changes in known and novel prognostic biomarkers

Abstract High rates of overweight/obesity are commonly seen in breast cancer (BC) survivors. Observational data show an association between post-treatment increased weight and lack of physical activity (PA) and risk of BC recurrence and death. Increases in prognostic inflammatory associated biomarkers (BM) such as interleukin-6 (IL6) and C-reactive protein (CRP), and their downstream effects, are linked to overweight/obesity and provide a potential mechanistic explanation for this increase in recurrence risk, but studies are mixed regarding the effect of lifestyle interventions on these BM. In addition, better BM may exist. The Getting on Board with an Active Lifestyle (GOAL) study tested the feasibility of a PA and dietary counseling (DC) intervention in BC survivors and included known BM (IL6 , CRP) as well as a novel BM (advanced glycation end-products [AGEs]). AGEs are reactive metabolites produced by an uncontrolled reaction between sugars and proteins and were selected because they are seen in chronic diseases including: diabetes, neuro-degenerative disorders, stroke, heart disease and more recently, BC. Further, dietary AGEs are consumed in high fat and highly processed foods that contribute to overweight/obesity. Methods: Ten overweight/obese women (BMI≥25) within 36 months of BC diagnosis (stage I-III) participated in a 12-week supervised PA and DC intervention consisting of two supervised PA sessions per week and weekly DC sessions. Body mass index (BMI), resting heart rate (HR) and blood pressure (BP) and blood samples were collected at baseline, week 4, 8, 12, 24, 36, 52. IL-6, CRP and AGEs were assessed in serum using commercially available 96-well format ELISAs. Data through week 12 is presented here. Results: Ten participants (four African American) completed the 12-week intervention. The age range of participants was 50-68 years (mean 56 years). The average number of daily active minutes increased significantly between baseline (45) and week 11 (71). There was a drop off at week 12 due to right-censoring of the data. Dietary AGE intake decreased in 8 of 10 participants from baseline to week 12 (average reduction 53%). Significant reductions in mean serum AGEs were seen (baseline=53 ug/ml, week 12=38ug/ml, p&amp;lt;0.001). No correlating reductions in CRP or IL6 were found. Correlations were seen between AGE levels and AGE intake (r=0.24 at week 12). There were no significant correlations between AGE levels and IL6 or CRP. Decreases in BMI (average change -.54 kg/m2), resting HR and BP corroborated with AGE reductions. Conclusions: The GOAL intervention has the potential to improve PA and dietary AGE intake among overweight/obese BC patients. Participants improved weight, resting HR, BP, and number of daily active minutes; which are important metrics for overall health. There were no changes in IL6 and CRP, but reductions in AGEs correlated with reductions in dietary AGE levels, indicating that serum AGEs may be reduced through diet and PA. Serum AGEs may represent a better BM than IL6 and CRP in BC survivors. Further investigation of AGEs in BC survivors is warranted. Citation Format: Peterson LL, Ford ME, Gregoski MJ, Knight KD, Hilton EJ, Magwood G, Turner DP. A physical activity and dietary counseling intervention in breast cancer survivors and changes in known and novel prognostic biomarkers [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-07-12.

Hormonal therapy for breast cancer and diabetes incidence among postmenopausal women

PurposeThe purpose of this study was to evaluate associations between hormonal therapy for breast cancer and subsequent diabetes incidence. MethodsThe Surveillance, Epidemiology and End Results—Medicare linked data were used. Stage I–III breast cancer patients 65 years or older who filled at least two prescriptions for an aromatase inhibitor (AI) or tamoxifen by the end of 2008, and within 12 months of breast cancer diagnosis, were selected. Women without cancer from a 5% random sample of Medicare beneficiaries were frequency matched to patients by age group, and new onset diabetes was monitored for 24 months postbaseline in both groups of women. ResultsCox-proportional hazards analysis failed to show an association between AI use and subsequent diabetes onset after adjusting for age, race, and comorbidity (hazard ratio: 0.99; 95% confidence interval: 0.84–1.18). This study also failed to show an association between tamoxifen use and diabetes onset (hazard ratio: 0.79; 95% confidence interval: 0.54–1.17). ConclusionsStudy findings provide evidence that postmenopausal AI and tamoxifen users do not experience an increased risk of diabetes in the 2 years after treatment initiation. Whether these findings will hold with longer duration follow-up deserves a closer look.

Trajectories of depressive symptoms following breast cancer diagnosis.

This longitudinal study sought to identify groups of breast cancer survivors exhibiting distinct trajectories of depressive symptoms up to 24 months following diagnosis, and to describe characteristics associated with these trajectories. A total of 653 women completed baseline questionnaires within 8 months of breast cancer diagnosis on patient characteristics, symptoms, and psychosocial variables. Depressive symptoms were assessed at baseline and 6, 12, and 18 months after baseline. Chart reviews provided cancer and treatment-related data. Finite mixture modeling identified trajectories of depressive symptoms measured with the Beck Depression Inventory (BDI). Six distinct trajectories were identified. Just over half of the sample had consistently very low (3.8%) or low (47.3%) BDI scores well below the traditional BDI cutoff point of 10 thought to be indicative of clinically significant depression; 29.2% had consistently borderline scores; 11.3% had initially high scores that declined over time, but remained above the cutoff point; 7.2% showed increased BDI over time; and a small but unique group (1.1%) reported chronically high scores above 25. Women in groups with lower depressive symptom levels were older, had less rigorous chemotherapy, fewer physical symptoms (fatigue and pain), and lower levels of illness intrusiveness. Approximately 20% of women had levels of depressive symptoms indicative of clinical depression that were maintained 2 years postdiagnosis. Factors related to trajectory membership such as illness intrusiveness, social support, fatigue, pain, and vasomotor symptoms suggest targets for possible intervention. Results demonstrate the heterogeneity of depressive symptoms following breast cancer and the need for continued screening posttreatment.

Abstract B27: Overweight/obesity and physical activity rates in an ethnically diverse sample of breast cancer survivors

Abstract Background: High body mass index (BMI) is linked to poorer survival after breast cancer diagnosis. Physical activity (PA) could moderate this association. Objectives/Hypothesis: Prevalence of high BMI (overweight/obesity) and level of PA were evaluated in a statewide sample of women within 18 months of breast cancer diagnosis. Methods: In an ongoing study, 73 women (35 EA and 38 AA) were identified through the SC Central Cancer Registry, and were interviewed to obtain their self-reported body weight, height, PA and other data. Results: Age: Age ranged from 26 to 90 years (mean 61 years, SD 13.0), with AAs 2.1 years younger than EAs (p=0.49). Education: 62% had more than a high school (HS) diploma (58% of AAs and 66% of EAs, p=0.49). BMI: 77% were overweight/obese; 42% of AAs and 31% of EAs were overweight, 45% of AAs and 34% of EAs were obese (p=0.03). PA: 23% reported no PA (29% of AAs and 17% of EAs, p=0.23). Only 38% met CDC PA guidelines of at least 150 min/week of moderate PA (29% of AAs and 47% of EAs; p=0.11). PA and BMI: PA &amp;lt;90 min/week was associated with 4-fold higher risk of overweight/ obesity (p=0.023). No significant associations were seen by race. PA and Education: No significant association was observed between &amp;gt;HS education and meeting PA guidelines (p=0.15), or between &amp;gt;HS education and greater PA per week (p=0.57). Education and BMI: No significant association was seen (p=0.77). Conclusions: Prevalence of overweight/obesity was high, especially among AAs. Future Recommendations: It is imperative to identify strategies to reduce obesity/overweight in BRCA survivors. Citation Format: Joan E. Cunningham, Colleen E. Bauza, Erika T. Brown, Alberg J. Anthony, Emily Kistner-Griffin, Ida J. Spruill, Debbie C. Bryant, Nestor F. Esnaola, Melanie S. Jefferson, Keith Whitfield, Rita M. Kramer, Susan Bolick, Deborah Hurley, Catishia Mosley, Tonya R. Hazelton, Vivian J. Bea, Dana R. Burshell, Kendrea D. Knight, Marvella E. Ford. Overweight/obesity and physical activity rates in an ethnically diverse sample of breast cancer survivors. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr B27.

Abstract 3724: Race/ethnicity, genetic ancestry, and breast cancer-related lymphedema

Abstract Background: Breast cancer-related lymphedema (BCRL) is a serious chronic condition that can occur in about 30% of patients after breast cancer (BC) surgery and treatment. Patient risk factors include younger age, higher BMI, and less physical activity. With few studies to date, it is largely unknown if BCRL risk varies by race/ethnicity. Methods: In a prospective study of 2,953 BC patients, we examined the association of self-reported BCRL status at 12 and 48 months post-BC diagnosis with self-reported race/ethnicity and genetic ancestry. We also assessed associations with other clinical and patient factors. Race/ethnicity (White, African American (AA), Hispanic, Asian, and Other) was asked in the baseline interview at cohort entry. Genetic ancestry was estimated based on a validated panel of 124 ancestry informative markers (AIMs) using the STRUCTURE program. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated by multivariable Cox proportional hazards models, with follow-up until date of BCRL self-report or last patient contact, whichever occurred first. Results: 342 (11.6%) women reported having BCRL at 12 or 48 month follow-up, with 204 who were White, 37 AA, 41 Hispanic, 49 Asian, and 11 Other. Younger age at BC diagnosis, higher BMI at baseline, and less moderate-vigorous physical activity were associated with greater BCRL risk. After adjusting for sociodemographic and clinical factors, AA women had a significant 1.6-fold increased risk of BCRL (HR = 1.57; 95% CI: 1.09, 2.26) and Hispanic women had a borderline 1.4-fold increased risk (HR = 1.37; 95% CI: 0.99, 1.89), compared with White women. Consistent with self-reported race/ethnicity, African ancestry was associated with a 1.8-fold increased risk of BCRL (HR = 1.80; 95% CI: 1.15, 2.81). When the race/ethnicity and ancestry models were further adjusted for BCRL risk factors, i.e., age at BC diagnosis, BMI, and physical activity, associations became attenuated and non-significant among AA (HR = 1.26, 95% CI: 0.87-1.83) and Hispanic women (HR = 1.19, 95% CI: 0.85-1.68), and with African ancestry (HR = 1.38, 95% CI: 0.88-2.19). Results were similar when excluding BCRL events within 6 months of BC diagnosis to rule out transient post-operative swelling, except a suggestive increased risk of BCRL remained among AA women (HR = 1.47, 95% CI: 0.94-2.28) and with African ancestry (HR = 1.70, 95% CI: 0.99-2.91) after adjustment for BCRL risk factors. Further, the elevated BCRL risk seen in AA or Hispanic women, and with African ancestry, appeared to be stronger in non-obese compared with obese women. Discussion: AA women had increased risk of BCRL compared with White women, which is partly attributed to differences in age at BC diagnosis, BMI, and physical activity. This is the first large-scale, prospective study to examine a racial/ethnic disparity of BCRL risk with self-report and genetic ancestry data. Funded by R01 CA105274. Citation Format: Marilyn L. Kwan, Valerie S. Lee, Janise M. Roh, Isaac J. Ergas, Yali Zhang, Susan E. Kutner, Charles P. Quesenberry, Christine B. Ambrosone, Lawrence H. Kushi, Song Yao. Race/ethnicity, genetic ancestry, and breast cancer-related lymphedema. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3724. doi:10.1158/1538-7445.AM2015-3724

CMF-regimen Preferred as First-course Chemotherapy for Older and Sicker Women With Breast Cancer

The objective of this study was to determine the sociodemographic and clinical characteristics associated with Cyclophosphamide, Methotrexate, and 5-Fluorouracil (CMF) utilization as a first-course chemotherapy regimen among female Medicare patients with early-stage breast cancer. A longitudinal study was conducted with women 66 years and older, diagnosed with stage I to III breast cancer from 1993 to 2004, and receiving chemotherapy using the Surveillance, Epidemiology, and End Result-Medicare data. First-course CMF chemotherapy was defined as chemotherapy initiation within 6 months of breast cancer diagnosis, with at least 1 claim of CMF each within 1 year of diagnosis. Logistic regression was used to perform the analysis. Older and sicker women, living in census tracts with lower average education, and diagnosed with advanced stage, hormone receptor-negative tumors have a higher probability of CMF administration. Receipt of lymph node dissection and nonreceipt of radiation therapy were also associated with CMF administration. CMF administration has declined over the years and has significant regional variation. Reduction in CMF use overtime indicates the increased use of newer and more effective systemic therapies among breast cancer patients. In spite of the reduction in CMF use over time, CMF is more frequently administered to older and sicker women, possibly because of higher risk of anthracycline-induced toxicities in these patients. Clinical guidelines have no recommendations for CMF administration in breast cancer patients with certain clinical characteristics. Hence, it is important to understand if the associations observed in this study can be clinically justified in order to reduce unjustified use of less-effective regimens.

Trajectories of Posttraumatic Growth and Associated Characteristics in Women with Breast Cancer.

Cancer survivors may experience posttraumatic growth (PTG), positive psychological changes resulting from highly stressful events; however, the longitudinal course of PTG is poorly understood. The purpose of the present study was to determine trajectories of PTG in breast cancer survivors and associated characteristics. Women (N = 653) participating in a longitudinal observational study completed questionnaires within 8months of breast cancer diagnosis and 6, 12, and 18months later. Group-based modeling identified PTG trajectories. Chi-square tests and ANOVA detected group differences in demographic, medical, and psychosocial variables. Six trajectory groups emerged. Three were stable at different levels of PTG, two increased modestly, and one increased substantially over time. Trajectory groups differed by age, race, receipt of chemotherapy, illness intrusiveness, depressive symptoms, active-adaptive coping, and social support. This first examination of PTG trajectories in US cancer survivors elucidates heterogeneity in longitudinal patterns of PTG. Future research should determine whether other samples exhibit similar trajectories and whether various PTG trajectories predict mental and physical health outcomes.

The effect of metformin on breast cancer outcomes in patients with type 2 diabetes.

Observational data suggest that metformin use decreases breast cancer (BC) incidence in women with diabetes; the impact of metformin on BC outcomes in this population is less clear. The purpose of this analysis was to explore whether metformin use influences BC outcomes in women with type 2 diabetes. Prospective institutional databases were reviewed to identify patients with diabetes who received chemotherapy for stages I–III BC from 2000 to 2005. Patients diagnosed with diabetes before or within 6 months of BC diagnosis were included. Males and those with type I, gestational, or steroid-induced diabetes were excluded. Patients were stratified based on metformin use, at baseline, defined as use at time of BC diagnosis or at diabetes diagnosis if within 6 months of BC diagnosis. Kaplan–Meier methods were used to estimate rates of recurrence-free survival (RFS), overall survival (OS), and contralateral breast cancer (CBC). We identified 313 patients with diabetes who received chemotherapy for BC, 141 (45%) fulfilled inclusion criteria and 76 (54%) used metformin at baseline. There were no differences in clinical presentation or tumor characteristics between metformin users and nonusers. At a median follow-up of 87 months (range, 6.9–140.4 months), there was no difference in RFS (P = 0.61), OS (P = 0.462), or CBC (P = 0.156) based on metformin use. Five-year RFS was 90.4% (95% CI, 84–97) in metformin users and 85.4% (95% CI, 78–94) in nonusers. In this cohort of patients with type 2 diabetes receiving systemic chemotherapy for invasive BC, the use of metformin was not associated with improved outcomes.

Abstract P3-07-05: Frequent BRCA1 and BRCA2 mutations are found in Mexican and Mexican-American women with breast cancer

Abstract Background: The Arizona Cancer Registry has shown that in Pima County, AZ, breast cancer diagnosed in young Latinas increased 40% from 2004-2008, compared to 1999-2003, and Latinas more likely to die of their cancer. This study seeks to characterize genetic variation in women of Mexican ancestry with breast cancer using next generation sequencing, with the goal of providing prevalence information to help guide screening and cancer prevention efforts. Methods: The ELLA Binational Breast Cancer Study enrolled women of Mexican ancestry living in either U.S. or Mexico within 24 months of breast cancer diagnosis. Mexican women from the state of Jalisco were collected through collaboration with the Universidad de Guadalajara and women of Mexican ancestry were recruited from Tucson and Phoenix, AZ. Genomic DNA from 92 ELLA study participants (49 from the U.S. and 43 from Mexico) was enriched for breast cancer influencing gene sequence using the BROCA panel with standard techniques. Samples were sequenced with next generation sequencing and variants identified. Results: Sequencing of breast cancer risk genes in 92 Mexican and Mexican-American women with breast cancer revealed the presence of deleterious mutations in 15% of women (14/92). Five carry mutations in BRCA1, 5 in BRCA2, 2 in CHEK2, 1 in PALB2 and 1 in RAD51C. An additional 9% of participants (8/92) carry rare mutations of unknown functional consequence in the same genes. Four carry mutations in BRCA1 or BRCA2 at sites predicted to alter splice enhancers and four carry missense mutations in CHEK2 that are predicted to damage to kinase function. None of these variants appear in public databases or are characterized functionally in gene-specific databases. Dozens of women carry VUS or novel variants. Women carrying BRCA1 mutations are significantly more likely to have had triple negative pathology. Women carrying other mutations known or thought to be deleterious are also more likely to have been younger at diagnosis, to have more aggressive breast cancer or to report a family history of breast cancer. Table 1. Deleterious MutationsGeneEffectTotalBRCA1185delAG1BRCA12569delC2BRCA1Del Complete Gene1BRCA1Del Exons 9-121BRCA2c.658delGT1BRCA2c.3264insT2BRCA2c.5195delT1BRCA2c.6024insG1CHEK2R160G2PALB2S779 Stop1RAD51CDel Exons 4-91 Conclusion: Deleterious BRCA1 and BRCA2 gene mutations are common among women of Mexican ancestry diagnosed with breast cancer. Within this cohort, the prevalence of BRCA1/2 mutations is 11%, and 4% of women carry mutations in other genes increasing breast cancer risk. This is higher than the 10% mutation prevalence estimated for Ashkenazi Jewish women with breast cancer. An additional 9% of women carry variants likely to disrupt gene function and dozens of VUS and novel variants are found in these women. Further analysis of samples from the remaining 942 women using genetic sequencing will help further elucidate the role of genetic risk factors in women of Mexican ancestry with breast cancer. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-07-05.

HIV Tropism and Decreased Risk of Breast Cancer

BackgroundDuring the first two decades of the U.S. AIDS epidemic, and unlike some malignancies, breast cancer risk was significantly lower for women with human immunodeficiency virus (HIV) infection compared to the general population. This deficit in HIV-associated breast cancer could not be attributed to differences in survival, immune deficiency, childbearing or other breast cancer risk factors. HIV infects mononuclear immune cells by binding to the CD4 molecule and to CCR5 or CXCR4 chemokine coreceptors. Neoplastic breast cells commonly express CXCR4 but not CCR5. In vitro, binding HIV envelope protein to CXCR4 has been shown to induce apoptosis of neoplastic breast cells. Based on these observations, we hypothesized that breast cancer risk would be lower among women with CXCR4-tropic HIV infection.Methods and FindingsWe conducted a breast cancer nested case-control study among women who participated in the WIHS and HERS HIV cohort studies with longitudinally collected risk factor data and plasma. Cases were HIV-infected women (mean age 46 years) who had stored plasma collected within 24 months of breast cancer diagnosis and an HIV viral load ≥500 copies/mL. Three HIV-infected control women, without breast cancer, were matched to each case based on age and plasma collection date. CXCR4-tropism was determined by a phenotypic tropism assay. Odds ratios (OR) and 95% confidence intervals (CI) for breast cancer were estimated by exact conditional logistic regression. Two (9%) of 23 breast cancer cases had CXCR4-tropic HIV, compared to 19 (28%) of 69 matched controls. Breast cancer risk was significantly and independently reduced with CXCR4 tropism (adjusted odds ratio, 0.10, 95% CI 0.002–0.84) and with menopause (adjusted odds ratio, 0.08, 95% CI 0.001–0.83). Adjustment for CD4+ cell count, HIV viral load, and use of antiretroviral therapy did not attenuate the association between infection with CXCR4-tropic HIV and breast cancer.ConclusionsLow breast cancer risk with HIV is specifically linked to CXCR4-using variants of HIV. These variants are thought to exclusively bind to and signal through a receptor that is commonly expressed on hyperplastic and neoplastic breast duct cells. Additional studies are needed to confirm these observations and to understand how CXCR4 might reduce breast cancer risk.

Quality of life among women recently diagnosed with invasive breast cancer: the Pathways Study

Few studies have assessed quality of life (QOL) of women diagnosed with breast cancer within the first few weeks of their initial diagnosis. We describe QOL among 950 women recently diagnosed with invasive breast cancer. Starting in January 2006, we invited women aged > or =21 years who were diagnosed with first primary invasive breast cancer within Kaiser Permanente Northern California (KPNC) to enroll in the Pathways Study, a prospective study of breast cancer survivorship. QOL was measured using the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B), along with sociodemographic and social support information. Clinical characteristics were obtained from the KPNC cancer registry and electronic medical record. We used multivariable linear regression models to identify factors associated with QOL scores calculated from the FACT-B. The mean age +/- SD of the sample was 59.6 years (+/-11.9 years), and the mean time +/-SD from diagnosis until interview was 8.0 weeks (+/-3.2 weeks). Younger age at diagnosis was associated with lower scores in all QOL domains (P < 0.01), and later stage at diagnosis was associated with lower scores in all domains (P < 0.05) except for social well-being. Higher levels of social support were associated with higher QOL except for physical well-being (P < 0.05). These associations were stronger within 2 months of breast cancer diagnosis. Quality of life as influenced by a diagnosis of breast cancer is an important factor in cancer survivorship. Age, stage at diagnosis, and social support are key factors in this important variable.

Re: Acute Myeloid Leukemia or Myelodysplastic Syndrome Following Use of Granulocyte Colony-Stimulating Factors During Breast Cancer Adjuvant Chemotherapy

Background Recently, increasing numbers of women receiving adjuvant chemotherapy for breast cancer have also received granulocyte colony-stimulating factors (G-CSFs) or granulocyte-macrophage colony-stimulating factors (GM-CSFs). Although these growth factors support chemotherapy, their long-term safety has not been evaluated. We studied the association between G-CSF use and incidence of leukemia in a population-based sample of breast cancer patients. Methods Among women aged 65 years or older in the Surveillance, Epidemiology, and End Results-Medicare database who were diagnosed with stages I-III breast cancer from January 1, 1991, to December 31, 1999, we identified those who received G-CSF or GM-CSF concurrently with chemotherapy. We used Cox proportional hazards models to estimate hazard ratios for the association of treatment with G-CSF or GM-CSF and subsequent (through December 31, 2003) diagnosis of acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). All statistical tests were two-sided. Results Of 5510 women treated with chemotherapy, 906 (16%) received G-CSF or GM-CSF therapy, and 64 (1.16%) were subsequently diagnosed with either MDS or AML before a cancer recurrence. Use of G-CSF and GM-CSF was associated with more recent diagnosis, younger age, urban residence, fewer comorbidities, receipt of radiation therapy, positive lymph nodes, and cyclophosphamide treatment. Of the 906 patients who were treated with G-CSF, 16 (1.77%) developed AML or MDS; of the 4604 patients not treated with G-CSF, 48 (1.04%) developed AML or MDS. The hazard rate ratio for AML or MDS among those treated with G-CSF or GM-CSF compared with those who were not was 2.14 (95% confidence interval [CI] = 1.12 to 4.08). AML or MDS developed within 48 months of breast cancer diagnosis in 1.8% of patients who received G-CSF or GM-CSF but only in 0.7% of patients who did not (hazard ratio = 2.59, 95% CI = 1.30 to 5.15). Conclusions The use of G-CSF was associated with a doubling in the risk of subsequent AML or MDS among the population that we studied, although the absolute risk remained low. Even if this association is confirmed, the benefits of G-CSF may still outweigh the risks. Meanwhile, however, G-CSF use should not be assumed to be risk free.