Non-metastatic HER2 Research Articles

Abstract P4-16-03: Cardiovascular outcomes and long term survival with discontinuation of adjuvant trastuzumab

Abstract Background: Trastuzumab (T) induced cardiomyopathy remains a significant limitation to adjuvant HER2 directed therapy. Recent studies have aimed to reduce cardiotoxicity through combination with non-anthracycline (non-A) chemotherapy or shorter treatment duration. However there is limited data regarding cardiac outcomes and long-term survival with early discontinuation of adjuvant T. Methods: An IRB-approved single-institution retrospective analysis was performed for 401 consecutive patients with non-metastatic HER2+ breast cancer treated at the Ohio State University Comprehensive Cancer Center from 2005-2015. Medical records were reviewed for clinicopathologic features, systemic treatment and survival information. Disease Free Survival (DFS) was defined as time from diagnosis to first recurrence (loco-regional or distant recurrence) including second primary breast cancer or death. Overall survival (OS) was defined as time from diagnosis to death or last known follow up. OS and DFS estimates were generated using Kaplan Meier methods and compared using Log-rank tests. Cox proportional hazard models were used to calculate univariate and multivariate hazard ratios for OS and DFS. Results: A total of 371/401 (92.5%) patients received adjuvant T (n= 401, mean age: 59.4 years; stage 1: 120, 30%; stage II: 194, 48%; stage III: 87, 22%; ER+: 235, 58%); among whom 106/371 (28.6%) patients held adjuvant T for any reason. Median duration of therapy in patients with any interruption with T was 11.3 (0.5-16.9) months and 23/371 (6.9%) received less than 6 months of adjuvant T. Cardiomyopathy (measured as LVEF decline on 2D echocardiogram or MUGA >= 15 points) was the most common reason for withholding T (66/106, 62.3%). The majority of these patients received a cardiology referral (77/ 106, 72.6%) with a 13 day mean time to evaluation in outpatient clinic. Patients receiving non-A chemotherapy and beta blockers or ACE inhibitors during treatment were significantly less likely to experience cardiomyopathy (A vs non-A: 49/190, 25.8% vs. 16/136, 11.8% p=0.002); (Med vs no Med: 7/148, 4.73% vs 59/184, 32.1%; p<0.001). Log-rank tests indicate a significant worsening in OS and DFS for patients who discontinued T (p=0.021, 0.001 respectively). Multivariate analyses confirmed significant worsening in DFS after adjusting for age, stage, ER , node status, and cardiomyopathy (Adjusted HR: 4.0[2.02 – 7.92], p< 0.001) Table 1- Discontinuation of adjuvant trastuzumab Number of patients (%)Initial treatment371Completed therapy with no interruption265 (71.4)Interruption of therapy for minimum of 2 weeks64 (17.2)Permanently discontinued42 (11.3) Conclusion: Discontinuation of adjuvant trastuzumab, most often from cardiomyopathy, is an independent prognostic marker for worse DFS in non-metastatic HER2 positive breast cancer. Non-anthracycline chemotherapy and use of cardio-protective medication is associated with significantly reduced incidence of cardiotoxicity in this population. Future prospective studies should consider optimizing cardiovascular function to avoid interruption in adjuvant HER 2 directed therapy. Citation Format: Sardesai S, Liu J, Palettas M, Stephens J, Stover D, Williams N, Reinbolt R, VanDeusen J, Wesolowski R, Lustberg M, Ramaswamy B. Cardiovascular outcomes and long term survival with discontinuation of adjuvant trastuzumab [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-16-03.

Variations in cost for non-metastatic HER2- breast cancer (BC), non-small cell lung cancer (NSCLC), and colorectal cancer (CRC).

e18106 Background: We aim to quantify economic outcomes of the most commonly used chemotherapy regimens for BC, NSCLC, and CRC in a commercially insured population. Methods: This analysis used clinical data from a prior authorization program for chemotherapy regimens linked with administrative claims data from 6/1/2015 to 5/31/2016. Clinical data included cancer type, stage at diagnosis, and biomarkers. Eligible patients were commercially insured members with a prior authorization request for one of the most commonly used NCCN recommended regimens for BC, NSCLC and CRC. Outcomes, including total healthcare cost and cost of chemotherapy were tracked from first claim for chemotherapy until end of treatment due to discontinuation, death or change in treatment. Patients were censored at 5/31/2016 or end of enrollment. Results: There were 1612 BC, 237 NSCLC, and 386 CRC non-censored patients who received therapy during the study period. Mean (SD) total and monthly drug costs and total health care costs for the most common regimens by cancer are summarized in the table. Conclusions: The relative value of the most common therapies for BC, NSCLC, and CRC varied significantly depending on the metric used underscoring the importance of comparing total healthcare costs when assessing the value of therapies. Information on these and other regimens will increase as the database grows over time. [Table: see text]

Variations in inpatient stays for non-metastatic HER2- breast cancer (BC), non-small cell lung cancer (NSCLC), and colorectal cancer (CRC) in a real world setting.

e18099 Background: We aim to compareprevalence and duration of inpatient stays during the most commonly used chemotherapy regimens for BC, NSCLC, and CRC in a commercially insured population. Methods: This analysis used clinical data obtained from a prior authorization program for chemotherapy linked with administrative claims data from 6/1/2015 to 5/31/2016. Clinical data included cancer type, stage at diagnosis, relevant biomarkers, and evidence of progression/relapse. Eligible patients included commercially insured members with a prior authorization request for one of the most commonly used NCCN recommended regimens for BC, NSCLC and CRC. Outcomes, including percent of patients experiencing an inpatient stay and number of inpatient days were tracked from the first claim for chemotherapy until end of treatment due to discontinuation, death or change in treatment, with remaining patients censored at 5/31/2016 or end of enrollment. Results: There were 1612 HER2- BC, 237 NSCLC, and 386 CRC patients who completed therapy during the study period. Incidence and inpatient stay days per 100 patient months for the most common regimens for each cancer are summarized in the table. Conclusions: The rates and duration of inpatient stays varied substantially across the most commonly used therapies for BC, NSCLC and CRC. These data show the importance of systematically incorporating the impact of hospitalizations alongside other clinical outcomes in treatment choice in routine clinical practice. As the database grows over time, these data will help clinicians and patients better evaluate regimen choices for various cancers. [Table: see text]

Retrospective study of the efficacy and safety of neoadjuvant docetaxel, carboplatin, trastuzumab/pertuzumab (TCH-P) in nonmetastatic HER2-positive breast cancer.

Pertuzumab is FDA approved in the preoperative setting in combination with trastuzumab and chemotherapy, in women with nonmetastatic HER2+breast cancer. The TRYPHAENA trial (n=77) reported a pathologic complete response rate (pCR), i.e., ypT0ypN0, of 52% in patients treated with neoadjuvant (docetaxel, carboplatin, trastuzumab, & pertuzumab) TCH-P. Aside from this study, there is limited information regarding the safety and efficacy of TCH-P in the neoadjuvant setting. Our goal was to evaluate the safety and efficacy of neoadjuvant TCH-P in a non-clinical trial setting. Cancer data registry was utilized to identify patients with HER2+nonmetastatic breast cancer that received neoadjuvant TCH-P. pCR was defined as the absence of invasive or noninvasive cancer in breast and lymph nodes, i.e., ypT0ypN0. 70 patients with a median age of 52years met our inclusion criteria. Clinical staging was I-8.5%; II-68.5%; and III-22.8%. 60% of patients had hormone receptor (HR)-positive tumors. 23% (16/71) of patients required dose reduction for rash, diarrhea, neuropathy, or thrombocytopenia. Overall, no patients developed grade 3-4 left ventricular systolic dysfunction(LVSD); an asymptomatic reduction in LVEF of>10% was observed in three patients. The overall observed pCR rate was 53%. As expected, the pCR rate was higher in patients with HR-negative breast cancer than for patients with HR+ disease: 69% (20/29) vs. 42% (17/41), respectively. The axillary downstaging rate was approximately 53% (19/36). Neoadjuvant TCH-P, in a nonclinical trial setting, was associated with a pCR rate of 53% similar the reported rate in TRYPHAENA. Toxicity was manageable, with no patients experiencing symptomatic heart failure.

Abstract P1-15-01: Adjuvant trastuzumab +/- anthracycline and cardiotoxicity in a community cohort of 962 HER2+ breast cancers from 2005-2011: Comparison of incidence by risk factors and by diagnostic codes vs clinical chart review

Abstract Background: Prospective clinical trials using clinical criteria and observational studies using diagnostic codes from electronic health records have reported seemingly contradictory cardiotoxicity risk for adjuvant trastuzumab (T). Accurate estimates of individualized patient specific cardiotoxicity risk are essential for treatment decisions in early HER2+ breast cancer (BC). Methods: 1,109 consecutive non-metastatic HER2+ invasive BC's diagnosed 5/1/2005 to 12/31/2011 at Kaiser Permanente Northern California receiving adjuvant T were reviewed for symptomatic congestive heart failure (SxCHF), baseline and post-T cardiac ejection fraction (EF), anthracycline (A) use, and CHF risk factors (RF) including age, race, hypertension (HTN), diabetes (DM), obesity, smoking. Records of patients with CHF ICD9 codes or an EF drop to <50% were reviewed by a RN, a cardiologist, and an oncologist. Primary outcomes were SxCHF (NYHA Class II or higher), EF fall to <50%, and < 38 weeks of T (75% of prescribed). Results: Median age of 962 eligible patients was 54 years (range 24-95). 305 (31.7%) were > 60 years old. During a median follow-up of 4.1 years, 4.6% of patients had CHF ICD9 codes, but only 2.5% had SxCHF or cardiac death confirmed by clinical review. At 1 year, cumulative incidence of an EF fall to <50% was 5.7% with T alone and 17.7% with T+ A. A total of 15.3% finished <38 weeks of T, 9.4% with T alone and 20.6% with T+A. The overall 2- and 5-year cumulative incidence of SxCHF/cardiac death was low: 1.3% and 2.7% with T alone and 2.2% and 3.1% with T + A. These rates were lower than reports based solely on diagnostic or billing codes, and varied substantially by RF (see table). The rates were similar to those predicted by the NSABP B-31 Cardiac Risk Score. Clinical heart failure based on diagnostic codes was not confirmed at chart review 48% of the time. Results from multivariable analyses will be presented. Predictors of Trastuzumab Cardiotoxicity Cumulative Incidence (%)PredictorsNFall EF to<50%Symptomatic CHF 1-year2-year5-yearAll96212.01.82.8Anthracycline50517.72.23.1Non-anthracycline4575.71.32.7Age<6065711.71.11.1Age 60-6922212.61.43.8Age 70-797112.77.111.0Baseline EF 50-55%9230.78.88.8HTN dx39212.63.44.7BMI 30+31516.32.64.5DM Dx10315.55.06.9Smoking (ever)33314.23.76.1HTN and BMI 30+18215.53.96.0HTN, BMI 30+, DM5016.08.212.2Age<50, BMI<30, No HTN/DM2197.30.00.0Age>60, 2+ RF(HTN, DM, BMI 30+)10114.95.08.9 Conclusions: Risk of clinically confirmed CHF/cardiac death was substantially lower than risk based on ICD codes alone. Risk was consistent with prior clinical trials and differed substantially by age, baseline EF, use of A, and other CHF risk factors. Greatest risk was with age of 70+, borderline baseline EF, and comorbidities known to increase CHF risk. Quite low risk (1.1% at 5 years) was seen in patients under 60 years old. Citation Format: Fehrenbacher L, Capra A, Krishnaswami A, Quesenberry C, Habel L. Adjuvant trastuzumab +/- anthracycline and cardiotoxicity in a community cohort of 962 HER2+ breast cancers from 2005-2011: Comparison of incidence by risk factors and by diagnostic codes vs clinical chart review. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-15-01.

ReCAP: Treatment Patterns and Cost of Care Associated With Initial Therapy Among Patients Diagnosed With Operable Early-Stage Human Epidermal Growth Factor Receptor 2-Overexpressed Breast Cancer in the United States: A Real-World Retrospective Study.

Overexpression of the human epidermal growth factor receptor 2 (HER2) protein negatively affects survival in breast cancer. This study aimed to assess real-world treatment patterns and costs associated with resected nonmetastatic HER2-positive breast cancer in the United States. Commercially insured patients with HER2-positive breast cancer were identified from oncology registry data linked to a large US commercial administrative claims database. Treatment patterns and health care use and costs in the initial phase of care were examined. Among the 915 patients who met the study criteria, 662 (72%) were hormone receptor (HR) positive, and 253 (28%) were HR negative. Overall, 72% (n = 662) of patients received HER2-targeted therapy (HR positive, 69% v HR negative, 80%; P < .01), specifically trastuzumab. The most common treatment regimens, regardless of HR status, were carboplatin, docetaxel, and trastuzumab (47% of patients) during neoadjuvant therapy and carboplatin, docetaxel, and trastuzumab ± hormone therapy (30% of patients) during adjuvant therapy. Overall unadjusted cost of treatment per patient per month (HR positive, $11,906 v HR negative, $14,367; P < .001) was mainly cancer related (HR positive, $10,513 v HR negative, $13,073; P < .001). Adjusted 12-month cost was $176,779 (HR positive, $167,088 v HR negative, $180,226; P > .05). Although trastuzumab-based therapy is considered standard of care among patients with HER2-positive early-stage breast cancer, approximately 28% of these patients did not receive HER2-targeted therapy. Additional studies are warranted to examine whether patients who have not received targeted therapy are eligible for and would benefit from an HER2-targeted approach.

Efficacy and safety of neoadjuvant docetaxel, carboplatin, trastuzumab/pertuzumab [TCH-P] in non-metastatic HER2+ breast cancer: The Cleveland Clinic experience.

531 Background: Pertuzumab is FDA approved for use in combination with trastuzumab and chemotherapy as neoadjuvant therapy in women with non-metastatic HER2+ breast cancer. The TRYPHAENA trial repo...

Abstract P4-15-10: Initial therapy among patients newly diagnosed with operable early stage human epidermal growth factor receptor 2-overexpressed (HER2+) breast cancer in the US: A real-world retrospective study

Abstract BACKGROUND: Prognosis and appropriate treatment of breast cancer patients (pts) is influenced by tumor molecular characteristics. However, few existing retrospective studies have investigated the treatment patterns and outcomes of breast cancer pts by tumor biomarkers. The objective of this study was to assess the current real-world treatment patterns associated with resected non-metastatic HER2+ breast cancer in the US. METHODS: This was a retrospective study of physician-reported clinical information (including date and stage at diagnosis, HER2 status and hormone receptor (HR) status) for commercially insured breast cancer pts from the Oncology Management Registry linked with medical and pharmacy claims from a large, national health plan in the US from 01/2008 to 8/2013. The date of initial diagnosis was the index date. The inclusion criteria were: adult pts (≥18 years old), enrolled in the health plan for ≥6 months after the index date, diagnosed with HER2+ Stage I-III disease, known HR status, received breast cancer specific surgery (mastectomy or lumpectomy) and anti-cancer systemic therapy (ACST) and/or radiation within 6 months of index date. Pts with other primary cancers during the study period were excluded. The initial phase of care included initial therapy (surgery and ACST and/or radiation) until 30 days after the last therapy received (surgery, ACST or radiation) prior to a 90-day gap in treatment. Treatment patterns during the initial phase of care by HR status were examined. RESULTS: Among 915 pts who met all study criteria, 662 (72%) and 253 (28%) were HR+ and HR-, respectively. Mean age was 52 years (standard deviation=9) and was not significantly different by HR cohort. Approximately 82% (n=749) were diagnosed with Stage I/II disease. Most pts (80%, n=732) received adjuvant therapy only, 19% (n=177) received both neo-adjuvant and adjuvant therapy, and &amp;lt;1% (n=6) were observed to have neo-adjuvant therapy only. Among pts who received neo-adjuvant therapy, mean time from diagnosis to ACST was 21 days (median=21). Among pts who received only adjuvant therapy, mean time from diagnosis to initial breast cancer specific surgery was 24 days (median=20). Overall, 72% of pts received HER2 targeted therapy (69% HR+, 80% HR-; p&amp;lt;0.01) during their initial phase of care. During neo-adjuvant therapy, 72% of pts received trastuzumab (67% HR+, 81% HR-; p&amp;lt;0.05). During adjuvant therapy, 72% of pts received trastuzumab (69% HR+, 81% HR-; p&amp;lt;0.05). The most common neo-adjuvant regimen regardless of HR status was carboplatin+docetaxel+trastuzumab (&amp;gt;40% pts). The most common regimens during the adjuvant therapy period were carboplatin+docetaxel+trastuzumab with or without hormone therapy (∼30% of pts). CONCLUSION: In this real-world population of commercially insured breast cancer pts treated for operable, early stage HER2+ disease in the US, 28% of pts did not receive targeted therapy. More pts with HR- status received targeted therapy than those with HR+ status. Further studies are warranted to examine whether pts that have not received targeted therapy are eligible and would benefit from an HER2 targeted approach. Citation Format: Stacey DaCosta Byfield, Philip O Buck, Cori Blauer-Peterson, Sara A Poston. Initial therapy among patients newly diagnosed with operable early stage human epidermal growth factor receptor 2-overexpressed (HER2+) breast cancer in the US: A real-world retrospective study [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-15-10.

Abstract 3842: Relationship between weight change and response to trastuzumab-based neoadjuvant chemotherapy among women with operable HER2 overexpressing breast cancer

Abstract Purpose Weight change (gain or loss) in early breast cancer patients is associated with worse survival. However, limited research investigates the impact of weight change in the neoadjuvant setting in women with HER2 overexpressing breast cancer. The goals of this study were to examine i) the relationship between weight change during trastuzumab-based neoadjuvant chemotherapy and pathologic response, and ii) determine whether weight change during post-operative trastuzumab was associated with outcome. Patients and methods From March 2004 to March 2013, 52 patients diagnosed with invasive non-metastatic HER2 overexpressing breast cancer were recruited from H.S. Kaplan Cancer center, France. They received trastuzumab-based neoadjuvant chemotherapy (NAC) before surgery, followed by adjuvant trastuzumab. Patients were distributed in the “weight loss” or “weight gain/stable” categories according to their relative weight change after NAC, and after adjuvant trastuzumab. Logistic regression was used to examine associations between weight change and pathologic response. The Kaplan-Meier method and Cox proportional hazards regression analysis were used to evaluate the relationship between weight change and progression free survival (PFS). Results Median age was 50 years (range 21 to 71 years); 25% of women experienced body weight loss during NAC, 40% had stable body weight, and 35% gained weight. In multivariate analysis, weight loss was significantly associated with worse pathologic complete response (pCR) in tumor compared with the weight gain/stable group (OR = 0.18; 95% CI, 0.04 to 0.84). There was no difference in pCR in nodes according to weight change (OR = 0.34; 95% CI, 0.06 to 1.76). Body mass index was not associated with pCR. At a median follow up time of 3 years, PFS was not associated with weight change during NAC but with weight change during adjuvant trastuzumab. PFS was worse in patients loosing weight during adjuvant trastuzumab (OR = 0.05; 95% CI, 0.01 to 0.34). Conclusion Weight loss was associated with worse pCR to trastuzumab-based neoadjuvant chemotherapy. In addition, weight loss during adjuvant trastuzumab was associated with worse PFS. These results suggest that weight control and promotion of weight maintenance in women with HER2 overexpressing breast cancer should be integrated within cancer treatment to optimize patient outcomes. Citation Format: Nawale Hajjaji, Dorothee Chocteau, Sylvie Gerard, Marie Brigitte Orgerie. Relationship between weight change and response to trastuzumab-based neoadjuvant chemotherapy among women with operable HER2 overexpressing breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3842. doi:10.1158/1538-7445.AM2014-3842

Improved Clinical Outcomes Associated With Vitamin D Supplementation During Adjuvant Chemotherapy in Patients With HER2+ Nonmetastatic Breast Cancer

BackgroundVitamin D (VD) supplementation has pleiotropic effects that extend beyond their impact on bone health, including the disruption of downstream VD receptor signaling and human epidermal growth factor receptor 2 (HER2) signaling through the ErbB2/AKT/ERK pathway. In the present study, we examined our institutional experience with patients having nonmetastatic HER2-positive (HER+) breast cancer and hypothesized that those patients who received VD supplementation during neoadjuvant chemotherapy would have improved long-term outcomes. Patients and MethodsWe performed a retrospective review of all patients (n = 308) given trastuzumab-based chemotherapy between 2006 and 2012 at the University of Miami/Sylvester Comprehensive Cancer Center (UM/SCCC). We identified 2 groups of patients for comparison—those who received VD supplementation during neoadjuvant chemotherapy (n = 134) and those who did not (n = 112). Univariate and multivariate Cox proportional hazard regression models were fitted to overall survival (OS) and disease-free survival (DFS). ResultsMore than half of the patients received VD during neoadjuvant chemotherapy (54.5%), with 60% receiving a dose < 10,000 units/wk and 33.3% having a VD deficiency at the start of therapy. In our final multivariate model, VD use was associated with improved DFS (hazard ratio [HR], 0.36; 95% confidence interval [CI], 0.15-0.88; P = .026], whereas larger tumor size was associated with worse DFS (HR, 3.52; 95% CI, 1.06-11.66; P = .04). There were no differences in OS based on any of the categories, including VD use, tumor size, number of metastatic lymph nodes, age at diagnosis, or lymphovascular invasion (LVI). ConclusionVD supplementation in patients with nonmetastatic HER2+ breast cancer is associated with improved DFS.

High Serum miR-19a Levels Are Associated with Inflammatory Breast Cancer and Are Predictive of Favorable Clinical Outcome in Patients with Metastatic HER2+ Inflammatory Breast Cancer

IntroductionAltered serum microRNA (miRNA) levels may be correlated with a dysregulated expression pattern in parental tumor tissue and reflect the clinical evolution of disease. The overexpression of miR-21, miR-10b, and miR-19a is associated with the acquisition of malignant characteristics (increased tumor cell proliferation, migration, invasion, dissemination, and metastasis); thus, we determined their utility as serum biomarkers for aggressive breast cancer (HER2-overexpressed or -amplified [HER2+] and inflammatory breast cancer [IBC]).Experimental DesignIn this prospective study, we measured miR-21, miR-10b, and miR-19a levels using quantitative reverse transcriptase-polymerase chain reaction in the serum of 113 breast cancer patients and determined their association with clinicopathologic factors and clinical outcome. Thirty healthy donors with no history of cancer were enrolled as controls.ResultsPatients with non-metastatic HER2+ breast cancer had higher serum miR-21 median levels than patients with non-metastatic HER2− disease (p = 0.044); whereas patients with metastatic HER2+ breast cancer had higher serum miR-10b median levels than patients with metastatic HER2− disease (p = 0.0004). There were no significant differences in serum miR-19a median levels between HER2+ and HER2− groups, regardless of the presence of metastases. High serum miR-19a levels were associated with IBC (p = 0.039). Patients with metastatic IBC had significantly higher serum miR-19a median levels than patients with metastatic non-IBC (p = 0.019). Finally, high serum miR-19a levels were associated with longer progression-free survival time (10.3 vs. 3.2 months; p = 0.022) and longer overall survival time (median not reached vs. 11.2 months; p = 0.003) in patients with metastatic HER2+ IBC.ConclusionHigh levels of miR-21 and miR-10b were present in the serum of patients with non-metastatic and metastatic HER2+ breast cancer, respectively. High levels of serum miR-19a may represent a biomarker for IBC that is predictive for favorable clinical outcome in patients with metastatic HER2+ IBC.

Abstract P6-09-02: Improved clinical outcomes associated with vitamin D supplementation during adjuvant chemotherapy in patients with HER2+ non-metastatic breast cancer

Abstract Background Vitamin D (VitD) supplementation decreases the risk of osteoporotic fractures in the elderly; however, its extraskeletal benefits, especially in the prevention and treatment of breast cancer, are less well-established. Many studies have shown an association of low VitD levels with higher cancer incidence, including breast cancer and poorer outcomes, but whether this association merely reflects a selection bias to healthier lifestyles, remains an area of controversy. We hypothesized that women with more aggressive HER2+ breast cancer would have improved clinical outcomes while on VitD supplements. Methods We performed a retrospective review of all patients (n = 300) given trastuzumab chemotherapy between 2006 and 2012 at UM/SCCC. We identified two groups of patients for comparison - those who received VitD supplementation (VD) during adjuvant chemotherapy (n = 130) or none (NVD) during adjuvant chemotherapy (n = 123). Patients who lacked sufficient records to clarify VitD supplement use, men, patients with de-novo-metastatic breast cancer, bilateral breast cancers, and patients without follow-up were excluded. Five-year disease-free survival (DFS) and overall survival (OS) were calculated. Univariate and multivariate analyses were performed using a Cox proportional hazards (CPH) model to evaluate the relationship between VD supplementation and death. Results The median age at diagnosis was 54 and 50 in the VD and NVD groups. In the VD group, the average VitD dose was 10,890 IU/wk, and the baseline and post-25-H VitD serum level was 35 and 41ng/ml, respectively. Descriptive analysis of the VD and NVD groups were as follows: postmenopausal (55.4%, 43.9%), tumor &amp;lt;2cm (42.3%, 36.6%), no lymph node involvement (42.3%, 36.6%), LVI (46.4%, 33.3%), high nuclear grade (60%, 61.5%), HR+ (66.2%, 54.5%), African American race (4.6%, 9.8%), and BMI&amp;gt;30 at end of chemotherapy (26.2%, 31.7%). At a median follow-up of 31 and 23 months, the estimated five-year DFS (69.4% vs. 44.7%, p = 0.009) and OS (97.5% vs. 85.6%, p = &amp;lt;0.0001) were significantly superior in the VD group versus the NVD group. These differences remained significant after adjustment for age, ethnicity, menopausal state, tumor size, node positivity, LVI, high-grade tumor, HR+, and BMI&amp;gt;30. Analysis showed an interaction between OS and ethnicity (African American = 0.008) and node positivity (p = 0.02) and near-significance for LVI (p = 0.07). Despite those confounding variables, VitD use remained significantly associated with improved OS (p = 0.003) and had a HR or 0.10 with a 95% CI of 0.02-0.45. Conclusion Our study suggests that Vitamin D supplementation in non-metastatic HER2 breast cancer patients is associated with improved DFS and OS, and the relationship remains significant after adjusting for potential confounding factors. It is unclear whether vitamin D supplementation might have pre-selected for HER2+ breast cancers with more favorable prognosis or synergized with anti-HER2 therapy. To our knowledge, this is the first study reporting improved outcomes associated with relatively high dose Vitamin D supplementation in the HER2+ breast cancer population. Further research is warranted to define the role of Vitamin D in breast cancer treatment. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-09-02.

Abstract P6-09-03: Improved clinical outcomes associated with statin use during adjuvant chemotherapy in patients with HER2+ non-metastatic breast cancer

Abstract Background Statins are established as first line therapy in patients with hypercholesterolemia and are thought to have pleiotropic effects including inhibition of signaling pathways known to drive cell proliferation and survival responses. Numerous preclinical and observational studies have demonstrated activity and improved outcomes in breast cancer patients who received statins, particularly lipophilic statins, as part of their adjuvant therapy. In the Life After Cancer Epidemiology (LACE) Study, 1,945 early-stage breast cancer survivors were shown to have a 33% decreased risk of breast cancer recurrence with post-diagnosis statin use, an effect that was magnified with increasing duration of statin use. We hypothesized that statin use concurrent with trastuzumab based chemotherapy in patients treated for non-metastatic HER2 positive breast cancer would be associated with improved outcomes. Methods We performed a retrospective review of all patients (n = 300) with HER2+ breast cancer who received trastuzumab from 2006-2012 at UM/SCCC. We identified two groups of patients for comparison - those who received statins (ST) during adjuvant chemotherapy (n = 45) or no statins during chemotherapy (NST) during adjuvant chemotherapy (n = 200). Patients with unclear documentation of concurrent statin use, men, patients with de-novo-metastatic breast cancer or prior primary cancer, bilateral breast cancers, and patients without follow-up were excluded. 5-year disease free (DFS) and overall survival (OS) were calculated. A univariate analysis was performed. Multivariate analysis for time-to-event data, using the Cox and extended Cox regression model will be performed and reported. Results The median age at diagnosis was 58 and 48, in the ST and NST groups, respectively. The most commonly used statin was lipophilic simvastatin (34.1%). The average baseline and post chemotherapy total cholesterol level in the ST group was 200.8 and 218.1mg/dL, respectively. Descriptive characteristics of the ST and NST groups respectively are as follows: postmenopausal (77.8% vs. 43.5%) tumor size &amp;lt;2cm (48.9% vs. 41.0%), node-negative disease (40.0% vs. 40.0%), HR+ status (64.4% vs. 60.5%), diabetes mellitus (26.7% vs. 9.0%), baseline BMI &amp;gt;30 (40.0% vs. 27.0%), and concomitant metformin (28.9% vs. 11.5%). The NST group was more likely to have a reduction of greater than 10% in their EF (9.0% vs. 6.7%). At a median follow-up of 32 and 26 months, the estimated 5-year DFS was significantly improved in the ST group (81.8% vs. 51.5%, p = 0.046). Meanwhile, the estimated 5-year OS was not significantly different between both groups (93.4% vs. 91.6%, p = 0.121). Metformin was not associated with a significant improvement in DFS or OS. Conclusion Our study demonstrated that statin use concurrent with trastuzumab-based chemotherapy for non-metastatic HER2 breast cancer was associated with improved estimated 5-year DFS, but not OS. The retrospective nature of our study does not allow for a definitive answer but further research needs to be done to define the role of statins in HER2+ breast cancer treatment. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-09-03.

Obesity increases the incidence of distant metastases in oestrogen receptor-negative human epidermal growth factor receptor 2-positive breast cancer patients

BackgroundObesity is a major negative determinant of breast cancer outcome. However, there are contrasting data on the differential impact of obesity on specific breast cancer subtypes. In particular, very little is known on human epidermal growth factor receptor 2-positive (HER2+) tumours. Patients and methodsWe assessed the prognostic role of increased body mass index (BMI) on a consecutive series of non-metastatic HER2+ patients treated at our institution before the introduction of adjuvant Trastuzumab. We separately analysed oestrogen receptor-positive (ER+) and -negative (ER−) HER2+ cases. ResultsIn ER−/HER2+ tumours we observed a significantly worse overall survival (Hazard ratio (HR) 1.79, p-value 0.041) and cumulative incidence of distant metastases (HR 2.03, p-value 0.019) in obese (BMI>30) versus normal/underweight (BMI<25) patients. Local relapses appeared to be non-significantly reduced in obese patients, masking the overall effect on disease-free survival. Outcome in ER+ tumours, instead, was not significantly different between BMI groups. ConclusionsObesity significantly correlates with worse overall survival and cumulative incidence of distant metastases in ER−/HER2 positive breast cancer. Differences in the biology of breast tumours may determine individual susceptibility to obesity. The biology of the underlying tumour should be taken into account in the design of dietary intervention trials in breast cancer.

Do oncology patients in an outpatient hospital receive the same care as patients in an office/clinic setting? A case study evaluating patients with non-metastatic HER2+ breast cancer (BC) receiving adjuvant trastuzumab.

e11603 Background: It is unknown if quality of care received by patients (pts) with BC is impacted by the location at which care is received. Using a sample of pts with HER2+ BC receiving adjuvant trastuzumab (T), we compared T treatment patterns between pts treated in office/clinic (MD) or outpatient hospital (HOSP) settings. Methods: Non-metastaticBCadult women who received ≥2 T infusions in an MD or HOSP setting from 2008-2012 were selected from the US-based Humana database. Based on the site of care where T was received, pts were classified into MD or HOSP cohorts. Pts were followed from first T infusion date to treatment discontinuation, first metastasis, or end of continuous eligibility, for a maximum of 12 months (mos). T treatment duration, discontinuation (treatment gap of ≥45 consecutive days), and the proportion of pts completing the recommended 12 mos treatment indication were compared between cohorts. Results: 730 pts were included; 67% received T in an MD setting vs. 33% in a HOSP setting. Differences between cohorts were observed in terms of healthcare insurance plan: more pts in the HOSP setting had Medicare coverage (55.5% vs. 67.1%; p=.003). Average T duration was shorter in the HOSP setting (MD cohort: 241.9 days ; HOSP cohort: 191.3 days). Among pts observed for 12 mos, a higher proportion in the MD cohort completed the 12-mo treatment (84.3% in MD vs. 75.6% in HOSP [p=.034]). After adjusting for confounding factors, the HOSP cohort was 2.4 times more likely to discontinue treatment compared to the MD cohort ( p&lt;.001). Conclusions: Duration of adjuvant T treatment for pts with non-metastatic HER2+ BC differed based on the site at which treatment was received. This suggests that oncology pts treated in an HOSP setting, vs. MD, may be at higher risk for treatment discontinuation or to receive a shorter course of treatment than recommended. Further research should explore the impact of these differing treatment patterns on outcomes.

Cerebral metastases in metastatic breast cancer: disease-specific risk factors and survival

BackgroundSurvival of patients suffering from cerebral metastases (CM) is limited. Identification of patients with a high risk for CM is warranted to adjust follow-up care and to evaluate preventive strategies. Patients and methodsExploratory analysis of disease-specific parameter in patients with metastatic breast cancer (MBC) treated between 1998 and 2008 using cumulative incidences and Fine and Grays’ multivariable regression analyses. ResultsAfter a median follow-up of 4.0 years, 66 patients (10.5%) developed CM. The estimated probability for CM was 5%, 12% and 15% at 1, 5 and 10 years; in contrast, the probability of death without CM was 21%, 61% and 76%, respectively. A small tumor size, ER status, ductal histology, lung and lymph node metastases, human epidermal growth factor receptor 2 positive (HER2+) tumors, younger age and M0 were associated with CM in univariate analyses, the latter three being risk factors in the multivariable model. Survival was shortened in patient developing CM (24.0 months) compared with patients with no CM (33.6 months) in the course of MBC. ConclusionYoung patients, primary with non-metastatic disease and HER2+ tumors, have a high risk to develop CM in MBC. Survival of patients developing CM in the course of MBC is impaired compared with patients without CM.