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Supplemental Figure 1. Consort Diagram 03-311. Supplemental Figure 2. Consort Diagram 211B. Supplemental Figure 3. Subtype-specific changes in Immune Index upon brief-exposure to nab-paclitaxel in the 211B trial. Supplemental Figure 4. Evaluation of the Immune Index upon brief-exposure to trastuzumab in the 03-311 and 211B trials according to ER/PR status. Supplemental Figure 5. Evaluation of the Immune Index upon brief-exposure to nab-paclitaxel in the 211B trial according to ER/PR status. Supplemental Figure 6. Correlation between Immune Index and tumor content. Supplemental Figure 7. Association of CD4+ Th1 and Treg signatures with response. Supplemental Table 1. Immune Index genes discriminative of response at the post-exposure timepoint in the discovery (03-311) and validation (211B) datasets. Supplemental Table 2. Immune cell subset signatures discriminative of response at baseline and post-exposure timepoints in the discovery (03-311) and validation (211B) datasets. Supplemental Table 3. CD8+ T-cell cytolytic activity genes discriminative of response at the post-exposure timepoint in the discovery (03-311) and validation (211B) datasets.

Purpose: Recent data suggest that intrinsic subtype and immune cell infiltration may predict response to trastuzumab-based therapy. We studied the interaction between these factors, changes in immune signatures following brief exposure to trastuzumab, and achievement of pathologic complete response (pCR) to subsequent preoperative trastuzumab and chemotherapy in HER2-positive breast cancer.Experimental Design: In patients enrolled on two multicenter trials (03-311 and 211B), tumor core biopsies were obtained at baseline and after brief exposure to single-agent trastuzumab or nab-paclitaxel. Gene expression profiles were assessed to assign PAM50 subtypes, measure immune cell activation, and were correlated with response.Results: The pCR rate was significantly higher in HER2-enriched tumors in the Discovery, 03-311 (36%, P = 0.043) dataset, as compared with other subtypes, which validated in 211B (50%, P = 0.048). Significant increases in a signature of immune cell admixture (Immune Index) were observed only following brief exposure to trastuzumab in HER2-enriched tumors (Discovery/03-311, P = 0.05; Validation/211B, P = 0.02). Increased Immune Index was predictive of response after brief exposure (03-311, P = 0.03; 211B, P = 0.04), but not at baseline, in addition to increased expression of a CD4+ follicular helper T-cell signature (03-311, P = 0.05; 211B, P = 0.04). Brief exposure to trastuzumab significantly increased gene expression of the T-cell marker PD-1 in HER2-enriched tumors (Discovery/03-311, P = 0.045) and PD-1 positivity by IHC (Validation/211B, P = 0.035).Conclusions: Correlations between pCR rates, increases in Immune Index and markers of T-cell activity following brief exposure to trastuzumab in HER2-enriched tumors provide novel insights into the interaction between tumor biology, antitumor immunity, and response to treatment, and suggest potential clinically useful biomarkers in HER2+ breast cancers. Clin Cancer Res; 22(13); 3249–59. ©2016 AACR.

In HER2-positive breast cancer (HER2+ BC), neoadjuvant chemotherapy (NACT) with dual HER2-targeted therapy achieves high pathologic complete response (pCR) rates. Anthracycline-free NACT regimens avoid toxicities associated with anthracyclines, but every 3-week TCHP also has substantial side effects. We hypothesized that a weekly regimen might have equivalent efficacy with less toxicity; we also investigated whether poorly responding patients would benefit from switching to AC. Patients with clinical stage II–III HER2+ BC received weekly paclitaxel 80 mg/m2 and carboplatin AUC2 with every 3-week trastuzumab and pertuzumab (wPCbTP), with the option of splitting the pertuzumab loading dose. After 12 weeks, responding patients continued wPCbTP for another 6 weeks, while non-responders switched to AC. Dose modifications and post-op therapy were at investigator discretion. In 30 evaluable patients, the pCR rate was 77% (95% CI 58–90%); 12/14 (86%) in ER-negative and 11/16 (69%) in ER-positive. Only two patients transitioned to AC for non-response, of which one achieved pCR. There were no episodes of febrile neutropenia or grade ≥ 3 peripheral neuropathy, though several patients who continued wPCbTP stopped before week 18. Split-dose pertuzumab was associated with less grade ≥ 2 diarrhea (40%) than the standard loading dose (60%). pCR rates with our regimen were as high as reported with TCHP with fewer grade ≥ 3 toxicities, though diarrhea remains a concern. Too few patients had a suboptimal response to adequately test switching to AC. The wPCbTP regimen should be considered an alternative to TCHP as neoadjuvant therapy for HER2+ BC. ClinicalTrials.gov identifier: NCT02789657.

For patients who complete treatment for breast cancer, national oncologic guidelines recommend yearly mammography surveillance and oncology follow-up especially during the first five years of survivorship. Some studies have shown that older age and insurance type may be risk factors for timely initial follow up after abnormal mammogram however the role in which racial and socioeconomic disparities may contribute to long term non-adherence or loss to follow-up (LTFU) is not known. Investigation into causes of LTFU or non-receipt of recommended surveillance are crucial in improving health care delivery and targeting interventions that prevent LTFU in high-risk patients. An ongoing study at Lifespan Breast Oncology aims to evaluate this issue further among patients treated for stage 1-3 breast cancer. We have completed data collection on 139 of 300 eligible patients diagnosed in 2014 and for whom 5 years of follow up have been completed. We measured adherence to yearly mammography, visit with breast oncologist, continuation of ET, and LTFU in each year of survivorship. LTFU was defined as patient without any further contact with the Lifespan Breast Oncology clinic. We then examined the association between these adherence measures and age, ECOG performance status at diagnosis, Medicaid insurance status, socio-economic factors, and specific adjuvant therapies, using univariate and multivariate generalized estimating equation models for longitudinal data. The models reported odds ratios (OR) for non-adherence or LTFU, with 95% confidence intervals (CI). Patients who experienced relapse or death were removed from the pool in the year of event. Adherence decreased for all measures between year 1 and year 5 of survivorship: from 99% to 82% for oncology visits, 92% to 80% for mammography, and 86% to 71% from ET. LTFU increased from 0% to 17%, respectively (OR per year, 1.96; 95%CI, 1.55-2.48). In univariate analysis, patients age >70 (compared with age ≤50) had a significantly higher risk of LTFU (Table), non-adherence to visits (OR=6.64 versus age ≤50, P=.002), mammography (OR=4.18, P=.020), or ET (OR=5.42, P=.002). Patients with performance status ECOG ≥2 had significantly lower adherence to all measures. Medicaid insurance was associated with significantly higher LTFU, non-adherence to mammography (OR=5.58, P=.008) or oncology visits (OR=6.53, P=.002). Marital, employment, or parenting status were not significantly associated with the risk of LTFU, but employed patients had a higher adherence to mammography and ET. Cancer stage, ER, or HER2 status were not associated with any adherence measure. LTFU was lower among recipients of ET, but not recipients of chemotherapy. In a multivariable model, Medicaid insurance (OR=3.99, P=.027) and receipt of ET (OR=0.32, P=.027) retained significant association with LTFU. Our findings show that Medicaid patients represent a high risk group with potential need for increased resources to ensure adequate follow-up. We plan to continue to expand this cohort and analyze more patients at our institution. Interventions to change barriers and circumvent financial limitations that these patients face in obtaining care could potentially decrease rates of recurrence and potentially impact overall survival. This data could be utilized in future studies to create a risk stratification tool to identify patients who would be at high risk for LTFU. Table. Factors associated with loss to follow-up.N (%)% LTFU at 5yOR95%CIPAll13917Age ≤5032 (23)161.00351-7070 (50.4)120.890.27-2.90>7037 (26.6)223.511.19-10.4ECOG 015 (10.8)71.0071108 (77.7)153.650.43-31.1> 214 (10.1)2920.281.90-216Insurance: private78 (56.1)91.001Medicaid15 (10.8)466.762.03-22.5Medicare45 (32.4)195.131.98-13.3Children: no70 (50.4)121.34yes66 (47.5)191.710.56-5.22Married: no56 (40.3)171.68yes83 (59.7)160.840.38-1.88Employed: no70 (50.4)201.32yes66 (47.5)150.660.29-1.49Stage:187 (62.6)181.66239 (28.1)120.640.24-1.69313 (9.4)220.80.19-3.46ER-23 (16.5)261.27ER+115 (82.7)150.580.22-1.54No ET38 (27.3)291.033ET101 (72.7)120.410.18-0.93No chemotherapy87 (62.6)171.25Chemotherapy52 (37.4)160.60.25-1.43 Citation Format: Rani Chudasama, Adam Olszewski, Don Dizon, Mary Anne Fenton. Patient risk factors for loss to breast oncologic follow up [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS7-57.

In H+BC, neoadjuvant chemotherapy (NACT) with dual HER2-targeted therapy achieves high pathologic complete response (pCR) rates, but the most common anthracycline-free regimen, every 3-week docetaxel and Cb with T and P (TCHP), causes significant hematologic and non-hematologic toxicities. We conducted a pilot study to assess the efficacy and toxicity of a weekly anthracycline-free regimen, and to assess whether patients (pts) with a suboptimal response to this regimen benefit from switching to doxorubicin/cyclophosphamide (AC). Methods Pts with clinical stage II-III H+BC receive wP 80 mg/m2 and Cb AUC 2 weekly with every 3-week T and P (wPCbTP). Investigators may split the week 1 loading dose of P (840 mg) into two weekly doses, and hold the 2nd dose for early onset toxicity, particularly diarrhea. Pts are restaged after 12 weeks with ultrasound or MRI. Responding pts receive another 6 weeks of wPCbTP, while nonresponders are switched to AC x 4, followed by surgery. Study participation is complete after a 3-month post-op visit. Dose modifications and post-op therapy are at investigator discretion. Results Enrollment (30 pts) is complete. Pathologic findings are available for 23 pts; the other 7 are due to undergo surgery by 10/2019. No pts have required switching to AC for suboptimal response at week 12; 2 have been switched for toxicity (1 each for diarrhea and recurrent cytopenias). pCR (T0/isN0) rates are tabulated below: Pt grouppCR% (95% CI)All18/2378 (56-92) %ER(-)10/1191 (59-100) %ER(+)8/1267 (35-90) %Operable (Stage IIA-IIIA)14/1782 (57-96) %Inoperable (Stage IIIB-C)4/667 (22-96) % In 23 pts, grade 3/4 toxicities observed include neutropenia (10/2, but no febrile neutropenia), anemia (3/0), thrombocytopenia (1/0), diarrhea (4/1), and 5 cases of grade 2 (but no grade ≥3) peripheral neuropathy. One pt each has required hospitalization for recurrent urinary tract, port site or breast infections while not neutropenic. wP has been dose-reduced for neuropathy after week 12 in 8 pts. Two pts discontinued Cb after hypersensitivity reactions in week 10. Treatment was discontinued during weeks 12-18 in 8 pts. P was held during weeks 1-6 for diarrhea in 5 pts and discontinued before week 12 in 3 pts; splitting the loading dose of P has not substantially reduced the incidence or severity of diarrhea. Conclusions Treatment with wPCbTP is associated with a high pCR rate (78%), comparable to those reported with TCHP in multicenter phase II-III trials, and is generally well tolerated, with fewer grade ≥3 toxicities, though diarrhea remains a concern. In some pts, cumulative toxicities make it difficult to continue treatment beyond week 12. Thus far, we have failed to identify a subset of pts in whom to test the efficacy of switching to AC after a suboptimal response to wPCbTP. This regimen appears to be worth exploring further, though we might consider switching to a less toxic regimen, or taking pts with an excellent response to surgery, after week 12. Supported by LifeCycle and the Lura Cook Hull Trust Citation Format: Mary Lorraine Lopresti, Jessica J. Bian, Bachir J Sakr, Rochelle S Strenger, Robert D. Legare, Mary Anne Fenton, Sabrina M Witherby, Don S Dizon, Sonali V Pandya, Ashley R Stuckey, David A Edmondson, Jennifer S Gass, Christine M Emmick, Theresa A Graves, Marlene Cutitar, Adam J Olszewski, William M Sikov. Neoadjuvant weekly paclitaxel (wP) and carboplatin (Cb) with trastuzumab (T) and pertuzumab (P) in HER2-positive breast cancer (H+BC): A Brown University oncology group (BrUOG) study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-16-19.

Background: The prognosis of patients with estrogen receptor positive (ER+) bone-only metastatic breast cancer (B-MBC) is good, with the average life expectancy extending years with contemporary management. In the general population, studies investigating the impact of screening programs designed to detect disease as early as possible in otherwise asymptomatic patients have consistently shown reduction in morbidity and mortality but outcomes among patients living with B-MBC has not been adequately addressed. This study aimed to investigate the rate at which patients with ER+ breast cancer metastatic only to bone underwent cholesterol, breast cancer, colon cancer, and lung cancer screening and to determine if this screening had any impact on overall survival and cause of death. Methods: We conducted a retrospective chart review of patients treated for ER+ B-MBC at the Lifespan Cancer Institute in Providence, RI between 1/1/15 and 5/31/18. Each patient’s medical records and tumor registry information were reviewed. Data on these patients’ disease history were collected along with data on cholesterol, breast cancer, colon cancer, and lung cancer screening. Descriptive statistics were calculated using STATA statistical software. Results: A total of 48 patients with ER+ B-MBC were identified. Median overall survival from initial diagnosis of breast cancer was 148 months; measured from the diagnosis of bone metastasis, it was 52.4 months. Twenty-nine out of the 48 patients received cholesterol screening (60%), 14/48 had mammograms (29%), and only 8/48 had colonoscopy (17%). No patients underwent screening lung CT (Table 1). Compared to those who did not undergo screening, patients who were screened for cholesterol had significantly longer median overall survival (175.4 vs 106 months, respectively, p=.02) and those undergoing mammogram had a trend towards longer survival (187 vs 131 months, p=.08). Screening was not associated with a difference in rates of death attributed to breast cancer. No deaths due to other malignancies were identified. Of those undergoing mammography, only one abnormal report was identified, and biopsy of the lesion was benign. Table 1: Rate of abnormal screening results, median overall survival from index diagnosis, and death from index breast cancer.Abnormal screening resultMedian OS (months)95% CIp valueDeath from IBCp valueCholesterolscreened18/25175.4135 - 2160.02**1/20.30not screened10668 - 1445/6Mammogramscreened1/14187116 - 2590.08*3/40.60not screened131101 - 1626/10OS=overall survival. CI=confidence interval. IBC=index breast cancer. ** = p < 0.05. *= p < 0.1 Conclusions: A large proportion of patients with B-MBC undergo primary preventative screening measures, and of these, cholesterol screening is the most common. Screening was associated with longer overall survival, but did not change the rates of death due to breast cancer. These results suggest that clinicians are offering screening to a subgroup of women who are healthy despite B-MBC. However, our data suggest there is little benefit to screening, and this should be addressed in a larger dataset. Citation Format: Kristina A Fanucci, Mary Anne Fenton, Christine Duffy, Camille Higel-McGovern, Don Dizon. For women with bone-only metastatic breast cancer, is there a benefit to primary prevention? [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-13-13.

Rationale: Choosing Wisely: In an era of genomic medicine, what role does nodal information play in decisions regarding adjuvant chemotherapy for early-stage, hormone receptor-positive breast cancer ? Authors: Fowler RL, Lew KP, Dizon DS, Ciambella CC, Wakeley M, Taneja C, Wiggins DL, Lopresti ML, Constantinou M, Strenger R, Wang Y, Fenton MA, Graves TA. BACKGROUND/OBJECTIVES: For women with hormone receptor-positive (HR+) breast cancer, the Recurrence Score (RS) informs prognosis and impacts treatment decisions; whether and to what degree nodal information impacts these decisions is not clear. We conducted a retrospective review of patients with newly diagnosed HR+ early stage breast cancer who underwent a sentinel lymph node biopsy (SLNB) and had the RS obtained to discriminate the impact both evaluations had on the use of adjuvant chemotherapy. We hypothesized that for these patients, the RS supersedes nodal information in determining adjuvant treatment. METHODS: 416 patients with T1 to T2 breast cancers seen at our multidisciplinary clinic between 2013 and 2017 were identified. Data collected included demographics, node stage, RS, and adjuvant therapies. RS was stratified in to High, Intermediate, and Low Risk according to criteria used in the TAILORx trial. Continuous variables were analyzed using descriptive statistics and categorical variables were analyzed by Chi-Square or Fisher’s Exact Test. All statistics were performed using STATA 15.0. RESULTS: For this cohort, the median age was 59 years (range 27-79). The vast majority (94%) underwent initial surgical excision or mastectomy with SLNB. Of these, 338 patients (81%) had node-negative disease. Of the remaining, 37 patients (8.9%) had micro-metastasis to a single node, 39 (9.3%) had N1a disease, including one patient with 3 positive lymph nodes. RS risk was characterized as high, intermediate, and low in 12, 65, and 23%, respectively. On multivariate analysis, only age at diagnosis (p0.05). CONCLUSIONS: For women with early-stage, clinically node-negative, HR+ breast cancer, the RS and age of the patient was associated with the administration of adjuvant chemotherapy. Although these data are limited to recommendations surrounding adjuvant chemotherapy and not decisions surrounding adjuvant radiation therapy, these data support the Choosing Wisely™ campaign against routine use of SLNB in low-risk patients. Citation Format: Rachel L Fowler, Kaitlyn P Lew, Don S Dizon, Chelsey C Ciambella, Michelle Wakeley, Charu Taneja, Doreen L Wiggins, Mary L Lopresti, Maria Constantinou, Rochelle Strenger, Yihong Wang, Mary A Fenton, Theresa Graves. The impact of recurrence score versus sentinel lymph node biopsy on treatment decisions in early breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-14-20.

Purpose: In HER2-positive breast cancer (HER2+BC), neoadjuvant chemotherapy (NACT) with dual HER2-targeted therapy achieves high pathologic complete response (pCR) rates. Anthracycline-free NACT regimens avoid toxicities associated with anthracyclines, but every 3-week TCHP also has substantial side effects. We hypothesized that a weekly regimen might have equivalent efficacy with less toxicity; we also investigated whether poorly responding patients would benefit from switching to AC. Methods:Patients with clinical stage II-III HER2+BC received weekly paclitaxel 80 mg/m2 and carboplatin AUC2 with every 3-week trastuzumab and pertuzumab (wPCbTP), with the option of splitting the pertuzumab loading dose. After 12 weeks, responding patients continued wPCbTP for another 6 weeks, while non-responders switched to AC. Dose modifications and post-op therapy were at investigator discretion. Results:In 30 evaluable patients, the pCR rate was 77% (95% CI 58-90%); 12/14 (86%) in ER-negative and 11/16 (69%) in ER-positive. Only two patients transitioned to AC for non-response, of which one achieved pCR. There were no episodes of febrile neutropenia or grade >3 peripheral neuropathy, though several patients who continued wPCbTP stopped before week 18. Split-dose pertuzumab was associated with less grade >2 diarrhea (40%) than the standard loading dose (60%). Conclusions:pCR rates with our regimen were as high as reported with TCHP with fewer grade >3 toxicities, though diarrhea remains a concern. Too few patients had a suboptimal response to adequately test switching to AC. The wPCbTP regimen should be considered an alternative to TCHP as neoadjuvant therapy for HER2+BC.ClinicalTrials.gov identifier: NCT02789657

Background Patients with cancer experience stress surrounding diagnosis and treatment. Many cancer centers employ a nurse-led education session to alleviate patient anxiety and confusion. . Objectives The goal was to evaluate the effect of a nurse-led chemotherapy teaching session on patients' knowledge, anxiety, and preparedness for cancer-directed therapy. . Methods After discussing treatment with their oncologist, participants completed a survey assessing their perceived understanding of various treatment topics. After, they underwent a teaching session with an oncology nurse. The survey was readministered when patients returned for their first and second treatment cycles. . Findings Significant increases were observed in patients' understanding of their treatment schedule, potential adverse effects, and antiemetic medication regimen by the first cycle of therapy and a reduction in treatment-related anxiety by the second cycle of therapy.

Background Although landmark trials in the metastatic (CLEOPATRA) and neo-adjuvant (NeoSphere; TRYPHAENA) settings identified all-grade diarrhea as a pertuzumab-associated adverse event, it was not classified as dose-limiting. In actual practice, diarrhea is often a reason for treatment modifications. Objectives To compare the risk of pertuzumab-associated diarrhea in actual practice to the risks in randomized controlled trials. Methods We conducted a retrospective cohort study of HER2/neu-positive breast cancer patients who received a pertuzumab-containing regimen between January 2012 and August 2015. We calculated the risk of diarrhea with 95% confidence limits (CLs), and then used two-sample t-tests to compare the risk between trials and actual practice. Results A total of 27 patients in the study cohort received a pertuzumab-containing treatment regimen for HER2/neu-positive breast cancer. The overall risk of all-grade and severe diarrhea in actual practice was 70% (95% CLs 55–90%) and 37% (95% CLs 20–66%), respectively. No severe diarrhea was observed in the metastatic setting, and the risk of all-grade diarrhea (44%, 95% CLs 21–92%) was similar to the CLEOPATRA study (67%). The risk of all-grade diarrhea in the neo-adjuvant setting was 83% (95% CLs 68–100%), compared to 46% in the NeoSphere trial (p = 0.03). The risk of severe diarrhea (Grade 3–4) in the neo-adjuvant setting was 47% (95% CLs 27–80%) versus 6% in the NeoSphere (p Conclusions The risk of all-grade and severe diarrhea associated with neoadjuvant pertuzumab use for HER2/neu-positive breast cancer was greater in actual practice than in trials.

Purpose To evaluate cardiac imaging abnormalities after modern radiotherapy and trastuzumab in breast cancer patients. Patients and Methods All patients treated with trastuzumab and radiotherapy for breast cancer between 2006 and 2014 with available cardiac imaging (echocardiogram or multigated acquisition scan) were retrospectively analyzed. Cardiac abnormalities included myocardial abnormalities (atrial or ventricular dilation, hypertrophy, hypokinesis, and impaired relaxation), decreased ejection fraction > 10%, and valvular abnormalities (thickening or stenosis of the valve leaflets). Breast laterality (left vs. right) and heart radiation dose volume parameters were analyzed for association with cardiac imaging abnormalities. Results A total of 110 patients with 57 left- and 53 right-sided breast cancers were evaluated. Overall, 37 patients (33.6%) developed a new cardiac abnormality. Left-sided radiotherapy was associated with an increase in new cardiac abnormalities (relative risk [RR] = 2.51; 95% confidence interval [CI], 1.34-4.67; P = .002). Both myocardial and valvular abnormalities were associated with left-sided radiotherapy (myocardial: RR = 2.21; 95% CI, 1.06-4.60; P = .029; valvular: RR = 3.30; 95% CI, 0.98-10.9; P = .044). There was no significant difference in decreased ejection fraction between left- and right-sided radiotherapy (9.6% vs. 2.1%; P = .207). A mean heart dose > 2 Gy as well as volume of the heart receiving 20 Gy (V20), V30, and V40 correlated with cardiac abnormalities (mean heart dose > 2 Gy: RR = 2.00; P = .040). Conclusion New cardiac abnormalities, including myocardial and valvular dysfunction, are common after trastuzumab and radiotherapy. The incidence of new abnormalities correlates with tumor laterality and cardiac radiation dose exposure. Long-term follow-up is needed to understand the clinical significance of these early imaging abnormalities.

10523 Background: Breast cancer is a heterogenous disease and management is complex. Advances in next generation sequencing has allowed genetic testing to be more accessible. However, conveying results to patients and care team can be challenging due to various variant classifications. Diagnostic results have the potential to guide management. Nondiagnostic results can be misinterpreted. The extent to which preoperative genetic testing affects management of newly diagnosed breast cancer is unknown. Methods: Newly diagnosed breast cancer patients were identified via review of breast tumor board between May 2019 and March 2019 followed by chart review to collect detailed information. Results: 408 newly diagnosed breast cancer cases were queried. Genetic evaluation was recommended and completed in 68%, not recommended (did not meet NCCN criteria) in 30% and declined in 2.7%. The genetic evaluation recommended cohort was associated with a higher mastectomy rate in comparison with when not recommended (31% vs. 9%, p=0.0001). Of those who completed genetic testing: 12% harbored a pathogenic/likely pathogenic variant (PV/LPV), 26% had a nondiagnostic variant of uncertain significance (VUS) and 61% had negative testing. Comparison between nondiagnostic test results (negative and VUS) and diagnostic test results revealed significantly increased number of women in the diagnostic group who chose mastectomy over breast conservation therapy (BCT, nondiagnostic 20% vs diagnostic 39%, p=0.018). When negative, VUS, and PV/LPV were each independently analyzed, diagnostic test results again revealed a significantly increased number of mastectomies over BCT (p0.5). Conclusions: Germline genetic testing in patients with newly diagnosed breast cancer impacts clinical management. Those harboring a diagnostic result were more likely to choose mastectomy over BCT. Not surprisingly, mastectomy rate was higher among those where genetic evaluation was recommended, possibly due to concerning personal or family history. The mastectomy rate was higher among those with a diagnostic result, indicating an understanding of the genetic testing significance by patients and the care team. More importantly, those who harbored nondiagnostic VUS did not make significantly different surgical choices compared with negative genetic testing, highlighting the critical role of proper genetic counseling and being part of the care team. We conclude consideration of genetic evaluation is clinically useful and feasible without affecting the surgical timeline.[Table: see text]

e24048 Background: Many people with cancer have medical and psycho-social-sexual sequelae following completion of treatment, which can extend well in to the future and impact both caregivers and families. In response to the unmet needs of people with cancer, the Survivorship Care Plan (SCP) was proposed as a roadmap for patients starting from diagnosis and treatment and preparing them for future care, both inside and beyond oncology-specific issues. However, the SCP does not address needs of families or caregivers, nor was it meant to. We sought to identify the needs of caregivers to determine whether a tailored SCP for the caregiver (SCP-C) should be considered. Methods: People who were at least 6 months out from the end of treatment were invited to participate, along with their designated caregiver. Volunteers with cancer completed the National Comprehensive Cancer Network Survivorship Assessment Survey at the time of consent. Caregivers participated in a semi-structured interview using an adaptation of the Veterans Affairs Caregiver Self-Assessment worksheet, supplemented by open-ended questions. Descriptive statistics were used; categorical variables were compared using chi-square or Fisher’s Exact Test. Results: 24 dyads (patient and caregiver pairs) were enrolled. Median age for patients was 70 (60.7 to 73) and caregivers was 66 (52.2-72). Time since end of treatment was 32 months (9.7 to 69.6) for patients and 32.8 months (8.3 to 51.3) for caregivers. The majority of patient respondents were female (87.5%) and caregiver respondents were male (70.8%); the majority had early-stage disease (63%). About 65% of caregivers were spouses and 74% of them lived with the person with cancer. 75% of caregivers spent 6 months to 3 years as a caregiver. They reported multiple types of support to patients, including help with ADLs, transportation, medical management and emotional support, regardless of time elapsed since their loved one’s diagnosis. Intimate support was significantly less among married couples less than 3 years out from diagnosis (23 vs 73%, respectively, p < .05). 100% of caregivers reported that they understood the diagnosis and follow up plan. However, almost 20% felt they did not fully understand potential side effects of treatment. Caregivers coped well in all domains with the exception of maintaining mental and physical health; compared to those out 3 years or less, those out for longer were more likely to report doing well (90% vs 45%, p < 0.5). Conclusions: Although caregivers reported high satisfaction with cancer-specific information, a large minority reported issues related to the side effects of treatment. In addition, while caregivers did well after completing treatment, those still within the first 3 years of the index diagnosis reported more issues with physical and mental health. These data point toward targeted resources that could be provided specific in an SCP-C.

Purpose: Recent data suggest that intrinsic subtype and immune cell infiltration may predict response to trastuzumab-based therapy. We studied the interaction between these factors, changes in immune signatures following brief exposure to trastuzumab, and achievement of pathologic complete response (pCR) to subsequent preoperative trastuzumab and chemotherapy in HER2-positive breast cancer. Experimental Design: In patients enrolled on two multicenter trials (03-311 and 211B), tumor core biopsies were obtained at baseline and after brief exposure to single-agent trastuzumab or nab-paclitaxel. Gene expression profiles were assessed to assign PAM50 subtypes, measure immune cell activation, and were correlated with response. Results: The pCR rate was significantly higher in HER2-enriched tumors in the Discovery, 03-311 (36%, P = 0.043) dataset, as compared with other subtypes, which validated in 211B (50%, P = 0.048). Significant increases in a signature of immune cell admixture (Immune Index) were observed only following brief exposure to trastuzumab in HER2-enriched tumors (Discovery/03-311, P = 0.05; Validation/211B, P = 0.02). Increased Immune Index was predictive of response after brief exposure (03-311, P = 0.03; 211B, P = 0.04), but not at baseline, in addition to increased expression of a CD4+ follicular helper T-cell signature (03-311, P = 0.05; 211B, P = 0.04). Brief exposure to trastuzumab significantly increased gene expression of the T-cell marker PD-1 in HER2-enriched tumors (Discovery/03-311, P = 0.045) and PD-1 positivity by IHC (Validation/211B, P = 0.035). Conclusions: Correlations between pCR rates, increases in Immune Index and markers of T-cell activity following brief exposure to trastuzumab in HER2-enriched tumors provide novel insights into the interaction between tumor biology, antitumor immunity, and response to treatment, and suggest potential clinically useful biomarkers in HER2+ breast cancers. Clin Cancer Res; 22(13); 3249–59. ©2016 AACR.

259 Background: The Lifespan Cancer Institute (LCI) identified strategies to improve the palliative care experience and outcomes by providing clinic to home telehealth services. LCI is an integrated academic medical center program combining three hospital programs operating at five outpatient sites. One quality goal is to embed and increase palliative care within the fabric of oncology by providing palliative telehealth in the home to avoid office visits, ED and hospital admissions. Methods: LCI’s multidisciplinary palliative care team, including administrators, physicians, advanced practice providers and community partner physicians assessed telehealth challenges with a vulnerable patient in the home setting. Process development included operations, technology, patient and staff education. The group modified existing Lifespan system workflows, clinic to clinic video for behavioral health and clinic to clinic for providers, to create the clinic to home method. This process benchmarked patient and behavioral health noting video differences with the clinic setting versus the home. Results: Outcome metrics include no show rate, chemotherapy within 14 days of death, ED/ICU within 30 days of death, patient and provider experience. Initial data shows no show rates decreased from 10% (January) to 6% (May) as telehealth increased. Patients marked deceased within 3 months of a LCI visit for January (n = 52) and May ( = 61) unfortunately did not have a negative trend for chemotherapy in the last 14 days of life (Jan: 8%, May 15%). ED and ICU visits both had modest decreases from January (ED 50%, ICU 29%) to May (ED 48%, ICU 21%). In anticipation of future Press Ganey results, patient feedback includes an increase of comfort while at home. Provider satisfaction increased with the ability to assess the patient in their own home instead of the sterile clinic environment. Encountered challenges include insurance restrictions for Rhode Island (not a rural state), technology, and remote trouble shooting. Conclusions: The success of clinic-to-home telehealth services set the foundation for the COVID-19 telehealth insurgence and led to the palliative team acting as role models to medical and radiation oncology. End of life oncology patients stayed home while having their palliative needs addressed remotely. The innovative approach to implementing telehealth services will serve as a model for future LCI telehealth programs including treatment education sessions, oral chemotherapy follow-up, survivorship and post hospital discharge assessments.

214 Background: The ASCO Quality Oncology Practice Initiative identifies ICU admission in the last 30 days and systemic anticancer therapy in the last 14 days of life as indicators of overly aggressive end-of-life care. We sought to delineate clinical factors associated with these indicators. Methods: An IRB approved retrospective chart review was conducted on patients with solid tumors at LCI who died in timepoints ending in January, July and November of 2016 and 2017. Patients were identified through our tumor registry. Patients’ medical records were reviewed for cancer stage, care received, palliative care contact, site of death, ICU admission in last 30 days, and receipt of systemic anticancer therapy (excluding antihormonal therapy) in last 6 months and 2 weeks of life. Results: A total of 250 patients were included in our analysis. 18.8% of LCI patients were admitted to the ICU in the last 30 days of life, 12.8% received systemic anticancer therapy in the last 2 weeks of life, and 19.2% experienced death in the hospital. Significant factors associated with an ICU admission in the last 30 days of life were a diagnosis of lymphoma compared to breast, gynecologic, gastrointestinal, lung, genitourinary, melanoma/carcinoma of unknown primary/head and neck cancer, or other (42.9% vs 20% vs 14.3% vs 9% vs 23.1% vs 25% vs 0% vs 26.3%; P = 0.01), systemic anticancer therapy in last 2 weeks of life (40.6% vs 16.1%; P < 0.005), and age ≤ 45 years at time of metastatic disease compared to age 46-65 or age ≥ 66 (50% vs 15.9% vs 18.1%; P < 0.05). A significant factor associated with systemic anticancer therapy in the last 2 weeks of life was age ≤ 45 years at time of metastatic disease compared to age 46-65 or age ≥ 66 (35.7% vs 16.9% vs 9.4%; P < 0.05). Lastly, a significant factor associated with death in the hospital was lack of palliative care team contact (28.9% vs 15%; P < 0.05). Conclusions: Understanding factors associated with intensive care at the end of life is critical to the provision of value-based cancer care. In this study, a diagnosis of lymphoma, systemic anticancer treatment in the last 2 weeks of life, and age ≤ 45 years at time of metastatic disease were associated with ICU stays in the last 30 days of life. Age ≤ 45 years at time of metastatic disease was associated with systemic anticancer treatment in the last 2 weeks of life, while lack of palliative care involvement was associated with greater chance of death in the hospital. Further understanding of the complex interplay that governs care and decision making at the end of life is required.

e19202 Background: Admission to the ICU in the last 30 days of life and use of systemic anticancer therapy in the last 2 weeks of life are indicators of overly aggressive end-of-life care and have been incorporated into the American Society of Clinical Oncology (ASCO) Quality Oncology Practice Initiative (QOPI) as benchmarks to assess care across cancer centers. We sought to better define the proportion of patients at our institution who met either of these endpoints and to delineate factors that might be associated with them. Methods: A retrospective chart review was conducted on patients with solid tumors, who underwent anticancer therapy at the LCI, and died in timepoints ending in January, July and November of 2017. After IRB approval, patients were identified through our tumor registry. Patients’ electronic medical records were reviewed for past history, cancer stage, type of care received, palliative care contact, site of death, ICU admission in last 30 days of life, receipt of immunotherapy and biologic (precision) therapy in last 6 months of life, and systemic anticancer therapy (excluding antihormonal therapy) in last 2 weeks of life. Results: A total of 134 patients died in this time period; 18 were excluded (leukemia/myeloma) leading to 116 patients for this analysis. Our review showed that 16.4% of LCI patients were admitted to the ICU in the last 30 days of life and 9.5% received systemic anticancer therapy in the last 2 weeks of life. Significant factors associated with an ICU admission in the last 30 days of life were receipt of biologic (precision) therapy in the last 6 months of life (41.7% vs. 13.9%; P

251 Background: Addressing the opioid epidemic can be challenging in a large academic cancer program and necessitates the need for a multidisciplinary approach for implementation of a successful program. The oncologist has a challenging role caring for patients with preexisting pain conditions, acute cancer-related pain, pain at the end of life and cancer survivors who live with cancer as a chronic condition after treatment. Methods: A structured program was developed to address the mounting pressure from many fronts related to the opioid epidemic including insurance companies, pharmacies, and the Department of Health. In April 2018, the Lifespan Cancer Institute implemented a system wide opioid program including patient education, an electronic patient-provider treatment agreement, and an electronic template for provider documentation. The intent of the program is to implement safe processes to safe guard the patient and their family along with the providers. The patient-provider treatment agreement clearly describes the roles and responsibilities of both groups with a goal of reducing risks by improving education. Our responsibility is to provide optimal management while addressing patient concerns and maintaining patient safety. Results: The opioid program has been well received by both caregivers, patients and families. All are engaged in the embedded education process and fully appreciate the need to use opioids safely. The program has been helpful in managing patient expectations and focusing difficult conversations in cases of potential abuse. In April 2018, only 13% of patients prescribed an opioid had a signed patient-provider treatment agreement. As of April 2019, 75% of patients have a signed agreement. Conclusions: The transitioning of care for the patient with chronic pain after completion of active cancer treatment continues to be a focus of future initiatives. Patient satisfaction remains a top priority as the patient-provider agreement becomes a standard of care for all patients receiving opioids. As oncology healthcare providers, our responsibility is to screen and educate patients on the risk of opioid addiction and diversion while providing compassionate palliative care.

11618 Background: The Commission on Cancer has made the provision of survivorship care plans (SCPs) a prerequisite for accreditation of cancer programs. However, whether all patients desire or derive benefits from an SCP is not established. This study sought to characterize the provision of survivorship care at the Lifespan Cancer Institute (LCI) to (1) determine clinical and distress characteristics at first visit to the LCI among patients treated with curative intent for a solid tumor diagnosis; (2) characterize which factors are associated with receipt of an SCP with or without a survivorship care visit (SCV); and (3) determine referral patterns and outcomes among patients with an SCP with or without an SCV. Methods: We have retrospectively reviewed 650 patients at Lifespan Cancer Institute so far, all of whom were initially seen between the years 2014-2017. As part of routine practice, all new patients are screened with the NCCN Distress Thermometer (DT). Data related to demographics, treatment variables, and presenting distress score were gathered using our electronic medical records. Categorical data were analyzed using Fisher’s Exact Test or Chi-Square. Multinomial logistic regression was performed for multivariate analysis. All analyses were performed in STATA 15.0. Results: The median age was 63 (range 29 to 90), 74.8% were female, and 39.5% were married or partnered. The major cancers represented included breast (52.2%), lung (16.6%), and prostate (6%) cancers. Severe distress (DT≥4) was reported in 49.5% of patients at their first visit with top concerns being worry (54.3%), nervousness (46.6%) and fatigue (37.3%). An SCP was documented in 461 patients (71.1%) and of these, 267 (57.9%) were seen in an SCV as well. On multivariate analysis, gender, marital status, and stage were significantly associated with the receipt of an SCP. However, only disease site was significantly associated with being seen in an SCV. Compared to those with an SCP but not seen in an SCV, those who attended an SCV were significantly more likely (p < 0.005) to be referred for post-treatment evaluation, including psychological counseling (15.7 vs 6.7%), physical therapy (56.9 vs 22.7%), and nutrition (26.6 vs 8.2%). The majority of patients followed up with referrals, though it was significantly higher among those with an SCV (95.4 vs 87%, p = 0.015). Conclusions: Survivorship care varies by cancer type, with highest rates of visits for patients with gynecologic and GI cancers. Referral to other resources is significantly higher among those seen in visits, and those who are referred will follow up.

Global gene expression profiling studies led to the recent classification of breast cancer into 4 distinct molecular subtypes including luminal, human epidermal growth factor receptor 2 enriched, basal like, and unclassified. Here, we used immunohistochemistry to evaluate expression of the antiapoptotic protein Survivin and its recently described acetylated form, Survivin acetyl129, in normal breast tissue and in 226 primary breast tumors of different molecular subtypes. Correlation of Survivin expression with molecular markers and its impact on patient outcomes were analyzed. Eighty-four percent of basal-like tumors expressed high levels of total Survivin, whereas 52% of luminal tumors expressed high levels of acetylated Survivin (P < .001). Overall survival (91%) for tumors expressing low levels of total Survivin was better than that for tumors expressing high levels of total Survivin (72%, P = .02), whereas the reverse was true for tumors expressing acetylated Survivin. In hierarchical cluster analysis, total Survivin clustered with basal marker expression, whereas acetylated Survivin clustered with luminal marker expression. In multivariate analysis, high total Survivin expression was an independent predictor of worse overall survival in patients with breast cancer (relative risk, 11; P < .01). These data indicate that high levels of total Survivin predict poor outcome in patients with grade 3 invasive ductal carcinoma and correlate directly with a basal-like phenotype. In contrast, high expression of the acetylated form of the protein associates with a favorable outcome and preferentially correlates with luminal-type tumors. Survivin likely has different functions in distinct breast cancer subtypes, and diagnostic strategies that incorporate immunohistochemical markers that detect both Survivin forms may help better strategize patient risk and direct therapy.

Background: Recent studies (Coombs et al., Cell Stem Cell 2017) have identified presence of clonal hematopoiesis of indeterminate potential (CHIP) in samples of solid tumors. CHIP is more prevalent among cancer survivors who subsequently develop therapy-related myeloid neoplasm (Gillis et al., Lancet Oncol 2017; Takahashi et al., Lancet Oncol 2017; Gibson et al., J Clin Oncol 2017). However, the relationship between CHIP and exposure to myelotoxic chemotherapy delivered as part of treatment for solid tumor is uncertain. We hypothesized that CHIP is more prevalent among recipients of myelotoxic chemotherapy compared with age-matched population. Methods: In this prospective, cross-sectional study, we collected peripheral blood samples from survivors of breast cancer or lymphoma who had received anthracycline- and/or alkylator-containing chemotherapy as part of their curative cancer therapy. All subjects had to be clinically free of cancer, and not have any hematologic disorders or unexplained cytopenias. We recruited patients age 50 to 70, because according to published population datasets (Jaiswal et al. and Genovese et al., NEJM 2014) in a cohort with mean age of 60 the expected CHIP prevalence would be about 5%. To minimize any potential contamination by circulating tumor cells, we isolated genomic DNA from purified CD45+ cells. We determined presence of CHIP by next-generation sequencing using an Illumina TruSeq Custom Amplicon kit (MiSeq V2.2). The assay targeted 757 coding exons of 96 genes commonly mutated in hematologic malignancies, including 20 CHIP-defining genes. To establish presence of CHIP, we required a known pathogenic variant with variant allele fraction (VAF) ≥ 2%. According to a pre-specified statistical plan, assuming one-sided alpha of 0.05, the study had 80% power to reject the null hypothesis of baseline CHIP prevalence of 5% in a cohort with sample size of 80. Results: Among 80 enrolled subjects, median age was 62 years (interquartile range, 56-67). There were 78% women, and 88% of subjects were white non-Hispanic. Patients had received doxorubicin- and/or cyclophosphamide-containing adjuvant or curative chemotherapy for breast cancer (56%) or lymphoma (44%). Median time from completion of chemotherapy to enrollment was 27 months (interquartile range, 11-59). We have completed sequencing of 72 samples (updated analysis will be provided at the meeting). Mean coverage depth was 1418x (±224), and ≥200x coverage was achieved in a mean 91.4% (±1.8%) of target amplicons. We detected CHIP in 12 subjects (17%; binomial 95% confidence interval: 10-27%; P=.0002 for the null hypothesis test of 5% prevalence). Mean VAF for the CHIP mutations was 5.3% (range, 1.4% to 29.9%), and patients had up to 4 CHIP-associated mutations (Fig. A). The CHIP-associated mutations had a typical distribution with most common mutations in DNMT3A, ASXL1, SRSF2, and TET2 (Fig. B). There was only 1 TP53 mutation, previously suggested to associate with exposure to chemotherapy (Coombs et al., 2017). Potentially germline variants of unknown significance (VUS) were found in 78% of patients, at mean VAF 49% (Fig. C), most commonly in ATM (12%), NOTCH2 (7%), BCORL1, and DNMT3B (6% each). Additionally, 2 patients had low-VAF variants suspicious for CHIP: ATM c.6059G>A (3.0%); PRPF8 c.790T>C (VAF 2.3%). Presence of CHIP was not significantly associated with age (within the narrow age range in the study cohort), sex, race, type of cancer (breast or lymphoma), count of white cells, red cells, platelets, or time elapsed from completion of chemotherapy. Conclusions: We have detected a significantly increased, more than 3 times the expected value, prevalence of CHIP among cancer survivors who had received myelotoxic chemotherapy. However, the distribution of mutations was typical for CHIP, without previously suggested over-representation of TP53. Further research is ongoing to determine whether presence of CHIP is related to a direct mutagenic effect of chemotherapy or competitive advantage of pre-existing CHIP clones after the hematopoietic stress of chemotherapy. Our data indicate that an affordable next-generation sequencing screen may be useful for detection of CHIP in cancer patients who are planning adjuvant chemotherapy, or as a surveillance tool after such therapy, to predict the risk of a therapy-related myeloid neoplasm and optimize personalized treatment strategies. Disclosures Olszewski: TG Therapeutics: Research Funding; Genentech: Research Funding; Spectrum Pharmaceuticals: Consultancy, Research Funding. Kim:Aushon Biosciences: Consultancy; LabCorp, Inc.: Consultancy; Papgene, Inc: Consultancy. Fenton:Astellas Pharma US: Other: Spouse employment. Reagan:Alexion: Honoraria; Takeda Oncology: Research Funding; Pfizer: Research Funding.

146 Background: The Lifespan Cancer Institute (LCI) is one program based at three hospitals in the Lifespan healthcare system, a main teaching affiliate of Brown Medical School. All sites are ASCO QOPI certified. In 2017, 1,742 patients from radiation, surgical, and medical oncology were diagnosed and/or treated for cancer. The Commission on Cancer guidelines specify patients with a new diagnosis of cancer treated with curative intent receive a survivorship care plan (SCP) within one year of diagnosis extended to 18 months for those receiving hormone therapy. Methods: The LCI Quality team is a multidisciplinary group comprised of nursing, leadership, physicians, midlevel providers, administrative assistants, and tumor registry staff. Our Quality Improvement Project for 2017 was generation and distribution of survivorship care plans to 50% of eligible patients. Our project underwent 5 plan/do/study/act cycles (PDSA). Prior to the intervention only 271 care plans were prepared and delivered for 2016 diagnoses. Results: For the total 2017 diagnoses, 843 eligible patients were treated within the LCI (medical and radiation oncology). Survivorship Care plans completed by midlevel providers were generated and distributed to 100% of LCI patients during January -April 2018 (244 in total), a 37% increase compared to the same timeframe, one year previous. The electronic medical record provides tools for SCP preparation including auto population of demographics and chemotherapy plan. Staging, radiation, and surgery are manually entered. On average, each SCP required 1 hour to complete for approximately 244 hours of midlevel provider time for January -April 2018. This abstract’s time and effort does not include the time for patient calls, survivorship visits or administrative monitoring. Conclusions: Survivorship care plans provide patients and primary care providers a summary of the treatment plan and recommendations for follow up/survivorship goals in transitions of care. Significant time and effort is required to generate an individual SCP therefore the goal should be to increase electronic efficiencies within the medical record, and focus on the clinically relevant patient population who are most likely to survive 5 years and be impacted by diagnosis and treatment.

Purpose To evaluate the efficacy and safety of neoadjuvant carboplatin and weekly paclitaxel ± weekly trastuzumab in resectable and locally advanced breast cancer. Patients and Methods Women with stages IIA to IIIB disease received carboplatin dosed by six times the area under the curve every 4 weeks and paclitaxel 80 mg/m2 weekly for 16 weeks, and weekly trastuzumab was added for human epidermal growth factor receptor 2 (HER2) –positive status. The primary end point was the pathologic complete response (pCR) rate, defined as the absence of invasive disease in the breast and axillary nodes. Postoperative therapies were at the discretion of the treating physicians. Results Fifty-five patients were enrolled, and of these 43 had resectable disease. The median age was 54 years (range, 31 to 74 years). Treatment was well tolerated; there were no episodes of febrile neutropenia or grade 4 thrombocytopenia, and there were only two instances of grade 3 peripheral neuropathy. Overall, the pCR rate was 45%. The pCR rate was 43% (95% CI, 28% to 58%) in patients with resectable disease. Higher pCR rates occurred in patients with HER2-positive tumors (76% v 31% for HER2-negative tumors; P = .003), with estrogen receptor (ER) –negative tumors (75% v 27% for ER-positive tumors; P = .001), or with triple-negative tumors (67% v 12% ER-positive and HER2-negative tumors; P = .002). At a median of 28 months postoperation, recurrence-free survival (RFS) was 88.7%. If patients with ER-positive and HER2-negative tumors are excluded from analysis, patients who achieved a pCR were less likely to experience disease recurrence (RFS, 86%) than those who did not achieve a pCR (RFS, 75%). Conclusion Neoadjuvant carboplatin and weekly paclitaxel ± trastuzumab achieve high pCR rates in patients with HER2-positive and triple-negative disease without exposure to an anthracycline. Preliminary RFS results are encouraging but are likely influenced by adjuvant therapy received. Additional study of this regimen in high-risk patients is warranted.

Recruiting cancer patients for randomized trials investigating psychosocial interventions presents several unique challenges. This paper describes the challenges and yields for different recruitment methods used in Moving Forward, a randomized trial of a home-based moderate-intensity physical activity program for early-stage breast cancer survivors. Recruitment methods included letters sent to patients by their oncologists, direct referrals from oncologists, in-person recruitment in oncology clinics, referrals from nurses and medical assistants, passive recruitment, other mailings, and community outreach strategies. Of the 424 screenings completed, 86 (20.3%) participants were randomized. Physician letters yielded the greatest number of initial screenings (147; 34.7%) and participants randomized (28; 32.5%). In-person recruitment also proved to be a productive recruitment strategy; 14 (16.3%) of the participants were recruited via this strategy. Community outreach efforts did not provide as great a yield and were labor intensive. We discuss suggestions for recruitment of cancer patients in future trials.

A pilot study of the antiandrogen bicalutamide at 150 mg. a day for androgen independent prostate cancer was performed. This study was based on the possibility that androgen independent cases might display responses to additional hormonal agents.The study included 31 androgen independent cases with an increasing prostate specific antigen (PSA) and progressive disease. PSA measurements were used as the primary method of assessing response. However, PSA decline was also correlated with clinical status.Seven patients demonstrated PSA declines of greater than 50% for 2 months or more, for an overall response rate of 22.5%. Responses were observed almost exclusively in patients treated with long-term flutamide as part of a complete androgen blockade regimen (43% response rate) in contrast to patients treated with androgen deprivation without flutamide (6% response rate). Of the 7 PSA responding patients bicalutamide resulted in a significant improvement in performance status and a decrease in analgesic requirement in 4 and 3 remained asymptomatic. Bicalutamide at 150 mg. a day was well tolerated, with the most frequent side effect being mild exacerbation of hot flashes.Bicalutamide at this dose is modestly effective for some patients with androgen independent prostate cancer, particularly for those previously treated with long-term flutamide. This study indicates that previous antiandrogen therapy alters the response to subsequent hormonal agents.

77 Background: Patients are often overwhelmed at the time of hospital discharge and focus on home rather than the discharge process. Fragmented communication and lack of planning between the hospital team, patient, family and primary oncologist can lead to frustration and delays in implementation of palliative or curative therapies and potential hospital readmission when the plan of care is not followed in a timely manner. Our goal is to avoid medication errors, delays in implementation of a care plan and reemergence of symptoms or new symptoms as a result of a suboptimal discharge transition. Methods: A multidisciplinary care transition team including phone nurses, social workers, pharmacists, physicians, nursing leadership and a palliative care practitioner meet monthly to review and refine discharge transitions. Our intervention is a proactive phone call, by specially trained ambulatory oncology nurses, to patients within 1-2 business days after discharge from the inpatient Hematology Oncology service. The nurse asks consistent questions to address common issues in the discharge transition including review of symptoms, understanding of discharge medications, confirmation of new medication initiation, side effects, coping, and next appointment with the oncologist. The nurse reinforces the ambulatory nurse phone line and availability of same day sick visits. Results: Preliminary discharge phone call results from the nurses’ interventions include clarification of discharge medications, interventions when a patient had not obtained the ordered medication including antibiotics, referrals for same day sick visits, referrals to social work for emotional and financial distress, education on medications or side effect management, and follow-up appointments. The average time for the post discharge call is 13 minutes. Conclusions: Our follow up discharge intervention by the oncology nurse has shown many patients are uncertain of medications and follow-up even when provided with detailed discharge paperwork and medication reconciliation. A proactive discharge phone call may help resolve these issues and prevent future readmissions. A six month summary of our intervention will be presented.

128 Background: Emergency department (ED) utilization for non-emergent medical problems is an inefficient use of medical resources. During calendar year 2013, 224 RIH adult cancer patients presented to the RIH ED. Retrospective review indicated up to 50% of these ED visits were avoidable. Methods: This project was developed for the ASCO Quality Training Program. A multidisciplinary team was assembled to address ED utilization. Retrospective chart review of ED visits included time and reason for visit and primary tumor site. The team selected the Lung Cancer as the target group, developed a cause-and-effect analysis for ED visits, administered a patient survey, and implemented a series of Plan-Do-Study-Act (PDSA) cycles. The team implemented a patient education process of nurse sick-line symptom management and same-day sick visits at RIH CCC as well as developing a single-page patient “sick-line tool” with oncology nurse sick-line contact telephone numbers. A patient navigator introduced the sick-line tool at the first visit and its usage was reinforced at subsequent visits. Results: For RIH CCC lung cancer patients, a standardized symptom-control education process correlated with 30% decrease in ED visits for any presenting complaint (42 visits vs. 60 visits) and 32% decrease in ED visits with presenting complaint of pain (13 visits vs. 19 visits) during January/February 2014 compared to January/February 2013. We did not find significant differences between the proportion of ED visits during Cancer Center business hours, evenings, or weekends. Sick-line calls were found to increase by 53% during January 2014 compared to December 2013 with an additional 35% increase in February 2014. Conclusions: A standardized patient education process resulted in a significant decrease in ED visits, concurrent with an increase in outpatient sick-line utilization. This may reflect an improvement in efficiency of outpatient cancer patient care in a single-institution setting. Given other reports of increased ED utilization by lung cancer patients for similar presenting reasons, these improvements may be generalizable to other institutions.

75 Background: ASCO Quality Oncology Practice Initiative (QOPI) provides tools for oncology practices to assess quality and adherence to clinical guidelines. Following each data submission a QOPI measures summary report is published providing practices the opportunity to compare themselves to QOPI Aggregates. In 2011, QOPI initiated a more stringent evaluation of family history documentation, which would improve rates of referral to genetic counseling for breast and colon cancer. Methods: A review of QOPI measure summary reports is performed by Rhode Island Hospital’s (RIH) Comprehensive Cancer Center Quality Improvement Team after each round of chart abstraction. Following review of QOPI practice results for genetic evaluation in 2011, our interventions included development and implementation of a 3 generation maternal and paternal family history intake form, genetics referral form with criteria to refer patients for genetic evaluation and initiation of a Genetics Clinic on site at the Cancer Center. Results: Presented is a summary of QOPI results for the Breast Cancer measures of complete family history documented and Genetic testing addressed appropriately. Conclusions: Our interventions included a patient intake form, genetics referral form with criteria to refer patients and a Genetics Clinic on site at the Cancer Center. The institution of a patient intake form resulted in a 19-fold improvement in complete family history documentation. The genetics referral form and establishment of an on-site Genetics clinic resulted in a 10% increase in referrals for genetic risk assessment. In spite of these interventions review of our Genetic Risk Evaluation data is notable for a 39% no show rate for the genetic risk assessment appointments. [Table: see text]

130 Background: Patient navigator programs (PNP) aid in evaluation and treatment of cancer in underserved populations. Along a patient’s journey obstacles to medical care can include cultural, financial, language, physical and transportation barriers, fear and anxiety, comprehension and retention of critical information and coordination of visits. PNP research has focused on addressing ethnic and racial barriers, with scant attention paid to the impact of PNP in the disabled. The Americans with Disabilities Amendments Act of 2008 defines as a “physical or mental impairment that substantially impairs one or more of major life activities." Methods: A retrospective analysis was performed of patients with stage I-III breast cancer under age 70 with disabilities enrolled in the PNP at Rhode Island Hospital or the Miriam Hospital (RIH/MH) from 2006-2012. Charts were reviewed and assessed for quality measures as defined by the National Comprehensive Cancer Center (NCCN) guidelines and American Society of Medical Oncology Quality Practice Initiative (QOPI) benchmarks, for demographics, stage at diagnosis, treatment recommended and received, and patient outcomes. Results: 44 patients were identified. All patients were recommended treatment in accordance with NCCN guidelines. Compliance with radiation and endocrine therapy guidelines was excellent. In the smaller cohort of patients for whom adjuvant chemotherapy was indicated, there was a higher rate of nonconcordance (25%) compared to 13% in the NCCN database. All nonconcordance was attributed to patient refusal (6) or delay due to comorbid conditions (3). Conclusions: Our analysis suggests PNP may enhance compliance with recommended treatment and thus quality care in breast cancer patients with disabilities. Integration of PNP in cancer care serves as a valuable adjunct in removing obstacles to cancer care for the disabled. [Table: see text]

619 Background: Patients (pts) with human epidermal growth factor receptor-2 amplified (HER2+) breast cancers (BrCa) who achieve a pathologic complete response (pCR) with neoadjuvant chemotherapy (NAC) + trastuzumab (T) have an excellent prognosis (Cortazar, SABCS 2012). We tested a novel NAC + T regimen, designed to avoid potential cardiac and other toxicities associated with anthracyclines (A) and eliminate steroid premedication by replacing standard paclitaxel with nab-paclitaxel (nP). Methods: Clinical stage IIA-IIIC HER2+ BrCa pts received single agent either nP or T, with research biopsies and MRIs obtained before and after, then carboplatin (Cb) AUC 6 q3wks, nP 100 mg/m2and T 2 mg/kg weekly x 18 wks. If present, residual tumor was collected at surgery. Post-op pts complete a year of T; other adjuvant treatment is at MD discretion. Endpoints include clinical + pathologic response (pCR is defined as no invasive BrCa in breast + axillary nodes), residual cancer burden (RCB), treatment delivery and toxicities. Results: 53 pts (of 60 planned) are evaluable for response, median age 51 (34-72). Median delivered dose intensity for nP was 89 mg/m2/week; nP doses were omitted or reduced for neutropenia (ANC) (in 20% of pts) and neurotoxicity (Nt) (5%). Cb was reduced for thrombocytopenia (tcp) in 15%. Grade 3-4 toxicities: ANC 65%, tcp 22%, anemia 37%, Nt 7%. Serious adverse events: febrile neutropenia (5 pts), infections w/o neutropenia (4), vomiting, diarrhea or dehydration (7), thrombosis (2). LVEF fell by >10% in 3 pts with no clinical CHF. Response data are tabulated below: 28 pts (53%) achieved pCR or RCB class I; 15/21 who did not received A-based adjuvant chemotherapy. Of 38 clinically node-positive pts, 26 (68%) were node-negative at surgery. Conclusions: The Cb/nP/T regimen was well tolerated, with pCR rates comparable to those reported with A-containing regimens. Final treatment and response data will be presented; correlative studies will be reported separately. Clinical trial information: NCT00617942. [Table: see text]

260 Background: Pre-chemotherapy teaching sessions, often coordinated by nursing personnel, are an opportunity to educate patients on treatment side effects, schedule, medications for toxicities such as nausea, and how to contact the oncology team if adverse events develop. Our institution provides a structured 60-minute nurse-coordinated pre-chemotherapy teaching session. The aims of this study were to evaluate whether pre-chemotherapy teaching sessions improve patient knowledge, preparedness, and anxiety in relation to chemotherapy. Methods: Patients were offered the opportunity to participate in the study after their medical oncologist had reviewed their treatment regimen. After informed consent was obtained, participants were administered a 10-question survey assessing knowledge of treatment adverse effects, treatment schedule, management of complications, accessing their medical team, and patient anxiety. Subjects then participated in a pre-chemotherapy teaching session with an oncology nurse. The survey was readministered when patients returned on day 1, cycle 1 of treatment and on day 1, cycle 2. The questionnaire used a 1 to 4 rating scale (1=no knowledge, 2= minimally informed, 3= reasonably informed, 4= well informed). A pre-defined mean change of 1 on the rating scale was considered to be clinically significant. Paired one-sided t-tests were performed to evaluate the mean change in groups between each of the three surveys. p values

206 Background: The ASCO QOPI is an instrument for community and academic practices to assess quality and adherence to guidelines in areas of treatment planning and goals, chemotherapy consent documentation, smoking cessation, symptom control, palliative care, and disease specific measures. Following data submission QOPI summary reports for the submitting practice and QOPI aggregate are available for review and comparison. Methods: The academic practice of Rhode Island Hospital Comprehensive Cancer Center has participated in QOPI since the fall of 2008. QOPI measure summary reports for our practice and comparison to the Academic Aggregate are reviewed by our physicians after each round of chart abstraction, measures are identified for improvement. Interventions include education on practice improvement and development of policy and procedures for implementation by our Quality Control Officer in compliance with hospital policies. Results: Presented is a summary of quality improvement interventions implemented. Additional areas of quality improvement have been identified based on QOPI data, and improvement plans are ongoing including treatment summaries for patient and primary care physicians, tools to assess patient emotional well being, documentation of family history and referral for genetic assessment. Conclusions: QOPI provides a platform for collection, analysis and comparison of quality measures. For the measures of formulating a pain plan the intervention was a reminder to document the plan. For the measure hospice enrollment, a reflection on our hospice enrollment has lead to an increase in referral to palliative care. The ASCO QOPI program is a tool for quality improvement, our Quality Control Officer was essential in implementation of our improvement projects. [Table: see text]

1045 Background: High risk BrCa patients (pts) often receive weekly paclitaxel (wP) as well as ddAC. Switching to wA(Abraxane) or adding B or Cb may enhance its efficacy, especially in TN pts. Methods: Pts with clinical stage IIA-IIIC BrCa received wA 100 mg/m2, Cb AUC 6 + B 15 mg/kg q3wks x 12 wks only (cohort 1/Yale) or followed by ddAC + B x 4 (cohort 2/Brown). Endpoints: pathologic complete response (pCR) - absence of invasive BrCa in breast + axillary nodes, residual cancer burden (RCB), clinical CR/partial response (cCR/cPR), and toxicity. Correlative studies are being performed on biopsies obtained at baseline and after run-in doses of wA or B only. Post-op pts resume B for 34 wks; other systemic therapy, including ddAC in cohort 1, is at MD discretion. Results: 55 of 60 pts (median age 47, range 25-68; 31 HR+/29 TN) are evaluable for response (see table below). Median # doses wA 11,Cb 4, ddAC 4. Dose reductions: wA 25% for neutropenia (ANC), Cb 15% for thrombocytopenia (tcp). B 7% held for hypertension. Grade 3-4 toxicities (>5%): ANC 85%, tcp 35%, anemia 25%. Serious adverse events during wA: 3 nausea/dehydration (N/D), 3 infection w/o neutropenic fever (FN), 2 GI bleed; during ddAC: 6 (21%) FN despite G-CSF, 3 N/D. Conclusions: The combination of wA, q3wk Cb + B was well tolerated, with cCR+cPR 84%. However, overall pCR was only 11% (27% in TN) after 12 wks of this regimen (cohort 1). Subsequent preop ddAC raised overall pCR to 54%, and 81% in TN, demonstrating that longer treatment duration or inclusion of anthracycline-based therapy improves responses. Results for cohort 2 compare favorably with those from I-SPY, GeparQuinto and NSABP B-40; the addition of Cb and/or B in TN is being evaluated in CALGB 40603. [Table: see text]

e11573 Background: To evaluate CbwAbAv NAC in HER2- BrCA. Methods: 60 patients (pts) with HER2- (IHC 0-1+ or FISH

e11010 Background: To evaluate the efficacy and safety of neoadjuvant weekly (w) nanoparticle albumin-bound paclitaxel (Abraxane, NP) and every-3-week (q3wk) carboplatin (Cb) with either bevacizuma...

785 Background: Gemcitabine (G) and capecitabine (C) have antitumor activity as single agents in MBC. Each inhibits DNA synthesis, though by different mechanisms. By increasing the activity of pyri...

759 Background: In resectable breast cancer (BrCa), pathologic complete response (pCR) to anthracycline-based neoadjuvant chemotherapy (NAC) reduces risk of recurrence and death. Adding a taxane in...

Canine transmissible venereal sarcoma (CTVS) is a contagious neoplasm which regresses spontaneously in adult dogs but metastasizes and kills puppies transplanted with the neoplasm at a very young age. Immunofluorescence studies showed that 30 +/- 14% of cells from steady-state and 22 +/- 7% of cells from regressing tumors had membrane-bound antibodies which could be eluted out with warm washes at 24 degrees C, whereas the cells from progressor tumors had very little such antibody (6 +/- 6%). Time-course kinetics of anti-CTVS antibodies in the serum of tumor-bearing dogs did not correlate well with tumor volume, however, the presence of such antibodies in adult dogs (47 +/- 13%) but absence (0%) in the puppies with tumor metastasis suggested the importance of antibodies in resistance to metastasis.

Background The influence of the tumor microenvironment and tumor-stromal interactions on the heterogeneity of response within breast cancer subtypes have just begun to be explored. This study focuses on patients with estrogen receptor-positive/human epidermal growth factor receptor 2-positive (ER+/HER2+) breast cancer receiving neoadjuvant chemotherapy and HER2-targeted therapy (NAC+H), and was designed to identify novel predictive biomarkers by combining gene expression analysis and immunohistochemistry with pathologic response. Methods We performed gene expression profiling on pre-NAC+H tumor samples from responding (no or minimal residual disease at surgery) and non-responding patients. Gene set enrichment analysis identified potentially relevant pathways, and immunohistochemical staining of pre-treatment biopsies was used to measure protein levels of those pathways, which were correlated with pathologic response in both univariate and multivariate analysis. Results Increased expression of genes encoding for stromal collagens, including Col10A1, and reduced expression of immune-associated genes, reflecting lower levels of total tumor-infiltrating lymphocytes (TILs), were strongly associated with poor pathologic response. Lower TILs in tumor biopsies correlated with reduced likelihood of achieving an optimal pathologic response, but increased expression of the Col10A1 gene product, colXα1, had greater predictive value than stromal abundance for poor response (OR = 18.9, p = 0.003), and the combination of increased colXα1 expression and low TILs was significantly associated with poor response in multivariate analysis. ROC analysis suggests strong specificity and sensitivity for this combination in predicting treatment response. Conclusions Increased expression of stromal colXα1 and low TILs correlate with poor pathologic response in ER+/HER2+ breast tumors. Further studies are needed to confirm their predictive value and impact on long-term outcomes, and to determine whether this collagen exerts a protective effect on the cancer cells or simply reflects other factors within the tumor microenvironment. Electronic supplementary material The online version of this article (doi:10.1186/s12885-016-2302-5) contains supplementary material, which is available to authorized users.