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Background: The approved dosing schedule of capecitabine monotherapy in metastatic breast cancer (MBC) is 1250 mg/m2/dose administered days 1 through 14 of a 21-day cycle, but many patients (pts) have difficulty with this schedule due to side effects. Use of a lower starting dose such as 1000 mg/m2/dose or use of an alternative 28-day administration schedule (7 day on, 7 day off, repeat) allows for greater tolerability. Given limited data regarding efficacy of the alternative 28-day schedule, the primary objective of this study was to compare the efficacy of different schedules of capecitabine in patients with MBC. Methods: A retrospective chart review of pts with metastatic breast cancer who received capecitabine as monotherapy between 2002 and 2014 at the Ohio State University James Cancer Hospital was performed. We excluded any HER2-positive patients who had received concurrent HER2-targeted therapy. Pts who initiated therapy at a dose of 1000 mg/m2/dose were classified by these dosing schedules: Arm A (21 day), B (28 day), and C (changeover from 21 day to 28 day). Time to treatment failure (TTF) and overall survival (OS) were compared between dosing schedules using Kaplan Meier curves and log-rank tests. Results: A total of 181 MBC patients (Arm A: n = 113, Arm B: n = 25, Arm C: n = 43) with the following patient characteristics met eligibility criteria; 86.2% Caucasians, 13.8% non-Caucasians, 64.64% estrogen receptor (ER)-positive, 3.31% ER positive/HER2-positive, 2.22% ER negative/HER2-positive, and 29.83% triple-negative. The HER2-positive patients were excluded as they received concurrent therapy. A significant difference was seen in TTF (Arm A: 2.7 mo, Arm B: 2.8 mo, Arm C: 7.1 mo, p = 0.001) when comparing all dosing schedules as well as in OS (Arm A: 5.7 yrs, Arm B: 9.6 yrs, Arm C: 7.8 yrs, p = 0.006). After an initial dose reduction, patients on Arm B tolerated capecitabine for a longer period of time than patients on Arm A before needing a second dose reduction (Table 1). The median time on capecitabine for Arm A was 11.9 weeks and 12.6 weeks for Arm B, and the mean time of both Arm A and Arm B on capecitabine was 22.2 weeks. Patients with ER-positive breast cancer had improved TTF (4.45 months vs 2.32 months, p < 0.001) and OS (7.26 years vs 3.99 years, p < 0.001) compared to ER-negative breast cancer. Caucasians had improved TTF compared to African Americans (AA) and other races (3.90 mo vs 2.87 mo, p = 0.004); however, there was no significant difference in OS. Median starting dose (mg/m2): Arm A - 1000; Arm B - 1043; Arm C - 1000 Time to 1st dose reduction (weeks): Arm A - 6; Arm B - 6; Arm C - 6.5 Dose after 1st reduction (mg/m2): Arm A - 808; Arm B - 848.5; Arm C - 802 Time to 2nd dose reduction (weeks): Arm A - 6; Arm B - 20; Arm C - 8 Dose after 2nd reduction (mg/m2): Arm A - 599.5; Arm B - 690; Arm C - 697 Time to 3rd dose reduction (weeks): Arm A - 6; Arm B - 0; Arm C - 24 Dose after 3rd reduction (mg/m2): Arm A - 575; Arm B - 0; Arm C - 557 Table 1: Median dose (mg/m2) and median time to reductions (in weeks) Conclusions: Our study shows that patients who received the 28-day cycle initially or who were switched to the 28-day cycle appeared to have improved TTF and OS compared to patients on the 21-day cycle. It also shows that AA women had worse TTF on capecitabine when compared to Caucasians. One hypothesis for the improved TTF and OS is that this could be due to a higher total dose of capecitabine received in Arm B and C as shown in Table 1. We acknowledge that the limitations of our study include the sample size and the retrospective nature, and that further work needs to be done. However, the 28-day dosing schedule for capecitabine could be an alternative for elderly patients or patients with poor performance status who are at higher risk for drug toxicities. Citation Format: Nicole Olivia Williams, Anupama Suresh, Julie Stephens, Marilly Palettas, Michael J. Berger, Akaansha Ganju, Raquel Reinbolt, Robert Wesolowski, Anne M. Noonan, Jeffrey Bryan VanDeusen, Sagar Sardesai, Maryam Lustberg, Maryam B. Lustberg, Bhuvaneswari Ramaswamy. Efficacy of alternative 28-day capecitabine dosing schedule in metastatic breast cancer [abstract]. In: Proceedings of the AACR Special Conference: Advances in Breast Cancer Research; 2017 Oct 7-10; Hollywood, CA. Philadelphia (PA): AACR; Mol Cancer Res 2018;16(8_Suppl):Abstract nr A69.

Introduction: The effect of chemotherapy on the presence of tumor-infiltrating lymphocytes (TILs) and expression of PD1 and PD-L1 is unclear. We sought to describe the differences in the percentage (%) of TILs, cytotoxic T lymphocytes (CTL), and expression of PD1/PD-L1 in tumors of patients (pts) with operable breast cancer (BC) treated with neoadjuvant chemotherapy (NAC) who were enrolled in a biomarker study at our institution (IRB protocol# 2010C0036). Methods: A multicolor immune-histochemical multiplex assay simultaneously detecting PD1, PD-L1, and CD8 expressing cells was performed on formalin-fixed, paraffin-embedded diagnostic pretreatment biopsy or resected tumor specimen following NAC in 18 of 26 pts participating in the study. A cut-off of ≥1% was considered positive for PD1 and PD-L1 expression. We evaluated stromal and intratumoral CTLs by estimating % of stroma and tumor that contained CD8+ cells. In addition, stromal TILs (sTILs) were identified on full-face hematoxylin and eosin stained sections and defined as the % of tumor stroma containing infiltrating lymphocytes. Pathologic complete or near-complete response (pCR) was analyzed based on residual cancer burden (RCB) score and defined as RCB class 0 or I. Analysis of all slides was performed by an expert breast pathologist. Since the number of pts was limited, we only provide descriptive statistics (mean, range). In addition, because most pts had only a biopsy or only residual tumor available for the analysis, we divided pts into 2 separate cohorts based on what tissue was available. Results: Of 18 pts, biopsy was analyzed in 7 (Bx cohort) and residual tumor was analyzed in 11 pts (RT cohort). The median age of study pts was 48 (range 32-70); 11 (61%), 6 (33%), and 1 (6%) of pts were Caucasian, African American, and Hispanic, respectively. Ten pts (5 in Bx and RT cohorts each) had triple-negative BC (TNBC), 4 had HER2+ BC (1 and 3 in Bx and RT cohorts, respectively), and 4 had hormone receptor-positive, HER2- BC (1 and 3 in Bx and RT cohorts, respectively). Eight pts (44%) had pCR. In the bx cohort, 85% of pts had pCR while 18% of pts in the RT cohort had minimal residual disease (RCB class I). In the Bx cohort, average % of sTILs was 30% (range 2-70%), including 1 pt (14%) with lymphocyte predominant tumor (≥50% of sTILs). The % of sTILs was similar in the 11 residual tumors (mean 22, range 2-60) with 2 pts having lymphocyte predominant tumors. Average % of CTLs was 19 (range 1-50) in the Bx cohort and 14 (range 1-50) in the RT cohort. An average % of intratumoral CTLs was 8 (range 1-30) and 7.5 (range 0-40) while the average % of stromal CTLs was 25 (range 1-60) and 19 (range 1-60) in the Bx and RT cohorts, respectively. Similar % and trends were seen in 10 TNBC pts. PD-L1 expression was seen in 86% and 36% of tumors in the Bx and RT cohorts, respectively, with majority of expression present in the stroma. All cases of intratumoral PD-L1 expression were also positive for stromal PD-L1 expression. This difference was also seen in the TNBC pts (80% vs. 40% of tumors were PD-L1+ in Bx and RT cohorts, respectively). An average PD-L1 intensity was approximately 3% in both cohorts (range 1-20%). Expression of PD1 was very low (1% intensity in 3 pts in Bx cohort and in 1 pt in RT cohort) and it was seen on CD8+ CTLs. Conclusion: Our study preliminarily shows that percent of sTILs and stromal and intratumoral CTLs does not differ between pretreatment biopsy and residual tumors following NAC. Lower proportion of residual tumors were PD-L1+ compared to pretreatment biopsy specimen. The study limitations include small number of subjects and lack of comparison in the same pts. Future studies are needed to confirm these findings. Citation Format: Robert Wesolowski, Zaibo Li, Christopher McQuinn, Maryam Lustberg, Bhuvaneswari Ramaswamy, Anne Noonan, Raquel Reinbolt, Sagar Sardesai, Jeffrey B. VanDeusen, Nicole Williams, William E. Carson, III. Analysis of tumor infiltrating lymphocytes and expression of PD1 and PD-L1 in breast tumors prior to and after neoadjuvant chemotherapy [abstract]. In: Proceedings of the AACR Special Conference: Advances in Breast Cancer Research; 2017 Oct 7-10; Hollywood, CA. Philadelphia (PA): AACR; Mol Cancer Res 2018;16(8_Suppl):Abstract nr A20.

Background: Adults over age 65 are the fastes- growing segment of the US population. However, clinicians have less evidence of how to treat older adults, because they are underrepresented in clinical trials, and studies designed specifically for older adults are rare. Therefore, clinicians have to extrapolate from trials conducted in younger, healthier populations when developing treatment plans for older adults. Over 40% of new breast cancer diagnoses in the US occur in women aged over 65 years. In general, breast cancer in the older woman has distinct biologic features, including less aggressive characteristics and greater expression of estrogen receptor and progesterone receptor. Increasing age is associated with higher rates of comorbidity and frailty, which has been shown to potentially reduce the survival advantage of more aggressive breast cancer therapies. We are conducting a prospective cohort study of adults > or = 65 years with a new diagnosis of breast cancer (OSU-16153) in order to better understand the complex health issues faced by this population, and to collect data with which to support future studies designed to improve the management of these patients. Specific Aims: 1) To assess overall and progression-free survival of breast cancer patients ages 65 and older seen in the Breast Medical Oncology clinics at the Stefanie Spielman Comprehensive Breast Center at The Ohio State University; 2) to examine the association of demographic, diagnostic, and treatment data with patient outcomes, such as progression-free and overall survival, within this patient population; 3) to evaluate the unique needs of breast cancer patients ages 65 and older by implementing a Comprehensive Geriatric Assessment (CGA) within the Breast Medical Oncology clinics at The Ohio State University. Methods: The study will enroll patients > or = 65 years with a new diagnosis of breast cancer. Participants will complete a brief baseline questionnaire, including items addressing demographics, lifestyle, and health history. Patients will then be asked to complete a Comprehensive Geriatric Assessment (CGA) at the time of enrollment, and approximately every six months while on follow-up. The CGA contains both performance-based assessments of patients’ function, completed by study staff, as well as the patients’ self-reports of symptoms and quality of life. The CGA contains a multifaceted battery of clinical instruments including the PROMIS Global Short Form, Functional Assessment of Cancer Therapy-Breast (FACT-B), Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale, The Pittsburgh Sleep Quality Index, Geriatric Depression Scale, The James Supportive Care Screening Tool, Timed Up & Go Test, Grip Strength, Blessed Orientation-Memory-Concentration Test, Mini-Cog Test, Charlson Comorbidity Index, Mini Nutritional Assessment, Katz Index of Independence in Activities of Daily Living, and Instrumental Activities of Daily Living. Participant medical records will be reviewed every three months to assess survival, disease progression, and treatment changes. All questionnaire data will be completed using iPads, and will be directly recorded into the REDCap database. Electronic medical records will be reviewed by research staff, and relevant data will be manually entered into the REDCap database. The aim is to enroll 1,000 participants, and the recruitment period will be five years from study initiation. Participants will be followed for five years from the time of enrollment, resulting in a total study length of ten years. The study opened to accrual on 18 April 2017. To date 3 patients have been enrolled and have completed baseline assessments. Citation Format: Anne M. Noonan, Janine A. Overcash, Anupama Suresh, Laura K. Flora, Julie Stephens, Geetika Bhatt, Raquel Reinbolt, Nicole O. Williams, Robert Wesolowski, Jeffrey B. VanDeusen, Sagar D. Sardesai, Maryam B. Lustberg, Bhuvaneswari Ramaswamy. A prospective geriatric breast cancer cohort study to define unique features and outcomes in older breast cancer patients [abstract]. In: Proceedings of the AACR Special Conference: Advances in Breast Cancer Research; 2017 Oct 7-10; Hollywood, CA. Philadelphia (PA): AACR; Mol Cancer Res 2018;16(8_Suppl):Abstract nr A55.