Y Yuan

Abstract P3-03-15: Synergistic suppression of triple negative breast cancer with the combination of PI3K inhibitor (alpelisib, BYL719) and CDK inhibitor (ribociclib, LEE011)

INTRODUCTION. Triple negative breast cancer (TNBC) is an aggressive form of BC that lacks effective targeted therapy. It is a biologically heterogeneous disease with several molecular subtypes: basal-like 1 (BL1), basal-like 2 (BL2), mesenchymal (M), mesenchymal-stem-like (MSL), immune-modulatory (IM) and unclassified (UNC). The PI3K/AKT/mTOR pathway affects cell proliferation, survival, and apoptosis through growth receptor interaction with downstream targets such as AKT and mTOR. TNBC frequently has activation of this pathway by mutation and other means across several subtypes. Recently the PI3K inhibitor alpelisib (BYL719) has been found to have efficacy in a combination study in ER positive metastatic BC (MBC) with a Phase 3 trial in progress. Ribociclib (LEE011) is a CDK inhibitor targeting cyclin D1/CDK4 and cyclin D3/CDK6 that recently met its primary endpoint in a phase 3 trial in a combination study in hormone receptor positive BC. As with all BC, TNBC has intact or mutant RB which affects susceptibility to CDK inhibitor. We hypothesize that targeting both PI3K with alpelisib and CDK with ribociclib may provide enhanced suppression of TNBC. MATERIALS AND METHODS. HCC38 and MDA468 are TNBC subtype BL1; MDA468 is RB1 and PTEN mutant. HCC1187 is IM. BT549 is M, mutant RB1 and PTEN. Hs578T, MDA157, and MDA231 are MSL. Cells were treated with alpelisib and ribociclib alone with 2-fold increase in concentrations, or the combination, for 72h and assessed by MTT assay. Western blot was performed using probes for pAkt (T308 and S473), Akt, pS6K1, S6K1, pS6, S6, and β-actin. RESULTS. Synergy in growth inhibition was seen combining alpelisib and ribociclib as reflected by combination indices Conclusion. Our study demonstrates that alpelisib plus ribociclib can synergistically enhance suppression of BC across multiple subtypes of TNBC. Cancer cells within the same subtype may not demonstrate a synergistic response, depending on RB status. Nevertheless, if RB mutant cells are susceptible to ribociclib then synergy can be seen even in these cancer cells. Antagonism can be seen independent of RB status in the same subtype. These findings point to a potential role for combination therapy with alpelisib and ribociclib in the treatment of TNBC. Citation Format: Yuan Y, Mortimer J, Xing Q, Yan J, Wen W, Han E, Yim JH. Synergistic suppression of triple negative breast cancer with the combination of PI3K inhibitor (alpelisib, BYL719) and CDK inhibitor (ribociclib, LEE011) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-03-15.

Abstract OT2-01-03: Phase II Trial of the addition of pembrolizumab to letrozole and palbociclib in patients with metastatic estrogen receptor positive breast cancer who have stable disease on letrozole and palbociclib

Background: The combination of palbociclib and letrozole has become the standard of care for patients with newly diagnosed estrogen receptor positive (ER+) metastatic breast cancer (MBC), with promising prolongation of progression free survival (PFS). However, nearly half of all patients achieved stable disease only after the first 6 months of therapy. Check-point inhibitor pembrolizumab was effective in ER+ MBC with a response rate of 13-17%, this study will evaluate the efficacy of adding pembrolizumab for patients with ER+ MBC who have achieved stable disease (SD) on letrozole and palbociclib. Trial Design:This is an open-label single institutional study. Patient will receive letrozole (2.5 mg) once a day and palbociclib (125 mg, 100 mg, or 75 mg as established tolerated dose) once a day for 3 weeks on and 1 week off. Pembrolizumab will be given at 200 mg IV every 3 weeks. Eligibility Criteria: Eligible patients must be postmenopausal women with ER+ MBC with measurable disease by RECIST1.1, ECOG performance status 0-1; must have received letrozole and palbociclib for at least 6 months, and have documented SD per RECIST 1.1. Up to3 lines of previous systemic therapy including endocrine therapy and/or chemotherapy are allowed. Patients are excluded if they had prior treatment with anti--PD1 or anti-PD-L1therapy, immunodeficiency; currently using systemic steroids active tuberculosis infection; major surgery within 28 days; active or untreated CNS metastases; history of interstitial lung disease; active infection requiring systemic therapy; or active cardiac disease. Specific Aims: The primary objective is to evaluate the objective response rate(ORR). The secondary objective is to determine the safety and tolerability of pembrolizumab plus the letrozole/palbociclib combination. We will use clinical benefit rate (CBR), duration of response (DOR), PFS, and OS to test the efficacy of this novel drug combination. Statistical Design: We will employ a three-at-risk design (modified rolling design) for the initial cohort of this Phase II study to insure the triplet is well-tolerated. This design permits only 3 patients to be a risk for DLT at any one time during the “safety lead-in” .When the first 6 patients have completed the observation period and treatment with ≤1 DLT, the safety lead-in for the triplet will be considered successful, and accrual will proceed to a total of 18 patients. Response (CR or PR by RECIST version 1.1) in patients who have demonstrated only SD on letrozole and palbociclib can be reasonably attributed to the addition of pembrolizumab. As a result, we set the probability of a response occurring without the addition of pembrolizumab as 3% or less. With 18 patients, a true response rate of 20% would result in at least 2 responders with 90% power and a type I error of 10%. With 18 patients, the response can be estimated with a 95% CI half-width of 23%. Target Accrual: 18. Citation Format: Yuan Y, Frankel P, Synold T, Yost S, Lee P, Waisman J, Somlo G, Hurria A, Mortimer J. Phase II Trial of the addition of pembrolizumab to letrozole and palbociclib in patients with metastatic estrogen receptor positive breast cancer who have stable disease on letrozole and palbociclib [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT2-01-03.

Abstract OT1-02-05: Phase II clinical trial of neratinib in patients 60 and older with HER2 over-expressed or mutated breast cancer: Trial design considerations for older adults

Background: This study addresses a key knowledge gap identified by the Institute of Medicine report on quality cancer care. Although there has been a growth in the number of targeted agents approved for the treatment of breast cancer, there are limited data regarding the efficacy, toxicity, and management of side effects in older adults. Neratinib is a potent oral small molecule tyrosine kinase inhibitor. Early clinical data have demonstrated the activity of neratinib in patients who have already progressed through HER2 targeted therapies. This study is designed to evaluate the tolerability and toxicity profile of neratinib in older adults with metastatic breast cancer (MBC) incorporating geriatric oncology design considerations. Trial Design : This is an open label, single arm, phase II study of single agent neratinib in patients with HER2 positive MBC. Neratinib is given at 240mg orally in 28 day cycles. Unique factors of this geriatric oncology trial design include: 1) pre-treatment and on-treatment geriatric assessment; 2) additional nurse toxicity visits; 3) an algorithm for aggressive management of diarrhea; 4) measurements of the pharmacokinetics (PK) of neratinib; 5) inclusion of biomarkers of aging; 6) measurement of patient adherence; and 7) evaluation of quality of life. Eligibility Criteria: Patients must be age≥60 with histologically-proven HER2 positive MBC or MBC with HER2 receptor activating mutations. There is no limitation on the number of previous lines of therapy, but patients must have adequate organ and bone marrow functions, and a baseline LVEF ≥ 50%. Exclusion Criteria include: prior treatment with neratinib; major surgery within 28 days; uncontrolled cardiac disease; concurrent use of digoxin; or chronic diarrhea. Specific Aims: The primary objective of this study is to identify the rate of grade 2 or higher toxicities attributed to neratinib in adult age ≥60 with HER2 over-expressing breast cancer. The secondary objectives are to describe the full toxicity profile (including all grades of gastrointestinal toxicities); to estimate the rate of dose reduction, holds and hospitalizations; to describe the PK parameters; to estimate the adherence rate to neratinib; and to estimate the overall response, clinical benefit rate, progression-free and overall survival. Furthermore, we will explore the role of a cancer-specific geriatric assessment and serum biomarkers of aging (IL-6, CRP, and D-dimer) in predicting treatment toxicities and PK parameters. Statistical Design: We plan to enroll 40 patients age ≥60 (at least 5 patients age 75 years or older, and no more than 15 patients 60-70) in order to assure that our sample is representative of the entire age range of older adults. Given a sample size of 40 subjects, the widest half-width of the 95% confidence limits for the rate of grade 2 or higher toxicities will be less than or equal to 0.16. An interim analysis will be performed after 20 subjects have been on study for at least one cycle. Accrual goal: 40 Contact information: Yuan Yuan MD PhD, Email: yuyuan@coh.org. Citation Format: Yuan Y, Blanchard S, Li D, Mortimer J, Waisman J, Somlo G, Yost S, Katheria V, Hurria A. Phase II clinical trial of neratinib in patients 60 and older with HER2 over-expressed or mutated breast cancer: Trial design considerations for older adults [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT1-02-05.

Abstract P4-21-35: Phase II trial of pertuzumab, trastuzumab, and nab-paclitaxel in patients (pts) with HER2 overexpressing (HER2+) locally advanced or inflammatory breast cancer (LABC) or untreated stage IV metastatic breast cancer (MBC)

Background: Pathologic complete response (pCR) to HER2-targeting neoadjuvant therapy (NT) predicts for improved survival (Cortazar et al, Lancet, 2014). The addition of pertuzumab to trastuzumab and docetaxel increased pCR rates, and, as first line treatment for MBC led to longer overall survival ([OS] Swain et al, NEJM 2015). Avoidance of anthracyclines in the adjuvant setting for HER2+ BC reduced the risk of secondary hematologic malignancies without a detriment to OS (Slamon et al, NEJM, 20111). Finally, nab-paclitaxel (nab) might provide an advantage over other taxanes via decreased use of steroids and may lead to increased response rates (RR). We designed a study of pertuzumab (pert), trastuzumab (trast), and nab, testing the feasibility and efficacy of this regimen in the LABC and metastatic breast cancer settings. Materials and Methods: Pts with Stages II-III LABC received six cycles of NT with pert (day 1 q 21 days), trast, and nab 100 mg/m2 (both given IV, weekly). Pts with untreated MBC received the same regimen until progression, toxicities, or patient or physician preference led to stopping therapy. Primary endpoints included pCR (LABC) and RR and progression-free survival (PFS) in MBC. Forty pts with LABC and 25 pts with MBC were to be accrued. The study was designed to test whether the pCR rate of Neosphere (Gianni et al, Lancet Oncol, 2012, > 45.8%) and the PFS rate of CLEOPATRA (median of > 18.5 months) can be matched or exceeded. Procurement of serial samples for assessment of tumor gene expression, circulating tumor cells, miRNA, and serum DNA profiling for exploratory biomarker analysis was carried out. Results:Twenty-two of 28 already enrolled pts with LABC (clinical stage II:15, stage III: 7) completed NT. The median age was 53 (34-77). The pCR rate was 86% (6/7) for hormone receptor negative (HR-) and 40% (6/15) for HR+ pts, with an overall pCR of 55%. Three pts without pCR following NT had residual BC with a HER2 negative phenotype. Eighteen of 22 pts required nab dose modifications. The most frequent toxicities following NT included elevated liver function tests:27%, peripheral neuropathy:23%, hematological toxicities:17%, diarrhea:18%, infusion reactions:18%. In the MBC cohort there were 13 of 16 enrolled pts with > 2 months of follow-up. The median age was 47 (31-65), 62% had HR+ disease. A CR rate of 4/13 (31%) and confirmed RR of 77% were observed. The median number of cycles with pert, trast, nab was 9 (3+ to 41); 11 of 13 pts required dose modifications or delays (3 of the delays were due to primary breast surgery performed upon response to treatment). At a median follow-up of 19 months, PFS and OS estimates are 63% (95% CI 0.09-0.93), and 89% (95% CI 0.61-1.0). Conclusion: The non-anthracycline-containing regimen of pertuzumab, trastuzumab, and nab-paclitaxel induced a high pCR rate in HER2+ BC. PFS is encouraging in MBC. Outcome of the fully accrued cohorts inclusive of residual cancer burden scores in the LABC cohort, and correlative data with exploratory biomarker analysis will be presented. Citation Format: Somlo G, Frankel P, Yeon C, Yuan Y, Yim J, Kruper L, Taylor L, Mortimer J, Waisman J, Jones V, Vito C, Paz B, Huria A, Li D, Gaal C, Tong T, Tumyan L. Phase II trial of pertuzumab, trastuzumab, and nab-paclitaxel in patients (pts) with HER2 overexpressing (HER2+) locally advanced or inflammatory breast cancer (LABC) or untreated stage IV metastatic breast cancer (MBC) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-21-35.

Abstract P1-10-19: Skin, and nail, infections associated with the addition of pertuzumab to trastuzumab-based chemotherapy

Objectives: We have maintained a local registry of skin and nail infections in patients receiving pertuzumab and trastuzumab as treatment for HER2 positive breast cancer. Over the past 16 months, we have continued to observe an increase in infectious complications in patients receiving the combination of pertuzumab and trastuzumab with or without chemotherapy. We expand a series of prospectively identified patients who developed infections while on these regimens. Methods: We became concerned about an increased incidence of infections shortly after the FDA approval of pertuzumab, and created an IRB approved registry of these patients. Results: Twenty-eight women were identified to have 32 separate infections (often at more than one site); 9 after cycle 1; 6 after cycle 2, 9 after cycle 3 and 8 after 4 or more cycles. The median age was 51 (Range 25-67); 14 received pertuzumab, trastuzumab, carboplatin, and docetaxel (PTCH), 5 pertuzumab, trastuzumab, and docetaxel, 7 pertuzumab, trastuzumab, and nab-paclitaxel, and 2 pertuzumab and trastuzumab. Folliculitis of the scalp, abdomen, and/or buttocks was observed in 19 patients, abscesses in 8 patients (4 of whom required incision and drainage) and cellulitis in 2. Severe paronychial infections involving one to 16 digits were observed in 4; 2 pt required surgical removal of 2 nails. Quantitative immunoglobulins were found to be low in 8 of 17 women tested; 2 patient had low total protein but did not have an assessment of quantitative immunoglobulins. All patients were initially treated with oral antibiotics, and 6 required hospitalization. Cultures were obtained in 10 patients; Staphylococcus aureus was identified in 4, methicillin resistant Staphylococcus aureus (MRSA) in 5, Enterococcus faecalis in 1. A 57 year old pt receiving neoadjuvant PTCH died on cycle 2 day 7. Autopsy was consistent with sepsis and gram positive cocci were identified. A 62 year old became septic and developed renal failure. Skin biopsies were performed in 3 patients and are consistent with changes associated with EGFR inhibition. Conclusions: We believe these infections are a result of combining pertuzumab with trastuzumab as 2 pts received no concurrent chemotherapy. An awareness of this complication is critical as some infections may be life-threatening. We have initiated patient education to ensure awareness of this potential complication. Citation Format: Mortimer JE, Yuan Y, Jung J, Kruper L, Stewart D, Chung S, Yu WK, Mendelsohn M, D9Apuzzo M, Tegtmeier B, Dadwal S. Skin, and nail, infections associated with the addition of pertuzumab to trastuzumab-based chemotherapy. [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 P1-10-19.

Abstract P6-13-17: The combination of eribulin and everolimus results in enhanced suppression of tumors in mouse models of triple negative breast cancer

INTRODUCTION. Triple negative breast cancer (TNBC) is an aggressive form of breast cancer with poor overall and relapse free survival. TNBC does not have targeted or matched therapies. Patients have worse outcomes after chemotherapy than with other subtypes of breast cancer. TNBC accounts for 12-17% of all breast cancers, leaving an unmet need for targeted therapy. Efforts to profile these tumors have revealed several potential targets. The PI3K/AKT/mTOR pathway is a signal transduction pathway that links growth related hormone receptor interaction to downstream targets such as AKT and mammalian target of rapamycin (mTOR). This pathway targets affect cell proliferation, survival, and apoptosis. Patients with TNBC have high levels of AKT expression and activation of this pathway. Microtubule-targeting agents have been used in TNBC. Eribulin mesylate is a microtubule-targeting agent with benefits in treating taxane and anthracycline refractory breast cancer via a microtubule targeting anti-mitotic mechanism. It has been approved for the treatment of TNBC in heavily pretreated patients. Despite targeted therapy, breast cancer cells can grow resistant. Targeting multiple cancer growth pathways has been used in patients that progress on therapy or fail to respond. We hypothesized that targeting both mitotic blockade and PI3K/AKT/mTOR pathway may provide enhanced suppression of TNBC growth in both syngeneic and xenogeneic mouse models. MATERIALS AND METHODS. MDA-MB-468 is a human TNBC cell line. 4T1 is a highly metastatic mouse TNBC cell line derived from a spontaneously arising Balb/c mammary tumor. 4T1 and MDA-MB-468 tumor cells were injected into the mammary fat pad of female Balb/c and NOD/SCID/IL2Rgamma null (NSG) mice (with matrigel) respectively. After tumors were formed Balb/c mice were treated three times per week with vehicle, eribulin (0.75 mg/kg i.v.), RAD001 (5 mg/kg via oral gavage) or a combination of both. NSG mice were treated three times per week with vehicle, eribulin (0.5 mg/kg i.v.), RAD001 (5 mg/kg by oral gavage), or a combination of both. Tumor volumes and body weights were measured. Student t-test was used to compare the means of two groups and determine the p value (p RESULTS. In the 4T1 syngeneic breast cancer mouse model, the combination of Eribulin and Everolimus resulted in marked suppression of tumor growth which was statistically significant versus vehicle treatment alone, or Eribulin or Everolimus alone (Table I). In the MDA-MB-468 model, the combination of Eribulin and Everolimus demonstrated marked suppression of tumor growth which was statistically significant compared to either agent alone (Table II). Citation Format: Marcinkowski E, Luu T, Yuan Y, Mortimer J, Leong L, Portnow J, Xing Q, Wen W, Yim J. The combination of eribulin and everolimus results in enhanced suppression of tumors in mouse models of triple negative breast cancer. [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 P6-13-17.

Abstract P1-14-10: Phase II trial of neoadjuvant chemotherapy with carboplatin and nab-paclitaxel in patients with triple negative locally advanced and inflammatory breast cancer

Background: Pathologic complete response (pCR) and residual cancer burden (RCB scores of 0 [pCR] or 1[near CR]) after neoadjuvant chemotherapy (NCT) may predict for improved survival (Symmans et al. J Clin Oncol 25:4414-22, 2007). We set out to test the pCR rate with an anthracycline-free regimen of carboplatin (carb) and nab-paclitaxel (nab) in patients (pts) with triple negative breast cancer (TNBC). Materials and Methods: Forty-nine pts with stages II-III BC were to receive carb (AUC 6) on day 1 of a 28 day cycle, and nab 80 mg/m2 weekly, for a total of 4 cycles. Core biopsies were performed prior to NCT. Blood procurement for circulating tumor cell (CTC) analysis using the CellSearch platform was carried out pre-treatment, mid-treatment, and at surgery. We set out to assess the predictive value of Mammaprint (poor vs. good), BluePrint (basal, vs. luminal, vs. HER2) molecular subtype as well as microarray RNA and miRNA profiling, for pCR. Responses were also dichotomized as complete or near complete response (Symmans RCB scores of 0-1) vs. suboptimal response (RCB score > 1). Results: The median age was 53 (28-75). Pts presented with clinical stages II (63%) and III (37%). So far, 38 of the 49 pts accrued between 2/2012 and 6/2015, have undergone surgery, 68% of whom underwent modified radical mastectomy. The pCR rate (breast and lymph nodes in CR) was 53%, and RCB 0 and 1 were seen in 68% of pts. Toxicites included grade ¾ anemia (45%), thrombocytopenia (13%) and neutropenia (53%,1 pt with neutropenic fever). Dose adjustments were needed in over 80% of pts. Grades 2 or 3 peripheral neuropathy were seen in 8% each, and grades 3-4 fatigue (13%), hypokalemia (3%), and hyponatremia (3%) were observed. The median number of CTCs (pre-NCT) observed in 7 CTC positive pts of the first 27 pts who completed surgery was 1 (0-7), and 2 of the 7 pts continued to have CTCs at the time of surgery (1 CTC each), while 2 pts without CTCs pre-NCT had CTCs (1 each) detected at surgery. The final pt enrolled is expected to complete surgery by 10/2015. Results of sequential CTC assessments, MammaPrint/Blueprint and RNA/miRNA analysis of pre- and post-treatment specimens and their correlation with pCR will be presented. Conclusion: The non-anthracycline-containing regimen of carb and nab-paclitaxel induced a high pCR rate in TNBC, in preliminary analysis. Ongoing profiling may allow for future subset-specific modification of this regimen to increase pCR across all molecular subtypes of TNBC. Citation Format: Somlo G, Chung S, Frankel P, Hurria A, Koehler S, Kruper L, Mortimer JE, Paz B, Robinson K, Taylor L, Vito C, Waisman J, Yeon C, Yim J, Yuan Y, Tong T. Phase II trial of neoadjuvant chemotherapy with carboplatin and nab-paclitaxel in patients with triple negative locally advanced and inflammatory breast cancer. [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 P1-14-10.

Abstract P6-03-18: Outcome of FoundationOne testing in metastatic breast cancer therapy: A single center experience

Background: Next generation sequencing (NGS) has made genomic, mutation-driven, cancer medicine feasible. However, few studies have reported the importance of NGS in identifying mutation-driven treatment or whether such therapies are effective in women with metastatic breast cancer (MBC). We reviewed the impact of NGS in women with MBC at our institution. Methods: Among the medical oncologists who treat metastatic breast cancers at the City of Hope Comprehensive Cancer Center, we identified 21 patients with HER2 negative cancers, whose tumors were submitted for FoundationOne genomic profiling. We report the individual mutation profile, potential therapeutic options, and treatment outcome. Result: Of the 21 patients (pts), 13 had triple negative breast cancer (TNBC) and 12 of 13 (92%) had actionable mutation(s). Mutation profiles have been heterogeneous. Loss or mutations of TP53 were the most common genomic alteration in TNBC (12 of 13). Four pts received targeted therapies (everolimus in 3, pazopanib in 1) and all experienced at least partial clinical response. An additional 3 pts were treated with directed therapy but are too early to evaluate, 4 pts were not treated because of disease progression or clinical deterioration, and 1 pt was lost to follow-up. All 8 pts with ER+ disease had actionable mutations identified and 7 (88%) received targeted therapy (pazopanib in1, everolimus in 3, palbociclib in 3). All experienced at least partial clinical response; 1 was too ill for treatment. The most common genomic alterations are: PIK3CA mutation, PTEN loss, P53 mutation, FGFR mutation, and ZNF mutation. Conclusion: Targeted genomic sequencing through FoundationOne can identify mutations that are amenable to treatment with agents that are not generally approved for use in breast cancer. In order to test the benefit of target-directed therapy, tumor should be submitted for NGS while patients have a good performance status. Citation Format: Yuan Y, Mortimer JE. Outcome of FoundationOne testing in metastatic breast cancer therapy: A single center experience. [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 P6-03-18.