L van 't Veer

ESO-ESMO 2nd international consensus guidelines for advanced breast cancer (ABC2)†

Advanced Breast Cancer (ABC) is a treatable but still generally incurable disease. The goals of care are to optimize both length and quality of life. Due to continuous research, several advances have been made, particularly for the HER-2-positive and for Luminal-like subtypes. Notwithstanding these advances, median overall survival of patients with ABC is still only 2–3 years, although the range is wide [1–5], and survival may be longer for patients treated in specialized institutions [6]. Implementation of current knowledge is highly variable among countries and within each country.

1st International consensus guidelines for advanced breast cancer (ABC 1)

The 1st international Consensus Conference for Advanced Breast Cancer (ABC 1) took place on November 2011, in Lisbon. Consensus guidelines for the management of this disease were developed. This manuscript summarizes these international consensus guidelines.

Abstract S5-02: Veliparib/carboplatin plus standard neoadjuvant therapy for high-risk breast cancer: First efficacy results from the I-SPY 2 TRIAL

Background: I-SPY 2 is a multicenter, phase 2 screening trial using adaptive randomization within biomarker subtypes to evaluate a series of novel agents/combinations when added to standard neoadjuvant therapy (paclitaxel q wk x 12, doxorubicin & cyclophosphamide q 2-3 wk x 4, T/AC) vs. T/AC (control arm) for women with high-risk stage II/III breast cancer. The primary endpoint is pathologic complete response (pCR) at surgery. Our goal is to identify/graduate regimens that have ≥85% Bayesian predictive probability of success (statistical significance) in a 300-patient biomarker-linked Phase 3 neoadjuvant trial. Experimental regimens can “graduate” in at least 1 of 10 possible signatures defined by hormone-receptor (HR) & HER2 status & MammaPrint (MP), with a maximum number of 120 total patients enrolled. We report final efficacy results of the oral PARP inhibitor veliparib (V, ABT-888) in combination with carboplatin (carbo), 1 of 7 experimental regimens evaluated in the trial to date. Methods: Women with tumors ≥2.5 cm by clinical exam and ≥2 cm by imaging are eligible for screening. Tumors that are MP low/HR+/HER2- are ineligible for randomization. MRI scans (baseline, 3 weeks after start of therapy, at completion of weekly T, and prior to surgery) were used in a longitudinal statistical model to improve the efficiency of adaptive randomization. V+carbo was assigned to HER2- tumors only, which limits its possible signatures to: all HER2-, HR+/HER2-, HR-/HER2-. For these 3 signatures we provide estimated pCR rates with associated 95% Bayesian probability intervals for V+carbo and concurrently randomized controls. Analysis is intent to treat with patients who switched to non-protocol therapy regarded as non-pCRs. For each signature we provide probabilities of superiority for V+carbo over control and Bayesian predictive probabilities of success in a neoadjuvant Phase 3 trial equally randomized between V+carbo and control. Results: When V+carbo met the 85% predictive probability criterion in HR-/HER2- and all HER2-, this regimen graduated and accrual to V+carbo was stopped. V+carbo was assigned to 72 patients, and there were 62 concurrently randomized controls (44 HER2- controls). The following table shows final results based on available pCR information. Two patients assigned to V+carbo withdrew consent during treatment and are not included in the table. Conclusion: Adaptive randomization successfully identified a biomarker signature for V+carbo on the basis of a modest number of patients. V+carbo has graduated with a triple-negative (TN) breast cancer signature, and is the subset recommended for this regimen9s subsequent development. There is a suggestion that HR+/HER2- tumors benefit little from this regimen and inclusion of tumors in this subset would therefore dilute its effect in a subsequent trial. Analyses are currently underway to define additional biomarkers that may be predictive of response. The I-SPY 2 standing trial mechanism efficiently evaluates agents/combinations in biomarker-defined patient subsets, with future agents/combinations reported as available. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr S5-02.

High concordance of protein (by IHC), gene (by FISH; HER2 only), and microarray readout (by TargetPrint) of ER, PgR, and HER2: results from the EORTC 10041/BIG 03-04 MINDACT trial

BACKGROUND To investigate the correlation of TargetPrint with local and central immunohistochemistry/fluorescence in situ hybridization assessment of estrogen (ER), progesterone (PgR), and human epidermal growth factor receptor 2 (HER2) in the first 800 patients enrolled in the MINDACT trial. PATIENTS AND METHODS Data from local (N = 800) and central (N = 626) assessments of receptor status were collected and compared with TargetPrint results. RESULTS For ER, the positive agreement (the percentage of central pathology positive assessments that were also TargetPrint/local laboratory positive) for TargetPrint in comparison to centralized assessment was 98% with a negative agreement (the percentage of central pathology negative assessments that were also TargetPrint/local laboratory negative) of 96%. For PgR, the positive agreement was 83% with a negative agreement of 92%. For HER2, the positive agreement was 75% with a negative agreement of 99%. Even though the local assessment showed higher positive agreement for PgR (89%) and higher positive agreement for HER2 (85%), the range of discordant local versus central assessments were as high as 6.7% for ER, 12.9% for PgR, and 4.3% for HER2. CONCLUSION TargetPrint and local assessment of ER, PgR, and HER2 show high concordance with central assessment in the first 800 MINDACT patients. However, there are concerns about the higher discordance rates for some local sites. TargetPrint can improve the reliability of hormone receptor and HER2 testing for those centers with a lower rate of concordance with the reference laboratory, with the limitation of a positive agreement of 75% for HER2. TargetPrint consequently has important implications for treatment decisions in clinical practice and is a reliable alternative to local assessment for ER. CLINICAL TRIALS NUMBER NCT00433589.BACKGROUND To investigate the correlation of TargetPrint with local and central immunohistochemistry/fluorescence in situ hybridization assessment of estrogen (ER), progesterone (PgR), and human epidermal growth factor receptor 2 (HER2) in the first 800 patients enrolled in the MINDACT trial. PATIENTS AND METHODS Data from local (N = 800) and central (N = 626) assessments of receptor status were collected and compared with TargetPrint results. RESULTS For ER, the positive agreement (the percentage of central pathology positive assessments that were also TargetPrint/local laboratory positive) for TargetPrint in comparison to centralized assessment was 98% with a negative agreement (the percentage of central pathology negative assessments that were also TargetPrint/local laboratory negative) of 96%. For PgR, the positive agreement was 83% with a negative agreement of 92%. For HER2, the positive agreement was 75% with a negative agreement of 99%. Even though the local assessment showed higher positive agreement for PgR (89%) and higher positive agreement for HER2 (85%), the range of discordant local versus central assessments were as high as 6.7% for ER, 12.9% for PgR, and 4.3% for HER2. CONCLUSION TargetPrint and local assessment of ER, PgR, and HER2 show high concordance with central assessment in the first 800 MINDACT patients. However, there are concerns about the higher discordance rates for some local sites. TargetPrint can improve the reliability of hormone receptor and HER2 testing for those centers with a lower rate of concordance with the reference laboratory, with the limitation of a positive agreement of 75% for HER2. TargetPrint consequently has important implications for treatment decisions in clinical practice and is a reliable alternative to local assessment for ER. CLINICAL TRIALS NUMBER NCT00433589.

Identification of a low risk subgroup in Her2-positive breast cancer by the 70-gene prognosis signature.

Abstract #4171 Introduction:
 Her2/neu-overexpression is observed in 15-20% of invasive breast cancers and considered a negative prognostic factor. Most Her2-positive patients are classified as high risk by current treatment guidelines and thus allocated to adjuvant trastuzumab and chemotherapy. However, 74% of patients remained distant recurrence-free at 3 years without trastuzumab in the HERA-trial (HERceptin Adjuvant). In the present study the 70-gene prognosis signature (MammaPrint™), validated as an independent prognostic indicator for patients with up to three positive lymph nodes, was used to identify a subgroup of patients with low risk and favorable outcome.
 Methods:
 One-hundred-sixty-nine patients with Her2-positive breast cancer were selected from a pooled dataset of 1280 patients with known Her2-status. Patients had a unilateral T1-3, N0-1 tumor and were treated with either breast-conserving therapy or mastectomy. Samples were analyzed and classified by the 70-gene signature as good or poor prognosis by Agendia Laboratories.
 Results:
 After a median follow-up of 65 months (range 4-303) 49 (29%) distant recurrences and 41 (24%) breast cancer-specific deaths occurred. The 70-gene signature classified 27 (16%) patients as good prognosis, with a 10-year distant disease-free survival (DDFS) of 89% (25/27), compared to 142 (84%) patients classified as poor prognosis, who had a DDFS of 64%. The estimated hazard ratios (HR) for genomic risk were 4.9 (95%CI 1.2-20.1,p=0.029) and 4.4 (95%CI 1.1-18.4,p=0.040) for DDFS and breast cancer-specific survival at 10 years, respectively. In multivariate analysis, adjusted for known prognostic factors and adjuvant therapy, only the 70-gene signature and tumor size were independent predictors for 10-year-DDFS with HRs of 5.4 (95%CI 1.3-23.4,p=0.024) and 1.05 (95%CI 1.02-1.08,p=0.001), respectively. The good prognosis group had positive hormone-receptors in 85%, and fewer patients received adjuvant therapy: 16 patients (59%) received no adjuvant treatment, 6 (22%) received adjuvant chemotherapy, 8 (30%) hormonal therapy and 1 (4%) received trastuzumab. For the subgroup of 90 patients who were not treated with adjuvant chemotherapy or trastuzumab, the HR for low versus high 70-gene signature for 10-year DDFS was 4.75 (1.13-19.92,p=0.033).
 Discussion:
 The 70-gene signature is a strong independent prognostic indicator that can identify a subgroup with good clinical outcome in Her2-positive early breast cancer even in the absence of adjuvant chemotherapy and trastuzumab. This subgroup will be further studied in the ongoing MINDACT-trial (MIcroarray for Node-negative and 1-3 positive node Disease may Avoid ChemoTherapy) and beyond. The MINDACT-trial will prospectively evaluate if it is acceptable to withhold chemotherapy and/or trastuzumab in Her2-positive, genomic low risk patients. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4171.

Abstract S2-06: DNA repair deficiency biomarkers and MammaPrint high1/(ultra)high2 risk as predictors of veliparib/carboplatin response: Results from the neoadjuvant I-SPY 2 trial for high risk breast cancer

Background: The PARP inhibitor veliparib in combination with carboplatin (VC) was one of the experimental regimens evaluated in the phase 2 neoadjuvant I-SPY 2 standing trial for high risk breast cancer patients. VC graduated in the triple negative (TN) signature. However, not all TN patients achieved pathologic complete response (pCR) and some HR+HER2- patients responded. The I-SPY 2 biomarker component provides a platform for rigorous evaluation of mechanism-of-action-based markers in the context of established biomarkers (HR, HER2, MammaPrint) within the trial. Here, we report results from 5 investigator-submitted biomarker proposals and the MammaPrint High1/High 2 (MP1/2) classification as specific predictors of VC response. Methods: Data from 116 HER2- patients (VC: 72 and concurrent controls: 44) were available. BRCA1/2 germline mutation was assessed by Myriad Genetics. 3 expression signatures relating to DNA damage repair deficiency (PARPi-7, BRCAness and CIN70) and MP1/2 classification were evaluated on Agilent 44K arrays. PARP1 levels were measured using reverse phase protein arrays. We used logistic modeling to assess biomarker performance. A biomarker is considered a specific predictor of VC response if it associates with response in the V/C arm but not the control arm, and if the biomarker x treatment interaction is significant (likelihood ratio test, p Results: BRCA1/2 germline mutation status associates with VC response, but its low prevalence in the control arm precludes further evaluation. Of the biomarkers evaluated, three (PARPi-7, BRCAness, and MP1/2) associate with response in the VC arm but not the control arm, and have biomarker x treatment interactions with p Conclusion: If verified in a larger trial, PARPi7, BRCAness and MP1/2 signatures may help refine predictions of VC response, thereby improving patient care. Evaluation of the combined signature for patients treated with platinum-based chemotherapy is ongoing. Citation Format: Wolf DM, Yau C, Sanil A, Glas A, Petricoin C, Wulfkuhle J, Brown-Swigart L, Hirst G, I-SPY 2 TRIAL Investigators, Buxton M, DeMichele A, Hylton N, Symmans F, Yee D, Paoloni M, Esserman L, Berry D, Rugo H, Olapade O, van 9t Veer L. DNA repair deficiency biomarkers and MammaPrint high1/(ultra)high2 risk as predictors of veliparib/carboplatin response: Results from the neoadjuvant I-SPY 2 trial for high risk breast cancer [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 S2-06.

Abstract OT3-03-01: Preference-Tolerant randomized trial of risk-based vs. annual breast cancer screening: WISDOM study in progress

Purpose: Women Informed to Screen Depending on Measures of risk (WISDOM) trial is a pragmatic study comparing two real world approaches to clinical care for breast screening: annual screening versus personalized screening. The novelty of the personalized arm of the study is that we are combining known risk factors (age, family history, history of breast disease, ethnicity, BIRADS breast density, and genetics) into a single risk assessment model. All components of the model have been tested and established, but have never been used jointly. The goal of the WISDOM study is to examine the effectiveness of personalized breast cancer screening and to bring objective recommendations to the current mammography screening debate. Methods: The WISDOM trial will enroll 100,000 women with a preference-tolerant design that will determine if risk-based screening vs. annual screening, is as safe, less morbid, enables prevention, and is preferred by women. Women 40 - 74 years of age with no history of breast cancer or DCIS, and no previous double mastectomy can join the study from the WISDOM Study website (wisdomstudy.org). All participants sign up, elect randomization or self-select the study arm, provide electronic consent using DocuSign (eConsent), and sign a Medical Release Form. For all participants, 5-year risk of developing breast cancer is calculated according to the Breast Cancer Screening Consortium (BCSC) model. For participants in the personalized arm, the overall 5-year risk BCSC score is combined with a Polygenic Risk Score, based on a genetic test including mutations in 9 genes (BRCA1, BRCA2, TP53, PTEN, STK11, CDH1, ATM, PALB2, and CHEK2) and a panel of 75 common single nucleotide polymorphisms known to increase breast cancer risk. Risk stratification will determine frequency of screening. The study is registered on ClinicalTrials.gov as NCT02620852. Results: As of June 12th 2017, the WISDOM study is live at all UC medical centers and recruitment is open to all eligible women in California. Up to date 4,769 eligible women registered at all sites. 2,823 women have consented in the trial. 64% were randomized and 36% chose their screening arm. A pilot was conducted to test the logistics of online participation and examine the acceptance of the study design and approach. We are partnering with health insurance companies and self-insured companies to reach our recruitment goal. Conclusions: Enrollment will be completed by end of 2018. Acknowledgment: support by the Patient-Centered Outcomes Research Institute (PCORI), PCS-1402-10749 to L.J.E. (*) Authors equally contributed to this work. Citation Format: Acerbi I, Abihider K, Ling J, Layton T, DeRosa D, Madlensky L, Tice J, Shieh Y, Ziv E, Sarrafan S, Firouzian R, Tong B, Blanco A, Lee V, Heditsian D, Brain S, Kaplan C, Borowsky A, Anton-Culver H, Naeim A, Cink T, Stover Fiscalini A, Parker B, van 9t Veer L, Wisdom Study and Athena Breast Health Network Investigators and Advocate Partners, LaCroix A, Esserman L. Preference-Tolerant randomized trial of risk-based vs. annual breast cancer screening: WISDOM study in progress [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OT3-03-01.

Abstract P5-02-03: Evaluating the feasibility of a web-based preference-tolerant randomized trial of risk-based vs. annual breast cancer screening: WISDOM study pilot

Background: The WISDOM Study (Women Informed to Screen Depending on Measures of risk) aims to examine the effectiveness of personalized breast cancer screening and to bring objective recommendations to the current mammography screening debate. The WISDOM Study is a 100,000 woman randomized trial with a preference-tolerant design that will determine if risk-based screening (RBS) vs. annual screening, is as safe, less morbid, enables prevention and is preferred by women. A pilot was conducted to test the logistics of online participation and examine the acceptance of the study design and approach. Methods: Women were recruited from the UCSF site of the Athena Breast Health Network, a clinical care-research cohort of 110,000 women from the 5 University of California Medical Centers and Sanford Health. The pilot recruited women via email who were 40 -74 years of age with no history of breast cancer and a normal mammogram in the past year. Those interested visited the WISDOM Study website (wisdomstudy.org), signed up, elected randomization or self-selection, provided electronic consent using DocuSign (eConsent), and completed genetic testing (RBS arm). The Breast Cancer Surveillance Consortium (BCSC) model (standard risk factors, ethnicity, and breast density) in addition to genetic testing (9 genes and 75 SNPs) was used to calculate breast cancer risks that informed the start and frequency of screening for women in the RBS arm. BCSC was also used in the annual screening arm but did not inform mammography screening recommendations. The pilot used a mixed method approach (using enrollment data, Exit Survey data, individual interviews and focus groups) to assess enrollment preferences, randomization acceptance and overall study workflow. Results: The online electronic enrollment process and patient engagement portal was successfully implemented. In total, 639 women were invited, 235 registered (34%), and 171 (27%) consented to the pilot. Of these, 74% (127) elected to be randomized, and 26% chose to self-assign (66% chose annual screening (29)). Mean age was 56 years and the ethnic breakdown of the cohort was: 79% White, 10% Asian, 7% Latino, 3% Black, 1% other. 92% of those in the risk-based arm of the study completed genetic testing and were given results; only one genetic mutation was identified and occurred in CHEK2. Within the RBS arm (78), mammography recommendations were: 61% no further mammography until the age of 50, 22% biennial, 11% annual, and 6% every 6 month alternating MRI and mammogram. Exit Survey data illuminated confusion in study arm names (risk-based vs. annual), randomization acceptance (74%), annual arm preference in the self-selection group (66%), eConsent satisfaction (90%), enrollment process ease of use (88%), and website content, navigation and appearance satisfaction (66%). The pilot concluded in May 2016 to allow for refinements prior to the full trial. Conclusion: Our pilot demonstrates that the majority of women are willing to be randomized and participate in an online screening study to answer the important question on optimal breast cancer screening. The pilot study results will inform implementation of the 100,000 women WISDOM Study which launches in fall of 2016. Citation Format: Stover Fiscalini A, Theiner S, Kaplan C, Sarrafan S, Sawyer S, Liang A, Rosenberg-Wohl S, Gordon D, Frick M, Borowsky A, Anton-Culver H, Naeim A, LaCroix A, Cink T, Collaboration Athena Breast Health Network and Advocate Partners, Esserman L, van 9t Veer L. Evaluating the feasibility of a web-based preference-tolerant randomized trial of risk-based vs. annual breast cancer screening: WISDOM study pilot [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 P5-02-03.

Abstract P5-08-12: Co-expression modules identified from published immune signatures reveals five distinct immune subtypes in breast cancer

Introduction Immune modulating therapies offer an attractive novel approach in the treatment of breast cancer. There is a growing body of literature demonstrating that immune-related expression signatures predict breast cancer prognosis and chemo- and/or targeted therapy responsiveness. However, it is unclear how these signatures relate to one another. Here we evaluated 58 immune signatures in breast cancer and generated co-expression modules to classify patients into immune subtypes. Methods We evaluated 58 published expression signatures related to immune function in 5 breast cancer gene expression datasets (TCGA (n=817), METABRIC (n=1992), EMC344 (n=344), pooled triple negative: GSE31519 (n=579), pooled neoadjuvant chemotherapy treated: GSE25066 (n=508)). For each dataset, consensus clustering was used to subset the signatures based on their co-expression pattern. Signatures in the same consensus cluster across all 5 datasets were used to define immune modules. Module scores were computed as the average across their constituent signatures. Patients were classified into immune subtypes based on their module scores using consensus clustering. Overall survival (OS) differences between immune subtypes were assessed using Cox proportional hazard modeling in basal breast cancers from the METABRIC dataset (n=329). Results Consensus clustering of the 58 expression signatures consistently yields four distinct co-expression modules across the five datasets. These modules appear to represent distinct immune components and signals, with constituent signatures relating to: 1) T-cells and/or B-cells (T/B-cell), 2) interferon (IFN), 3) transforming growth factor beta (TGFB), 4) core serum response, dendritic cells and/or macrophages (CSR). Of note, the T/B-cell module contains 20 of the 58 signatures evaluated; and the CSR module is highly correlated to proliferation (r=0.81). Subtyping of patients based on these co-expression modules consistently yields subsets that fall into five major immune subtypes. The expression pattern of the four modules within each immune subtype is summarized below: These immune subtypes are associated with differences in overall survival in the METABRIC basal breast cancer cases, where the CSR High subtype has the worst outcome (10-year OS: 23%). In comparison, the subsets corresponding to the T/B-cell/IFN High subtype have better outcomes (Hazard ratio: 0.43, p = 0.018). In contrast, no significant outcome differences were observed between the poor outcome CSR-High subtype and the remaining three immune subtypes (p>0.05). Conclusion Our exploratory study identified four distinct immune co-expression modules (T/B-cell, IFN, TGFB, or CSR) from a collection of published immune signatures. Using these modules, we identified 5 immune subtypes with prognostic significance in basal breast cancers. We propose to test representative signatures from the 4 modules and the combined immune subtypes as predictive biomarkers of response to immunotherapies. Citation Format: Amara D, Wolf D, van 9t Veer L, Esserman LJ, Campbell MJ, Yau C. Co-expression modules identified from published immune signatures reveals five distinct immune subtypes in 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 P5-08-12.

Abstract P1-14-03: The evaluation of trebananib plus standard neoadjuvant therapy in high-risk breast cancer: Results from the I-SPY 2 TRIAL

Background: I-SPY 2 is a multicenter phase 2 trial using response-adaptive randomization within biomarker subtypes to evaluate a series of novel agents when added to standard neoadjuvant therapy for women with high-risk stage II/III breast cancer. The primary endpoint is pathologic complete response (pCR). The goal is to identify/graduate regimens with ≥85% Bayesian predictive probability of success (statistical significance) in a 300-patient phase 3 neoadjuvant trial defined by hormone-receptor (HR), HER2 status & MammaPrint (MP). Regimens may also leave the trial for futility ( Methods: Women with tumors ≥2.5cm were eligible for screening. MP low/HR+/HER2- tumors were ineligible for randomization. Serial MRI scans (baseline, 2 during treatment and pre-surgery) were used in a longitudinal model to improve the efficiency of adaptive randomization. Participants are categorized into 8 subtypes based on: HR status, HER2 status and MP High 1 (MP1) or High 2 (MP2). MP1 and MP2 are determined by a predefined median cut-point of I-SPY 1 participants who fit the eligibility criteria for I-SPY 2. Trebananib was initially assigned to HER2- patients only; once safety data with trastuzumab (H) were obtained, it was also assigned to HER2+ patients. Analysis was intent to treat -- patients who switched to non-protocol therapy were designated non-pCRs. Results: Trebananib +/-H did not meet the criteria for graduation in any of the 10 signatures tested. When the maximum sample size was reached, accrual ceased. We report probabilities of trebananib +/-H being superior to control and Bayesian predictive probabilities of success in a 1:1 randomized neoadjuvant phase 3 trial for the 10 biomarker signatures, using the final pCR data from all patients. Citation Format: Albain KS, Leyland-Jones B, Symmans F, Paoloni M, van 9t Veer L, DeMichele A, Buxton M, Hylton N, Yee D, Lyandres Clennell J, Yau C, Sanil A, I-SPY 2 Trial Investigators, Berry D, Esserman L. The evaluation of trebananib plus standard neoadjuvant therapy in high-risk breast cancer: Results from the I-SPY 2 TRIAL. [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 P1-14-03.