Ballman, KV

1521 Background: Gliomas are known to progress from low to high grade at relapse, but the frequency is not well understood. It is unclear whether survival of these pts differ as a function of histologic subtype, and as measured from initial diagnosis and from relapse; yet such pts are frequently combined in clinical trials. Methods: Central review of paired glioma tissues obtained at initial diagnosis (DX) and recurrence was performed in 208 pts enrolled in prospective NCCTG trials (recurrence ≤ 90 d excluded). Kaplan-Meier, log rank, ANOVA, and chi-square tests were utilized. Results: Relapse from low (1–2) to high grade (3–4) occurred in 18/42 (43%) oligodendrogliomas (oligo), 28/41 (68%) oligoastrocytomas (OA), and 14/20 (70%) astrocytomas (astro); p=0.031. There were differences in median OS (in yrs; 95% CI) from initial DX: oligo-7.5 (5.0, 12.6); OA-4.5 (3.8, 5.6); and astro-3.3(1.8, 5.1), p=0.002; and OS from high grade recurrence: oligo-2.1 (0.9,3.0); OA-1.0 (0.8,1.3); and astro-0.7 (1.8, 5.1); p=0.02. Median OS from initial DX (yrs, 95% CI) also differed between primary (initial DX) GBM-1.7 (1.5–2.2); secondary (at recurrence) GBM-3.7 (2.8, 4.2) and non-GBM (initial+recurrence)- 5.5, (4.9–7.0) respectively, p < 0.001. Mean time to recurrence (TTR), (yrs ± S.D.) also differed: 1.1±1.1; 2.9±1.8; and 4.0±2.9, respectively, p < 0.001; as did median OS from recurrence (yrs, 95% CI) [0.7 (0.5, 1.1); 0.6, (0.5, 1.0); and 1.6 (1.1, 2.1), respectively], p <0.001. OS differed between primary vs. secondary GBM from time of initial DX (p=0.041) and also from recurrence (p=0.017). Conclusions: Low grade astro and OA progressed to grade 3–4 more frequently than did pure oligo; these groups had significant differences in OS from initial diagnosis and from recurrence. There were significant differences in OS between pts with primary and secondary GBM from initial diagnosis and recurrence. These data have important implications in design of clinical trials. [Table: see text] No significant financial relationships to disclose.

Abstract Background: Locoregional recurrence (LRR) is a concern after neoadjuvant chemotherapy. Absolute risk of LRR and risk factors associated with LRR among women with node positive breast cancer treated with neoadjuvant chemotherapy on ACOSOG Z1071 were examined. Methods: ACOSOG Z1071 (Alliance for Clinical Trials in Oncology) enrolled cT1-3, N1-2 breast cancer patients treated with neoadjuvant chemotherapy from 2009-2011. All patients underwent axillary dissection. Data was analyzed for locoregional recurrence-free survival (LR-RFS) and multivariable analysis performed to identify factors impacting locoregional recurrence. Results: Of 756 women enrolled, 701 patients were eligible. Median follow-up was 4.0 years (range 0.03–6.2). 39 pts (5.6%) experienced LRR (32 LRR alone and 7 LRR concurrent with metastatic disease) and 96 patients (13.7%) died. LR-RFS was lowest in patients with triple negative tumors (TNBC) (87.6% at 3 years), followed by HER2-positive tumors (94.1%) compared with Hormone Receptor (HR) positive/HER2-negative tumors (96.9%). Residual in-breast disease was present in 57% of patients undergoing BCT and 73% of patients undergoing mastectomy (p&lt;0.0001). LRR was higher in BCT compared to mastectomy (p=0.018), however when evaluated by subtype there was no significant difference in LRR by BCT vs mastectomy. There was no difference in LRR by clinical T stage at presentation or pathologic N stage, however LRR increased with higher pathologic T stage (p=0.006). Overall LRR was lower in patients who achieved a pathologic complete response (pCR) across all tumor subtypes (0% in HR positive/HER2-negative, 2.1% in TNBC, 4% in HER2-positive at 3 years) than in non-pCR patients (HR=0.37, p=0.04). By tumor subtype, pCR was associated with a lower LRR in patients with TNBC (HR=0.17, p=0.019), but was not significantly different by pCR in HER2-positive (HR=0.50, p=0.31) or HR-positive/HER2-negative tumors (HR=inestimable). In the multivariable model, factors associated with increased LRR risk were tumor subtype (TNBC and HER2-positive tumors, p&lt;0.0001), lack of pCR in the breast (p=0.013), breast conservation surgery (p=0.018) and omission of adjuvant radiation therapy (p=0.010). Predictors of locoregional recurrence UnivariableMultivariableVariableHR (95% CI)p-valueHR (95% CI)p-valueClinical T stageT0-T2REF0.34REF0.087T3-T41.38 (0.72-2.65) 1.87 (0.91-3.84) Tumor BiologyHR+/Her2-REF0.002REF&lt;0.0001Her2+1.49 (0.65-3.45) 2.11 (0.89-5.00) Triple negative3.59 (1.68-7.68) 5.53 (2.53-12.13) Path CR breastNoREF0.019REF0.013Yes0.35 (0.15-0.84) 0.27 (0.09-0.76) Path CR breastNoREF0.064REF0.81Yes0.51 (0.25-1.04) 0.67 (0.29-1.59) SurgeryBCTREF0.067REF0.018Mastectomy0.55 (0.29-1.04) 0.43 (0.22-0.87) RadiationYesREF0.033REF0.010No2.18 (1.06-4.48) 2.60 (1.26-5.39) Conclusion: In patients with node-positive breast cancer treated with neoadjuvant chemotherapy, early LRR is higher in TNBC and HER2-positive tumors. In TNBC patients pCR is associated with lower LRR than residual disease. In this contemporary cohort of node-positive, HER2-positive tumors treated with anti-HER2 therapy, patients achieving a pCR had low LRR rate. Adjuvant radiation appears to be important for locoregional control regardless of pCR. Citation Format: Boughey JC, Ballman KV, McCall LM, Mittendorf EA, Hunt KK. Predictors of locoregional recurrence after neoadjuvant chemotherapy and surgery for node positive breast cancer: Results from ACOSOG Z1071 (Alliance) [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 P6-09-01.

CRA506 Background: Sentinel node biopsy (SNB) eliminates the need for axillary dissection (ALND) in patients whose sentinel node (SN) is tumor-free. However, completion ALND remains the gold standard for patients with a tumor-involved sentinel node. ALND achieves regional control, but its effect on survival remains controversial. The main objective of ACOSOG Z0011 was to compare outcomes of patients with hematoxylin and eosin (H&E) detected metastasis in SN managed with or without ALND and no axillary irradiation. Methods: Clinically node-negative patients who underwent SN biopsy and had 1 or 2 SN with metastases detected by H&E were randomized to ALND or no further axillary specific treatment. All patients were treated with lumpectomy and opposing tangential field irradiation. Adjuvant systemic therapy was at the discretion of their physicians. Overall survival (OS), disease-free survival (DFS), and locoregional control were evaluated. Results: 446 patients were randomized to SNB alone and 445 to SNB plus ALND. Patients treated with SNB alone were similar to those treated with SNB + ALND with respect to age, tumor size, Bloom-Richardson score, estrogen receptor status, adjuvant systemic therapy, tumor type, and T stage. Patients randomized to SNB alone had a median of two lymph nodes removed whereas patients randomized to ALND had a median of 17 lymph nodes removed. 17.6% of ALND patients had 3 or more involved nodes compared to 5.0% of SNB patients (p < 0.001). Median follow-up is 6.2 years. 5-year in breast recurrence after ALND was 3.7% compared to 2.1% for SNB (p = 0.16) while 5-year nodal recurrence was 0.6% compared to 1.3% (p = 0.44) respectively. The five-year OS for patients undergoing SNB + ALND is 91.9% compared to 92.5% for SNB alone (p = 0.24), and DFS is 82.2% compared to 83.8% respectively (p = 0.13). Conclusions: Despite the widely held belief that ALND improves survival, no significant difference was recognized by this study of SN node-positive women. Although the study closed early because of low accrual/event rate, it is the largest phase III study of ALND for node-positive women, and it demonstrates no trend toward clinical benefit of ALND for patients with limited nodal disease. [Table: see text]

CRA504 Background: SN biopsy (SNB) with immunohistochemistry (IHC) of histologically negative SN identifies metastases (mets) not seen by standard histology. The impact of IHC-detected BM mets has been reported in several large single-institution studies. 5,539 patients (pts) were entered into this prospective multicenter observational study to determine the clinical significance of SN and BM mets. Methods: Patients underwent lumpectomy and SNB with bilateral iliac crest BM aspiration. BM and histologically negative SN were evaluated with IHC in a central laboratory (results not clinically reported). Overall survival (OS), disease-free survival, and locoregional recurrence were determined. Results with OS (the primary endpoint) are reported here. Results: SN were successfully identified in 5,184 of 5,485 pts (94.5%). Histologic SN mets were found in 1,239 pts (23.9%). IHC detected an additional 350 pts (10.5%) with SN mets. BM mets were identified by IHC in 105 of 3491 examined (3.0%). 5-yr overall survival is shown in the Table . BM IHC positivity significantly predicted decreased OS (p=0.015). A multivariable analysis that included SN and BM status, ER, PR, grade, size, and age showed that neither IHC detected mets in SN (p=0.66) or BM (p=0.08) were independent predictors of OS, although BM status showed a strong trend. Conclusions: The detection of BM mets by IHC in pts with clinical T1/2 N0M0 breast cancer identifies those pts at significantly increased risk for death; the impact of BM mets on outcome supports and confirms prior studies. In this study, SN IHC-detected mets appear to have no significant impact on OS. The routine examination of SN by IHC is not supported in this patient population by this study. [Table: see text] [Table: see text]

Abstract Importance: 20-25% of patients with early stage HER2-positive breast cancer develop tumor relapse after adjuvant trastuzumab. Identification of such patients is a key goal for clinical management decisions. Objective: To assess molecular heterogeneity among early stage HER2-positive patients using the Prosigna™ algorithm, to define intrinsic subtypes, and to determine the clinical significance of such heterogeneity. Design: The NanoString® platform was used to measure the abundance of the PAM50 subtype signature transcripts. Samples from the NCCTG (Alliance) N9831 trial were analyzed using the Prosigna™ algorithm to define intrinsic subtype and risk scores. Subtypes were evaluated for recurrence-free survival following chemotherapy with or without trastuzumab. Setting: Samples were obtained from a multi-center randomized phase III trial of chemotherapy versus chemotherapy plus trastuzumab. Participants: All tumors were centrally evaluated for HER2 positivity, defined as IHC 3+ and/or FISH &gt;2.0; 1392 patients were evaluated for molecular subtype. Intervention(s): Patients received adjuvant chemotherapy (doxorubicin plus cyclophosphamide followed by paclitaxel) (n=484) or chemotherapy plus trastuzumab (n=908). Main Outcome Measure(s): The primary outcome was recurrence-free survival as a function of subtype and treatment. Results: Patients with HER2-positive tumors with HER2-enriched features comprised about 70% of the sample cohort, and these individuals received significant benefit from adjuvant trastuzumab (HR=0.68, 95%CI: 0.52, 0.89, p=0.005), as did the relatively fewer patients (291/1392) with Luminal-type tumors (HR=0.52, 95%CI: 0.32, 0.85, p=0.01). The sample cohort contained a small number of patients with tumors having Basal-like features (97/1392), and the data suggest that these individuals may have received less benefit from trastuzumab, beyond that received from chemotherapy alone (HR=1.06, 95%CI:0.53,2.13, p=0.87). Conclusions: The majority of HER2-positive tumors are classified as HER2-enriched or Luminal using the Prosigna algorithm, and patients with such tumors benefit from adjuvant trastuzumab. About 10% of HER2-positive tumors exhibit Basal-like genomic features, and such tumors appear to recur at fairly similar frequency irrespective of treatment with chemotherapy or chemotherapy plus trastuzumab. Patients with HER2-positive/Basal-like tumors may represent a cohort that should be considered for enrollment in trials to evaluate emerging novel HER2-targeted agents, other targeted therapies, or combinations of both approaches. Support provided in part by CA129949 and CA15083. Citation Format: Perez EA, Ballman KV, Mashadi-Hossein A, Tenner KS, Kachergus JM, Norton N, Necela BM, Carr JM, Ferree S, Perou CM, Cheang MCU, Thompson EA. Intrinsic subtype and therapeutic response among early stage HER2-positive breast tumors from the North Central cancer treatment group (Alliance) N9831 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 P3-07-04.

Abstract Background: Epidermal Growth Factor Receptor (EGFR, HER1) is known to heterodimerize with HER2 and may impact the effectiveness of trastuzumab. Historically, EGFR has been difficult to measure; thus there is no evidence regarding its effects on trastuzumab clinical therapy. Here we use a new, standardized, quantitative immunofluorescence assay and a novel EGFR antibody to evaluate the correlation between EGFR expression and clinical outcome in a cohort from the North Central Cancer Treatment Group (NCCTG, Alliance) N9831 trial. Methods: Of the 3505 women in the N9831 trial, tissue microarrays were constructed that allowed analysis of 1,444 patients randomly assigned to receive chemotherapy alone (Arm A), sequential trastuzumab after chemotherapy (Arm B) or concurrent trastuzumab with chemotherapy (Arm C). Fluorescence-based, standardized measurement of EGFR was done using the rabbit monoclonal EGFR antibody D38B1 on the AQUA platform (HistoRx). EGFR expression levels were analyzed as a continuous variable and dichotomized using recursive partitioning to define an optimal cut point. The cut point was validated on an independent retrospective cohort comprised of 130 patients with HER2-positive metastatic breast cancer who received trastuzumab. Results: EGFR assessed as a continuous variable shows an association with disease free survival (DFS) in Arm C (p = 0.002) but not in Arms A or B. Dichotomizing EGFR expression shows that high level expression is associated with worse outcome (HR = 2.2; 95% CI 1.33–3.59, p = 0.002) in arm C. Five year DFS within the low level EGFR expression group was 71%, 74% and 90% for Arms A, B and C, respectively (log-rank p-value=0.02) and within the high level EGFR expression (n = 213) group was 62%, 76% and 74% respectively (log-rank p-value 0.22). As validation, the same cut-point was used to define high EGFR expression in a retrospective metastatic breast cancer cohort. The median progression free survival difference between EGFR high group and EGFR low group was 6.1 months (p = 0.0063) and the hazard ratio of high EGFR was 1.92 (p = 0.0073). Conclusions: High expression of EGFR by the AQUA platform appears to be associated with decreased benefit from adjuvant concurrent (not sequential) trastuzumab and shorter PFS in the metastatic setting. The biological underpinning for these observations is being considered. Since there are other treatment options for HER2-driven tumors, this marker, once validated, could help select patients for alternative or additive therapy. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr S5-4.

Abstract Background: Adding adjuvant trastuzumab to chemotherapy for patients (pts) with resected HER2+ breast cancer (BC) improves disease free and overall survival (Perez EA, et al. J Clin Oncol 2011). Understanding which pts are most likely to benefit from these therapies is a goal of our team. Methods: Baseline 1639 annotated tumor specimens from pts enrolled in the phase III N9831 adjuvant trastuzumab trial (NCT00005970) were processed via the &gt;29,000 gene probe DASL technology (Illumina) to identify genomic predictors of pt outcome to Arm A chemotherapy or Arm C chemotherapy plus concurrent trastuzumab. Samples were spotted in 96 well plates, with appropriate replicates. Extensive quality control and internal validation were performed. The association of each gene with recurrence-free survival (RFS) was determined for each treatment arm separately using CoxPH models adjusted for clinical and tumor risk factors. A p &lt; 0.0001 was used to define significance. A geneset analysis (using 408 Kegg/BioCarta genesets) was performed to determine pathways associated with RFS. Results: PRPF4B, EWSR1, BMI1, CNNM1, FOXO4, CLIP2, MCCC1, CHRM2 were found to be significantly associated with RFS for Arm A and AAK1, DAZAP2, TP53INP1, MACF1 and ADHFE1 were associated with RFS for Arm C. The most significant pathway associated with RFS in Arm A was the KEGG hypertrophic cardiomyopathy pathway and for Arm C, the BioCarta pertussis toxin-insensitive CCR5 signaling in macrophage pathway. Conclusions: We have identified 8 genes associated with RFS for pts treated with adjuvant chemotherapy, and 5 genes associated with RFS for pts treated with concurrent trastuzumab and chemotherapy in pts with HER2 early stage BC. In addition, geneset analysis identified BioCarta and Kegg pathways associated with RFS for each arm. Validation in an independent cohort is expected to be completed by the end of 2012. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr PD10-04.

Abstract Background: Cognitive changes for older women who receive chemotherapy are poorly understood. Methods: Cancer and Leukemia Group B (CALGB) 49907 enrolled 633 women ≥65 years with early stage breast cancer and randomized them to standard adjuvant chemotherapy (AC or CMF) or capecitabine (N Eng J Med 360:2055, 2009). Patients enrolled on the Quality of Life companion study (N = 350) included women who had cognitive and psychological functioning sufficient for providing informed consent and participation in the trial (J Clin Oncol 29:1022, 2011). Participants completed an 18 item questionnaire focusing on their subjective report of cognitive function (attention, problem-solving, speed, new learning, and remote memory) at 6 time points (baseline, mid-treatment, within 1 month post treatment, and at 12, 18, and 24 months post treatment). Possible scores for each item ranged from 1–7 (‘above average’ - ‘severe problem’). Cognitive function score (CFS) was defined as the mean score of items 1–18. Cognitive impairment was defined as CFS 1.5 standard deviations above the overall average baseline. Univariate associations were tested between baseline CFS and patient characteristics (treatment, race, education, number of positive nodes, hormone receptor status, HER2 status, performance status, number of comorbidities, fatigue and depression) using Kruskal-Wallis testing. Frequency distributions were used to describe cognitive impairment. Multivariate analyses were not completed because few women reported subjective cognitive impairment during the study period. Results: 297 assessments were received at baseline, 280 at both mid-treatment and within 1 month post-treatment, 259 at 12 months, 245 at 18 months and 240 at 24 months post-treatment. The median age was 72 (65–85); 32% received AC, 21% CMF, and 47% capecitabine. Most women were white (87%) and had a performance status of 0 (73%). Approximately half of women had a high school degree or less and the majority had stage I-II (78%), hormone-receptor positive (68%) cancers and most did not experience depression or fatigue at baseline. At baseline, the overall mean CFS was 2.1 (‘normal ability’) and 19 women (6%) had mild to severe impairment. Baseline scores did not differ by treatment (p = 0.35). Worse cognitive function at baseline was associated with less education (p &lt; 0.01), increased number of positive nodes (p = 0.02), 4+ comorbid conditions (p &lt; 0.01) and fatigue (p = 0.02), although differences for these groups were small. During the study period, overall mean cognitive function scores remained at ‘normal ability’. At mid-treatment, within 1 month post treatment, 12, 18 and 24 months, cognitive impairment was present in 19 (6%), 19 (6%), 29 (10%), 31 (12%), 18 (7%), and 22 (9%), respectively. Conclusions: Our data suggest that in a healthy group of women without baseline cognitive impairments on objective screening, chemotherapy does not seem to be associated with changes in self-reported cognitive function over time. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-08-05.

Abstract Purpose: The stage IB designation was added to the AJCC 7th edition staging system to denote micrometastasis in patients with T1 tumors. We have previously examined this group and found that receptor status and nuclear grade were better survival discriminates than the presence of micrometastases. The current study was undertaken to validate this finding in a larger cohort from the American College of Surgeons Oncology Group (ACOSOG) Z0010 study. Methods: Clinicopathologic and outcomes data from patients enrolled on ACOSOG Z0010 were recorded. All patients underwent breast conserving surgery, sentinel lymph node biopsy and whole breast radiation for clinical T1-2, N0 breast cancer. Sentinel lymph nodes were evaluated by H&E locally and if negative, by immunohistochemistry (IHC) at a central laboratory. Patients were staged according to the 7th edition AJCC system and recurrence-free (RFS), disease-specific (DSS) and overall survival (OS) were determined using the Kaplan-Meier method and compared using the log-rank test. Results: There were 5210 eligible and evaluable patients enrolled on ACOSOG Z0010. AJCC stage distribution was known in 4590 and included: 2849 (62.0%) stage IA, 376 (8.2%) stage IB, 878 (19.1%) stage IIA, 322 (7.0%) stage IIB, and 170 (3.7%) stage III. Median follow-up for the cohort was 9.0 years (range 0–12.6). Five and 10-year RFS, DSS and OS rates for patients with stage IA versus IB disease are shown in table 1. There were no significant differences between groups. When all stage I patients (stage IA and IB) were evaluated by ER status (positive vs negative) or grade (grade 1 vs 2 vs 3), these biologic factors were able to significantly discriminate patients with respect to RFS, DSS and OS (table 2). Conclusion: Differentiating patients with micrometastases (stage IB) from node negative patients (stage IA) does not stratify patients well with respect to survival. Biologic factors including ER status and grade are better discriminants of survival than the presence of small volume nodal metastases in patients with early stage breast cancer. Breast cancer staging should include biologic factors from the primary tumor. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-01-06.

Abstract Background Trastuzumab (T) combined with chemotherapy improves survival of women with HER2-positive breast cancer. Dual therapy with T and other HER-2 targeted agents (lapatinib/pertuzumab) has demonstrated improved efficacy compared to T alone in advanced breast cancer, and is in clinical trials in early stage disease. We hypothesize that subgroups of patients with HER2-positive tumors and limited tumor burden (tumor size and no or few positive lymph nodes) have a favorable outcome and would not be candidates for dual therapy. This study will analyze the disease-free survival (DFS)and overall survival (OS) of patients with early stage breast cancer treated with chemotherapy and T in the seminal randomized studies (RCTs). Methods RCTs were identified by a Medline search from 2004-2013. Trial groups from five phase III RCTs agreed to provide data. TrialNumberEligibilityRegimenNSABP B312130T1-3; pN1, pN2a, or pN3a; M0ACx4 then Tx4 VSACx4 then THx4 then Hx40wkNCCTG N98313505T1-3; pN1-2; M0ACx4 then Tx12wk VS ACTx4 then Hx52wk VS ACx4 then Tx12wk then Hx40wkHERA5102T1-3; pN1-2; M0Any (neo)adjuvant regimen, then H q3wk x1yr VS H q3wk x 2yr VS observationFinHER232T1-4; N0-3; M0Vx3 or T*x3 then FECx3 VS Vx3 or T*x3 with Hx9wk then FECx3PACS043010(528 HER2+)T1-3; pN1-2; M0FE(100)Cx6 VSFE(100)Cx6 then Hx1yr VS T*E(75) x6 VS T*E(75) x6 then Hx1yrA, adriamycin; C, cyclophosphamide; T, paclitaxel; T*, docetaxel; H, trastuzumab; P, carboplatin; F, 5-fluorouracil; E, epirubicin; Treatment regimen also included 5 years of hormonal therapy for ER positive patients. The ER+/HER2+ and the ER-/HER2+ cohorts will be analyzed separately. Patients with tumors 3 cm or smaller (T1a, T1b, T1c and &gt;2 cm- 3cm) and 0, 1, 2 and 3 positive lymph nodes will be included. Initially a log rank test will be used to determine if the survival results are different by study. If there is no difference across studies, Kaplan-Meier survival curves with confidence intervals will be estimated. If there is a difference between studies, individual Kaplan-Meier curves will be estimated and the mean of the curves will be estimated along with confidence intervals using the adjusted standard deviation. Estimates at 3, 5 and 8 years will be presented as well as estimates of the event rates within each subpopulation defined by tumor size, number of positive lymph nodes, and ER status. Survival endpoints of DFS, and OS as defined in the original studies will be analyzed. Results and Conclusion Data from the five trials will be analyzed and an abstract provided prior to the meeting. Subgroups of patients with a very favorable outcome when treated with adjuvant chemotherapy and T will be identified. Our survival estimates might serve as benchmarks for future trials evaluating therapy reduction. Our results will complement those of the Dana Farber single arm multicenter trial in patients with “low risk” HER2-positive disease (APT trial; NCT00542451), being submitted to SABCS 2013. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr S6-03.