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Objective The goal was to compare the 5‐year DFS and 5‐year OS in patients with early‐stage human epidermal growth factor receptor 2 breast cancer (HER2+ BC) and triple‐negative breast cancer (TNBC) in relation to the amount of stromal tumor‐infiltrating lymphocytes (TILs) after locoregional management by either mastectomy without radiation or lumpectomy and whole‐breast radiotherapy (RT). Methods This was a retrospective review of HER2+ BC and TNBC patients’ charts and histopathology slides with clinical stage of T1‐T2 N0 who presented at our facility between January 2009 and December 2019. Locoregional treatment included either mastectomy without RT (M) or lumpectomy with RT (L+R). TILs were assessed by three pathologists using the guidelines of the 2014 TILs working group. A competing risk model and Kaplan–Meier analysis were used to analyze correlations between TILs levels and clinical outcome. Results We reviewed 211 patients’ charts. Of them, 190 proceeded to the final analysis. Patients were split into groups of "low TILs" and "high TILs" based on a 50% TILs cut‐off. Of them 26% had high TILs, 48% received RT, 97% received chemotherapy, all HER2+ BC patients received HER2‐directed therapy and all HER2+ BC that were also hormone receptor positive (HR+) received endocrine therapy (ET). In patient with low TILs, L+R did not improve outcomes compared to M. Moreover, patients with high TILs had a significant improvement of their DFS and OS with L+R when compared to M. Conclusion The results of our study reflect that a selected group of HER2+ BC and TNBC with elevated TILs, L+R is associated with improvement of 5‐year DFS and 5‐year OS., A quarter of HER2+ and triple‐negative breast cancer patients have high levels of tumor‐infiltrating lymphocytes. HER2+ and triple‐negative breast cancer patients have high levels of tumor‐infiltrating lymphocytes have improved 5‐year DFS and OS if they receive radiation as part of their locoregional therapy.

Background: The utilization of bilateral (B/L) mastectomy for ductal carcinoma in situ (DCIS) has been rising within the last two decades. This is occurring despite the lack of convincing evidence to support the positive impact of this approach on disease-specific or overall survival (OS.) Notably, the estimated annual risk of developing a contralateral breast cancer is only 0.1% per year. Method: This is a retrospective cohort analysis of National Inpatient Sample database between the years 2005 and 2014 of adult females who underwent B/L mastectomy. ICD-9-CM procedure codes were used to identify two subpopulations; those who had only DCIS without invasive breast cancer or high risk genetic syndrome (DCIS mastectomy) and all others. The aim of this study is to assess the demographic predictors of undergoing B/L mastectomy for DCIS. Statistical analysis done using STATA. Results: The total number of B/L mastectomies performed within the study period was 144,754, of which 24,766 (17.1%) were performed for DCIS with no invasive cancer and no high risk genetic syndrome. There was no significant difference between the two groups in age (average 52.8 years), length of stay (average 2.34 days) and total charge for hospitalization (average $51,209). Among DCIS mastectomy patients, 56.3% were >50 year-old and only 0.7% were 18-30 year-old, 80.7% were Caucasian and 7.5% were African American, 42% were from highest income quartile neighborhoods and 12.6% were from lowest income quartile neighborhoods and 77.8% had private insurance while 15.9% and 5.2% had Medicare and Medicaid, respectively. Interestingly, 95.6% of B/L mastectomies for DCIS were performed at urban centers, 63.6% in teaching hospitals and 64.2% were in large hospital by bed size. Univariate regression showed no significant predictive value for undergoing B/L mastectomy for DCIS indication by age, race, hospital geographic region, teaching status of hospital or hospital size. The odds of undergoing B/L mastectomy for DCIS was higher for age category for 30-50 year-old compared to 18-30 year-old (OR=2.6, p Conclusion: A significant proportion of B/L mastectomies are being performed for DCIS. While this approach has not convincingly yielded an OS benefit, it has significant clinical and psychological morbidity along with considerable financial toxicity. We found inequity in populations that receive this procedure by age, race, insurance status, income quartile and urban or rural location of center. Further studies would be helpful to delineate this disparity among patients and assess the utility of B/L mastectomy in the era of molecular prediction and superior therapeutic modalities. YearTotal charge of hospitalization ($)200528,722.3200632,192.5200738,492.2200845,168.5200945,752.2201053,326.5201156,128.0201259,118.7201372,193.6201473,783.9 Citation Format: Sindhu Janarthanam Malapati, Sunny RK Singh, Rohit Kumar, Jason Mouabbi, Ahmed Abdalla, Carrie Dul, Tarik Hadid. Bilateral mastectomy in ductal carcinoma in situ: 10-year analysis of national inpatient sample database [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-08-04.

Background: There is a strong evidence indicating that locoregional control of early-stage breast cancer either by lumpectomy with radiation therapy or by mastectomy yields similar rates of disease-free survival (DFS) and overall survival (OS). Recent retrospective review of a Danish prospective database demonstrated a strong favorable interaction between radiotherapy (RT) and all breast cancer subtypes that contain high amount of tumor infiltrating lymphocytes (TILs). Objective: We aim to compare the DFS and OS rates in patients with early-stage triple negative breast cancer (TNBC), whose tumors demonstrate high involvement by TILs after locoregional management by either mastectomy or lumpectomy and whole breast radiotherapy. Methods: We retrospectively reviewed the charts and histopathology slides of patients with TNBC with the clinical stage of T1-T2 N0 who were treated in our center between January 2009 and December 2018. Locoregional management included either mastectomy (no radiation group) or lumpectomy with whole breast irradiation (radiation group). Stromal TILs were estimated by 3 pathologists independently using hematoxylin-eosin staining, following the recommendations of the TILs working group 2014. A competing risk model, Kaplan-Meier analysis and multivariate Cox regression analysis were used to analyze correlations between TILs and clinical outcome. Results: A total of 101 charts were reviewed and 91 were included in the final analysis. Patients were dichotomized into groups of “low TILs” and “high TILs” using a 40% cut off. Approximately 26% of patients (24/91) were “high TILs”. About 46% of the “high TILs” group and 52% of “low TILs” group received RT. In patients with high TILs, 82% received chemotherapy in the "radiation group" and 100% in "no radiation group". In the patients with low TILs, 77% received chemotherapy in the "RT group" and 75% in "no RT group”. Table 1 and 2 depict the 5-year DFS and 5-year OS in "high TILs" and "low TILs" groups in relation to RT, respectively. Conclusion: Our data indicate that in a selected group of high TILs TNBC, RT is associated with significant improvement of 5-year DFS and OS. This improvement is unlikely to be due to improved locoregional control as local failure was rare in all patient groups. This study is limited by its retrospective nature and the low number of subjects. Despite that, our results are important and deserve further confirmation using larger prospective clinical trials. Table 1. 5-year DFS5-year DFSHigh TILsLow TILsRT group100%83.9%No RT group47.1%79.3%p-value0.010.96 Table 2. 5-year OS5-year OSHigh TILsLow TILsRT group100%83.7%No RT group65.6%76.7%p-value0.050.98 Citation Format: Jason Aboudi Mouabbi, Momal Chand, Ramen Sakhi, Daniel Ockner, Susan Szpunar, Carrie L Dul, Tarik Hadid, Zyad Kafri, Amr Aref. Improvement of survival with radiation therapy in early stage triple negative breast cancer patients with high level of tumor infiltrating lymphocytes [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-12-09.

Background POLARIS is an ongoing, prospective, real-world (RW) study of palbociclib (PAL) in patients (pts) with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer (HR+/HER2- ABC). A biomarker goal of this study was to evaluate serial changes in circulating tumor DNA (ctDNA) dynamics among pts with long-term clinical response to PAL plus endocrine therapy (ie, received ≥18 cycles). Methods The data set included pts who received PAL combination therapy, gave consent for blood collection to obtain ctDNA, and had long-term clinical response. The Guardant360 Next-Generation Sequencing platform, which analyzed approximately 73 genes, was used to sequence ctDNA for somatic single-nucleotide variants, including copy number variants. Longitudinal ctDNA changes (at baseline and various time points) and the RW clinical response to PAL are described. Results As of December 17, 2020, 35 pts of 1280 enrolled received ≥18 cycles of PAL combination therapy, with blood samples collected over a minimum of a 24-month period. Pts received PAL plus an aromatase inhibitor (n=16) or fulvestrant (n=19). Median age was 64 years. Thirty pts (85.7%) were white, 29 (82.9%) were postmenopausal, 31 (88.6%) had an Eastern Cooperative Oncology Group score of 0 or 1, 12 (34.3%) had visceral disease, 9 (25.7%) had de novo disease, and 24 (68.6%) had recurrent disease. Six pts (17.1%) had a RW best overall response (BOR) of complete response (CR), 9 (25.7%) had partial response (PR), and 20 (57.1%) had stable disease (SD). Two pts had disease progression resulting in change of therapy at cycles 25 and 38, respectively. Biomarker samples were collected from a median (range) total number of 9 (3-12) visits. The median (range) number of somatic variants detected was 4 (0-11) and included the most prevalent somatic mutations (eg, PIK3CA, TP53, BRCA1/2, FGFR2, GATA3). No ctDNA mutations were detected in 6 pts (17%) post baseline up to 24 months. Among 15 pts who achieved CR/PR, 12 (80%) either had no detectable or sustained very low ctDNA burden or had corresponding ctDNA decrease. Among 16 pts who remained with SD, 12 (75%) either had no detectable or sustained very low ctDNA burden or had ctDNA decrease. Among 8 pts whose disease progressed, 5 (63%) had an increasing trend in ctDNA mutation frequency. Conclusions This study is among the first to provide serial blood-based tumor genotyping data from routine clinical practice. Interim data indicate that even pts with ongoing detectable ctDNA have a BOR of CR, PR, or SD with PAL for HR+/HER2- ABC, suggesting certain mutations might not be drivers of PAL resistance. Dynamic changes of ctDNA mutations may be predictive for treatment response, and may have clinical utility in disease surveillance monitoring. Additional longitudinal data will be presented. Pfizer; NCT03280303 Citation Format: Joanne L. Blum, Aditya Bardia, Sharon Wilks, Steven L. McCune, Carrie L. Dul, John J. Migas, Derrick W. Spell, Zhe Zhang, Yuan Liu, Yao Wang, Debu Tripathy. Longitudinal ctDNA changes in patients with long-term response to palbociclib combination therapy for advanced breast cancer: A preliminary analysis from the real-world POLARIS study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB033.

Background: Scientific evidence strongly indicates that locoregional control in early-stage breast cancer (BC) by lumpectomy with radiation therapy or by mastectomy yields similar disease-free survival (DFS) and overall survival (OS). A recent retrospective review of a Danish prospective database demonstrated strong favorable interaction between radiotherapy (RT) and all BC subtypes that contain high amount of tumor infiltrating lymphocytes (TILs). Objective: We aim to compare DFS and OS in patients with early-stage HER2-positive BC, whose tumors demonstrate high involvement by TILs after locoregional treatment by either mastectomy or lumpectomy and whole breast radiotherapy. Methods: We retrospectively reviewed the charts and histopathology slides of patients with HER2-positive BC with clinical stage T1-T2 N0, who were treated in our center between January 2009 and December 2018. Locoregional management included either mastectomy (no radiation group) or lumpectomy with whole breast irradiation (radiation group). Stromal TILs were estimated using hematoxylin-eosin staining, according to the recommendations of the TILs working group 2014. This was performed by 3 independent pathologists who were blinded to the clinical course of the patients. A competing risk model, Kaplan-Meier analysis and multivariate Cox regression analysis were used to estimate correlations between TILs and clinical outcomes. Results: A total of 110 charts were reviewed and 99 were included in the final analysis. Patients were dichotomized into groups of “low-TILs” and “high-TILs” using a 40% cut off. Approximately 25% of patients (26/99) were “high-TILs” and around 50% of the “high-TILs” and “low-TILs” patients received RT. In all groups, around 90% of patients received chemotherapy and anti-HER2 therapy. All hormone receptor-positive patients received adjuvant endocrine therapy. While RT did not result in significant DFS or OS advantage in the low-TILs group, patients with high-TILs had significant improvement of DFS and OS with the addition of RT. Table 1 depict the 5-year DFS and 5-year OS in "high-TILs" and "low-TILs" groups in relation to RT, respectively. Conclusion: In this retrospective analysis, our findings indicate that in high-TILs early-stage HER2-positive BC, RT was associated with significant improvement of 5-year DFS and OS. The exact mechanism is not well understood. However, this observation is important and warrants confirmation in prospective clinical trials. 5-year DFS5-year OSHigh TILsLow TILsHigh TILsLow TILsRT group100%90%100%83%No RT group65%90%72%93%p-value0.0270.960.0250.184 Citation Format: Jason A Mouabbi, Momal Chand, Ramen Sakhi, Ishaq A Asghar, Daniel Ockner, Tarik Hadid, Carrie L Dul, Mothaffar F Rimawi, Amer Aref. Radiation therapy improves survival in early-stage HER2-positive breast cancer with high-level of tumor infiltrating lymphocytes [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS15-01.

Background: The risk of distant recurrence gene signature, MammaPrint (MP), together with the molecular subtyping gene signature, BluePrint (BP), stratifies breast tumors into Luminal A, Luminal B, HER2, and Basal subtypes, independent of immunohistochemistry (IHC) or fluorescent in situ hybridization (FISH) expression. In the Neoadjuvant Breast Registry Symphony Trial (NBRST), MP and BP identified patients likely to respond to neoadjuvant treatment with higher accuracy compared to conventional methods. Here, we report 5-year follow up (FU) data in breast cancer (BC) patients from the NBRST registry with discordant clinical and genomic subtyping.Methods: This prospective study enrolled 1072 early-stage BC patients from 2009-2014 who received MP and BP testing. Patients received neoadjuvant therapy following standard of care and consented to 5 years post-surgery FU. IHC determined hormone receptor (HR) status, including ER and PR, and IHC and/or FISH determined HER2 status. Median FU for distant metastasis free survival (DMFS) and overall survival (OS) was 4.6 and 5 years, respectively. Differences in DMFS and OS was assessed by Kaplan Meier analysis and log-rank test.Results: Overall, BP reclassified 22% of tumors into different molecular subtypes compared to IHC/FISH (Table). BP reclassified 17% of ER+HER2- tumors as BP Basal, with higher pathological complete response (pCR) rates compared to ER+/BP Luminal tumors (36% vs. 4%). ER+/BP Basal patients had similar pCR rates as triple negative BC (TNBC)/BP Basal patients (36% vs. 37%) following neoadjuvant treatment, and pCR correlated with improved survival outcomes. The 5-year DMFS and OS probabilities were lower in ER+/BP Basal patients compared to TNBC/BP Basal patients and were substantially lower compared to ER+/BP Luminal patients (P < 0.001). There were 106 HR-HER2+ patients, of whom BP reclassified 23.6% to Basal and 2.8% as Luminal B; the remaining 73.6% were confirmed HER2 by BP. The 5-year DMFS and OS probabilities were worse in HER2+/BP Basal patients compared to HER2+/BP HER2 patients. Of 142 triple positive (TP, ER+PR+HER2+) patients, BP classified 55% as Luminal, 39% as HER2, and 6% as Basal, with higher pCR rates observed in BP Basal and BP HER2 tumors compared to BP Luminal. The 5-year DMFS and OS probabilities were substantially lower in TP/BP Basal patients compared to TP/BP HER2 and TP/BP Luminal patients (P < 0.05 and P < 0.04). Of clinical HER2+ patients (HR+ or HR-) that received pertuzumab, patients that reclassified as BP Basal had worse OS compared to BP HER2 patients (P < 0.04).Conclusion: ER+HER2- and HER2+ patients that reclassified as BP Basal are more likely to achieve pCR and have improved survival, demonstrating the clinical utility of BP in the neoadjuvant setting. These patients may benefit from optimized chemotherapy used for TNBC, including novel emerging treatments such as PD-1 and PARP1 inhibitors, in addition to HER2-targeted therapy. Furthermore, HER2+ tumors that were confirmed HER2 by BP may have high response rates to regimens containing TDM-1. Lastly, BP identified a subgroup of triple positive BC patients, who reclassified as BP Luminal, that may avoid overtreatment. Overall, molecular subtyping using MP and BP is more accurate in stratifying patients and predicting treatment responses and 5-year disease outcomes than conventional methods and thus, facilitates successful treatment decisions. Clinical subtypeFrequency of BP classificationBluePrint subtypepCR%5-yr DMFS (95% CI)5-yr OS (95% CI)TNBC (n=236)0.42% (1/236)Luminal A100% (1/1)N/AN/A2.54% (6/236)Luminal B16.67% (1/6)N/AN/A1.27% (3/236)HER233.33% (1/3)N/AN/A95.76% (226/236)Basal36.73% (83/226)100% (pCR)100% (pCR)60.5% (50.5-69.1)(non-PCR)64.3%(52.1-71.2) (non-PCR)ER+HER2- (n=520)28.84% (152/520)Luminal A1.97% (3/152)91.1% (84.0-95.2)94.6% (88.3-97.6)52.37% (276/520)Luminal B5.43% (15/276)75.2% (69.0-80.4)84.5% (79.0-88.7)1.33% (7/520)HER214.29% (1/7)N/AN/A17.46% (92/520)Basal35.9%(33/92)84.1% (67.8-92.5) (pCR)86.3% (70.1-94.1) (pCR)54.6% (42.0-65.5) (non-pCR)57% (43.7-68.2) (non-pCR)HR-HER2+ (n=106)2.83% (3/106)Luminal B66.67% (2/3)100%100%73.59% (78/106)HER269% (54/78)82.8% (69.9-90.5)88.6% (76.0-94.8)23.58% (25/106)Basal40% (10/25)79.0% (52.5-91.7)79.0% (52.5-91.7)Triple Positive (n=142)12.68% (18/142)Luminal A22.22% (4/18)88.8% (76.5-94.8)94.5% (83.8-98.2)42.25% (60/142)Luminal B11.67%(7/60)38.73% (55/142)HER244.44% (24/55)87.5% (72.0-94.7)97.9% (83.8-98.2)6.34% (9/142)Basal55.56%(5/9)62.5% (22.9-86.1)70.0% (22.5-91.8)HER2+ (HR+ or HR-)treated with pertuzumab (n=105)28.6%(30/105)Luminal37% (11/30)84.7% (63.8-94.1)92.2%(71.8-98.0)57%(60/105)HER282% (49/60)91.4% (78.3-96.8)92.9%(79.2-97.7)14%(15/105)Basal40% (6/15)66.0%(31.1-86.3)64.0% (29.1-85.1) Citation Format: Pat Whitworth, James Pellicane, Jr, Paul Baron, Peter Beitsch, Laura Lee, Michael Rotkis, Angela Mislowsky, Carrie Dul, Charles Nash, Bichlien Nguyen, Mary Murray, Paul Richards, Mark Gittleman, Stephanie Akbari, Shiyu Wang, Andrea Menicucci, Erin B Yoder, Lisa Blumencranz, William Audeh. Molecular subtyping by BluePrint improves prediction of treatment responses and survival outcomes in patients with discordant clinical and genomic classification [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS4-04.

Background: MammaPrint (MP) is used to identify breast cancer (BC) patients who can safely forego adjuvant chemotherapy. MP combined with the BluePrint (BP) molecular subtyping signature identifies BC subtypes with distinct therapeutic response rates and survival outcomes. In the Neoadjuvant Breast Symphony Trial (NBRST), MP and BP (MP/BP) predicted rates of pathologic complete response to neoadjuvant chemotherapy (NCT) and partial response to neoadjuvant endocrine therapy (NET). Here, we report 5-year overall survival (OS) and distant metastasis-free survival (DMFS) in patients from the NBRST registry according to MP/BP molecular classification. Methods: The NBRST trial (NCT01479101) prospectively enrolled 1072 patients from 2011 to 2014, who received MP and BP testing. Patients were assigned to receive NCT or NET according to NCCN guidelines and consented to 5 years post-surgery follow-up (FU). Clinical outcomes were available for 913 patients from 67 US institutions. Median FU for OS and DMFS was 5 and 4.6 years, respectively. Tumors classified by MP as High Risk (HR) or Low Risk (LR) were further stratified into four molecular subtypes by BP: Luminal A, Luminal B, HER2, and Basal. Differences in OS and DMFS at 3 and 5 years were assessed by Kaplan Meier analysis and log-rank test. Results: MP results from neoadjuvant patients (N=913) classified 16% of tumors as MP LR and 84% as MP HR. MP and BP classified 15.7% (143/913) of tumors as Luminal A, 32.5% (297/913) as Luminal B, 17.1% (156/913) as HER2, and 34.7% (317/913) as Basal. The 5-year OS and DMFS probabilities were significantly lower in HR compared to LR patients (p < 0.001 for OS and DMFS), and lowest in Basal and Luminal B compared to Luminal A and HER2 subtypes (p < 0.001 for OS and DMFS). Most DMFS events in BP Basal tumors occurred within the first 3 years. Of 841 patients that received NCT with or without HER2-targeted therapy, 12.2% (103/841) were LR and 87.8% (738/841) were HR. MP and BP classified 11.9% (100/841) of these patients as Luminal A, 32.6% (274/841) as Luminal B, 8.3% (154/841) as HER2 subtype, and 37.2% (313/841) as Basal. The 5-year OS and DMFS probabilities were lowest in HR, Basal or Luminal B patients (p < 0.001). In 59 patients who received NET alone, 5-year OS and DMFS were significantly worse in HR patients that had Luminal B or HER2 tumors compared to LR Luminal A patients. In the 39 patients with Luminal A tumors, response to NET at the time of surgery was: 46.2% partial response, 41.0% stable disease, 5.1% progressive disease, 2.6% not reported. Five year DMFS in patients with Luminal A tumors treated with NCT or NET was not significantly different (p=0.67).Conclusions: MammaPrint remained prognostic in BC patients undergoing neoadjuvant therapy. Long -term prognosis was excellent in LR groups who received NCT or NET alone. MP and BP can accurately classify patients into specific subtypes with distinct OS and DMFS outcomes at five years, with BP Basals having the worst outcomes, followed by Luminal B, HER2, and Luminal A subtypes. BP Basal patients had the highest frequency of events within the first 3 years post-surgery, suggesting a genomic risk timeline distinct from other BP subtypes and a potential benefit from a secondary therapeutic immediately post-surgery. Additionally, Luminal A patients had a very low risk of progressive disease while on NET alone prior to surgery, with similar DMFS outcomes to Luminal A-types who received NCT. Number of patientsObserved events% at 5 year (95% CI)p-valueAll patients - MammaPrint Risk GroupOS913134p Citation Format: Pat Whitworth, James V Pellicane, Jr., Paul Baron, Peter Beitsch, Laura Lee, Michael Rotkis, Angela Mislowsky, Carrie Dul, Charles Nash, Bichlien Nguyen, Mary Murray, Paul Richards, Mark Gittleman, Stephanie Akbari, Shiyu Wang, Erin B Yoder, Andrea Menicucci, Lisa Blumencranz, William Audeh, NBRST Investigators Group. 5-year outcomes in the NBRST trial: Preoperative MammaPrint and BluePrint breast cancer subtype is associated with neoadjuvant treatment response and survival [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD9-01.

TPS7088 Background: Genomic expression profiles have enabled the classification of breast cancers into molecular sub-types and provide prognostic information about the metastatic potential of the tumor, both of which have implications for the personalized treatment of breast cancer beyond clinical and pathological features. However, to precisely stratify tumors into actionable subgroups, full genome expression data should be combined with comprehensive clinical information. The FLEX Registry aims to aggregate a large, real-world dataset, which will enable discovery of novel genomic profiles, particularly for patient subsets that are underrepresented in traditional clinical trials and will contribute to improved precision in the management of breast cancer. Methods: The FLEX Registry (NCT03053193) is a multi-center, prospective, observational trial for patients with Stage I, II, and III breast cancer. Patients with stage I-III breast cancer who receive the 70-gene signature risk of recurrence test, with or without the 80-gene signature molecular sub-typing test, on a primary tumor are eligible for enrollment. The primary objective of FLEX is to create a large scale, population-based registry that links complete clinical data with full genome expression data to elucidate new prognostic and/or predictive gene associations in a real-world setting. The FLEX Registry employs a shared study infrastructure to develop and investigate hypotheses for targeted subset analyses and/or clinical trials based on full genome expression data. The adaptable protocol is designed to be amended with the inclusion of targeted sub-studies. Patients enrolled in the initial study are eligible for inclusion in sub-studies for which they meet all eligibility criteria and additional consent is not required. Data will be collected on patients from diagnosis through 10 years of follow-up and any necessary additional clinical data will be collected as specified in the appendix protocols. Target enrollment is a minimum of 10,000 patients; >4,000 patients have enrolled since April 2017 at more than 80 sites, including seven National Cancer Institute-designated comprehensive cancer centers. The FLEX collaborative platform enables participating investigators the opportunity to author their own sub-study protocols, as approved by the FLEX Steering Committee. Fifteen sub-studies have been approved for investigation within the FLEX Registry. Clinical trial information: NCT03053193 .

Background: Rates of implant failure, wound healing delay, and infection are higher in patients having RT after tissue expander (TE) and permanent implant reconstruction. Some have suggested greater complications with increased body mass index (BMI) and with diabetes. Patients and Methods: 127 patients had bilateral TE reconstruction and radiation from 2003 to 2013 at two centers. In 95% (121/127) of cases RT was performed while the TE was in place with the permanent implant inserted after RT. 3D-CRT technique included 50 Gy with daily or every other day bolus and forward planned segments. The supraclavicular and/or internal mammary lymph node bearing regions were treated in 82.7% (105/127) cases. The non-irradiated breast provided an internal control. Chi-squared testing of pretreatment factors included radiation, chemotherapy, and medical history of hypertension, diabetes, cardiovascular, and pulmonary disease. BMI, tobacco and alcohol use, use of antiestrogen, statin, antidepressant, antihypertensive, anxiolytics, and antidiabetic medications were also studied. Comparison of differences in means for continuous variables used analysis of variance, then multiple pairwise comparisons with Bonferroni correction of p-value. Results: Mean age was 53 ± 10.1 years with just 14.6% African- American. Twelve (9.4%) were BRCA positive (9 BRCA1, 4 BRCA2, 1 Both). Nearly all complications were in the radiated breast. Complications were: Grade 0 (no complication; 43.9%), Grade 1 (tightness and/or drifting of implant or Baker grade II capsular contracture; 30.9 %), Grade 2 (infection, hypertrophic scarring, or incisional necrosis; 9.8%), Grade 3 (Baker grade III capsular contracture, wound dehiscence, or impending exposure of implant; 5.7%), Grade 4 (implant failure, exchange of implant, or Baker grade IV capsular contracture; 9.8%). 15.3 percent (19 cases) experienced grade 3 or 4 complication and 9.8% (12 cases) had grade 4 complication. Considering non-irradiated breasts, there were two (1.6%) Grade 3-4 complications. For BMI, there was no significant difference by category as defined by the CDC (p=0.91). Patients history of HRT tended to be more likely to have Grade 3 or 4 complications (31.8% vs 12.4% respectively; p=0.08). Patients with depression were more likely to experience a Grade 3 or 4 complication (29.4% vs 13.2%; p=0.01). Multiple logistic regression was used to predict the probability of a Grade 3 or 4 complication with HR use and depression as independent variables. Patients with depression were 4.2 times more likely to have a Grade 3 or 4 complication (OR=4.2, p=0.03) and patients with a history of HRT use were 3.4 times more likely to experience a Grade 3 or 4 complication (OR = 3.4, p=0.04). Only clinical diagnosis of depression was considered as 12/31 (38.7%) with antidepressants used only venlafaxine. Neither BRCA status (p=0.72) nor chemotherapy factors (p=0.42) were associated with complication rates. Conclusions: Higher rates of TE reconstruction complications may be expected in patients receiving radiotherapy. Patients reporting medical history of depression or HRT use showed statistically significant increase in complication rates. This effect might be attributed to a drug effect or to patient factors such as body image. Citation Format: Wagner RM, Spzunar SM, Stefani WA, Falk JS, Williams JL, Edhayan E, Dul CL, Rodriguez D, Busuito MJ, Browne CH, Aref A, Rabbani AN, Chuba PJ. Radiation and depression associated with complications of tissue expander reconstruction. [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 P2-13-02.

Background Ideally classification by subtype predicts treatment response and overall outcome. BluePrint 80-gene functional molecular subtype is based on mRNA expression (as is intrinsic subtype) associated with intact translation to protein (unlike intrinsic subtype). BluePrint (BP) classifies patients into Luminal, Her2 or Basal-type. Presently subtype is approximated using conventional immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) ("conventional subtype") or assigned by gene expression profiling. The main objective of the prospective neo-adjuvant NBRST study is to compare drug sensitivity as defined by pathological Complete Response (pCR), using 80-gene functional subtype vs. conventional IHC/FISH subtyping. NBRST enrolled over 1,000 US patients between June 2011 and December 2014. In this analysis we present the results for IHC/FISH Her2-positive patients. Methods Here we report findings in the 260 NBRST patients who had IHC/FISH Her2+ breast cancer, according to ASCO CAP guidelines at the time of diagnosis. Treatment, including chemotherapy and HER2-targeted agents, was at the discretion of the physician adhering to NCCN approved or other peer-reviewed, established regimens over the course of the study. pCR was defined as T0/isN0. Fisher's exact test was used to compare pCR rates among IHC/FISH and functional subtypes and treatment groups. Results The 260 IHC/FISH Her2+ patients had median age 53 (range 23-81) and included T1-4, N0-3 tumors. Of 169 ER+/Her2+ tumors 49% were re-classified as BP Luminal, 43% as BP HER2, and 8% as BP Basal. The median ER% of ER+/Her2+/BP Luminal tumors was 93% (range 3-100), compared to 79% in ER+/Her2+/BP HER2 (range 1-91) and 8% in ER+/Her2+/BP Basal-type (range 2-99).The overall pCR rate in ER+/Her2+/BP Luminal was 17% (4% with chemo/trastuzumab; 39% chemo/trastuzumab/pertuzumab, p Conclusions In the NBRST study, BP 80-gene functional subtype (based on mRNA expression and translation): 1. Re-classifies over half of all IHC/FISH ER+/Her2+ patients; 2. Predicts treatment response or resistance in Her2+ patients not segregated by conventional IHC/FISH classification and 3. Identifies ER+/Her2+ tumors that are sensitive to chemo/trastuzumab/pertuzumab but resistant to chemo/trastuzumab. Citation Format: Whitworth P, Beitsch P, Baron P, Beatty J, Pellicane JV, Murray MK, Dul CL, Mislowsky AM, Nash CH, Richards PD, Lee LA, Stork-Sloots L, de Snoo F, Untch S, Gittleman M, Akbari S, Rotkis MC. Three distinct HER2 subtypes identified by BluePrint 80-gene functional subtyping predict treatment-specific response in the prospective neo-adjuvant NBRST registry. [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 P1-14-05.

Background The prospective Neo-adjuvant Breast Registry Symphony Trial (NBRST) enrolled over 1000 US patients between June 2011 and December 2014. The aim of NBRST study is to compare chemosensitivity as defined by pathological Complete Response (pCR) using the 80-gene BluePrint functional subtype profile vs. conventional IHC/FISH subtyping. Treatment was at the discretion of the physician utilizing standard NCCN regimens. Pertuzumab, a monoclonal antibody, inhibits the dimerization of HER2 with other HER receptors. Pertuzumab received US FDA approval for the neo-adjuvant treatment of HER2-positive breast cancer in September 2013. Essentially all patients with HER2 positive cancers were treated with chemotherapy + trastuzumab and after this date pertuzumab was added, creating 2 distinct groups of Her2 treated patients. The aim of the current analysis is to compare the pCR rate of trastuzumab (H) vs trastuzumab and pertuzumab (H + P) by conventional and BluePrint functional subtype. Methods The current analysis includes women from the NBRST study, with histologically proven breast cancer, who received neo-adjuvant chemotherapy plus H or H + P and who provided written informed consent. Pathological assessment of Her2 was done according to ASCO CAP guidelines at the time of diagnosis. BluePrint (BP) classifies patients into Luminal, HER2 or Basal-type. pCR is defined as T0/isN0. All pCRs were verified with a de-identified copy of the surgical pathology report. Fisher's exact test was used to compare pCR rates within different subgroups. Results 252 IHC/FISH Her2+ patients received H (166) or H + P (86). The median age was 53 (range 23-81). 8% was stage I, 68% stage II and 24% stage III. 65% were ER positive. BP classified 55% of patients as HER2, 32% as Luminal, and 14% as Basal-type. The pCR rates and p-values within different subgroups of clinical Her2+ patients are provided in the table below. pCR rates and p-values within different subgroups of clinical Her2+ patients(n)H (pCR rate)H + P (pCR rate)p-valueTotal (n=252)40%59%0.005IHC/FISH Her2+/ER+ (163)30%57%0.001IHC/FISH Her2+/ER- (89)69%63%0.82BP HER2 (138)57%78%0.01BP Luminal (80)4%38%0.0002BP Basal (34)47%38%0.69 Conclusions Addition of pertuzumab to trastuzumab significantly increased response rate in ER+/Her2+, BP HER2 and BP Luminal patients but not in ER-negative and BP Basal patients. Pertuzumab overcame resistance to NCT/trastuzumab in a substantial proportion of the IHC/FISH Her2+/BP Luminal subgroup; indicated by a significantly increased pCR rate. Citation Format: Peter B, Pat W, Paul B, Jennifer B, Pellicane JV, Murray MK, Dul CL, Mislowsky AM, Nash CH, Richards PD, Lee LL, Stork-Sloots L, de Snoo F, Untch S, Gittleman M, Akbari S, Rotkis MC. Pertuzumab overcomes chemotherapy/trastuzumab resistance in ER+/Her2+ tumors classified as luminal functional subtype by the 80-gene BluePrint assay in the prospective neo-adjuvant breast registry symphony trial (NBRST). [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 P4-14-10.

Background The phase 4 Neo-adjuvant Breast Registry Symphony Trial (NBRST) enrolled over 1,000 US patients between June 2011 and December 2014. The aim of NBRST study is to compare chemo-sensitivity as defined by pathological Complete Response (pCR) using the 80-gene BluePrint (BP) functional subtype profile vs. conventional IHC/FISH subtyping. Treatment was at the discretion of the physician utilizing standard NCCN regimens. Pertuzumab, a monoclonal antibody, inhibits the dimerization of HER2 with other HER receptors. Pertuzumab received US FDA approval for the neo-adjuvant treatment of HER2-positive breast cancer in September 2013. Essentially all patients with HER2 positive cancers were treated with chemotherapy + trastuzumab and after this date pertuzumab was added, creating 2 distinct groups of Her2-treated patients. The aim of the current analysis is to compare the pCR rate of chemo-trastuzumab (c-t) vs chemo-trastuzumab plus pertuzumab (c-t-p) by conventional and 80-gene BP functional subtype. 80-gene BP functional subtype was derived by supervised cluster analysis for concordant mRNA and protein expression. Methods The current analysis includes women from the NBRST study, with histologically proven breast cancer, who received neo-adjuvant treatment, had 80-gene subtyping and provided written informed consent. Pathological assessment of HER2 was performed according to ASCO CAP guidelines at the time of diagnosis. 80-gene BluePrint (BP) classifies patients into Luminal, HER2 or Basal-type. pCR is defined as T0/isN0. All pCRs were verified with a de-identified copy of the surgical pathology report. Fisher's exact test was used to compare pCR rates within different subgroups. Results 286 IHC/FISH HER2+ patients received c-t (175) or c-t-p (111). Of these 80-gene BP subtype classified 53% as HER2-type, 33% as Luminal-type and 14% as Basal-type. 64% were ER positive. The pCR rates and p-values within different subgroups of clinical HER2+ patients are provided in the table below. c-tc-t-p (n)pCR ratep-valueTotal (n=286)41%57%0.01BP HER2 (153)58%73%0.06 BP Luminal (93) 6% 39% 0.0002BP Basal (40)45%1.0IHC/FISH HER2+/ER+ (183)31%53%0.003IHC/FISH HER2+/ER- (103)59%64%0.68 Conclusions One-third of ASCO/CAP Her2+ patients had 80-gene BP Luminal subtype and demonstrated resistance to c-t (pCR 6%). Addition of Pertuzumab overcame resistance in this group (pCR 39%). This finding in the neoadjuvant setting suggests a substantial potential benefit in the adjuvant setting and thus an urgent need to consider treatment in at-risk patients as well as confirmatory tissue analysis from independently reported trials. Citation Format: Beitsch P, Whitworth P, Baron P, Beatty J, Pellicane JV, Murray MK, Dul C, Mislowsky AM, Nash CH, Richards PD, Lee LA, Stork-Sloots L, de Snoo F, Untch S, Gittleman M, Akbari S, Rotkis MC. One-third of HER2 positive patients have 80-gene luminal subtype that is resistant to chemo-trastuzumab but sensitive to chemo-trastuzumab-pertuzumab: Critical implications for the adjuvant setting from the NBRST phase 4 neoadjuvant study. [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 P4-14-29.

Background Ideally classification by subtype predicts treatment response and overall outcome. BluePrint 80-gene functional molecular subtype is based on mRNA expression (as is intrinsic subtype) associated with intact translation to protein (unlike intrinsic subtype). BluePrint (BP) classifies patients into Luminal, HER2 or Basal-type. Presently subtype is approximated using conventional immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) ("conventional subtype") or assigned by gene expression profiling. The aim of the prospective NBRST study was to compare chemosensitivity as defined by pathological Complete Response (pCR), or endocrine sensitivity as defined by partial response (PR) using 80-gene functional subtype vs. conventional IHC/FISH subtyping. In this analyses we present the results of all IHC/FISH Hormone Receptor (HR) positive/Her2 negative patients. Methods The neo-adjuvant NBRST study enrolled over 1000 US patients between June 2011 and December 2014. Women aged 18–90 with histologically proven breast cancer, who were scheduled to start neo-adjuvant chemotherapy (NCT) or neo-adjuvant endocrine therapy (NET), and who provided written informed consent were included. Additional inclusion criteria were no excision biopsy or axillary dissection, no confirmed distant metastatic disease, and no prior therapy for breast cancer. Treatment was at the discretion of the physician adhering to NCCN approved or other peer-reviewed, established regimens. BluePrint in combination with MammaPrint classifies patients into four molecular subgroups: Luminal A, Luminal B, HER2 and Basal. pCR is defined as T0/isN0 and PR is according to RECIST and defined as at least a 30% decrease in the tumor bed. Results 418 IHC/FISH HR+/Her2- T1-4, N0-3, patients were enrolled (median age 54, range 22-87). MammaPrint and BluePrint (MP/BP) classified 28% as Luminal A, 54% as Luminal B, and 18% as Basal-type. The distribution of locally assessed ER% in BP Luminal tumors was 2% ER 0-10%; 3% ER 11-50%; and 95% ER>50% compared to 45% ER 0-10%; 28% ER 11-50%; and 27% ER >50% in BP Basal tumors. Tumors classified as BP Luminal 370 (89%) received NCT and the overall pCR rate was 9%. There was a significantly higher (p Conclusions Molecular subtyping using MammaPrint and BluePrint classified 1 out of 5 pathological luminal patients as BP Basal-type with a significant higher response rate to NCT compared to BP Luminal patients. BP Luminal patients have an excellent partial response rate to NET. Citation Format: Pellicane JV, Whitworth P, Beitsch P, Baron P, Beatty J, Murray MK, Dul CL, Mislowsky AM, Nash CH, Richards PD, Lee LL, Stork-Sloots L, de Snoo F, Untch S, Gittleman M, Akbari S, Rotkis MC. Chemosensitivity and endocrine sensitivity predicted by MammaPrint and BluePrint in clinical luminal patients in the prospective NBRST study. [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 P3-07-67.

Rates of implant failure, wound healing delay, and infection are higher in patients having radiation therapy (RT) after tissue expander (TE) and permanent implant reconstruction. We investigated pretreatment risk factors for TE implant complications. 127 breast cancer patients had TE reconstruction and radiation. For 85 cases of bilateral TE reconstruction, the non-irradiated breast provided an internal control. Comparison of differences in means for continuous variables used analysis of variance, then multiple pairwise comparisons with Bonferroni correction of p value. Mean age was 53 ± 10.1 years with 14.6% African-American. Twelve (9.4%) were BRCA positive (9 BRCA1, 4 BRCA2, 1 Both). Complications were: Grade 0 (no complication; 43.9%), Grade 1 (tightness and/or drifting of implant or Baker Grade II capsular contracture; 30.9%), Grade 2 (infection, hypertrophic scarring, or incisional necrosis; 9.8%), Grade 3 (Baker Grade III capsular contracture, wound dehiscence, or impending exposure of implant; 5.7%), Grade 4 (implant failure, exchange of implant, or Baker Grade IV capsular contracture; 9.8%). 15.3% (19 cases) experienced Grade 3 or 4 complication and 9.8% (12 cases) had Grade 4 complication. Considering non-irradiated breasts, there were two (1.6%) Grade 3–4 complications. For BMI, there was no significant difference by category as defined by the CDC (p = 0.91). Patients with depression were more likely to experience Grade 3 or 4 complication (29.4 vs 13.2%; p = 0.01). Using multiple logistic regression to predict the probability of a Grade 3 or 4 complications in patients with depression were found to be 4.2 times more likely to have a Grade 3 or 4 complication (OR = 4.2, p = 0.03). Higher rates of TE reconstruction complications are expected in patients receiving radiotherapy. An unexpected finding was that patients reporting medical history of depression showed statistically significant increase in complication rates.

Pertuzumab became a standard part of neoadjuvant therapy for human epidermal growth factor receptor 2-positive (HER2+) breast cancers approximately halfway through Neoadjuvant Breast Registry Symphony Trial (NBRST) enrollment, providing a unique opportunity to determine biologically which clinical HER2+ patients benefit most from dual targeting. As a neoadjuvant phase 4 study, NBRST classifies patients by both conventional and molecular subtyping. Of 308 clinical HER2+ patients enrolled in NBRST between 2011 and 2014 from 62 U.S. institutions, 297 received neoadjuvant chemotherapy (NCT) with HER2-targeted therapy and underwent surgery. This study compared the pathologic complete response (pCR) rate of BluePrint versus clinical subtypes with treatment, specifically differences between trastuzumab (T) treatment and trastuzumab and pertuzumab (T/P) treatment. In this study, 60% of the patients received NCT-T, and 40% received NCT-T/P. The overall pCR rate (ypT0/isN0) was 47%. BluePrint classified 161 tumors (54%) as HER2 type, with a pCR rate of 65%. This was significantly higher than the pCR rate for the 91 HER2+ tumors (31%) classified as luminal (18%) (p = 0.00001) and the 45 tumors (15%) classified as basal (44%) (p = 0.0166). The patients treated with T/P had higher pCR rates than those treated with trastuzumab alone. The difference was most pronounced in the BluePrint luminal patients (8 vs. 31%). The highest pCR was reached by the BluePrint HER2-type patients treated with T/P (76%). The addition of pertuzumab leads to increased pCR rates for all HER2+ patient groups except for the BluePrint basal-type patients. This better response was most pronounced for the BluePrint luminal-type patients.

Purpose Hormone receptor-positive (HR+) tumors have heterogeneous biology and present a challenge for determining optimal treatment. In the Neoadjuvant Breast Registry Symphony Trial (NBRST) patients were classified according to MammaPrint/BluePrint subtyping to provide insight into the response to neoadjuvant endocrine therapy (NET) or neoadjuvant chemotherapy (NCT). Objective The purpose of this predefined substudy was to compare MammaPrint/BluePrint with conventional ‘clinical’ immunohistochemistry/fluorescence in situ hybridization (IHC/FISH) subtyping in ‘clinical luminal’ [HR+/human epidermal growth factor receptor 2-negative (HER2−)] breast cancer patients to predict treatment sensitivity. Methods NBRST IHC/FISH HR+/HER2− breast cancer patients (n = 474) were classified into four molecular subgroups by MammaPrint/BluePrint subtyping: Luminal A, Luminal B, HER2, and Basal type. Pathological complete response (pCR) rates were compared with conventional IHC/FISH subtype. Results The overall pCR rate for ‘clinical luminal’ patients to NCT was 11 %; however, 87 of these 474 patients were reclassified as Basal type by BluePrint, with a high pCR rate of 32 %. The MammaPrint index was highly associated with the likelihood of pCR (p

Angiogenesis plays a role in breast cancer development. Preclinical and clinical evidence is reviewed. Development of targeted antiangiogenic agents provides new challenges to clinical trial design. Current antiangiogenic therapy with traditional agents and novel agents are classified and reviewed.

114 Background: Classification by molecular subtype can aid in the selection of therapy for patients with breast cancer. However at present, the methodology for molecular subtyping is not standardized. The aim of the prospective NBRST study is to compare chemosensitivity as defined by pathological Complete Response (pCR) using the 80-gene BluePrint (BP) functional subtype profile vs. conventional IHC/FISH subtyping. Methods: The study includes women aged 18–90 with histologically proven breast cancer, written informed consent, no excision biopsy or axillary dissection, and no prior therapy for breast cancer. Neo-adjuvant Chemotherapy (NCT) was at the discretion of the physician adhering to NCCN approved or other peer-reviewed regimens. BP in combination with MammaPrint classifies patients into 4 molecular subgroups: Luminal A, Luminal B, HER2 and Basal. Results: 721 patients had definitive surgery. 58/335 (17%) IHC/FISH HR+/HER2- patients were re-classified by BP as Basal (57) or HER2 (1). 92/222 (41%) IHC/FISH HER2+ patients were re-classified as BP Luminal (67) or BP Basal (25). 7/164 (4%) IHC/FISH triple negative (TN) patients were re-classified as BP Luminal (5) or BP HER2 (2). NCT pCR rates were 3% in Luminal A and 9% in Luminal B patients versus 10% pCR in IHC/FISH luminal patients. The NCT pCR rate was 54% in BP HER2 patients. This is significantly superior (p = 0.02) to the pCR rate in IHC/FISH HER2+ patients (40%). BP Basal and IHC/FISH TN had a pCR rate of 35%. Functional BP subtyping divided the 137 IHC/FISH triple positive patients into two major subgroups: BP Luminal (n = 66, pCR = 11%) and BP HER2 (n = 60, pCR = 45%).11 patients were re-classified as BP Basal with pCR = 45%. Conclusions: Molecular subtyping using BP leads to a reclassification of 23% of tumors. The re-classification is most prominent in classically assessed triple positive patients where 48% of patients are re-assigned to the less responsive BP Luminal-type group vs. 44% of patients assigned to the responsive BP HER2-type group. These findings confirm the more accurate identification of molecular subgroups for treatment decision by BluePrint functional subtype classifier. Clinical trial information: NCT01479101.

596 Background: Classification by molecular subtype can aid in the selection of therapy for patients with breast cancer. However at present, the methodology for molecular subtyping is not standardi...

1559 Background: Memantine, an N-methyl-D-aspartate receptor noncompetitive antagonist, has been proposed for smoking cessation by virtue of opposing the effects of glutamate in the CNS “addiction ...