The pathogenesis of breast cancers that do not express estrogen receptors or Her-2/neu receptors (ERx/HER2x phenotype) is incompletely understood. We had observed markedly elevated gene expression of gamma-aminobutyric acid type A (GABA A ) receptor subunit p (GABAp, GABRP) in some breast cancers with ERx/HER2x phenotype. In this study, transcriptional profiles (TxPs) were obtained from 82 primary invasive breast cancers by oligonucleotide microarrays. Real-time reverse transcription-polymerase chain reaction (RT-PCR) was used to measure GABAp gene expression in a separate cohort of 121 invasive breast cancers. GABAp gene expression values from TxP and RT-PCR were standardized and compared with clinicopathologic characteristics in the 203 patients. GABAp gene expression was increased in 16% of breast cancers (13/82 TxP, 20/ 121 RT-PCR), particularly in breast cancers with ERx/HER2x phenotype (60%), and breast cancers with basal-like genomic profile (60%). The profile of genes coexpressed with GABAp in these tumors was consistent with an immature cell type. In multivariate linear regression analysis, the level of GABAp gene expression was associated with ERx/HER2x phenotype (P<0.0001), younger age at diagnosis (P = 0.0003), and shorter lifetime duration of breastfeeding (£ 6 months) in all women (P = 0.017) and specifically in parous women (P = 0.013). GABAp gene expression was also associated with combinations of high grade with ERx/HER2x phenotype (P = 0.002), and with Hispanic ethnicity (P = 0.036). GABAp gene expression is increased in breast cancers of immature (undifferentiated) cell type and is significantly associated with shorter lifetime history of breastfeeding and with high-grade breast cancer in Hispanic women.

We assessed the correlation between dynamic MRI results and clinical outcomes in patients with malignant gliomas. Rapid serial MRIs were obtained after bolus injection of gadolinium that resulted in an initial fast uptake followed by a slow uptake of contrast. The maximum rate of uptake and delayed rate of uptake were correlated with survival and prognostic covariates such as age and histology. In 121 subjects, higher maximum uptake rates, 3.6 signal intensity units per second or greater, were associated with shorter survival (p = 0.0066). The correlation of delayed rate of uptake with survival was less significant. After adjusting for age, histology, and Karnofsky performance score, the maximum rate of uptake remained more significantly correlated with survival than the delayed rate of uptake. Thirty-one patients had surgery within 1 month of dynamic MRI, and those with glioblastoma multiforme or anaplastic gliomas had higher maximum rates of uptake than those with pure necrosis or mixed tumor and necrosis (p = 0.022). No correlation between delayed rate of uptake and histology was seen in this group of patients. Our results suggest that the maximum rate of uptake in dynamic MRI can be a prognostic measure for patients with malignant gliomas. Further prospective study is needed to assess the utility of this technique for evaluating brain tumors.

10519 Objective. Triple-negative breast cancer is defined as a subtype of invasive breast cancer which lacks estrogen and progesterone receptor expression as well as HER2/neu expression and is highly similar to the basal-like subtype defined by gene expression profiling. Method. 1,143 patients treated at MD Anderson Cancer Center in neoadjuvant trials were included in a retrospective comparative analysis between triple-negative tumors and non-triple-negative tumors for response to neoadjuvant chemotherapy as well as long- term survival. Results. 827/1,143 (72%) patients had received taxanes, either as a single-agent (n=60) or in combination with anthracycline (n=767), whereas the remainder patients received an anthracycline-only chemotherapy. Overall 258/1,143 (23%) tumors were triple- negative. Complete pathological response (pCR) was achieved in 63/257 (25%) patients with triple-negative tumors compared to 99/888 (11%) in patients with non-triple-negative tumors (odds ratio [OR] 1.14, 95%CI: 1.09–1.20, p=.0082). Triple-negative status correlated significantly with high nuclear grade (p<.0001), whereas no significant correlation with any established clinicopathologic parameter was observed. However, 5-year overall survival (5yrOS) was 66% in the triple-negative group compared to 83% in the non-triple-negative control group (OR 2.1, 95%CI: 1.6–2.8, p<.0001). In multivariate analyses, triple-negative status (hazard ratio [HR] 2.0, 95%CI: 1.4–2.8, p<.0001), high nuclear grade, increased tumor size (HR 1.5, 95%CI: 1.3–1.8, p<.0001), positive nodal status (HR 1.4, 95%CI: 1.2–1.7, p=.0002) and high nuclear grade (HR 1.7, 95%CI: 1.1- 2.4, p=.0089) were significantly associated with decreased 5yrOS. When survival was analyzed according to both response rate and triple negative status, achievement of pCR was a stronger predictor of survival compared to triple-negative status. Conclusion. Triple- negative expression status among patients with breast cancer constitutes an independent unfavorable prognostic factor with regards to overall survival unless achieving pCR after neoadjuvant chemotherapy. No significant financial relationships to disclose.

Background: Image-guided percutaneous needle biopsy of the breast is a common procedure. In breast cancer patients (pts) undergoing core biopsies and surgical resection on the same day, the rate of tumor cell displacement along the needle track has been reported to be up to 50%. However, the clinical significance of this finding in triple negative breast cancer (TNBC) patients (pts) undergoing serial biopsies while receiving neoadjuvant chemotherapy (NACT) is unknown. Here we report the incidence of needle-track seeding (NTS) in a cohort of TNBC pts enrolled on a molecular triaging protocol involving serial biopsies of the index breast lesion. Methods: We reviewed the clinical records of 144 consecutive TNBC pts enrolled on a molecular triaging protocol at MD Anderson Cancer Center. Per protocol, all pts underwent a pre-treatment research biopsy and were initiated on anthracycline based NACT (AC). Pts with inadequate response to front-line NACT were encouraged to undergo additional biopsies of the index breast lesion prior to switching therapies. Serial breast ultrasound (US) was performed to monitor therapeutic response and incidental evidence of needle-track seeding noted on US was documented. Results: Clinicopathological characteristics of the pts are summarized in Table 1. 89% (128/144) of pts had a diagnostic breast biopsy done at another center prior to presenting at MDACC. To date, we have performed 209 US guided biopsies of index breast lesions in 144 pts. 92% (193/209) of these biopsies were done mainly for research purposes. 1.4% (2/144) of pts were found to have evidence of NTS on follow up US. The first pt had a T1N0 (1.9cm), grade 3, invasive ductal carcinoma (IDC) at diagnosis. She underwent a diagnostic biopsy followed by a research biopsy before initiating AC. She was found to have NTS as well as progression of disease (PD) on follow up US after 2 cycles of AC. The second pt had a T2N0 (3cm), grade 3 IDC at diagnosis. She underwent a diagnostic biopsy at another center, followed by a research biopsy before initiating AC. Like the first pt, she was found to have NTS and PD on follow up US after 2 cycles of AC. Both pts are currently on neoadjuvant clinical trials of novel agents. Conclusion: The rate of NTS detected on US in TNBC pts undergoing serial biopsies of index breast lesions while receiving NACT is low and further studies are needed to determine the impact of serial biopsies on long term outcomes in TNBC. Table 1: Patient CharacteristicsCharacteristicN=144Age - Median (years, interquartile range)55 (46-62)Tumor Size Mean (cm, standard deviation)3.4 (2.2)T1 – n(%)35 (24)T2 – n(%)89 (62)T3 – n(%)19 (13)T4 – n(%)1 (1)Clinical Nodal Status Negative – n(%)74 (51)Positive – n(%)70 (49)Grade 1 – n(%)1 (1)2 – n(%)17 (12)3 – n(%)124 (86)Unknown – n(%)2 (1)Histologic Subtype Invasive ductal carcinoma – n(%)121 (84)Invasive lobular carcinoma – n(%)2 (1)Mixed ductal and lobular carcinoma – n(%)3 (2)Metaplastic carcinoma – n(%)13 (9)Not specified – n(%)5 (3)Laterality Right – n(%)72 (50)Left – n(%)72 (50) Citation Format: Yam C, Santiago L, Candelaria RP, Adrada BE, Rauch GM, Hess KR, Litton JK, Piwnica-Worms H, Mittendorf EA, Ueno NT, Lim B, Murthy RK, Damodaran S, Helgason T, Huo L, Thompson AM, Gilcrease MZ, Symmans WF, Moulder SL, Yang W. Risk of needle-track seeding with serial ultrasound guided biopsies in triple negative breast cancer [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 P6-03-05.

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Background: Gene expression profiling (GEP) has identified several molecularly distinct subtypes of triple negative breast cancer (TNBC). Currently, GEP-based molecular diagnostics are not routinely used in clinical decision making due to the lack of proven benefit, costs involved and long turnaround time. However, two molecularly distinct subtypes of TNBC, the luminal androgen receptor (AR) and mesenchymal subtypes, have surrogate CLIA-certified immunohistochemical (IHC) markers, AR and vimentin (VM), respectively, which have the potential for application in the clinic. Here we report the rates of AR and VM positivity and their association with clinicopathological characteristics in a cohort of TNBC pts receiving NACT. Methods: As part of an ongoing molecular triaging protocol, 144 pts with stage I-III TNBC underwent a pretreatment biopsy for molecular characterization (MC) prior to initiating neoadjuvant chemotherapy (NACT). IHC for AR and VM were performed using commercially available antibodies. AR+ and VM+ were defined as ≥10% and ≥50% staining, respectively. Pts were randomized 2:1 to know (intervention arm, n=93) and not know (control arm, n=51) the MC results. The charts of pts randomized to the intervention arm were reviewed. Categorical variables were analyzed using Fisher's exact test. Ordinal and continuous variables were analyzed using the Wilcoxon rank-sum test and Student's t test as appropriate. Results: 31% (29/93) and 16% (15/93) of pts were AR+ and VM+, respectively. Only 4% (4/93) of pts were both AR+ and VM+. Clinicopathological characteristics are summarized in Table 1. AR+ pts were more likely to have clinically node positive disease as compared to AR- pts (66% vs 34%, p=0.007). There were no significant differences in clinical tumor size or grade between AR+ and AR- pts. VM+ and VM- pts had similar clinicopathological characteristics. Conclusion: Pts with AR+ TNBC were more likely to have node positive disease. The impact of AR+ on long term outcomes should be investigated in prospective studies. Table 1: Association between patient characteristics and AR/VM status AR  VM   AR+ (n=29)AR- (n=64)p-valueVM+ (n=15)VM- (n=78)p-valueAge - Median (years, interquartile range)58 (48-65)52 (46-61)0.05855 (48-64)56 (47-62)0.88Clinical Tumor Size      Mean (cm, standard deviation)3.5 (1.8)3.0 (1.8)0.2872.7 (1.7)3.3 (1.9)0.31T1 – n(%)5 (17)21 (33)0.2307 (47)19 (24)0.098T2 – n(%)21 (72)36 (56) 7 (47)50 (64) T3 – n(%)3 (10)7 (11) 1 (7)9 (12) Clinical Nodal Status      Negative – n(%)10 (34)42 (66)0.0078 (53)44 (56)1.00Positive – n(%)19 (66)22 (34) 7 (47)34 (44) Grade      2 – n(%)6 (21)5 (8)0.0763 (20)8 (10)0.293 – n(%)23 (79)59 (92) 12 (80)70 (90)  Citation Format: Yam C, Huo L, Hess KR, Litton JK, Yang W, Piwnica-Worms H, Mittendorf EA, Ueno NT, Lim B, Murthy RK, Damodaran S, Helgason T, Thompson AM, Santiago L, Candelaria RP, Rauch GM, Adrada BE, Symmans WF, Gilcrease MZ, Moulder SL. Androgen receptor positivity is associated with nodal disease in triple negative breast cancer [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 P1-07-22.

Background: Pertuzumab (P) in combination with trastuzumab (H) based chemotherapy is FDA-approved as a standard neoadjuvant treatment for patients with clinical stage II-III HER2-positive (HER2+) breast cancer (BC). The goal of this study was to evaluate the pathologic complete response (pCR) rate for neoadjuvant HP-containing regimens compared to H-containing regimens and report the 3-year relapse-free survival (RFS) for patients who had a pCR compared to those with residual disease (RD). Methods: All patients with stage II-III non-inflammatory HER2+ BC who received neoadjuvant H-containing or HP-containing therapy and underwent definitive breast and axillary surgery were identified from 2005 to 2016 through an institutional database. Medical records were examined for patient demographics, breast cancer stage, pathology results, surgical outcomes, and treatment details. pCR was defined as ypT0/is, ypN0. RFS was defined as the interval from surgery to date of last followup or death from any cause. Descriptive statistics, Cox proportional hazards, and Kaplan-Meier estimates were used for statistical analysis. Results: Patient characteristics and results by pCR or RD status are shown in the table below. The median age was 51 (22-84) years for the HP group and 50 (21-87) years for the H group. The median follow-up time was 1.9 (0-4.2) years for the HP group and 5.3 (0.1-12) years for the H group. For the HP group, the 3-year RFS was 98% (95% CI: 95, 100) for the pCR group and 90% (95% CI: 83, 97) for the RD group; HR 0.17 (0.04, 0.82), p=0.012. For the H group, the 3-year RFS was 91% (95% CI: 88,94) for the pCR group and 75% (95% CI: 71-79) for the RD group; HR 0.31 (0.22, 0.44), p&lt;0.0001. Among the 520 patients who achieved pCR and the 502 patients who had RD, the effect of HP vs. H was statistically significant (pCR: HR 0.24 (0.06, 1.00); p=0.015) (no pCR: HR 0.46 (0.22, 0.94); p=0.017). Conclusion: Patients who achieve pCR have an improved 3-year RFS compared to patients who have RD. Treatment with HP-containing neoadjuvant regimens is associated with a high 3-year RFS. VariableHP (n=215)H (n=807)  pCR n=121RD n=94pCR n=399RD n= 408Age at Diagnosis&lt;5043%46%46%51% ≥5057%54%54%49%Menopausal StatusPremenopausal46%50%53%57% Postmenopausal54%50%47%43%Clinical Stage at DiagnosisIIA40%29%34%29% IIB29%31%23%28% IIIA14%15%17%16% IIIB0%5%5%9% IIIC17%20%21%18%Clinical Nodal StatusNode (+)63%76%69%73% Node (-)37%24%31%27%Nuclear Grade1II25%32%22%28% III75%65%78%72%HR statusHR(+)52%74%52%67% HR(-)48%26%48%33%Adjuvant therapyTrastuzumab88%80%100%100% Trastuzumab and Pertuzumab3%5%0%0% Unknown9%15%20%0%11 patient in the HP pCR group had nuclear grade 1; 2 patients in the HP RD group had nuclear grade 1 tumors 2 2 patients received adjuvant TDM-1 on the NSABP B50 protocol Citation Format: Murthy RK, Raghavendra AS, Hess KR, Barcenas CH, Lim B, Moulder SL, Giordano SH, Mittendorf EA, Thompson A, Ueno NT, Valero V, Litton JK, Tripathy D, Chavez-Macgregor M. 3-year relapse-free survival of stage II-III HER2-neu positive breast cancer treated with pertuzumab and trastuzumab-containing neoadjuvant therapy compared to trastuzumab-containing therapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-17-04.

Background: Serial biopsies (bx) of triple-negative breast cancer (TNBC) in the curative neoadjuvant setting provides critical information on dynamic changes in the tumor in response to neoadjuvant systemic therapy (NAST) and can help inform the development of novel therapeutic strategies. However, neoplastic seeding following image guided breast bx has previously been reported in TNBC, raising concerns that serial bx may worsen clinical outcomes. Thus, we sought to determine if serial bx were associated with poorer clinical outcomes (using rates of pathologic complete response [pCR]) in TNBC pts receiving NAST. Methods: We identified 370 TNBC pts who received NAST at MD Anderson Cancer Center from 2011-2017. 200 pts did not have any research bx done (controls) on the index breast carcinoma and 170 pts had at least one research bx done (cases) on the index breast carcinoma as part of the prospective molecular triaging ARTEMIS trial. Baseline characteristics were compared between cases and controls using the Student t-test, Wilcoxon Rank Sum test or Fisher's exact test as appropriate. Univariable and multivariable logistic regression was used to determine if rates of pCR following NAST were significantly different between cases and controls. Results: Demographic characteristics demonstrate no significant differences (Table). However, cases were more likely to have received an anthracycline (99% vs 96%, p=0.02) and a targeted agent (22% vs 0%, p&lt;0.01) in the neoadjuvant setting as part of the ARTEMIS trial. A total of 211 bx of the index carcinoma were performed in the 200 controls, of whom, 6% (11/200) had a second bx of the index carcinoma done solely for diagnostic purposes. In contrast, a total of 407 bx of the index carcinoma were performed in the 170 cases (mean: 2.4 biopsies). Of the 407 bx done in the 170 cases, 58% (237/407) were done for research purposes. The pCR rate in controls and cases was 48% (96/200, 95% confidence interval [CI]: 41-55%) and 42% (72/170, 95% CI: 35-50%), respectively. The odds of pCR following NAST were not significantly different between controls and cases on both univariable (odds ratio [OR]: 0.80; 95% CI: 0.53-1.20, p=0.28) and multivariable logistic regression (adjusted OR: 0.94; 95% CI: 0.58-1.51; p=0.79). Conclusion: This is the first study examining the impact of serial bx on clinical outcomes in TNBC pts in the curative neoadjuvant setting. Our data suggest that research bx in this setting do not compromise rates of pCR. Baseline and Treatment CharacteristicsCharacteristicControls (n=200)Cases (n=170)p valueMean age - years (standard deviation [SD])52 (12)53 (12)0.54Ethnicity   White – n (%)113 (57)115 (68)0.09Black – n (%)48 (24)29 (17) Other – n (%)39 (20)26 (15) Mean tumor size – cm (SD)3.2 (1.4)3.3 (1.7)0.62T stage – n (%)   T134 (17)35 (21)0.96T2145 (73)111 (65) T314 (7)17 (10) T47 (4)7 (4) N stage – n (%)   N0101 (51)89 (52)0.83N170 (35)55 (32) N27 (4)6 (4) N322 (11)20 (12) Stage – n (%)   I19 (10)21 (12)0.74II140 (70)113 (66) III41 (21)36 (21) Grade – n (%)   19 (5)00.14227 (14)22 (13) 3164 (82)148 (87) Neoadjuvant therapy – n (%)   Anthracycline191 (96)169 (99)0.02Taxane199 (100)166 (98)0.18Platinum23 (12)23 (14)0.63Targeted agent037 (22)&lt;0.01 Citation Format: Yam C, Raghavendra A, Hess KR, Adrada BE, Candelaria RP, Damodaran S, Gilcrease MZ, Helgason T, Hortobagyi GN, Huo L, Layman RM, Lim B, Litton JK, Mittendorf EA, Murthy RK, Piwnica-Worms H, Rauch GM, Santiago L, Symmans F, Thompson AM, Tripathy D, Ueno NT, Valero V, Barcenas CH, Moulder SL, Yang W. Impact of serial biopsies in triple-negative breast cancer patients receiving neoadjuvant systemic therapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-15-06.