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Can pathologic complete response (pCR) be used as a surrogate marker of survival after neoadjuvant therapy for breast cancer

Breast cancer is heterogeneous in clinical, morphological, immunohistochemical and biological features, as reflected by several different prognostic subgroups. Neoadjuvant approaches are currently used for the in vivo efficacy assessment of treatments. Pathological complete response (pCR) has been reported as a reliable predictive factor of survival in that setting. However, pCR remains a subject of controversy in terms of definition and its evaluation methods. In addition, its predictive value for patient outcome in various breast cancer biological subtypes has been under debate. In this review, we will present the existing definitions of pCR, the impact of its evaluation methods on its rate and the assessment of its predictive value for patient outcome in the molecular subtypes of breast cancer (luminal A and B, Triple Negative and HER2-positive).

Intraoperative Imprint Cytology Examination of Sentinel Lymph Nodes After Neoadjuvant Chemotherapy in Breast Cancer Patients

BackgroundIntraoperative imprint cytology (IC) is one of several accurate, proven methods to detect tumor cells in sentinel lymph nodes (SLN) from patients with operable breast cancer. In patients treated with neoadjuvant chemotherapy (NAC), studies have demonstrated the feasibility and accuracy of SLN biopsy procedure. We evaluated the validity of IC for SLN testing in patients after NAC.Material and MethodsPatients with infiltrating breast carcinoma receiving NAC (nxa0=xa0132) were studied prospectively. At surgery, SLN biopsy followed by axillary lymph node dissection was performed. SLN were evaluated using IC in 80 of 132 patients (60%). The results of IC in the adjuvant setting (100 patients) were used for comparison.ResultsSLN metastases were correctly identified using IC in 58 of 80 (72%) patients. False negative results were observed in 21 patients. The sensitivity of IC testing was 38.2% and specificity 97.8%. The positive and negative predictive values (PPV and NPV) were 92.9% and 68.2%, respectively. In univariate analysis and multivariate logistic regression analysis, patients with micrometastases or isolated tumor cells in SLN have 2.3 times higher risk of a false negative IC result than patients with macrometastases in SLN (Pxa0=xa0.00021; relative risk [RR]xa0=xa02.3; 95% confidence interval, 1.37–3.85). The non-NAC group, which contained fewer micrometastatic cases, showed better sensitivity (47.4%) and NPV (88.9%).ConclusionNAC does not seem to influence the accuracy and sensitivity of IC. Variations in sensitivity are related to the proportion of cases with micrometastases and ITC, as it was also shown in chemonaive patients.

ERCC1 and telomere status in breast tumours treated with neoadjuvant chemotherapy and their association with patient prognosis

Dysfunctional telomeres and DNA damage repair (DDR) play important roles in cancer progression. Studies have reported correlations between these factors and tumour aggressiveness and clinical outcome in breast cancer. We studied the characteristics of telomeres and expression of ERCC1, a protein involved in a number of DNA repair pathways and in telomere homeostasis, to assess their prognostic value, alone or in combination, in 90 residual breast tumours after treatment with neoadjuvant chemotherapy (NCT). ERCC1 status was investigated at different molecular levels (protein and gene expression and gene copy‐number variations) by immunohistochemistry, qRT‐PCR and quantitative multiplex fluorescent‐PCR (QMF‐PCR). A comprehensive analysis of telomere characteristics was performed using qPCR for telomere length and qRT‐PCR for telomerase (hTERT), tankyrase 1 (TNKS) and shelterin complex (TRF1, TRF2, POT1, TPP1, RAP1 and TIN2) gene expression. Short telomeres, high hTERT and TNKS expression and low ERCC1 protein expression were independently associated with worse survival outcome. Interestingly, ERCC1 gains and losses correlated with worse disease‐free (pu2009=u20090.026) and overall (pu2009=u20090.043) survival as compared to survival of patients with normal gene copy‐numbers. Unsupervised hierarchical clustering of all ERCC1 and telomere parameters identified four subgroups with distinct prognosis. In particular, a cluster combining low ERCC1, ERCC1 gene alterations, dysfunctional telomeres and high hTERT and a cluster with high TNKS and shelterin expression correlated with poor disease‐free (HR= 5.41, p= 0.0044) and overall survival (HR= 6.01, p= 0.0023) irrespective of tumour stage and grade. This comprehensive study demonstrates that telomere dysfunction and DDR can contribute synergistically to tumour progression and chemoresistance. These parameters are predictors of clinical outcome in breast cancer patients treated with NCT and could be useful clinically as prognostic biomarkers to tailor adjuvant chemotherapy post‐NCT.

P3-14-01: Panitumumab in Combination with FEC 100 (5-Fluorouracile, Epirubicin, Cyclophosphamide) Followed by Docetaxel (T) in Patients with Operable, Triple Negative Breast Cancer (TNBC): Final Results of a Multicentre Neoadjuvant Pilot Phase II Study.

Background: Panitumumab is an antibody targeting the epidermal growth factor receptor (EGFR) to which a role has been suggested in TNBC. Consequently, we evaluated the combination of a standard chemotherapy (FEC 100 followed by T) with panitumumab as neoadjuvant therapy of oprable TNBC. Methods: 60 patients with stage II-IIIA disease were prospectively included in this multicentre pilot study. Systemic therapy (ST) consisted of 4 cycles of FEC 100 (500/100/500 mg/m2) q.3 weeks followed by 4 cycles of T (100 mg/m2) q.3 weeks, in combination with panitumumab (9 mg/kg) for 8 cycles q.3 weeks. All patients underwent surgery at completion of ST. Complete pathologic response (pCR) was the primary endpoint (Sataloff/J Am Coll Surg 1995; Chevallier: Am J Clin Oncol 1993), with toxicity and biologic ancillary studies as secondary endpoints. Results: Patients characteristics are as follows: mean age 47 [27-72]; T2: 74%, T3: 26%, (mean tumor size: 40 mm [20-120]); N0: 65%, N1: 28% and N2: 7%; invasive ductal carcinoma: 96%; Scarff-Bloom-Richardson Grade III: 72%, grade II: 28%. The median number of cycles was: FEC 100: 4 [2-4], T: 4 [0-4], Panitumumab: 7 [1-8]. Pathological response showed a pCR according to Sataloff9s classification of 57.1% [95% IC: 40.7−73.5] and according to Chevallier9s classification of 51.4% [95% IC: 34.8−68.0] with an overall clinical response rate of 60% (29% CR) [95% IC: 43.8−76.2]. Conservative surgery was performed in 79% of cases. Skin toxicity was the main side-effect: Cutaneous toxicity grade IV: 12%, grade III: 26%, grade II: 23%. No ocular complications have been reported. Neutropenia grade IV: 23.7%; febrile neutropenia: 4.2%. Infection: 0%. Hand-foot syndrome grade III: 4%. Ungueal toxicity grade IV: 2.5%, grade II: 25 .5%. Conclusions: These results suggest that Panitumumab in combination with FEC100 followed by T appears efficacious with acceptable toxicity in the neoadjuvant therapy of operable TNBC. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-14-01.

Abstract 1819: Heterogeneity of triple-negative breast cancer response to neoadjuvant treatment: tumor EGFR, HER3 and MET expressions can provide clues for therapy tailoring

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CAnnBackground: We have recently demonstrated (AACR 2013, abstract 4669) that antibody (Ab)-based EGFR targeting, sequentially combined with cytotoxic agents, can achieve pathologic complete response in almost 50% of triple-negative breast cancer (TNBC) patients (pts). However, the pts left with a residual tumor (RT), need a modification of treatment approach. We investigated whether expression of EGFR and two of its major cooperators, HER3 and MET, can offer a simple and practical base for neoadjuvant therapy (NAT) improvement in TNBC.nnMethods: The study included pts with a post-NAT RT in 2 pilot clinical trials of anti-EGFR Abs in TNBC, conducted from 2009 to 2011 by our team. One trial combined panitumumab with standard fluorouracil-epirubicin-cyclophosphamide and docetaxel (P-FEC-T) while another applied cetuximab with docetaxel (C-T). EGFR, HER3 and MET were assessed by immunohistochemistry (IHC) on pre- and post-NAT BC tissue. Expressions were evaluated by Quick score (% of positive cells x stain intensity as 0, 0.5, 1, 1.5, 2, 2.5 or 3; score range 0-300). At least 30 points of difference qualified the post-NAT score as changed, compared to the pre-NAT level.nnResults: 44 pts were eligible (P-FEC-T: 26 pts, C-T: 18 pts). Using 150 (the middle of the score range) as cut-off, we separated the tumors in each study on pre-NAT EGFR-high (score ≥ 150) and EGFR-low (score < 150). The P-FEC-T trial had 13 EGFR-high tumors (median score 220) and 13 EGFR-low ones (median score 0). After NAT, the pre-NAT EGFR-high BC most frequently showed EGFR decrease (9/13), HER3 increase (6/10) and MET decrease (7/12). However, the pre-NAT EGFR-low tumors showed no change in EGFR (7/13) and HER3 (6/11) post-NAT, but most of them increased MET (7/11).nnThe C-T trial had 7 EGFR-high (median score 210) and 11 EGFR-low cases (median score 70). The EGFR-high BC from that trial showed a similar pattern of score changes as the same group from the P-FEC-T trial: frequent EGFR decrease (4/7), HER3 increase (5/7) and MET decrease (4/7). The EGFR-low BC were more heterogeneous than in P-FEC-T: most frequently EGFR, HER3 and MET were increased (4/11, 5/11, 5/11 respectively) or unchanged (4/11, 4/11, 3/11 resp.).nnConclusion: Our results indicate that: a) there is a TNBC subgroup with relatively high EGFR expression (score ≥ 150, median around 200) which resist to anti-EGFR treatment mainly by downregulating EGFR and upregulating HER3; b) TNBC with low EGFR expression (score < 150) are a heterogeneous subgroup, which will frequently upregulate HER3 and/or MET after exposure to the anti-EGFR agents. The IHC assessment of EGFR, HER3 and MET before and on-NAT can help improving TNBC treatment by introduction of currently available anti-EGFR/HER3, anti-HER3 and anti-MET agents.nnCitation Format: Nina Radosevic-Robin, Catherine Abrial, Marie-Melanie Dauplat, Matthieu Roche, Anne Cayre, Maud Privat, Fabrice Kwiatkowski, Nassera Chalabi, Marie-Ange Mouret-Reynier, Yves-Jean Bignon, Philippe Chollet, Jean-Marc Nabholtz, Frederique Penault-Llorca. Heterogeneity of triple-negative breast cancer response to neoadjuvant treatment: tumor EGFR, HER3 and MET expressions can provide clues for therapy tailoring. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1819. doi:10.1158/1538-7445.AM2014-1819

401PEVEROLIMUS PLUS HORMONOTHERAPY (HT) INDUCES SURVIVAL GAIN IN LATE METASTATIC BREAST CANCER (MBC) AFTER PROGRESSION: COULD THIS LINE BE BETTER THAN A LATE NEW CHEMOTHERAPY (CT) LINE?

ABSTRACT Aim: Everolimus (Afinitor®) is indicated for the treatment of hormone receptor-positive, HER2/neu negative MBC, combined with exemestane, in postmenopausal women without symptomatic visceral disease after recurrence or progression following a non-steroidal aromatase inhibitor. However late patients after several lines may also benefit from new therapies, and we report here our experience on MBC patients pre-treated by a median of 3 CT and 2 HT lines at metastatic stage. Methods: 63 MBC patients progressing under HT (30) or after CT (32) received between 2012 and 2014 the association of everolimus and HT for a median duration of 27.8 weeks, by addition to the same (12) or a different (18) HT at the initial dose of 5-10u2003mg /day until progression or toxicity. Dose was adapted to the clinical tolerance, similarly to the published experience. Overall survival (OS) was calculated from the onset of the association, to last report or death. Patients were compared with our published database of 530 MBC patients stratified by treatment line (Planchat et al, The Breast, 2011, 20:574-8). Results: At the cutoff date (02/2014), median OS was not reached after a median follow up of 18 months and 18 patients had died. At 12 months, the survival rate was respectively 100, 79 and 49 % for patients pre-treated by 0 (n = 13), 1-2 (n = 18 ), ≥3 (n = 32) CT lines when metastatic. Median Time-to-treatment failure (progression or everolimus stopped for toxicity) was 6.39 months, but the clinician did not always change HT treatment line immediately. We realized a paired study where 62 patients under association were randomly matched with 421 registered MBC on 2 criteria: (1) age by 5-year intervals; (2) number of previous CT lines. Then OS under everolimus plus HT tended to be better than a new CT (p = 0.062). The Everolimus-containing line resulted in a longer OS for patient pre-treated by ≤ 2 lines of CT (p = 0.026), but was similar to a new line after ≥ 3 previous CT-lines, respectively 12 versus 11 months. Conclusions: These results may support the use of everolimus plus HT, as a supplementary late line, whatever the number of previous CT lines, and deserves more prospective trials. Disclosure: All authors have declared no conflicts of interest.

Abstract P1-08-34: Is it possible to predict the efficacy of a combination of cetuximab plus docetaxel in patients with operable, triple negative breast cancer (TNBC)? Final biomarker results from a phase II neoadjuvant trial

Background: TNBC is a heterogenous group of tumors for some of which the Epithelial Growth Factor Receptor pathway (EGFR) may play an important role. We evaluated the efficacy and toxicity of an anti-EGFR antibody (cetuximab) combined with docetaxel, which were given to the TNBC patients (pts) in the neoadjuvant setting. A biomarker analysis accompanied this trial, aiming to identify predictors of response. Methods: 35 patients with stage II-IIIA TN breast disease were prospectively included in this multicentre pilot study. Systemic therapy (ST) consisted of 6 cycles of docetaxel (100 mg/m 2 ) each 3 weeks, in combination with weekly cetuximab (first dose 400mg/m 2 then 250 mg/m 2 /week) for 6 cycles. All patients underwent surgery at completion of ST. Patient characteristics : mean age 48 [28-67]; TNM: T1: 3%, T2: 73%, T3: 24%; N0: 61%, N1-N2: 39%; mean tumor size 40 mm [15-100]; SBR: grade III: 73%, grade II: 27%. The median number of cycles was for docetaxel 6 [1-6] and for cetuximab 15 [1-18]. Pathological complete response (pCR) rate was 24% according to the Chevallier and Sataloff classifications; 28% if we consider breast pCR only. Overall clinical response rate was 57% (22% CR). Conservative surgery was performed in 75% of cases. The main side effect was skin toxicity: grade II: 39%, grade III: 36%, grade IV: 3%. Other side effects were: neutropenia grade IV: 12.7%, febrile neutropenia: 1.3%, hand-foot syndrome grade III: 3%, grade II: 3%, ungueal toxicity grade III: 3%, grade II: 33%. Paraffin-embedded and frozen samples were systematically collected before and after ST for biomarker studies. Germinal BRCA1 mutations and EGFR, KRAS, BRAF and PI3KCA somatic mutations were analyzed by NGS. EGFR, MET, cytokeratins 5/6 and 8/18, PTEN, P-cadherin, ALDH1, Ki67, p53 and the number of FOXP3+ or CD8+ tumor-infiltrating lymphocytes (TIL) were evaluated by immunohistochemistry. Results: The biomarker analysis was interpretable on the samples from 21 pts (3 pCR and 18 non-pCR). We applied the ROC curve to identify the best cut-off value for Ki67, EGFR, MET, cytokeratin 5/6 and 8/18, p53, ALDH1, PTEN, P-cadherin and the FOXP3+ or CD8+ TIL counts. None of these biomarkers was predictive of pCR except for the CD8+/FOXP3+ TIL count ratio. pCR rate was higher in the pts with the ratio equal or higher than 2.75 than in the others (43% versus 0%, p = 0.047). BRCA1 mutations were detected in 16% of pts. PI3K and EGFR somatic mutations were observed in 1 and 3 patients, respectively. The presence of the mutations was not predictive of pCR. Conclusion: Similarly to the previously reported trial by our group (SABCS 2012, abstract 1081), the immune component of the tumor microenvironment plays a very important role in the TNBC response to cytotoxic therapy. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-08-34.

Abstract P3-14-19: Panitumumab in combination with FEC 100 (5-fluorouracil, epirubicin, cyclophosphamide) followed by docetaxel for operable, triple negative breast cancer (TNBC): Patient outcome

Background: Panitumumab is an antibody targeting the epidermal growth factor receptor (EGFR) for which an important role has been suggested in TNBC. Consequently, we evaluated a combination of the standard chemotherapy (FEC 100 followed by docetaxel) with panitumumab as neoadjuvant therapy of operable TNBC. Complete pathologic response (pCR) was the primary endpoint, with clinical response, toxicity, and outcome as secondary endpoints. An investigation of biomarkers possibly predictive of pCR accompanied this trial. Here we focus on tumor recurrence, after a median follow up of 33 months [25-40] as on April, 1, 2013. Methods: Sixty patients (pts) with stage II-IIIA TNBC were prospectively included. Systemic neoadjuvant treatment (ST) consisted of the anti-EGFR antibody panitumumab combined with FEC 100, followed by 4 cycles of docetaxel. All pts underwent surgery after ST completion. Patient characteristics: median tumor size: 40 mm [20-120]; SBR grade III: 71.7%; pCR rate: 55.3% and 46.8% (the Sataloff and the Chevallier classifications, respectively). Paraffin-embedded and frozen tumor samples were collected before and after ST for biomarker analysis. EGFR, IGF-1R, MET, cytokeratins 5/6 and 8/18, PTEN, P-cadherin, ALDH1, Ki-67, p53, tumoral FOXP3 expression and the number of FOXP3+ or CD8+ tumor-infiltrating lymphocytes (TIL) were evaluated by immunohistochemistry. Results : .We have observed 9 recurrences: 1 local and 8 distant recidives, including 1 both local and distant. The distant recidives (metastases) were as follows: brain (4 pts); brain and lungs (1 pt); lungs only (1 pt), pleura (1 pt); liver (1 pt). 6 out of the 8 metastatic pts died and all were non-pCR post-ST. The 2 alive pts had brain metastases, but reached a pCR after the ST. Among the 9 relapsed pts 6 were 55 years old or less at the diagnosis. Seven out of those 9 pts had tumors with the clinical size equal or higher than 4 cm. As previously reported (SABCS 2012, abstract 1081), the pCR-predictive biomarkers in this study were high CD8+ TIL count (p = 3.4.10 −6 ) and high ratio between the CD8+ and FOXP3+ TIL counts (CD8+/FOXP3+ > 1.23, p = 8.5.10 −5 ). With this in mind, we have evaluated whether those parameters, assessed before or after the ST, could predict the recurrences. No difference was found in the preoperative CD8+ and the FOXP3+ TIL counts, as well as in the CD8+/FOXP3+ ratio, between the patiens who have recurred and the others. Conclusion : As it has been reported in previous studies, in our cohort of TNBC pts, the relapses occurred early after the administration of the last systemic treatment. The patients who relapsed died rapidly and most of them have not reached pCR after the ST. In addition, half of the metastatic pts got brain deposits. This implies that research on the resistance factors in TNBC should focus on those important for seeding of the “sanctuaries”, like brain. This research is ongoing in our group. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-14-19.

Abstract P5-08-07: HER3, MET and immune pathways play important roles in the resistance of triple negative breast cancer (TNBC) after neoadjuvant anti-EGFR (panitumumab) combined with FEC 100

Background: Our group has previously reported (SABCS 2012, abstract 1081) a 2-fold higher pathologic complete response (pCR) rate in TNBC treated with panitumumab+FEC100 (47%) than with the standard therapy alone. However, in a half of the patients (pts) a residual tumor (RT) was detected. Having in mind the detrimental impact of resistant TNBC on patient outcome, we have investigated the tumor tissue factors that might have been important in development of resistance to this treatment. Methods: 40 TNBC pts, treated with 8 cycles the anti-EGFR antibody panitumumab combined with FEC 100 for the first 4 and with docetaxel only for the last 4 cycles, were eligible. All pts underwent breast surgery after the neoadjuvant chemotherapy (NACT) completion. Formalin-fixed, paraffin-embedded tumor samples were collected before and after NACT for biomarker analysis. EGFR, HER3, IGF-1R, MET and the number of FOXP3+ or CD8+ tumor-infiltrating lymphocytes (TIL) were evaluated by immunohistochemistry (IHC). Expression of the kinases was graded semi-quantitatively (histoscores). Results: Out of 40 treated pts, 21 demonstrated a RT (53%, according to the Chevallier classification, PMID 8338056). The IHC data were available for 17 pts. Since high EGFR expression was important for pCR achievement in this study (SABC 2012), we first investigated the expressions of EGFR, HER3 and MET in the RT. The results are presented in Table 1. Overall, among the 9 cases (cs) with increased post-NACT HER3 expression (HER3 up), only 1 had increased MET (MET up), while among the 7 cs with no change in HER3 post-CTNA (HER3 flat), 4 had MET expression increased. Interestingly, although the pre-NACT IGF-1R expression was a strong predictor of pCR (p = 0.028, SABCS 2012), no significant changes in this kinase expression were observed in the RT, compared to the pre-NACT levels. Most RT had low IGF-1R scores ( The density of TIL post-NACT correlated principally with the% of tumor mass (TM) reduction. Among the 7 pts with average reduction of 20%, there was only 1 cs with a good InSitu Immune Response (ISIR: dense TIL, with CD8+/FOXP3+ > 1.2). On the contrary, among the 9 pts with average TM reduction of 90%, 8 demonstrated a good ISIR. Conclusion: The results indicate that HER3 and MET play significant roles in development of TNBC resistance to the anti-EGFR agents. Those molecules seem to drive 2 different resistance pathways in TNBC, as it has been shown in other malignancies. As several anti-HER3 or anti-MET drugs are nowadays available, we find very important investigating the expression of HER3 and MET in each TNBC pt pre- and post-NACT, in order to rapidly detect and combat the resistance. The ISIR-stimulating agents may bring an additional therapeutic benefit to those patients. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-08-07.

Abstract P3-06-20: Is it possible to predict the efficacy of a combination of Panitumumab plus FEC 100 followed by docetaxel (T) for patients with triple negative breast cancer (TNBC)? Final biomarker results from a phase II neoadjuvant trial.

Background: TNBC is an heterogeneous group of tumors for some of which the Epithelial Growth Factor Receptor pathway (EGFR) may play an important role. We evaluated the efficacy and toxicity of an anti-EGFR antibody (panitumumab) combined with a standard neoadjuvant chemotherapy in order to identify predictive biomarkers of efficacy and target biologically defined subpopulations for potential further development. Methods: Sixty patients with stage II-IIIA disease were prospectively included in this multicentre neoadjuvant study. Systemic therapy (ST) consisted of panitumumab (9 mg/kg q.3 weeks x8) combined with FEC 100 (500/100/500 mg/m 2 q.3 weeks x4) followed by 4 cycles of T (100 mg/m 2 q.3weeks x4). All patients underwent surgery at completion of ST. Paraffin-embedded and frozen samples were systematically collected before and after ST for biologic studies. Patients characteristics are as follows: mean age 50 [27–72]; median tumor size: 40 mm [20–120]; invasive ductal carcinoma: 96.7%; Scarff-Bloom-Richardson Grade III: 71.7%, grade II: 28.3%. Complete pathological response (pCR) rate was 52.3% [95% IC: 37.3–67.5] (Sataloff9s classification) and 46.7% [95% IC: 31.6–61.4](Chevallier9s classification). Conservative surgery was performed in 88% of cases. Skin toxicity was the main side-effect: Cutaneous toxicity grade IV: 5%, grade III: 30%, grade II: 20%. Neutropenia grade IV: 27%; febrile neutropenia: 5%. Infection: 0%. Hand-foot syndrome grade III: 3.3%. Ungueal toxicity grade III: 1.6%, grade II: 20%. Results: We performed a ROC curve to identify the best cut-off value for KI-67, EGFR, cytokeratin 5–6 and p53 in order to predict a pCR. Tumors with more than 40% of positive cells for KI-67 and tumors with a score for EGFR greater than 70 tend to be associated with pCR according to Chevallier9s classification (p = 0.06). No predictive value was identified for Cytokeratin 5–6 and p53 (p = 0.61 and p = 0.27, respectively). Immunohistochemistry results show that two thirds of tumors have more than 40% of positive cells for KI-67 and that two thirds of tumors present a score for EGFR greater than 70. About half of the tumors express cytokeratin 5–6 and p53 (cut off: 1%). Chi-squared tests were performed to assess relations between cutaneous toxicities and pCR. The cutaneous toxicities were not predictive of pCR (p = 0.94) and no correlations were found with KI-67, EGFR, Cytokeratin 5–6 and p53. In terms of BRCA1 and BRCA2 status, 35 tumors were analysed so far: BRCA1: 6 mutations (17%); BRCA2 (30 patients): 1 mutation (3.3%). Conclusions: These results suggest the possibility to identify a subpopulation with high probability of pCR (KI-67 > 40%, EGFR score > 70). Further biological studies are ongoing and will be presented at the meeting, including EGFR polymorphisms, C-met, ALDH1, pCadherine and PTEN. This will help us further define subpopulations of TNBC patients, potential targets for antiEGFR development. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-06-20.