A Goncalves

Neurocognitive function impairment after whole brain radiotherapy for brain metastases: actual assessment

Whole brain radiation therapy (WBRT) is an effective treatment in brain metastases and, when combined with local treatments such as surgery and stereotactic radiosurgery, gives the best brain control. Nonetheless, WBRT is often omitted after local treatment due to its potential late neurocognitive effects. Publications on radiation-induced neurotoxicity have used different assessment methods, time to assessment, and definition of impairment, thus making it difficult to accurately assess the rate and magnitude of the neurocognitive decline that can be expected. In this context, and to help therapeutic decision making, we have conducted this literature review, with the aim of providing an average incidence, magnitude and time to occurrence of radio-induced neurocognitive decline. We reviewed all English language published articles on neurocognitive effects of WBRT for newly diagnosed brain metastases or with a preventive goal in adult patients, with any methodology (MMSE, battery of neurcognitive tests) with which baseline status was provided. We concluded that neurocognitive decline is predominant at 4 months, strongly dependant on brain metastases control, partially solved at later time, graded 1 on a SOMA-LENT scale (only 8% of grade 2 and more), insufficiently assessed in long-term survivors, thus justifying all efforts to reduce it through irradiation modulation.

Circulating tumor cells and brain metastasis outcome in patients with HER2-positive breast cancer: the LANDSCAPE trial

BACKGROUND Decrease of circulating tumor cells (CTC) during treatment is an independent prognostic factor in metastatic breast cancer (MBC). We specifically evaluated the impact of CTC on brain metastasis outcome. METHODS HER2-positive MBC with brain metastasis not previously treated with whole-brain radiotherapy received first-line combination of lapatinib and capecitabine in a phase II study. CTC were detected at baseline and day 21 (CellSearch). RESULTS Median follow-up of the 44 analyzed patients was 21.2 months. The central nervous system objective response (CNS-OR) rate was 66%. At baseline, 20 of 41 assessable patients for CTC (49%) had ≥1 CTC (range 1-301, median 3) and 9 (22%) had ≥5 CTC. At day 21, 7 of 38 patients (18%) had ≥1 CTC (P = 0.006, versus baseline), and CTC had disappeared in 11 patients. CNS-OR rate was significantly higher in patients with no CTC at day 21 [25 of 31 (80%) versus 2 of 7 (29%), P = 0.01]. The 1-year overall survival rate was 83.9% in patients with no CTC at day 21 versus 42.9% in patients with ≥1 CTC (P = 0.02). CONCLUSIONS This is the first report showing a correlation between CNS metastasis response, outcome and early CTC clearance under targeted treatment of HER2+ MBC. CLINICAL TRIALS NUMBER NCT00967031.

Rationale for the Use of Upfront Whole Brain Irradiation in Patients with Brain Metastases from Breast Cancer

Breast cancer is the second most common cause of brain metastases and deserves particular attention in relation to current prolonged survival of patients with metastatic disease. Advances in both systemic therapies and brain local treatments (surgery and stereotactic radiosurgery) have led to a reappraisal of brain metastases management. With respect to this, the literature review presented here was conducted in an attempt to collect medical evidence-based data on the use of whole-brain radiotherapy for the treatment of brain metastases from breast cancer. In addition, this study discusses here the potential differences in outcomes between patients with brain metastases from breast cancer and those with brain metastases from other primary malignancies and the potential implications within a treatment strategy.

Abstract P3-15-04: A French prospective pilot study to identify dihydropyrimidine dehydrogenase (DPD) deficiency in breast cancer patients receiving capecitabine

Background: Health Authorities point out that DPD deficiency confers a significant risk of major toxicity for patients receiving capecitabine. Identification of at-risk patients is thus of major concern. This multicentric prospective study of the French GPCO group (Groupe de Pharmacologie Clinique Oncologique, Unicancer) evaluated the sensitivity, specificity and predictive values of DPD phenotyping and genotyping to predict severe cap-related toxixity in metastatic breast cancer patients. Methods: 303 patients were included between February 2009 and February 2011 (15 institutions). Eighty-eight% received capecitabine as monotherapy, 28% were treated as first line (mean dose at 1 st cycle 1957 mg/m 2 /d). Pre-treatment uracil (U, physiological DPD substrate) plasma concentration was measured in 286 patients (HPLC assay). DPD genotyping (IVS14+1G>A, 2846A>T, 1679T>G, 464T>A) was performed on 281 patients. Severe toxicity (G3-4 CTCAE v3 criteria) was measured over cycles 1-2. Results: Grade 3-4 toxicity (diarrhea, vomiting, hematoxicity, hand-foot syndrome) has been observed in 19.6% of patients (one toxic death). A marked trend for higher U concentrations has been noted in patients developing severe toxicity vs those who didn9t (median 12.7 ng/ml (Q1-Q3 9-17) vs median 10.2 ng/ml (range 8-13), respectively, p = 0.014). However, ROC curve has showed that this difference was too small for use as a reliable toxicity predictor. The patient with toxic death had an elevated U concentration at 17 ng/ml. Among the 7 patients with a DPD mutation (3 pts IVS14+1, 3 pts 2846A>T, one 1679T>G, all heterozygous), 5 developed severe toxicity (including the toxic death, 2846A>T), one did not, and the last one was not documented. Relative risk for developing severe toxicity was 4.60 in mutated patients vs wild-type patients (95%CI 2.95-7.16, p = 0.001); positive and negative predictive values were 83.3% and 81.9%, respectively; specificity was 99.5% and sensitivity was 9.8%. Conclusions : Breast cancer patients harbouring a DPD variant allele are at risk to develop severe, up to lethal, capecitabine-related toxicity. Pre-treatment U measurement remains to be more firmly established as a reliable predictor of capecitabine toxicity. These observations are of major interest for breast cancer patients candidate for capecitabine therapy. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-15-04.

Abstract OT2-3-05: AVASTEM: a phase II randomized trial evaluating anti-cancer stem cell activity of pre-operative bevacizumab and chemotherapy in breast cancer

Background: Bevacizumab (BEV) in combination with chemotherapy (CT) improved response rate and progression-free survival without detectable impact on overall survival (OS) in metastatic breast cancer (BC). BC contains population of cells that display stem-cell properties. These cancer stem cells (CSC) are known to be relatively insensitive to cytotoxic chemotherapies and might play a major role in treatment resistance and relapse. Complex interactions exist between CSC and angiogenesis: whereas CSC may secrete VEGF and pro-angiogenic factors and may stay in VEGF-dependant vascular niche, recent preclinical data indicate that antiangiogenics may increase breast CSC population via hypoxia. CSC proportion may be monitored in human BC using IHC staining of ALDH1. AVASTEM trial was designed to evaluate whether the addition of BEV to conventional CT alters the proportion of CSC in BC patients receiving neo-adjuvant (NA) CT. Trial design: In this open-label phase II randomized study, patients are stratified by HER2 status and randomized 1:2 to receive NACT: – arm A (experimental): FEC100 (5FU 500 mg/m2, Epirubicin 100 mg/m2, Cyclophosphamide 500 mg/m2) + BEV (15 mg/kg, 3-weekly) × 4 followed by Docetaxel (100 mg/m2) + BEV +/− trastuzumab (T, 8 mg/kg and then 6 mg/kg, 3-weekly) if HER2-positive, × 4 – arm B (control): FEC100 × 4 followed by Docetaxel 100 +/− T if HER2-positive, × 4. Tumor biopsies are required at baseline and after the first 4 cycles of FEC. After NACT, appropriate surgery and radiation therapy are performed, followed by adjuvant T and hormonal therapy, if indicated. Eligibility criteria: - Primary HER2-positive or -negative BC candidate to NACT (inflammatory breast cancer and synchronous metastatic disease are eligible) – Primary BC accessible to initial biopsy – Left ventricular ejection fraction ≥ 55% – Appropriate haematological, liver, renal and coagulation functions Specific aims: – Primary endpoint: to measure the variations of CSC proportion (by measuring the amount of IHC ALDH1-positive cells) in tumor biopsies obtained before C1 and after C4 in patients treated with BEV-based NACT or with NACT alone. – Secondary endpoints: tolerance, pCR, disease-free survival, recurrence-free survival and OS; ancillary studies (CSC characterization by CD44/CD24 IHC staining and evaluation of tumor-initiating properties of fresh tumor cells; CTC counts; contrast-based breast ultra-sonography; transcriptomics and proteomics) Statistical design: The difference between percentage of ALDH1-positive cells after 4 cycles of BEV-based NACT and before treatment will be calculated. In the experimental arm, an equivalence test will be used to validate the hypothesis that the cell percentage does not increase more than 5% during treatment (under the following hypothesis: no difference of expression, difference variability σ = 13, significance level of 0.05, power of 0.8). With the assumption of approximately 20% of missing data, 50 patients will be included in the tested arm. The control arm (n = 25) is needed to confirm CSC increase during conventional CT. Present and target accrual: By May June 2012, 69 patients have been included. A total of 75 patients are to be enrolled. Funded by INCA-PHRC 2009. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr OT2-3-05.

Abstract PD7-06: MAAT: Menses after adjuvant treatment. Prediction of menses recovery after chemotherapy for early breast cancer (BC) by using a nomogram model in UNICANCER PACS04 and PACS05 trials

Purpose:The likelihood of menses recovery (MR) is largely variable in premenopausal patients (pts) receiving adjuvant chemotherapy for BC. Quantifying this probability for each single patient could impact discussion of chemotherapy side effects and better individualize fertility counseling.We performed a pooled analysis from PACS04 and PACS05 randomized trials aiming to develop a nomogram to estimate the probability of menses recovery at 6 and 18 months (mos) after the end of adjuvant chemotherapy (CT) for premenopausal pts with early BC. Patients and Methods: The analyzed population consisted of 1683 pts who were premenopausal and ≤ 50 (out of 4524 enrolled in both trials). In PACS05 node-negative BC pts were randomized to 4 or 6 cycles of FE100C (standard arm); in PACS04 node-positive pts were randomized to 6 cycles of FE100C or 6 cycles of Epirubicin 75mg/m2 and Docetaxel 75 mg/m2 (ED75). Endocrine therapy (ET) (Tamoxifen) x 5 years was mandatory for ER+ BC. Variables significantly associated with MR in the univariate analysis (P Results: Pts9 characteristics were: median age 43 (22-50), median body mass index (BMI) at baseline 22.6 (15.6-54.7), at the end of chemotherapy 22.8 (15.8-58.6). ED75 was administrated to 517 (30.7%), while 802 (47.7%) received 6FE100C, 364 (21.6) 4FE100C. Trastuzumab was given to 122 (7.2%), ET to 1229 (73%) pts. CT-induced amenorrhea was observed in 1407 (83.6%) pts. Factors associated to MR were assessed on 1210 pts (excluding pts who recovered menses during CT or of whom date of recovery was not specified). At a median follow-up of 90 mos, 28.2% (342/1210) of pts had recovered menstrual cycles: 11% (133/1210) at 6 mos and 24.3% (294/1210) at 18 mos. Multivariate analysis showed that younger age, higher BMI at the end of CT, non-alkylating agents and absence of ET were independently associated to MR. Nomogram concordance-index was 0.749 and 0.750 for predicting MR at 6 and 18 mos respectively. A better calibration was observed at 18 mos, comparing nomogram predictions with the actual probability of MR in the 1210 women. Conclusion:Our analysis confirmed the possibility of developing a user-friendly nomogram for predicting menses recovery after adjuvant chemotherapy. As next step, we will externally validate our nomogram on CANTO premenopausal population, one of the biggest national cohorts aiming to assess the long-term impact of cancer treatments toxicities (UNICANCERNCT01993498 - http://etudecanto.org/). Citation Format: Pistilli B, Mazouni C, Zingarello A, Faron M, Saghatchian M, Grynberg M, Spielmann M, Kerbrat P, Roche H, Lorgis V, Bachelot T, Campone M, Levy C, Goncalves A, Lesur A, Veyrat C, Vanlemmens L, Lemonnier J, Delaloge S. MAAT: Menses after adjuvant treatment. Prediction of menses recovery after chemotherapy for early breast cancer (BC) by using a nomogram model in UNICANCER PACS04 and PACS05 trials [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 PD7-06.

Abstract PD8-12: Mutational processes, genome evolution and outcome in metastatic breast cancers

Background: to determine the distribution and evolution of mutational processes in metastatic breast cancers (mBC), together with their clinical relevance Methods: Whole exome sequencing (Hi-Seq, Illumina) and determination of copy number alterations (CNA) (CGH array / SNP6.0) were performed in 240 and 692 metastatic breast cancers respectively. Mutational processes were defined according to Alexandrov (Nature, 2013). Homologous Recombination Deficiency (HRD) was determined by genome wide assessment of loss-of-heteroygosity (LOH) on SNP6.0 (n = 210). Finally, genomic instability was assessed by the % of genome altered assessed by CGH / SNP6.0 Results: Whole exome sequencing showed that HR+/Her2- metastatic breast cancer presented an increased contribution of APOBEC-related signatures, as compared to early breast cancer (TCGA) (58% of the mutations vs 31%, p 200 non-synonymous mutations). This acquisition of an hypermutator genotype was confirmed in five paired primary-metastatic samples. An operational APOBEC-related signature 13 was associated with a poor outcome in a multivariate analysis (HR: 1.75, 95%CI: 1.1-2.7, p = 0.017). High LOH score (HRD) was observed in 30% of HR+/Her2- mBC as compared to 13% of early HR+/Her2- early BC (p Citation Format: Patsouris A, Filleron T, Jacquet A, Goncalves A, Bonnefoi H, Letourneau C, Bachelot T, Jimenez M, Andre F. Mutational processes, genome evolution and outcome in metastatic breast cancers [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 PD8-12.

Abstract PD1-08: High-throughput genome analysis and therapeutic decision for patients with HER2-negative metastatic breast cancer: First feasibility and molecular results of the randomized phase II study SAFIR02 BREAST (UCBG-0105/1304)

Background A genomic-driven therapeutic strategy in metastatic breast cancer (MBC) was recently demonstrated as feasible in the clinical practice, but its actual impact on patient outcome remains elusive. SAFIR02 study is an ongoing national multicentric phase II randomized trial evaluating targeted therapies matching specific genomic alterations (GA) administered as maintenance after objective response and/or stable disease obtained with chemotherapy in HER2-negative MBC patients. This analysis reports on feasibility of the procedure and the rate of identified actionable targets. Methods Eligible MBC patients (PS=0/1, first- or second-line of chemotherapy, HER2-negative/hormone receptor (HR)-negative or endocrine resistant HR-positive; measurable per RECIST 1.1; accessible to tumor biopsy; no bone metastases-only disease, no major organ dysfunction) were subjected to tumor biopsy for genomic analysis (CGH arrays, Affymetrix Cytoscan; NGS, Ion Torrent PGM, AmpliSeq, panel of around 50 genes). Actionable GA were identified and corresponding targeted therapies were proposed by a multidisciplinary tumor board (MTB). Patients received cytotoxic-based treatment at physician9s choice and those with stable or responding disease after 6 to 8 cycles (or at least 4 if stopped for toxicity reason) and targetable GA, were offered randomization between targeted therapy or chemotherapy maintenance until progression or intolerance (main study). Since January 2016, an amendment was made to propose to patients without targetable alteration a randomization between anti-PD-L1 (MEDI4736) or standard chemotherapy maintenance (substudy). Results Between March 2014 and May 2016, 457 patients have been enrolled at 21 centers. Genomic analyses could not be obtained in 107 cases (23%) due to either biopsy failure (n= 40; 9%) or low cellularity (n=67; 14%). Of the 307 patients reviewed by the MTB, 197 (64%) had an actionable GA, including PIK3CA-PIK3CB-PIK3R1 (n=51), FGF4 or FGFR1/2 (n= 42), BRCA1/2 (n=15), AKT1/2/3 (n=13), BRAF/KRAS/NRAS (n=13), HER2/3 (n=10), NF1-FRS2 (n=10), MTOR-RPTOR-TSC2 (n=8), PTEN (n=7), STK11 (n=7), IGF1R (n=7), EGFR (n=5). Therapeutic proposals by MTB included AZD5363 (n=71), AZD4547 (n=42), AZD2014 (n=23), selumetinib (n=23), olaparib (n=16), AZD8931 (n=15), vandetanib (n=5), bicalutamide (n=2). In an exploratory analysis involving 157 patients, the rate of targeted therapy proposal by MTB markedly differed between triple-negative patients (TNBC; 24 of 48, 50%) and HER2-negative/HR-positive patients (92 of 109, 84%; p=6.14. 10-6, Chi-2 test). At the time of the analysis, 85 patients have been randomized (main study, 68; substudy, 17). Causes of randomization failure (n=108) included disease progression (n=45) or death (n=25), non-eligibility criteria (n=27), patient/physician9s decision (n=11). Conclusion A large number of patients had identified targetable GA. Of note, the rate of targeted therapeutic proposal was significantly lower in TNBC than in HER2-negative/HR-positive patients. Rapidly progressing disease may impede ultimate randomization. Citation Format: Goncalves A, Bachelot T, Lusque A, Arnedos M, Campone M, Bieche I, Lacroix L, Pierron G, Dalenc F, Filleron T, Sablin M-P, Jimenez M, Ferrero J-M, Lefeuvre-Plesse C, Bonnefoi H, Attignon V, Soubeyran I, Jezequel P, Commo F, Andre F. High-throughput genome analysis and therapeutic decision for patients with HER2-negative metastatic breast cancer: First feasibility and molecular results of the randomized phase II study SAFIR02 BREAST (UCBG-0105/1304) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr PD1-08.

Abstract P4-13-23: Next-generation sequencing (NGS), array comparative genomic hybridization (aCGH) and patient-derived tumor xenograft (PDX) for precision medicine in advanced breast cancer: A single-center prospective study

Background Genomic-based approaches in advanced breast cancer (ABC) were recently demonstrated as feasible in the clinical practice, but only a limited number of patients were actually treated with targeted therapies matching genomic alterations, with low antitumor activity. We conducted a pilot study to evaluate whether precision medicine using NGS and aCGH could be implemented prospectively at a single center in ABC patients. In addition, we examined whether PDX could be derived from ABC and thus could help inform therapeutic decision. Methods ABC patients accessible to tumor biopsy were prospectively enrolled at the Institut Paoli-Calmettes in the BC-BIO study (ClinicalTrials.gov, NCT01521676). Tumor tissue from locally recurrent or metastatic disease was immediately frozen after dedicated biopsy. Genomic profiling included high-resolution 4x180K aCGH (Agilent Technologies, Massy, France) and DNA sequencing, using a library of 365 cancer candidate genes (HaloPlex target enrichment kit, Agilent technologies, Santa Clara, CA, USA) and MiSeq analyzer (Illumina, San Diego, CA, USA) with 2x150-bp, paired-end at about 300x coverage. In a subset of patients, fresh tumor was implanted orthotopically in humanized cleared fat pads of NSG mice for establishing xenotransplants. Results A total of 34 ABC patients were included, with the following characteristics: median age 54 years (35-77); molecular subtypes: 11 triple-negative (32%), 12 luminal non-HER2 (35%), 4 luminal HER2 (12%), 3 HER2 non-luminal (9%), and 4 unknown (12%); 33 with previous chemotherapy (97%); 22 with previous endocrine treatment (35%); 7 with previous anti-HER2 (21%). Tumor biopsies were obtained from liver (15), skin (6), peritoneum (4), breast (3), node (3), lung (1), pleura (1), and ascitis (1), with a median tumor cellularity of 70% (range 10-90%). aCGH and NGS were available from 34 and 33 patients, respectively. An actionable target was found in 28 patients (82%), corresponding to 66 targets, including 37 mutations (8 in PIK3CA, 7 TP53, 4 ESR1, 2 AKT1, 2 BRCA2, 2 HER2), 22 amplifications (7 for CCND1, 2 CCNE1, 2 FGFR1, 2 IGF1R) and 7 homozygous deletions (3 for PTEN, 2 CDKN2A/B,1 BRCA2, 1 STK11). A targeted therapeutic proposal was possible, either in a clinical trial (N=18, 52%) or using already registered drugs (N=17, 50%). Ten patients actually received a targeted treatment, 1 of them experienced objective response and 1 showed stable disease for more than 6 months. Of 26 patients subjected to mouse implantation, 10 had successful xenografting (6 triple-negative, 2 HER2, 1 luminal non-HER2, 1 subtype non-attributed), with a median time to reach 10 mm of 148 days. These PDX will be used as models to understand the patient9s therapeutic response. Conclusion Precision medicine using high-throughput DNA sequencing and aCGH can be implemented at a single center in the context of clinical practice and may allow direct therapeutic proposal in 1/3 of patients, but antitumor activity was minimal. PDX may be obtained in a significant fraction of patients, especially in triple-negative and HER2 subtypes, and could phenotypically complement genomic data. Citation Format: Goncalves A, Bertucci F, Chaffanet M, Guille A, Garnier S, Adelaide J, Carbuccia N, Brunelle S, Piana G, Cabaud O, Thomassin-Piana J, Paciencia-Gros M, Chereau-Ewald E, Lambaudie E, Sabatier R, Tarpin C, Provansal M, Jalaguier-Coudray A, Extra J-M, Sarran A, Pakradouni J, Viens P, Lopez M, Ginestier C, Charafe-Jauffret E, Birnbaum D. Next-generation sequencing (NGS), array comparative genomic hybridization (aCGH) and patient-derived tumor xenograft (PDX) for precision medicine in advanced breast cancer: A single-center prospective 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 P4-13-23.

Abstract P6-12-08: Serum biomarkers identification using quantitative proteomics in patients with HER2-positive inflammatory breast cancer receiving trastuzumab plus bevacizumab-based chemotherapy (BEVERLY 2 trial)

Background Inflammatory breast cancer (IBC) is a rare but aggressive form of locally advanced breast cancer, the optimal systemic treatment of which is still discussed. Beverly 2 trial was a phase II study evaluating the efficacy and safety of a preoperative regimen associating bevacizumab, trastuzumab, and chemotherapy in 52 patients with non-metastatic HER2-positive IBC, reporting a promising rate of pathological complete response (pCR, 63.5%, 95% CI 49.4–77.5; Pierga et al, Lancet Oncol, 2012). During the study, serum samples were collected at baseline and subjected to proteomic-based approaches to identify circulating biomarkers predictive of treatment response. Methods Baseline serum samples from responsive (pCR, according to Sataloff classification, n = 12) and non-responsive (no pCR, n = 11) patients were subjected to isobaric Tag for Relative and Absolute Quantification (iTRAQ)-based proteomics. Samples were pooled according to pCR and hormone receptor (HR) status, to constitute 4 independent mixes (pCR/HR-positive, pCR/HR-negative, nopCR/HR-positive, nopCR/HR-negative). Each of them underwent immuno-depletion of highly abundant proteins, concentration, reduction, alkylation and tryptic digestion. Then, each mix was fractionated and subjected to iTRAQ identification and quantitation using nano-liquid chromatography (LC) and electrospray ionisation (ESI)-orbitrap tandem mass spectrometry (MS/MS) (LTQ-orbitrap, Thermofisher). Differentially expressed proteins were analysed using IPA (IngenuitySystems) to highlight biological functions and signalling pathways that were most significantly enriched. Results iTRAQ-based measurements identified and quantified a total of 302 serum proteins. Among them, 48 proteins displayed a significant (fold-change > 1.5 and p-value < 0.05) differential expression between pCR and noPCR pts (18 proteins down-regultated and 30 proteins up-regulated in pCR patients), some of them previously described to be involved in breast cancer biology and/or angiogenesis, including : Alpha-1-acid glycoprotein 1, von Willebrand factor, Galectin-3-binding protein, serum amyloid A-1, Apolipoprotein E, Pigment epithelium-derived factor, Corticosteroid-binding globulin (down-regulated proteins in pCR patients); serum amyloid P-component, angiotensinogen, plasma serine protease inhibitor, carbonic anhydrase 1, mannose-binding protein C, hyaluronan-binding protein 2, peroxiredoxin-2, properdin, ADAMTS13, tetranectin, biotinidase, lumican (up-regulated proteins in pCR patients). Proteins with differential expression during treatment were involved in various biological processes, including cell-to-cell signaling and interaction, lipid metabolism, small molecule biochemistry, molecular transport, cellular function and maintenance as well as various canonical pathways such as acute phase response signalling, LXR/RXR activation and coagulation system. Conclusion iTRAQ-based quantitative proteomics identify serum proteins that could predict the therapeutic response to pre-operative trastuzumab plus bevacizumab-based chemotherapy in HER2-positive IBC. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-12-08.