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Background In Western countries, ovarian cancer (OC) still represents the leading cause of gynecological cancer-related deaths, despite the remarkable gains in therapeutical options. Novel biomarkers of early diagnosis, prognosis definition and prediction of treatment outcomes are of pivotal importance. Prior studies have shown the potentials of micro-ribonucleic acids (miRNAs) as biomarkers for OC and other cancers. Methods We focused on the prognostic and/or predictive potential of miRNAs in OC by conducting a comprehensive array profiling of miRNA expression levels in ovarian tissue samples from 17 non-neoplastic controls, and 60 tumor samples from OC patients treated at the Regina Elena National Cancer Institute (IRE). A set of 54 miRNAs with differential expression in tumor versus normal samples (T/N-deregulated) was identified in the IRE cohort and validated against data from the Cancer Genoma Atlas (TCGA) related to 563 OC patients and 8 non-neoplastic controls. The prognostic/predictive role of the selected 54 biomarkers was tested in reference to survival endpoints and platinum resistance (P-res). Results In the IRE cohort, downregulation of the 2 miRNA-signature including miR-99a-5p and miR-320a held a negative prognostic relevance, while upregulation of miR-224-5p was predictive of less favorable event free survival (EFS) and P-res. Data from the TCGA showed that downregulation of 5 miRNAs, i.e., miR-150, miR-30d, miR-342, miR-424, and miR-502, was associated with more favorable EFS and overall survival outcomes, while miR-200a upregulation was predictive of P-res. The 9 miRNAs globally identified were all included into a single biologic signature, which was tested in enrichment analysis using predicted/validated miRNA target genes, followed by network representation of the miRNA-mRNA interactions. Conclusions Specific dysregulated microRNA sets in tumor tissue showed predictive/prognostic value in OC, and resulted in a promising biological signature for this disease.

Metronomic chemotherapy (mCHT) refers to the minimum biologically effective dose of a chemotherapy agent given as a continuous dosing regimen, with no prolonged drug-free breaks, that leads to antitumor activity. Aim of the present study is to describe the use of mCHT in a retrospective cohort of metastatic breast cancer (MBC) patients in order to collect data regarding the different types and regimens of drugs employed, their efficacy and safety. Between January 2011 and December 2016, data of 584 metastatic breast cancer patients treated with mCHT were collected. The use of VRL-based regimens increased during the time of observation (2011: 16.8% - 2016: 29.8%), as well as CTX-based ones (2011: 17.1% - 2016: 25.6%), whereas CAPE-based and MTX-based regimens remained stable. In the 1st-line setting, the highest ORR and DCR were observed for VRL-based regimens (single agent: 44% and 88%; combination: 36.7% and 82.4%, respectively). Assuming VRL-single agent as the referee treatment (median PFS: 7.2 months, 95% CI: 5.3–10.3), the longest median PFS were observed in VRL-combination regimens (9.5, 95%CI 88.8–11.3, HR = 0.72) and in CAPE-single agent (10.7, 95%CI 8.3–15.8, HR = 0.70). The VICTOR-6 study provides new data coming from the real-life setting, by adding new information regarding the use of mCHT as an option of treatment for MBC patients.

Breast cancer (BC) is a complex disease with primary or acquired incurability characteristics in a significant part of patients. Immunotherapeutical agents represent an emerging option for breast cancer treatment, including the human epidermal growth factor 2 positive (HER2+) subtype. The immune system holds the ability to spontaneously implement a defensive response against HER2+ BC cells through complex mechanisms which can be exploited to modulate this response for obtaining a clinical benefit. Initial immune system modulating strategies consisted mostly in vaccine therapies, which are still being investigated and improved. However, the entrance of trastuzumab into the scenery of HER2+ BC treatment was the real game changing event, which embodied a dominant immune-mediated mechanism. More recently, the advent of the immune checkpoint inhibitors has caused a new paradigm shift for immuno-oncology, with promising initial results also for HER2+ BC. Breast cancer has been traditionally considered poorly immunogenic, being characterized by relatively low tumor mutation burden (TMB). Nevertheless, recent evidence has revealed high tumor infiltrating lymphocytes (TILs) and programmed cell death-ligand 1 (PD-L1) expression in a considerable proportion of HER2+ BC patients. This may translate into a higher potential to elicit anti-cancer response and, therefore, wider possibilities for the use and implementation of immunotherapy in this subset of BC patients. We are herein presenting and critically discussing the most representative evidence concerning immunotherapy in HER2+ BC cancer, both singularly and in combination with therapeutic agents acting throughout HER2-block, immune checkpoint inhibition and anti-cancer vaccines. The reader will be also provided with hints concerning potential future projection of the most promising immutherapeutic agents and approaches for the disease of interest.

Background: Despite the sequential E therapy is recognized as the preferred approach for HR+/HER2- MBC, no data from clinical trials support the choice between the different sequential strategies. Methods: In this retrospective study descriptive statistics are reported using the median (Interquartile range, IQR) or frequency. Progression Free Survival (PFS) curves were estimated with the Kaplan-Meier method and compared with the log-rank test. Analysis were performed by SPSS version 21.0 (SPSS Inc., Chicago, IL). Results: From January 2006 to December 2017, 240 patients (pts) with HR+/HER2- MBC receiving at least two consecutive E therapies as first approach were selected from 12 italian cancer centers. The median age at the time of metastasis onset was 63.5 (IQR: 55-72.5) years; 184 (76.7%) pts were in menopausal status; 38 (16%) had de novo stage IV disease and the remaining 202 (84%) had recurrent BC with a median time of 78 months (5-396 months). At the beginning of MBC diagnosis, 148 (62%) pts had a single site of distant disease, 108 (45%) of whom had bone only disease and 45 (18.8%) presented visceral involvement too. The aromatase inhibitor (AI) was chosen as I-line therapy in 146 (60.9%) pts, followed by Fulvestrant (F) in 62 (25.8%) pts; the alternative I-line options were everolimus-exemestane (Eve-Exe), tamoxifene (T), Palbociclib (P)+AI and F+AI in 13 (5.4%), 14 (5.8%), 1 (0.4%) and 4 (1.7%) pts, respectively. The most favourite II-line option resulted F for 111 (46.2%) pts while the Eve-Exe combination was chosen in 70 (29.2%) pts, AI in 30 (12.5%) pts; T, AI+F, P+F and antiprogestincwere administered in 4 (1.7%), 4 (1.7%), 19 (7.9%) and 2 (0.8%) pts, respectively. For I and II-line, the AI followed by F (40%) and F followed by Eve-Exe (18%) were the most common sequential therapeutic approaches; the several alternative options were scanty used (in less than 10%). The median Progression-Free Survival (PFS) from first and second-line E therapies resulted 15.7 (95% CI 13.3-18.1) and 10.3 months (95% CI 8.7-11.9), respectively. Among 194 pts with disease progression after second-line E therapy, 87 (44.8%) received further E therapies with a median PFS 9.4 months (95% CI 7.9-10.9). The remaining 70 (29.2%) pts was treated with palliative chemotherapy. Interestingly, the median Overall Survival (OS) was even longer for pts receiving more lines of E therapies compared to the group with earlier introduction of chemotherapy (204.3 vs 92.8; p=0.007). Finally, in the subgroup analyses a longer PFS benefit was observed in pts with disease recurrence over 12 months from initial diagnosis (38.1 vs 30.3 months p=0.04) and limited sites of disease involvement at the time of MBC diagnosis (37.6 vs 28.3 months, p=0.03) Conclusions: The sequential use in first and second-line setting of E therapies for HR+/HER2- MBC improves median PFS up to 32.3 months. According to real practice experience the optimal sequences could be AIs followed by F and F followed by Eve-Exe. A role for these compounds should be redefined in the light of recently introduction of CDK 4/6 inhibitors in combination with AIs or F for the first or later lines. Citation Format: Fabi A, Giannarelli D, Botticelli A, Scagnoli S, Pellegrino A, Fabbri A, Corsi D, Magri V, Pizzuti L, Paris I, Bruni V, Pace R, Lanzetta G, Stani S, Moscetti L, Marchetti P, Piesco G, Cognetti F, Rossi V. SEQUERPLUS: A multicenter real practice observational study investigating the endocrine-based (E) therapies sequential approach in hormonal receptor positive (HR+) HER2 negative (-) metastatic breast cancer (MBC) [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 P4-13-07.

Immune checkpoint inhibitors have revolutionized treatment and outcome of melanoma and many other solid malignancies including non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC). Unfortunately, only a minority of patients have a long-term benefit, while the remaining demonstrate primary or acquired resistance. Recently, it has been demonstrated that the prevalence of programmed death-ligand 1 (PD-L1) and tumor-infiltrating lymphocytes (TILs) varies based on the anatomical site of metastases. In particular, liver seems to have more immunosuppressive microenvironment while both the presence of lymph nodal disease and lung metastases seem to have the highest prevalence of PD-L1 and TILs. The aim of the present study is to investigate the possible role of site of metastases as a predictive factor for response or resistance to immunotherapy in several types of cancer. In this multicenter retrospective study, we enrolled patients with metastatic NSCLC, melanoma, RCC, urothelial, merkel carcinoma, and colon cancer who received immunotherapy from April 2015 to August 2019. Major clinicopathological parameters were retrieved and correlated with patients&rsquo, survival outcomes in order to assess their prognostic value and build a useful tool to assist in the decision-making process. A total of 291 patients were included in this study. One hundred eighty-seven (64%) patients were male and 104 (36%) female. The tumor histology was squamous NSCLC in 56 (19%) patients, non-squamous NSCLC in 99 (34%) patients, melanoma in 101 (35%) patients, RCC in 28 (10%) patients, and other tumors in the remaining 7 (2%) patients. The number of metastatic sites was 1 in 103 patients (35%), 2 in 104 patients (36%) and 3 in 84 patients (29%). Out of 183 valuable patients, the entity of response was complete response (CR), partial response (PR), stable disease (SD), and progression disease (PD) in 15, 53, 31, and 79 patients, respectively. Using an univariate analysis (UVA), tumor burden (p = 0.0004), the presence of liver (p = 0.0009), bone (p = 0.0016), brain metastases (p &lt, 0.0001), the other metastatic sites (p = 0.0375), the number of metastatic sites (p = 0.0039), the histology (p = 0.0034), the upfront use of immunotherapy (p = 0.0032), and Eastern Cooperative Oncology Group (ECOG) Perfomance status (PS) &ge, 1 (p &lt, 0.0001) were significantly associated with poor overall survival (OS). Using a multivariate analysis (MVA) the presence of liver (p = 0.0105) and brain (p = 0.0026) metastases, the NSCLC diagnosis (p &lt, 0.0001) and the ECOG PS (p &lt, 0.0001) resulted as significant prognostic factors of survival. Regarding the progression free survival (PFS), using a UVA of the tumor burden (p = 0.0004), bone (p = 0.0098) and brain (p = 0.0038) metastases, the presence of other metastatic sites (p = 0.0063), the number of metastatic sites (p = 0.0007), the histology (p = 0.0007), the use of immunotherapy as first line (p = 0.0031), and the ECOG PS &ge, 1 (p &le, 0.0001) were associated with a lower PFS rate. Using an MVA, the presence of brain (p = 0.0088) and liver metastases (p = 0.024) and the ECOG PS (p &lt, 0.0001) resulted as predictors of poor PFS. Our study suggests that the site of metastases could have a role as prognostic and predictive factor in patients treated with immunotherapy. Indeed, regardless of the histology, the presence of liver and brain metastases was associated with a shorter PFS and OS, but these results must be confirmed in further studies. In this context, a deep characterization of microenvironment could be crucial to prepare patients through novel strategies with combination or sequential immunotherapy in order to improve treatment response.

We analyzed data from 738 HER2‐positive metastatic breast cancer (mbc) patients treated with pertuzumab‐based regimens and/or T‐DM1 at 45 Italian centers. Outcomes were explored in relation to tumor subtype assessed by immunohistochemistry (IHC). The median progression‐free survival at first‐line (mPFS1) was 12 months. Pertuzumab as first‐line conferred longer mPFS1 compared to other first‐line treatments (16 vs. 9 months, p = 0.0001), regardless of IHC subtype. Median PFS in second‐line (mPFS2) was 7 months, with no difference by IHC subtype, but it was more favorable with T‐DM1 compared to other agents (7 vs. 6 months, p = 0.03). There was no PFS2 gain in patients with tumors expressing both hormonal receptors (HRs; p = 0.17), while a trend emerged for tumors with one HR (p = 0.05). Conversely, PFS2 gain was significant in HRs‐negative tumors (p = 0.04). Median overall survival (mOS) was 74 months, with no significant differences by IHC subtypes. Survival rates at 2 and 3 years in patients treated with T‐DM1 in second‐line after pertuzumab were significantly lower compared to pertuzumab‐naïve patients (p = 0.01). When analyzed by IHC subtype, the outcome was confirmed if both HRs or no HRs were expressed (p = 0.02 and p = 0.006, respectively). Our results confirm that HRs expression impacts the clinical behavior and novel treatment‐related outcomes of HER2‐positive tumors when treatment sequences are considered. Moreover, multivariate analysis showed that HRs expression had no effect on PFS and OS. Further studies are warranted to confirm our findings and clarify the interplay between HER2 and estrogen receptor pathways in HER2‐positive (mbc) patients., What's new? About half of breast cancers positive for human epidermal growth factor (HER2) also express hormone receptors but the impact of hormone receptor status on the success of HER2‐directed treatments is not fully explored. Here the authors retrospectively assessed tumor behavior and treatment outcomes in 738 women with HER2+ metastatic breast cancer treated with new generation anti‐HER2 agents. Distinct hormone receptor expression patterns significantly affected the progression free and overall survival, justifying further studies to define optimal treatment regimens and the interplay between hormone receptor and HER2 signaling.

Immune checkpoint inhibitors (ICIs) have demonstrated significant overall survival (OS) benefit in lung adenocarcinoma (LUAD). Nevertheless, a remarkable interpatient heterogeneity characterizes immunotherapy efficacy, regardless of programmed death-ligand 1 (PD-L1) expression and tumor mutational burden (TMB). KEAP1 mutations are associated with shorter survival in LUAD patients receiving chemotherapy. We hypothesized that the pattern of KEAP1 co-mutations and mutual exclusivity may identify LUAD patients unresponsive to immunotherapy.KEAP1 mutational co-occurrences and somatic interactions were studied in the whole MSKCC LUAD dataset. The impact of coexisting alterations on survival outcomes in ICI-treated LUAD patients was verified in the randomized phase II/III POPLAR/OAK trials (blood-based sequencing, bNGS cohort, N = 253). Three tissue-based sequencing studies (Rome, MSKCC and DFCI) were used for independent validation (tNGS cohort, N = 289). Immunogenomic features were analyzed using The Cancer Genome Atlas (TCGA) LUAD study.On the basis of KEAP1 mutational co-occurrences, we identified four genes potentially associated with reduced efficacy of immunotherapy (KEAP1, PBRM1, SMARCA4 and STK11). Independent of the nature of co-occurring alterations, tumors with coexisting mutations (CoMut) had inferior survival as compared with single-mutant (SM) and wild-type (WT) tumors (bNGS cohort: CoMut versus SM log-rank P = 0.048, CoMut versus WT log-rank P0.001; tNGS cohort: CoMut versus SM log-rank P = 0.037, CoMut versus WT log-rank P = 0.006). The CoMut subset harbored higher TMB than the WT disease and the adverse significance of coexisting alterations was maintained in LUAD with high TMB. Significant immunogenomic differences were observed between the CoMut and WT groups in terms of core immune signatures, T-cell receptor repertoire, T helper cell signatures and immunomodulatory genes.This study indicates that coexisting alterations in a limited set of genes characterize a subset of LUAD unresponsive to immunotherapy and with high TMB. An immune-cold microenvironment may account for the clinical course of the disease.

Purpose Diarrhea in relation to the lapatinib–capecitabine regimen is a common and debilitating side effect which may interfere with optimal treatment delivery. We performed a post hoc analysis in human epidermal growth factor receptor 2-positive advanced breast cancer patients treated with a modified schedule in its administration, aimed primarily to evaluate grade (G) ≥2 diarrhea incidence and, secondarily, treatment efficacy. Patients and methods Treatment schedule consisted of lapatinib 1,250 mg daily for the first 10 days, then in combination with capecitabine, 2,000 mg/m2, starting day 11 for the first cycle, and thereafter from day 8, for 14 days of a 21-day cycle, in 3 daily administrations. Lapatinib was dissolved in water, and cholestyramine was continuously given twice a day. Results Among 38 patients treated and analyzed, the incidence of G ≥ 2 diarrhea was 13.2 %. In 28 patients diarrhea was not observed, while G1–2 diarrhea was reported in 9 (23.7 %) patients; a single episode of G3 diarrhea was observed in 1 (2.6 %) patient. Overall response rate was 34.2 %, clinical benefit 55.3 %, and median progression-free survival 10 months. Conclusion The results of the present post hoc analysis are very encouraging, both in terms of tolerability and treatment efficacy, and all data compare favorably with previous reports of “conventional” administration of the lapatinib–capecitabine regimen.

Purpose Recurrences and deaths are known to occur, even if less frequently, in small, node-negative breast cancer patients, and decision on adjuvant treatments remains controversial. In the present analysis, we evaluate recurrence risk in patients with pT1 a, b, c, node-negative, breast cancer, accordingly with some prognostic biological factors. Methods We retrospectively evaluated 900 node-negative patients (pT1a, b, c) surgery treated between 2000 and 2009 in four Italian oncologic centers. We defined 3 different cohorts: ER positive (ER+); Her-2 positive (Her-2+); and triple negative (TN). Results pT1a was seen in 7.6% of patients, 37.7 % pT1b, 54.8 % pT1c. Concerning the 3 different cohorts, 58.2 % were ER+; 10.8 % were Her-2+; 8.2 % were TN. Overall, chemotherapy was given to 3.0 %, 27.2 %, 69.8 % of pT1a, b, c, respectively, and to 22.7 %, 58.8 %, 68.9 % of ER+, Her-2+, TN subgroups. At a median follow-up of 67 months, 5-year DFS was 96.3 %, 89.2 %, 89.4 % in pT1a, b, c, respectively (100 %, 93.6 %, 89.8 % in ER+; 100 %, 78.7 %, 85.0 % in Her-2+; 100 %, 76.8 %, 85.2 % in TN) (p = ns). At multivariate analysis, histologic grade and Ki-67 resulted independent prognostic factors. Overall, 5-year OS was 98 %, without differences among pT1a, b, c, or among the 3 cohorts. Conclusions Overall, 5-year DFS was very favorable in this series of small, node-negative breast cancers, but Her-2+ and TN cohorts have a higher recurrence rate than ER+ cohort (p

Objective: To evaluate two docetaxel-based regimens as first-line treatment in advanced breast cancer patients. Methods: Patients were randomly assigned to docetaxel/gemcitabine (arm A: docetaxel 75 mg/m2 on day 1, gemcitabine 1,000 mg/m2 on days 1 and 8) or docetaxel/capecitabine (arm B: docetaxel 75 mg/m2 on day 1, capecitabine 1,250 mg/m2 twice daily on days 1–14); both chemotherapy regimens were repeated every 21 days. The primary objective of the study was to evaluate the response rate. Results: Seventy-two patients were enrolled (36 each in arms A and B). Responses according to intention-to-treat analysis were as follows: arm A, 41.7% [95% confidence interval (CI) 25.6–57.8]; arm B, 38.9% (95% CI 23–54.8). Median progression-free survival was 10.9 months (95% CI 8.1–13.7) in arm A and 10 months (95% CI 8.8–11.2) in arm B. Overall survival was 26 months (95% CI 22.0–30.0) in arm A and 28 months (95% CI 23.4–32.6) in arm B. Both treatments were well tolerated; myelosuppression was the dose-limiting toxicity, with grade 3–4 neutropenia in 13.8 and 19.4% of the patients in arms A and B, respectively. No relevant differences in other toxicities were observed in the two arms, except for diarrhea (13.9%) and hand-foot syndrome (11.1%), which occurred only in arm B. Conclusions: Both regimens were active and well tolerated in advanced breast cancer.

Aim: HER2-positive (HER2+) breast cancer (BC) is a heterogeneous disease, with a minority of patients presenting an excellent prognosis. Recent findings suggest that the efficacy of HER2-directed therapy may differ according to hormone receptor (HR) status, and this raised the question if HR status defines different subtypes of HER2+ BC. We conducted a multicenter analysis of HER2+ early BC patients to determine relapse free survival (RFS) and overall survival (OS), and to investigate the role of HR in outcome. Methods: We retrospectively enrolled HER2+ (IHC 3+ or 2+ amplified) early BC patients treated with adjuvant chemotherapy with or without trastuzumab (T) in 7 Italian oncologic centres until December 2011. A review of clinical and treatment data was carried out for analysis. Results: 769 chemotherapy-treated HER2+ early BC patients have been analysed and divided into two groups, T-untreated (N = 304, cohort A), and T-treated (N = 465, cohort B). Overall, the median follow-up was 68 months (range, 1-171). Three-year RFS for cohort A was 81.3%, whereas it was 92% for cohort B (p Conclusions: Although the benefit given by addition of T to adjuvant chemotherapy is clear in all subgroups analyzed, our data suggest the existence of a subset of TP BC, characterized by high levels of ER expression, that is driven both by HER2 and ER signalling, with a biological behaviour similar to ER-positive, HER2-negative BC. Disclosure: All authors have declared no conflicts of interest.

e11542 Background: This is a multicenter observational study with the aim to evaluate predictive factors of response to NAT in TNBC pts. Methods: 196 TNBC pts treated with NAT were enrolled from 7 ...

Aim: Eribulin (E) is a non taxane microtubule inhibitor indicated for treatment of MBC. To evaluate its tolerability, impact on Quality of Life (QoL) and symptoms improvement in MBC pts, from April 2012, we conducted a prospective observational study. Methods: Pts pretreated with anthracyclines (A) and taxanes (T) who have received 2 CHT lines for MBC, scheduled to be treated with E, were considered eligible. Pts completed ESAS at each cycle and FACT-B every 2 cycles. Outcome of QoL included the FACT-B total score, FACT-General (FACT-G) score and the Trial Outcome Index (TOI) score. Paired data were analyzed with non parametric Wilcoxon, McNemar and Friedman tests. Kaplan-Meier method was used for survival calculation. Results: 50 consecutive MBC pts entered the study. Median age 64 (range 31-85), 83% of pts had PS (ECOG) 0-1, 23% had triple-negative MBC, 75% ER/PgR positive and 63% HER2 positive. All pts were pretreated with A and T, 19 (76%) also with capecitabine. Median E cycles administered was 5 (range 1-17), 31% of pts received more than 6 cycles. Main side effects G2-G3 were: 42% alopecia, 38% asthenia, 15% peripheral neuropathy,16% neutropenia. At a median follow-up of 7 months (mo) (range 2-21), 17% (CI 95% 6-28) of pts achieved partial response (PR), 39% stable disease (SD) and 44% progressive disease; disease control rate (PR + SD ≥ 6 mo) occurred in 40% of pts. Median PFS is 4 mo (95% CI, 3-5); median OS is 9 mo (CI 95% 2-16); 1-yr overall survival is 49%. Items in ESAS which at baseline had score more than >5 in at least 25% of pts were anorexia, drowsy, anxiety, loss of activity and wellbeing; all these symptoms not worsened in subsequent evaluations. Data of ESAS and QoL are reported in table. ESAS and QoL assessments were adjusted for response, PS and age. Conclusions: Our results shows that treatment with E is associated with a good maintenance of QoL and ESAS scores with expected and manageable toxicities. Basal median score(range) Final median score (range) P value ESAS 30 (3-63) 28 (3-60) 0.91 FACT- B 79 (55-117) 81(45-119) 0.36 FACT-G 59 (40-88) 60 (30-93) 0.98 TOI 53 (33-78) 52 (29-78) 0.23 Disclosure: All authors have declared no conflicts of interest.

Background PST with taxanes, anthracycline-containing regimens and T showed a high percentage of pathologic complete response (pCR); T administered concurrently with chemotherapy is more effective, but the combination with anthracyclines may be at risk of cardiotoxicity. The present study evaluates efficacy and toxicity of T administered concurrently with a sequential regimen of D followed by EC in neoadjuvant setting. Materials and methods This phase II single stage trial is enrolling pts with cT2-T4, N0-2, M0, Her-2 positive (IHC 3+ or 2+ amplified) breast cancer. A core biopsy is required prior treatment start to evaluate hormonal receptors, Ki67, topoisomerase II, Her-2, with re-evaluation of these parameters, whenever possible, at definite surgery. LVEF is evaluated before and during treatment. Blood samples are collected at baseline for evaluation of 9 genetic polymorphisms related to higher risk of developing cardiac toxicity. We are quantitatively evaluating gene copy number by multiple ligand probe amplification (MLPA), PTEN, p-Akt, p-MAPK, and PIK3CA mutations. Pts receive 4 cycles of D (100mg/m2) plus T (loading dose 8mg/kg followed by 6mg/kg), followed by 4 cycles of EC (120/600mg/m2) plus T, every 3 weeks. Definite surgery is planned at the end of PST, and standard radiotherapy and hormonal adjuvant treatment in case of positive hormonal receptors are given; adjuvant T is given for 6 months. The primary objective of the trial is pCR (absence of invasive tumor cells in the breast and axilla); secondary objectives are cardiac safety, toxicity, disease-free survival. The planned sample size is 42 pts. Results To date, 29 pts have been enrolled; median age is 45 years, pre/postmenopausal 22/7, ER and/or PgR positive in 16 pts. 27 pts are evaluable for pathological response: we observed 20 pCR (74%, 95%C.I, 57.5-90.6). Grade 3-4 neutropenia was the most frequent toxicity, encountered in 75% of the pts, other toxicities were mild to moderate. No clinical cardiotoxicity was observed. Conclusions At preliminary analysis, PST with sequential administration of D followed by EC, given concurrently with T, appears to be very active and safe in stage II-III breast cancer pts. Disclosure All authors have declared no conflicts of interest.