1. COMPARING DISEASE OUTCOME OF WOMEN WITH HORMONE RECEPTOR NEGATIVE/HER2 POSITIVE (HR-/HER2+) OR TRIPLE NEGATIVE (TN) METASTATIC BREAST CANCER (MBC) RECEIVING MULTIPLE LINES OF CHEMOTHERAPY: A MONO-INSTITUTIONAL RETROSPECTIVE ANALYSIS Federico Sottotetti 1, Raffaella Palumbo 1, Alberto Riccardi 2, Emma Pozzi 1, Cristina Teragni 1, Erica Quaquarini 1, Barbara Tagliaferri 1 & Antonio Bernardo 1 1 Departmental Operative Unit of Oncology; Fondazione Salvatore Maugeri-IRCCS, PAVIA – ITALY 2 Dipartimento Terapia Medica, Sezione Oncologia Medica, Università degli Studi di Pavia BACKGROUND RESULTS - SURVIVAL DATA ● Current guidelines recommend HER2 blockade across subsequent chemotherapy (CT) lines to provide effective control of HER2+ MBC, while the benefit deriving from multiple lines in patients with TN disease is uncertain. We sought to evaluate outcome of women affected with HR-/HER2+ or TN disease receiving multiple lines for their MBC, aiming to identify potential prognostic and/or predictive factors for treatment response and disease outcome. ● Triple negative breast cancers (TNBC) are characterized for younger age of onset, unfavorable histopathological features, frequent progression to distant metastasis, particularly visceral, with a shorter median time to relapse and death. Because of the lack of expression of hormonal receptors and HER2, CT remains the only systemic option in the adjuvant and metastatic setting of the disease. ● The choice of therapeutic agents is relatively easy in HER2+subtype, and has been recently enriched by introduction of new effective agents. As for TN disease, the choice of therapeutic agents and their sequence is still difficult due to the lack of “ad hoc” prospective trials. ● To compare outcome of women bearing TNBC to HER2 + disease, during multiple lines of chemotherapy ● To identify potential predictive and/or prognostic factors for treatment response and disease outcome 1.Cardoso F et al. The Breast 2012 2.Isakoff SJ Cancer J 2010 3.Banerji U et al. The Breast 2007 4.Kumar Pal S et al. Breast Cancer Res Treat 2011 5.Vauléon E et al. Cancer Chemother Pharmacol 2009 6.Tacca O et al. Cancer Investigation 2009 7.Thientosapol ES et al. Intern Med J 2013 8.Palumbo et al. Ther Adv Med Oncol 2013 ● A retrospective analysis was performed on 980 women receiving CT for MBC in our Institution between 1992 and 2012 (data collected from the Department database) ● To the purpose of the study we identified 460 patients with ER-/PgR-/HER2+ disease (COHORT A) and TNBC (COHORT B) who had received CT for metastatic disease between February 2004 and January 2011 ● Overall survival (OS) was calculated according to the Kaplan-Meyer method for each CT line, as the time for starting first line CT until death or last follow-up ● Cox proportional hazards model was used to identify factors that could influence OS ● Median follow-up was 65 months (range 21-122), with cut-off data analysis as to March 2013 Overall survival for each CT line months (range) n°of CT lines COHORT ACOHORT B 1 line28.6 (6.8-58.6) 10,2 (2.3-31.2) 2 lines11.8 (5.4-18.6) 6.2 (3.9-9.4) 3 lines9.21 (4.8-11.4) 4.8 (2.8-5.3)  4 lines 6.7 (3.4-9.8) 3.8 (1.9-4.5) Our study of real life clinical practice adds informations in the debated field of the optimal therapeutic strategy in advanced disease, suggesting that multiple lines of CT could provide a benefit also in the subset of patients with unfavorable hystologic features In our experience such a population was identified with women bearing TNBC or HER2 positive/ER negative tumor Among this population, Cohort A exhibited a significantly better OS in comparison to Cohort B, and a significantly higher number of patients was able to receive further lines of treatment As expected, median OS decreased in each cohort with each line given, from 28.6 to 6.7 months (COHORT A) and from 10.2 to 3.8 months (COHORT B) Notably, median OS increased when evaluated as a function of total number of CT lines received, supporting the concept that each CT line could add a survival gain This may reflect the selection of more sensitive tumors with the treatment Consistent with previous published data, our analysis suggest that the prognosis of women with TNBC remains poor, also when compared to the one of other aggressive subtypes. Limits: Retrospective analysis QoL not evaluated PATIENTS CHARACTERISTICS COHORT A ER-/PgR-/HER2+ N=250 COHORT B ER-/PgR-/HER2- N=210 OVERALL POPULATION 460 Median age,years (range)54 (36-78)44 (26-58)52.2 (26-78) Pathology N°(%) Ductal carcinoma 207 (83)163 (77.6)370( 80.4%) Lobular carcinoma 35 (13.6%)19 (9.1) 54 (11.7%) Other carcinoma 8 (3.4%) 28 (13.3%) 36 (7.9%) Tumor size < 20 mm114 (45.6%)64 (30.4%)178 (38.6%) > 20 mm136 (54.4%)146 (69.6%)282 (61.4%) Node involvement Negative98 (39.2%)42 (20%)140 (30.5%) Positive152 (60.8%)168 (80%)320 (69.5%) SBR grade I29 (11.6%)12 (5.6%)41 (8.9%) II169 (67.6%)102 (48.6%)271 (58.9%) III52 (20.8%)96 (45.7%)148 (32%) Dominant sites of metastasis Liver125 (50%)89 (42.3%)214 (46.7%) Lung77 (30.8%)79 (37.6%)156 (33.9%) Other46 (19.2%)42 (20.1%)88 (19.2%) Multiple78 (31.2%)158 (75.2)236 (51.3%) Adjuvant treatment none32 (12.8%)24 (11.4%)56 (12.1%) taxane -based34 (13.6%)28 (13.4%)62 (13.5%) anthra-based82 (32.8%)13 (6.2%)95 (20.7%) CMF27 (10.8%)103 (49%)130 (28.2%) anthra /taxane75 (30%)42 (20%)117 (25.5%) trastuzumab206 (82.4%)0 (0%)206 (44.7%) ECOG PS 0144 (57.6%)87 (41.4%)231 (50.3%) 172 (28.8%)98 (46.6%)170 (36.9%) 234 (13.6%)25 (12%)59 (12.8%) STUDY POPULATION DISCUSSIONS RESEARCH OBJECTIVES PATIENTS & METHODS REFERENCES Overall survival related to total number of chemotherapy lines n° of CT lines COHORT ACOHORT B N° (%) OS (months) N° (%) OS (months) 1 line250 (100%)28.6210 (100%)10.2 2 lines223 (89.0%)31.2151 (72.0%)12.4 3 lines130 (52.0%)33.857 (27.1%)13.8 4 lines80 (32.0%)34.636 (17.1%)16.2 FACTORS PREDICTIVE OF LONGER MEDIAN OS: UNIVARIATE ANALYSIS Absence of liver metastases ● Prior adjuvant trastuzumab (Cohort A) ● Exposure to taxanes (Cohort B) 328P MULTIVARIATE ANALYSIS ● The number of received CT lines (≤2 versus ≥3) p= 0.003 Cohort A p< 0.001 Cohort B STATISTICAL ANALYSIS