Evidence That Neoadjuvant Anthracycline Based Combination Chemotherapy (Nact) In Breast Cancer (Bc) Induces Phenotypical Changes Which Guides The Optimal Adjuvant Therapy.

590 Background: We hereby evaluated the histopathological and radiological alterations of tumor characteristics after receiving NACT and the clinical significance of the changes of adjuvant therapy based on these findings. Methods: A pathological assessment of tumor features including ER, PR, HER2 and proliferation markers (Ki67 and SPAG5) status in pre and post NACT tumors tissue have been centrally evaluated in two cohorts [Nottingham University Hospital (NUH; n=850) and Australian cohort (n=250 patients)]. Since 2013 any change in the ER and HER2 status from negative (-) [in the pre NACT biopsies] to positive (+) [in the post NACT surgical specimens] received additional adjuvant therapy (Endocrine therapy (ET) for ER+ and Trastuzumab for HER2+ cases) in NUH. MRI volumetric and texture changes have been assessed in 400 cases. The primary end point was disease free survival (DFS; median follow-up = 62 months). Results: 10% of pre NACT HER2- cases had been converted to post NACT HER2+ and those cases who subsequently received adjuvant Trastuzumab had achieved 92% 5-year DFS compared to those who remained HER- in post NACT specimens (58% 5-year DFS); (HR (95% CI)= 0.25 (0.08-0.80); p=0.016). While 13% of pre NACT HER2+ tumors were converted into HER2- in post NACT surgical specimens and had similar 5-year DFS to those who remained post NACT HER2+ (5-year DFS= 94% vs., 87%; p=0.613). Loss of PR in the residual disease of pre NACT ER+ BC was associated with shorter 5-year DFS after ET compared to those who remained post NACT PR+ (HR (95% CI)=2.1 (1.25-3.46); p=0.005). After NACT, 40% of pre NACT SPAG5+ cases were converted into post NACT SPAG5- and these patients had prolonged DFS compared to those who remained SPAG5+ in post NACT specimens (27%) [5-year DFS=84% vs 49%; (HR (95% CI)= 3.8 (2.1-6.9); p<0.0001). A prognostic model has been generated including factors in table (AUC = 0.854 (95% CI) = 0.777-.0.931; p= 0.00000001]. Conclusions: We hereby showed evidences a change of treatment strategy based on the changes in the tumor post NACT phenotype gives the optimal choice of treatment eg., the introduction of HER2 targeting therapy for the conversion of HER2– to HER2+ phenotype after NACT improved DFS. Multivariate Cox regression model for 5-year DFS. [Table: see text]