Abstracts: Thirty-Third Annual CTRC‐AACR San Antonio Breast Cancer Symposium‐‐ Dec 8‐12, 2010; San Antonio, TX Background: Given that many patients with more locally advanced breast cancer are receiving neoadjuvant therapy, predictors of local recurrence will be important for learning how to optimize the use of local regional therapy. We investigated the local regional recurrence (LRR) rates in patients treated with neoadjuvant chemotherapy in the I SPY1 trial. Methods: Data were analyzed from 221 women that were enrolled in I-SPY1 and completed treatment. Final surgical procedure was not randomized. Multiple clinicopathologic factors were investigated in both the lumpectomy (BCS) and mastectomy cohorts. Logistical regression was applied to identify factors predicting LRR although this was not a specified endpoint for the I-SPY parent trial. Results: At 3.9 years median followup, 123 patients (56%) had mastectomy, 93 patients (42%) had breast conservation and 5 did not have a surgical procedure. The majority of patients in both groups received radiation with 77% and 94% in the mastectomy and breast conservation (BC) group respectively. Within the mastectomy group, there was no correlation between whether pts received PMRT and predictors of high LRR risk: LVI, grade, stage and nodal disease following neoadjuvant chemotherapy. Rates of PMRT in each residual cancer burden (RCB) category were 78%(RCB0), 80%(RCB 1), 81%(RCB2) and 66%(RCB3, highest residual burden of disease) for the mastectomy group. Median tumor size before chemotherapy was 6.0 cm and 5.0 cm mastectomy and BC groups, respectively. Fewer patients had pCR in the mastectomy group, compared to the BC group. LRR rates were very low for both the mastectomy and BC groups, with 9 (7.5%) and 7 (7.3%) total recurrences, respectively. Only 2 patients in each group had LLR without distant recurrence (2% total). For the mastectomy and BC groups, 4/7 and 3/5 patients had synchronous presentation of their local and distant disease. For patients with distant recurrence 44% and 29% had a local recurrence in the BC and mastectomy groups respectively. In a logistical regression model, patients with local progression in the BC group were 17 times more likely to develop distant progression (p=0.005) while in the mastectomy group, those with LLR were 10.5 times more likely to develop distant progression (p=0.001). Individual factors that appeared to be predictive of local recurrence included clinical size of tumor at presentation (p=0.032) for the BC group, and final pathologic tumor size in the mastectomy group (p=0.002). Patients with low risk molecular features (wound healing quiescent, luminal A, NKI low, and ROR-S low) did not have any local recurrences. Conclusion: Although the sample size was small, and the ability to discriminate between the two surgical groups was limited, in this high risk group of locally advanced breast cancer pts, BC does not appear to lead to an increased rate of LRR. In fact tumor biology that predicts for high risk of distant progression might be able to be applied to risk stratification for LRR. Patients with low risk of distant recurrence (e.g. those with pCR, RCB1or low-risk molecular markers) may be those that we can consider testing PMRT vs not in future neoadjuvant trials. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD06-03.