Abstract Background: Preoperative chemotherapy (PCT) is widely used to increase the possibility of breast-conserving treatment (BCT). However, the appropriate indication for BCT after PCT is controversial, because the rates of ipsilateral breast tumor recurrence (IBTR) may be higher than those reported for BCT when surgery is used first. We performed a multicenter retrospective study to evaluate factors that were associated with IBTR in patients with BCT after PCT, and validated M. D. Anderson Prognostic Index (MDAPI) (Cancer 2005;103:689–95) using our data set. Patients and Methods: From eight Japanese hospitals, data were extracted on a total of 381 patients with invasive breast cancer (BC) who were treated with ≥3 cycles of PCT followed by breast-conserving surgery and irradiation. The rates of IBTR were evaluated by MDAPI including clinical N2 or N3 disease, pathologic residual tumor >2 cm, multifocal pattern of residual disease, and lymphovascular space invasion in the specimen. Kaplan-Meier method was used to estimate cumulative recurrence rates. Log-rank test and Cox's proportional hazard model were used for statistical analyses. Results: Median age at diagnosis of the primary tumor was 48 years; median size of the primary tumor at diagnosis was 4.0 cm. One hundred and forty-six patients received postoperative chemotherapy and 211 received postoperative endocrine therapy. At a median follow-up period of 50 months, 18 of 381 patients developed IBTR, which resulted in 5-year IBTR-free rate of 94.1%. Univariate analyses revealed that estrogen receptor (ER) status both before and after PCT (positive vs. negative), pathological nodal status after PCT (≥4 vs. 0–3 positive nodes), and pathologically residual invasive tumor (≥1.8 vs. ≤1.7 cm) were significantly associated with IBTR (all P < 0.05). Pathological margin status did not affect IBTR rate (P=0.88). Multivariate analysis revealed that significant independent predictors of IBTR included ER status after PCT (Hazard Ratio [HR], 0.10; P<0.01), size of residual invasive tumor (HR, 5.29; P=0.03), and pathological nodal status after PCT (HR, 3.59; P=0.02). The rates of IBTR of patients with MDAPI 0–3 were 1.3%, 2.9%, 16.0%, and 3.6%, respectively. Based on the data of our multivariate analysis, ER status after PCT (ER positive;0 and ER negative; 1 was added to MDAPI. Total scores of the prognostic index including MDAPI and ER status after PCT ranged between 0 and 5. The rates of IBTR correlated well with this prognostic index. The 5-year IBTR-free survival rates were 0% for 23 patients in score 0, 3.4% for 89 in score 1, 3.9% for 51 in score 2, 21.2% for 33 in score 3, and 16.7% for 6 in score 4 (P < 0.01). Conclusion: Our prognostic index (MDAPI plus ER status) would be useful for clinical decision making according to surgical procedures after PCT. BCT is an appropriate treatment option for patients with the low prognostic index (0 to 2). The high risk population with the high prognostic index (3 to 5) may benefit from mastectomy. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-12-03.