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For ipsilateral breast cancer tumor (IBTR), radical mastectomy represents the treatment option frequently proposed to the patient. A second conservative treatment (SCT) has been proposed using either lumpectomy alone or associated with a second irradiation of the tumor bed. However, in both clinical situations, the proof level of such therapeutic approaches remains low, based on cased-series or retrospective studies. To analyze the clinical outcome of a SCT using lumpectomy and multicatheter interstitial brachytherapy (MIB) for IBTR, the GEC-ESTRO Breast Working Group retrospectively analyzed the results of 217 patients (pts) with an IBTR treated between 09/00 and 09/10 in 8 European institutions by lumpectomy and MIB (low - LDR, pulse - PDR, or high-dose rate - HDR). Survival rates without 2nd local (2nd LR) and metastatic recurrence, disease free survival (DFS) and specific and overall survivals were analyzed as well as late effects and cosmetic results. Dosimetric data were reported according to the dose rate used. Univariate and multivariate analysis were performed to find local, metastatic and/or DFS progression prognostic factors. With a median follow-up of 14.5 years [3.5–38.2] and 3.9 years [1.1–10.3] from primary tumor and IBTR respectively and a median time interval of 9.4 years [1.1–35.4] between primary and IBTR, 20.7% of the local recurrence were observed at distance from the primary tumor. Median tumor sizes were 15 mm [1–60] and 11 mm [1–40] for the primary and IBTR respectively. Thirty-nine percent of the patient underwent an axillary lymph node dissection at the time of IBTR. Median radiotherapy dose for the primary was 56 Gy [30–69.6]. Positive hormonal receptor status for IBCR was 72.8% while 65% and 19.8% received hormonal and chemotherapy respectively as adjuvant therapy for the IBTR. Five and 10-year actuarial 2nd LR rates were 5.6% [1.5–9.5] and 7.2% [2.1–12.1] respectively. Five and 10-year actuarial metastatic recurrence rates were 9.6% [5.7–15.2] and 19.1% [7.8–28.3] respectively. Five and 10-year actuarial DFS rates were 84.6% [78.9–90.6] and 77.2% [67.5–88.3] respectively. Five and 10-year actuarial overall/specific survival (OS) rates were 88.7% [83.1–94.8] and 76.4% [66.9–87.3] respectively. 141 pts developed 193 complications. Fibrosis was the most frequent complication with 11% of G3-4 complications. Cosmetic result was jugged as excellent/good in 85%. Focusing on multivariate analysis, prognostic factors for 2nd LR, metastatic recurrence and DFS are reported. The results of this study suggest that in case of IBTR, a SCT combining lumpectomy plus MIB is feasible with an overall survival rate at least equivalent to those obtain after salvage mastectomy. The rate of complication remains acceptable with encouraging cosmetic results. The literature analysis suggests that the rate of 2nd LR is 10% [3–32], 25% [7–36] and 10% [2–26], after salvage mastectomy, salvage lumpectomy alone or combined with a second irradiation respectively. However, the 5-y OS rates after salvage mastectomy and SCT seem to be equivalent (75%) mainly influenced by distant metastatic progression. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-15-01.