Background: An earlier published series of neoadjuvant radio-chemotherapy (NRT-CHX) in locally advanced noninflammatory breast cancer (LABC) has now been updated with a follow-up of more than 15 years. Long-term outcome data and predictive factors for pathologic complete response (PCR) were analyzed. Methods: 315 LABC patients (cT1-cT4 /cN0-N1) were treated during 1991-1998 with NRT-CHX. Preoperative radiotherapy (RT) consisted of external beam radiation therapy (EBRT) of 50 Gy (5 × 2 Gy/week) to the breast and the supra-/infraclavicular lymph nodes combined with an electron boost in 214 cases afterwards or—in case of breast conservation—a 10-Gy interstitial boost with 192Ir afterloading before EBRT. Chemotherapy was administered prior to RT in 192 patients, and concomitantly in 113; 10 patients received no chemotherapy. The update of all follow up ended in November 2011. Age, tumor grade, nodal status, hormone receptor status, simultaneous vs. sequential CHX and the time interval between end of RT and surgery were examined in multivariate terms with as endpoint pCR and overall survival. Results: The total PCR rate after neoadjuvant RT-CHX reached 29.2 % with LABC breast conservation becoming possible in 50.8%. In initially node-positive cases (cN+), a complete nodal response (pN0) after NRT-CHX was observed in 56% (89/159). The multivariate analysis revealed that a longer time interval to surgery increased the probability for a pCR (HR 1,17 [95% CI 1,05-1,31], p<0,01). However, in large tumors (T3-T4) a significantly reduced pCR rate (HR 0.89 [95% CI 0.80 to 0.99], p = 0.03) could be obtained. Importantly, a pCR was the strongest prognostic factor for long-term survival (HR 0.28 [95% CI 0.19-0.56], p<0.001). Conclusions: A PCR identifies patients with a significant better prognosis for long-term survival. However, a long time interval to surgery (> 2 months) increases the probability of a pCR after NRT-CHX.