Abstract Background: Women with large breast tumors are often treated with mastectomy as their definitive operation. However, women with large breasts can have a significant resection and still achieve an excellent aesthetic outcome if the partial mastectomy is combined with a reduction mammoplasty. It is not clear if the limitation for breast conservation should be made based on tumor size, or on the basis of the volume of tissue that needs to be resected relative to the total volume of breast tissue. Our study aims to assess the oncologic safety and cosmetic outcome of large partial mastectomies in large breasted women combined with reduction mammoplasty.Materials and Methods: All patients undergoing partial mastectomy and reduction mammoplasty performed at the University of California San Francisco were included. Medical records were reviewed for demographics, breast cancer data, oncologic and reconstructive operations, postoperative recurrences, complications, and need for additional operations.Results: Sixty-five patients undergoing partial mastectomy and reduction mammoplasty reconstruction were identified. Average tumor size was 2.8 cm (range 0.6 cm to 8.9 cm). The stage distribution for 63 patients was stage 0 (n=11), I (n=15), II (n=24), III (n=10), and IV (n=3), and 2 patients had Phylloides tumor. Twenty-five patients had neoadjuvant therapy, followed by breast reduction as their primary resection once chemotherapy was completed. Twenty patients (30.8%) required re-excision, four of whom required multiple re-excisions. Fifty nine patients (90.8%) were successfully treated with our approach, while 6 patients (9.2%) required completion mastectomy for their definitive resection, based on margin status after initial resection. There were a total of two recurrences, one in a patient who had a local DCIS recurrence after initial presentation with stage 0 disease and one in a patient who presented with metastatic disease. The patient with stage 0 disease and subsequent recurrence did not have radiation; the other patient presented initially with synchronous metastatic disease, had a poor response to chemotherapy, and her local recurrence occurred simultaneously with progression of distant disease. Of the patients with stage 0-III disease, the recurrence rate was 1.6% with a mean follow-up of 13 months. Eleven patients (15.9%) developed postoperative complications, including fat necrosis (n=1), hematoma (n=1), cellulitis (n=2), seroma (n=3), and wound healing complications (n=4). Despite complications and radiation therapy, all patients were exceptionally pleased with their reconstruction.Conclusion: Partial mastectomy with reduction mammoplasty breast reconstruction is a viable option that combines a safe oncologic procedure with immediate breast reconstruction. While further follow-up is needed, it is a viable alternative to mastectomy, enabling breast conservation and correction of significant breast redundancy and ptosis, which can impair the efficacy of radiation therapy. Prospective data collection should continue for these cases to establish the long term outcomes of large-breasted patients undergoing partial mastectomy and reduction mammoplasty. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4125.