Abstract P3-18-12: Achieving negative margin after repeated attempts for lumpectomy does not nullify the risk of ipsilateral breast tumor recurrences

Introduction: Currently, the widely accepted principle in managing lumpectomy margins in early breast cancer patients is to avoid the presence of tumor cell at the margin. The presence of tumor cells on lumpectomy margin can represent two different aspects of local control in breast cancer. One aspect is related to the potential technical failure that may lead to an incomplete resection of the tumor. The other aspect of positive margin is associated with a biologic nature of the tumor. For example, some tumors show features of extensive intraductal component which often result in positive lumpectomy margins and may lead to increased risk of local recurrence after breast conservation surgery. Therefore, the two-fold increase of IBTR risk with positive margin would be the reflection of the combined effect of both technical failure and the biologic features.In this study, we aimed to address this issue by investigating the IBTR rates of patients in whom negative margins were achieved by initial lumpectomy or by re-excision. Our assumption was if the IBTR rates of the two groups are identical, then the two-fold increase of IBTR risk is mostly caused by the technical incomplete resection and therefore the measures to achieve negative margins would be justified. Methods: We retrospectively reviewed the data of 5,633 patients who underwent breast conservation surgery and whole breast irradiation for invasive breast cancer between January 2004 and December 2018 from Seoul National University Hospital. During the period, a total of 828 patients had positive lumpectomy margin after their initial surgery. Among them, thirty-five patients who did not undergo re-operation were excluded due to the small sample size. Results: The median age of the studied patients was 49 years old (19-92), and nearly two third of the patients had T1 tumors (64.3%). 4,293 patients (76.7%) were node negative and 4,332 patients (77.4%) had hormone receptor positive tumors. During the median follow-up period of 76.6 ( ± 44.6) months, a total of 121 patients (2.2%) experienced IBTR. Patients who underwent re-excision to achieve negative margins experienced significantly higher rate of IBTR compared to patients in whom the margins were clear at the first lumpectomy (p=0.031, HR: 1.61; 95% C.I., 1.04-2.48). The survival curves began to separate around 4-5 years after surgery (98.5% vs 98.0% at 5 year and 97.4% vs 94.7% at 10 years of follow-up). The survival difference was more clearly observed for younger patients (p=0.033, HR 1.72; 95% C.I., 1.04-2.85 for age less than 50). When the patients were divided according to their hormone receptor and HER2 amplification status, we observed significant difference in HR+/HER2- and HR-/HER2- subtypes while the HER2-amplified tumors showed no significant differences.By using Cox regression analysis, we adjusted for other significant predictors of IBTR such as age, histologic grade, lymphovascular invasion, hormone receptor status, HER2 amplification status, and Ki-67 levels. The results of the Cox regression analysis showed that re-excision to achieve negative margin is significantly associated with the risk of IBTR after adjusting for these variables (p=0.023, HR: 1.72; 95% C.I., 1.08-2.74). Conclusion: Patients who underwent re-excision after lumpectomy for initial positive margin carry increased risk of developing IBTR even they achieve final negative margin when compared to patients with initially negative lumpectomy margin. Our observation indicate that a substantial proportion of the increasing risk of IBTR associated with positive lumpectomy margin can be attributed to the biologic characteristics of the tumor rather than technical incomplete resection. Citation Format: Jong Ho Cheun, Hong-Kyu Kim, Han-Byoel Lee, Wonshik Han, Hyeong-Gon Moon. Achieving negative margin after repeated attempts for lumpectomy does not nullify the risk of ipsilateral breast tumor recurrences [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-18-12.