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BACKGROUND: Most patients with breast cancer treated with neoadjuvant chemotherapy (NAC) experience clinical benefit, however, a small proportion progress. We aimed to characterize factors predicting in-breast tumor progression and impact on distant recurrence. PATIENTS AND METHODS: We reviewed all patients with clinical stage I-III breast cancer treated with NAC in 2006-2021 at our institution. We compared in-breast progressive disease (PD), defined as ≥ 20% increase in tumor size, with stable disease (SD) or response. Distant recurrence-free survival (DRFS) was analyzed using the Kaplan-Meier method and Cox proportional hazards regression. RESULTS: Of 1403 patients, 70 (5%) experienced in-breast PD, 243 (17%) SD, 560 (40%) partial response (PR), and 530 (38%) breast pathologic complete response (breast pCR, ypT0/Tis). The rate of PD varied by tumor subtype (8% in HR+/HER2-, 5% TNBC, 2% HER2+, p < 0.001). With median 48 months follow-up, the rates of DRFS were significantly different according to clinical breast response as follows: PD 56%, SD 68%, PR 82%, or breast pCR 93%, p < 0.001. In patients with PD on multivariable analysis, post-NAC grade (adjusted HR 2.9, p = 0.002) and ypT3-4 category (adjusted HR 2.4, p = 0.03) were the strongest predictors of DRFS. Combining these factors, 23% had neither, 44% had one, and 33% had both, which stratified outcome in PD with 3-year DRFS of 100%, 77%, and 30%, respectively (p < 0.001). CONCLUSIONS: While in-breast PD during NAC is uncommon (5%), it predicts poor survival. Among patients with in-breast PD, post-NAC tumor grade and T category predict outcomes and may be useful to guide treatment escalation.
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Background and Objective: While the axillary nodal basin is the most common lymphatic drainage pathway of the breast, the internal mammary (IM) lymph node chain plays a significant role in breast cancer staging and treatment. It has been identified as sentinel nodal drainage in approximately 13-37% of patients. Despite this, the data is still limited with regard to diagnosis and management when there is suspicion or confirmation of IM lymph node (IMLN) involvement by metastatic breast cancer. The objective of this publication is to provide a comprehensive assessment of the current body of literature surrounding the diagnosis, management and prognostic value of IMLNs in breast cancer treatment. Methods: Review of the literature published regarding IMLN diagnosis, significance, and management was completed in PubMed. Additional focus was placed on reviewing articles published within the past 10 years as foundation for an update regarding the current practice and future directions in this space. Key Content and Findings: Improved imaging techniques, with positron emission tomography-computed tomography and magnetic resonance imaging, have led to increase in the identification of IM lymphadenopathy, yielding surgical staging of the IM nodes nearly obsolete. While IM nodal metastases may play a role in overall survival (OS), it has not been demonstrated to be an independent risk factor for increased locoregional recurrence. IM nodal irradiation (IMNI) therapy has been a mainstay in the treatment of IM disease in the context of breast cancer. IMNI has demonstrated improvement in OS and risk of distant recurrence. Wide variations in radiation practices for patients with IM lymphadenopathy exist internationally, highlighting the lack of clear data driven consensus guidelines. Conclusions: Herein, we provide an updated assessment of the current diagnosis, clinical significance, and management of IM lymphadenopathy for breast cancer patients.