Abstract Objectives: Multifocal and multicentric breast cancer (MMBC) is generally defined as two or more malignant lesions in one breast, accounting for approximately 6% to 60% of breast cancers. MMBC may be more likely to spread to regional lymph nodes (LNs) and patients with MMBC are at higher risks of both distant metastasis and local recurrence than patients with unifocal breast cancer (UBC). Ongoing discussions persist concerning the prognosis of multifocal and multicentric breast cancer (MMBC) with low tumor burden, and pertinent adjuvant chemotherapy guidelines for these individuals are absent. Methods: Female patients diagnosed with cT1-T2 stage MMBC or unifocal breast cancer (UBC) were extracted from the Surveillance, Epidemiology and End Results database (2010-2020). Propensity score matching (PSM) was utilized to balance baseline characteristics. The log-rank test was used for each matched dataset to compare overall survival (OS) and BCSS between the pairs, respectively. The Kaplan-Meier curves for different groups were also provided. Additionally, univariate and multivariate Cox proportional hazards regression models were fitted to estimate the hazard ratios (HRs) and the 95% confidence intervals (CIs) for OS and breast cancer-specific survival (BCSS). Subgroups of different tumor sizes were defined based on typical cut-off values for chemotherapy in the NCCN guidelines, namely, less than 1 cm, between 1 and 2 cm, and greater or equal to 2 cm. Results: There were 9,751 pairs of MMBC and UBC patients effectively matched by PSM method. The survival analysis showed that the OS and BCSS of patients with MMBC were significantly worse than UBC (OS, p 0.001; BCSS, p 0.001, log-rank test). Multivariate analyses of the 9,751 cases revealed that MMBC patients who were under 50 years old, married, Caucasian, with low-grade tumor, had a smaller tumor size, had N0 stage disease, ER-positive subtype, PR-positive subtype, had fewer lesions, and received chemotherapy had better OS. Cox multivariate analyses of the 9,751 patients with MMBC showed that receiving chemotherapy was related to a better OS (hazard ratio, HR = 0.583, 95% confidence interval CI, 0.522-0.652) and a better BCSS (HR = 0.830, 95%CI, 0.702-0.980). Given that chemotherapy has shown an effect of improving survival in multivariate analyses, we further analyzed the value of chemotherapy in the population with LN-negative MMBC according to different tumor sizes. Intriguingly, as were shown in KM survival curves, chemotherapy was associated with a significantly improved OS in LN-negative patients when tumor size ≥ 1 cm (tumor size 1 cm, HR = 0.889, 95%CI, 0.549-1.438, p = 0.631; 1 cm ≤ tumor size 2 cm, HR = 0.617, 95%CI, 0.443-0.861, p = 0.004; tumor size ≥ 2 cm, HR = 0.449, 95%CI 0.347-0.582, p 0.001). Nevertheless, chemotherapy was not related to BCSS (tumor size 1 cm, HR = 2.019, 95%CI, 0.839-4.857, p = 0.117; 1 cm ≤ tumor size 2 cm, HR = 0.905, 95%CI, 0.528-1.55, p = 0.715; tumor size ≥ 2 cm, HR = 0.742, 95%CI, 0.510-1.081, p = 0.120). Conclusions: Multifocality and multicentricity were independent predictors for worse survival outcomes. Chemotherapy should be considered in patients with node-negative MMBC whose tumors are equal to or larger than 1 cm. Future prospective studies are expected to corroborate the findings. Citation Format: Y. Zheng, Z. Zhan, J. Ying. Tailoring escalated adjuvant chemotherapy for multifocal and multicentric breast cancer with low tumor burden abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS4-08-18.
Zheng et al. (Tue,) studied this question.