526 Background: Loco-regional recurrence (LRR) in breast cancer (BC) is addressed with multimodal treatment, yet the prognosis remains unfavorable. The benefit of adjuvant chemotherapy for the hormone receptor-positive, HER2-negative (HR+HER2-) subtype of BC is controversial. Methods: We performed a multi-institutional retrospective cohort study under the Japan Clinical Oncology Group. This study focused on patients without distant metastasis who developed HR+HER2- ipsilateral breast tumor recurrence (IBTR) or other LRR (oLRR) including recurrence in skin, chest wall, or regional lymph nodes. The patients received curative surgery for LRR between 2014 and 2018. Patients were divided into two groups: the chemotherapy group and no chemotherapy group before/after LRR. We performed a Cox proportional hazards model to evaluate invasive disease-free survival (iDFS) between the two groups. Sensitivity analysis was conducted using propensity score (PS) matching and IPTW. Results: A total of 967 patients were registered from 41 institutions, and 958 patients concordant with inclusion criteria were analyzed. There were 509 patients (53%) of only IBTR and 449 patients (47%) of oLRR. Neoadjuvant/Adjuvant chemotherapy was administered to 235 patients (25%), while 722 (75%) did not receive it. Compared to the no-chemotherapy group, the chemotherapy group included a higher number of patients aged 41-60, oLRR, and recurrences during adjuvant endocrine therapy. At a median follow-up of 5.2 years (Interquartile range: 4.1-6.5), the 5-year iDFS rate was 75.4% (95% CI: 72.4-78.2). Multivariate analysis showed an improvement in iDFS for the chemotherapy group (HR: 0.70, 95% CI: 0.49-0.99, p = 0.045). Sensitivity analysis also consistently suggested the effectiveness of chemotherapy (PS matching HR 0.76, IPTW HR 0.75). In the subgroup analysis, the chemotherapy group showed more significant iDFS improvement in cases with oLRR, recurrences during adjuvant endocrine therapy for primary BC, and those without perioperative chemotherapy for primary BC. Conclusions: Our study showed improvement in iDFS in patients who received perioperative chemotherapy for HR+HER2- LRR. This improvement was particularly notable in patients with oLRR, recurrences during adjuvant endocrine therapy, and those without perioperative chemotherapy for primary BC. [Table: see text]