Purpose: We aimed to determine the prognosis and potential benefit of postoperative chemotherapy according to subtype of medullary breast carcinoma (MedBC), a very rare invasive breast cancer. Methods: A cohort of 1518 female patients with unilateral MedBC and 284,544 invasive ductal carcinoma (IDC) cases were enrolled from the Japanese Breast Cancer Registry. Prognosis of MedBC was compared to IDC among patients with estrogen receptor (ER)-negative and HER2-negative subtype (553 exact-matched patients) and ER-positive and HER2-negative subtype (163 MedBC and 489 IDC patients via Cox regression). Disease free-survival (DFS) and overall survival (OS) were compared between propensity score-matched adjuvant chemotherapy users and non-users with ER-negative and HER2-negative MedBC. Results: Among ER-negative and HER2-negative subtype patients, DFS (hazard ratio (HR) 0.45; 95% confidence interval (95% CI), 0.30–0.68; log-rank P < 0.001) and OS (HR 0.51; 95% CI 0.32–0.83; log-rank P = 0.004) were significantly better in MedBC than IDC. Patients treated with postoperative chemotherapy showed better DFS (HR 0.27; 95% CI 0.09–0.80; log-rank P = 0.02) and OS (HR 0.27; 95% CI 0.09–0.80; log-rank P = 0.02) compared to those without. For the ER-positive and HER2-negative subtype, the point estimate for HR for DFS was 0.60 (95% CI 0.24–1.22) while that for OS was 0.98 (95% CI 0.46–1.84) for MedBC. Conclusion: In ER-negative and HER2-negative MedBC, the risk of recurrence and death was significantly lower than that of IDC, about half. Postoperative chemotherapy reduced recurrence and mortality. ER-positive and HER2-negative MedBC may have a lower risk of recurrence compared to IDC.
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