Reconceptualizing the clinicopathological features, locoregional therapy and prognostic factors of occult breast cancer in the era of molecular subtyping.

To evaluate the clinical features, molecular subtypes, therapeutic strategies, and prognostic factors of occult breast cancer (OBC). Patients with T0-3/N1-3/M0 breast cancer diagnosed in 2010-2018 ( = 114,303, including 691 with OBC) were retrieved from the Surveillance, Epidemiology, and End-Results (SEER) database. The endpoints were overall survival (OS) and breast cancer-specific survival (BCSS). Compared with non-OBC, OBC presented significantly more adverse clinicopathological prognostic features. More patients with OBC underwent breast-conserving treatment (BCT) and less had axillary lymphadenectomy (ALD). Outcomes were more favorable in OBC cases compared with non-OBC cases ( = .002 for OS,  = .002 for BCSS). Triple-negative (TNBC) and HER2-enriched were the subtypes with the worst prognosis in OBC ( < .05). Prognosis was better for triple-negative OBC compared with the same subtype of non-OBC. N-stage was not a strong prognostic indicator of OBC ( > .05 for OS). Cases who underwent systemic chemotherapy alone without surgery had the worst prognosis among OBC patients. For locoregional therapy, mastectomy and radiotherapy could confer survival advantage; standard axillary lymph node dissection (ALND) and positive lymph node dissection (PLND) contributed notably to OS in OBC patients. Both OS and BCSS were better in OBC cases compared with non-OBC. Systemic chemotherapy alone without surgery is not appropriate for OBC treatment, and mastectomy plus standard axillary surgery is recommended. Patients with hormone receptor-positive and low burden of axillary lymph node metastasis may be spared from radiotherapy after undergoing standard axillary lymphadenectomy.