Simple SummaryAlthough ER expression levels affect the prognosis of breast cancer, studies about PR expression levels are insufficient. Furthermore, there is a knowledge gap between single HR-positive and double HR-positive, especially according to PR expression. As HR positivity is an important prognostic factor, particularly in YBC patients, this research was conducted in a prospective cohort with only YBC patients in order to find out whether the expression of PR modifies the clinical course of breast cancer. We investigated clinicopathologic features and prognosis of ER-positive/HER2-negative breast cancer after stratifying them according to PR expression levels. Conclusively, low PR expression was correlated with worse clinicopathologic characteristics, and associated with increased risk of recurrence, distant metastasis, and death compared with strong PR expression group. Low PR might be a prognostic factor of ER-positive/HER2-negative YBC.AbstractBackground: Although estrogen receptor (ER) expression levels affect the prognosis of breast cancer, studies about progesterone receptor (PR) expression levels are insufficient, especially in young breast cancer (YBC). The purpose of this study was to compare clinical characteristics and prognosis according to PR expression levels in invasive breast cancer patients. Methods: A prospective cohort study was conducted to identify YBC patients with invasive carcinoma diagnosed at an age of less than 40 years old between 2013 and 2018. Clinicopathologic features and prognosis of ER-positive and human epidermal growth factor receptor 2 (HER2)-negative patients were investigated. Patients were stratified into strong PR (PR-positive cell proportion > 10%), low PR (PR-positive cell proportion = 1~10%), and PR-negative (PR-positive cell proportion < 1%). Results: Among 458 patients enrolled, 386 (84.3%), 26 (5.7%), and 46 (10.0%) were categorized into strong PR, low PR, and PR-negative groups, respectively. The median follow-up duration was 58.6 months. Compared with the strong PR group, low PR and PR-negative groups were more likely to have high Ki-67 and a high nuclear grade. Low R and PR-negative groups had significantly worse disease-free survival (DFS) and distant metastasis-free survival (DMFS) than the strong PR group (p= 0.0033,p= 0007). Low PR group had an even higher risk of distant metastasis than PR-negative patients. Low PR patients and PR-negative had significantly lower overall survival (OS) rates than strong PR. Conclusion: Low PR might be a prognostic factor of ER-positive/HER2-negative in YBC.