Abstract

Abstract Background Estrogen receptor (ER) positive, HER2 negative breast cancer (BC) can be classified into luminal A and luminal B-like tumors according to tumor grade. Several evidences point to the fact that IHC expression of the progesterone receptor (PR) has prognostic value. In this study, we assess to what extent a negative PR in luminal A BCs increases the risk of distant metastasis and whether or not luminal B BC might have a good prognosis if PR is positive. Patients and methods Women with primary operable ER positive, HER2 negative BC treated at University Hospitals Leuven between 2000 and 2009 were retrieved from our database. So called luminal A tumors were defined as grade 1-2 BC, whereas so called luminal B BC were defined as grade 3 BC. Distant metastasis free interval (DMFI) and breast cancer specific survival (BCSS) were investigated by their PR status. PR was considered negative if the semi-quantitative Allred score was 0-2. Before 2003 the semi-quantitative H-score was used and a score <50 was considered negative. Statistical analysis for DMFI was performed using the cox proportional hazards regression. For BCSS we used Fine & Gray’s competing risk regression. Covariates were age at diagnosis, tumor size, lymph node status, and therapy. Results In total, 3294 patients from Leuven were analyzed. From this cohort, 285 patients experienced metastases (8.7%) and 172 patients died of BC (5.2%). Details are shown in Table 1. The median age at diagnosis was 58 years with ages ranging from 22 to 95 years, 2358 patients (71.6%) were aged above 50 at diagnosis. The median follow-up period was 8.1 years. Table 1: Number of patients that metastasized and died of BC by luminal subgroup and PR status. MetastasesBC-related deathluminal APR positive110/2103 (5%)61/2103 (3%) PR negative16/267 (6%)9/267 (3%)luminal BPR positive120/786 (15%)75/786 (10%) PR negative39/138 (28%)27/138 (20%)BC: breast cancer, PR: progesterone receptor In Leuven, the reduction in risk of metastasis in patients with PR positive luminal A and luminal B BC was respectively 14% (Hazard ratio (HR): 0.86, 95% confidence interval (CI) 0.52-1.51) and 47% (HR: 0.53, 95% CI 0.37-0.78) compared with PR negative tumors. PR positive luminal A and luminal B BC patients had a 16% (HR: 0.84, 95 % CI 0.42-1.69) and 53% (HR: 0.47, 95% CI 0.30-0.75) reduction in the risk of BC-related death compared with PR negative tumors respectively. The same analysis was also carried out for postmenopausal patients (older than 50 years) only. In this subcohort, PR positivity was associated with a 9% (HR 0.91, 95% CI 0.50 to 1.83) and 59% (HR 0.41, 95% CI 0.28 to 0.63) reduction in the risk of metastatic events in luminal A and luminal B lesions, respectively. For BCSS, a 31% (HR 0.69, 95% CI 0.30 to 1.57) and 66% (HR 0.34, 95% CI 0.20 to 0.57) reduction in the risk of BC-related death for respectively PR positive luminal A and luminal B BC patients was found. Conclusion These results suggest that the prognostic effect of PR in primary operable BC depends on the tumor grade. Compared with luminal PR negative BC, PR positivity improves outcome more in luminal B than in luminal A lesions. Citation Format: Kathleen Van Asten, Ben Van Calster, Anneleen Lintermans, Olivier Brouckaert, Giuseppe Floris, Hans Wildiers, Patrick Neven. Prognostic value of the progesterone receptor by proliferation rate in patients with luminal HER2 negative breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-08-05.

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