Abstract P2-05-13: Negative progesterone receptor is associate early breast cancer relapse, even among good prognosis tumors
Authors: Winner M , Rosman M , Mylander C , Jackson RS , Pozo ME , Wolff AC , Tafra L , Umbricht CB 
Published: March 2017

Background/objective: A minority of estrogen-receptor (ER) positive breast cancers lack progesterone receptor (PR) expression, but little is known of the clinical meaning of PR negativity (PR-). In the present study we sought to clarify the association between PR- and outcomes of ER+, human-epidermal growth factor (HER2)-negative breast cancers using a large, single institution database.

Methods: We retrospectively analyzed consecutive, non-metastatic, unilateral HER2- invasive breast cancers diagnosed between 2000 and 2011. Records were reviewed for age at diagnosis, disease stage, tumor features, and histologically confirmed recurrence. ER+ and PR+ status was defined as ≥1% immunoreactive cells. We used Kaplan-Meier curves to determine the association between PR- and early (≤5 years) and late (&gt;5 years) disease recurrence, defined as locoregional or distant breast cancer relapse &gt;6 months after diagnosis.

Results: We identified 1,933 patients with TN (n=337) or ER+/HER2- (n=1,596) breast cancer. Patients with ER+/PR- (n=107) vs. ER+/PR+ (n=1,489) tumors did not differ in age or disease stage at diagnosis; however, PR- tumors were more frequently high grade (37.9% vs. 17.8%, p&lt;0.001), with higher median Ki67 indices (20.0% vs. 10.0%, p&lt;0.001). Median ER expression was also lower in PR- as compared to PR+ tumors (80.0% vs. 90.0%, p&lt;0.001).

Over a median follow-up of 84 months, there were 119 early and 54 late locoregional or distant breast cancer relapses. Negative PR was strongly associated with early relapse, with PR- tumors demonstrating a 2.1-fold higher hazard of relapse in the first 5 years as compared to PR+ tumors (95% CI 1.0-4.2)

Hazards of early (&lt;5 years) breast cancer relapse by hormone status. Shown are univariable Cox proportional hazard ratios and 95% confidence intervals among all tumors, and in subsets defined by %ER, node status, Ki67, and grade. All tumors n=1,933High ER (80-100%) n=1,383TN3.9 (2.6-5.6)*--PR 0%2.1 (1.0-4.2)*1.7 (0.6-4.6)PR 1-100%ReferenceReference Node-negative n=1,299Node-positive n=634TN4.3 (2.5-7.5)*3.6 (2.1-6.0)*PR 0%2.7 (1.0-7.0)*1.6 (0.6-4.5)PR 1-100%ReferenceReference Ki67 &lt;14% n=768Ki67 ≥14% n=997TN**2.4 (1.5-3.8)*PR 0%4.1 (1.2-14.1)*1.6 (0.7-3.8)PR 1-100%ReferenceReference Grade 1/2 n=1,337Grade 3 n=564TN3.4 (1.4-7.9)*1.9 (1.2-3.3)*PR 0%2.0 (0.7-5.7)1.2 (0.4-3.5)PR 1-100%ReferenceReference*p&lt;0.05; **too few subjects/events for analysis.

Negative PR remained significantly associated with a higher hazard of early relapse even in node-negative (HR 2.7, 95%CI 1.0-7.0) and low-proliferating tumors (Ki67&lt;14%, HR 4.1, 95%CI 1.2-14.1). There was no significant association between PR- and late breast cancer relapse (HR 0.7, 95%CI 0.2-2.9).

Conclusions: Compared to ER+/PR+ breast cancers, ER+/PR- breast cancers have a significantly greater risk of early recurrence, similar to triple-negative cancers. These results suggest that negative PR expression is importantly and independently associated with early breast cancer prognosis, and may be an indicator of unique tumor biology.

Citation Format: Winner M, Rosman M, Mylander C, Jackson RS, Pozo ME, Wolff AC, Tafra L, Umbricht CB. Negative progesterone receptor is associate early breast cancer relapse, even among good prognosis tumors [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-05-13.