Abstract P1-01-14: Do estrogen receptor negative and progesterone receptor positive breast tumors really exist? Attitude for not making them real
Authors: Molly D , Bertaut A , Blanchet C , Beltjens F , Charon-Barra C , Loustalot C , Desmoulins I , Arnould L 
Published: May 2016

Background: Breast tumors with negative estrogen receptor (ER-) and positive progesterone receptor (PR+) are rare (from 0 to 3.4 % according to the studies), and their existence is contested. These markers determine cancer molecular subtypes which play a determinant role for both the management and the prognosis of breast cancers. It is then essential to document the real existence of ER-/PR+ tumors. The present study aimed at determining if ER-/PR+ tumors share more basal or luminal characteristics.

Methods: Between 2000 and 2015, 50 patients with ER-/PR+ breast tumors, representing 0.6 % of all breast cancers diagnosed in our institution, were included in this study. Their clinical (age, node status), morphological (size, histological type, Elston and Ellis (EE) grade, necrosis, inflammation, pushing margins, central scar, mitotic index) and immunohistochemical characteristics (ER, PR, HER2, CK5/6 and EGFR status) were compared with those of 50 luminal and 50 triple negative (TN) tumors randomly selected in our lab database. At the time this abstract is written, the Ki67 index determination is still in progress. Five of these ER-/PR+ tumors were also given a molecular test (Nanostring). Qualitative variables were compared using Chi2 or Fisher test, quantitative variables were compared using Student or Mann & Whitney tests. To take into account for multiple comparisons, p-values less than 0.025 were considered as significant.

Results: The results are summarized in table 1. For almost all the analyzed criteria, ER-/PR+ tumors present statistical difference with luminal ones. On the contrary, they share most of TN tumors characteristics. The 5 molecular analyzes performed on ER-/PR+ samples showed the following phenotypes: 3 basal, 1 HER2 enriched and 1 luminal. For this last one, new immunohistological analyzes reveal in fact an ER+ staining.

Table 1: Study results ER-/PR+ tumorsER+ tumorsTN tumorsp ER-/PR+ vs ER+p ER-/PR+ vs TNSize (mm)23.12525.20.00440.4822Histological type0.00120.2424 ductal9480.4100  lobular219.60  neuro-endocrine40 Differentiation&lt;10-40.4497 well09.80  moderately12.548.818  poorly87.541.582 EE grade&lt;10-40.1016 14.135.34  236.74918  359.215.778 EE differentiation&lt;10-40.3197 105.90  214.341.222  385.752.978 EE nuclear atypia&lt;10-40.2227 102  234.774.522  365.325.576 EE mitosis&lt;10-40.0123 124.580.418  230.613.710  344.95.972 Mitotic index (mitoses/mm2)9.52.210.2&lt;10-40.1252Necrosis465.952&lt;10-40.5484Inflammation0.00030.0011 yes30224  no4474.516  weak2623.560 CK5/6 +78.74.280.4&lt;10-40.8378EGFR +44.74.252.2&lt;10-40.4697HER2 +29.87.800.0051&lt;10-4Results are given in %, excepting mitotic index and size

Conclusion: This study tends to support that ER-/PR+ tumors may not exist and are likely to be TN cancers or less frequently false negative ER+ tumors. In a practical point of view, we think that 1) when a tumor shows ER-/PR+ and TN characteristics, it is probably a false positive PR staining, and the tumor has to be considered as a TN one, 2) when an ER-/PR+ tumor don't fit the triple negative tumors characteristics, ER must be retested in order to exclude a true luminal tumor.

Citation Format: Molly D, Bertaut A, Blanchet C, Beltjens F, Charon-Barra C, Loustalot C, Desmoulins I, Arnould L. Do estrogen receptor negative and progesterone receptor positive breast tumors really exist? Attitude for not making them real. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-01-14.