Abstract P6-09-40: Her2 and hormonal receptor analysis in breast cancer synchronic node metastases could add therapeutic information
Authors: Rizzo MM , Mando P , Perez de la Puente C , Maino M , Ponce C , Fabiano V , Pombo MT , Loza CM , Costanzo MV , Nervo A , Nadal J , Colo F , Chacon RD 
Published: March 2017

Introduction: Breast cancer is the tumor with highest incidence and mortality in women in Argentina. Hormonal receptors (HR) and HER2 are the most important prognostic and predictive factors. It is suggested that estrogen receptors (ER), progesterone receptors (PR) and HER2 expression can vary during tumor progression and metastases development. Published evidence has reported discordance between primary tumors and its metastases ranging from 15-54% for HR and HER2 overexpression. A similar discordance situation may exist among primary tumor (PT) and its axillary nodal metastases (NM)

Objective: To describe the expression and discordance of ER, PR and HER2 in PT and its synchronic NM

Material and methods: Prospective analysis of surgical breast cancer patients (pts) at Instituto Alexander Fleming (Sept 2013 to Feb 2016). HR were analyzed by immunohistochemistry (IHC) according to CAP protocols; values ≥ 10% were considered positive. HER2 overexpression was defined by 3+ IHC or positive FISH. Paired t test was used to compare mean using Prims 5 software.

Results: In 587 breast cancer surgeries, 190 pts presented NM. HR and HER2 analysis was performed in 101 paired samples. Median age was 51 years (r 25-83). Mean tumor size was 3,3 ± 0,2 cm. 0,99% (1) were stage I, 68,3% (69) stage II and 30,7% (31) stage III. Most frequent histologic subtype was ductal carcinoma (66.3%). 78.2% presented lymphovascular invasion. Median positive nodes were 2 (r 1-21). Paired samples allowed ER analysis in 99 cases, PR in 98 and HER2 in 96; 8 NM were Her2++; FISH analysis was inconclusive in 4 of them due to insufficient tissue. No differences were observed on ER between PT and NM (72% vs 71.1%, OR: 0,91, IC95 -3.2-5.1; p&gt;0,05), nor PR expression (52.1% vs 54,5%, OR: -2.1, IC95 -7.1-3.01; p&gt;0,05). PT were ER+ in 86.1% of the cases; NM were ER+ in 82.2%. Regarding PR, PT were 74.3% PR+ and NM were 76.2% PR+. 28 of the 101 pts (27.7%) were discordant. 5 pts with ER+ PT had ER- NM, and 3 pts had PT ER- but ER+ NM, representing a 7.9% of discordance. 4 of 75 pts with PR+ in PT were PR- in NM, while 8 of 26 pts were PR- in PT but PR+ in NM. Of the 13 HER2+ pts, 2 (15%) did not present overexpression in NM. On the other hand, 6 (7%) of the 83 HER2- PT were HER2+ in NM. 4 of 9 pts had PT RH and Her2- (TN), but NM RH and/or Her2+.

Discussion: Tumor heterogeneity is an important issue that may affect clinical decisions. Axillary nodes are the first metastatic site for breast cancer and different studies have shown discrepancy between PT and NM. We described a discordant expression in ER, PR and HER2 of 8%, 12% and 9% respectively. These differences could be due to technical reasons, intratumor heterogeneity and/or a different cellular phenotype. Although the clinical importance of these changes are not completely understood, NM status could bring important prognostic and therapeutic information defining a particular group of patients in which a specific therapeutic strategy could influence long term results. In fact, in our series 44% of TN tumors presented NM with a therapeutic target, either HR or HER2. We therefore confirm that pathological analysis of NM may bring up additional information that could be useful in a prognostic or therapeutic point of view.

Citation Format: Rizzo MM, Mando P, Perez de la Puente C, Maino M, Ponce C, Fabiano V, Pombo MT, Loza CM, Costanzo MV, Nervo A, Nadal J, Colo F, Chacon RD. Her2 and hormonal receptor analysis in breast cancer synchronic node metastases could add therapeutic information [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 P6-09-40.