Comparison of HER2, estrogen and progesterone receptor expression profiles of primary tumor and synchronous axillary lymph node metastases in early breast cancer patients.

Background:

Targeted systemic therapy in early breast cancer with synchronous lymph node metastases (LNM) is currently based on the expression of the hormone receptors (ER/PR ≥1%) and overexpression of HER2 in the primary tumor. However, the expression of these predictive markers on LNM has not yet been taken into account. The aim of the present study was to compare the HER2/ER/PR expression profiles of primary tumors and synchronous LNM.

Patients and Methods:

177 patients with early breast cancer were enrolled in this study. Formalin-fixed and paraffin-embedded archival tissues of the primary tumors and the lymph node metastases were analyzed by two pathologists. ER, PR and HER2 expression was assessed by fully-automated immunohistochemistry (Ventana medical Systems, Tucson, AZ, USA) and HER2/CEN17 dual chromogenic in situ hybridization (Zytomed Systems, Berlin, Germany) according to modified ASCO/CAP guidelines (2010 and 2013, respectively).

Results:

The discordance rates between primary tumors and axillary LNM were 13% (22/177) for HER2, 9% (14/177) for ER and 19% (32/177) for PR.

The intrinsic subtypes between primary tumors and LNM changed in 20% of all cases (35/177 patients; gain of HER2 in 5/35, activation of HRs in 3/35 cases, loss of HER2 in 17/35 and loss of HRs in 10/35 cases becoming triple negative).

Conclusion:

Our preliminarily results demonstrate, that changes in subtypes are the rule rather than the exception.

Subtype shift may be of essential therapeutic significance for individual patients, larger studies should be enrolled to validate these data.