Abstract PS13-32: Hormone- and HER2 receptor change in non-pCR breast cancer specimens after neoadjuvant treatment
Authors: Dimpfl Moritz , Degenhardt Tom , Mayr Doris , Schmoeckel Elisa , Harbeck Nadia , Wuerstlein Rachel 
Published: February 2021

Introduction: This study aimed at identification of breast cancer patients with a switched hormone- or HER2 receptor status after neoadjuvant chemotherapy. Therefore, patients without pathological complete response (pCR) were evaluated. The hormone and HER2 receptor status determined prior to neoadjuvant chemotherapy was compared with the corresponding receptor status determined in the surgical specimen after neoadjuvant chemotherapy.

Methods: Clinicopathological data of 249 patients, who received neoadjuvant treatment between 2016 and 2019 at the LMU breast center, Munich were reviewed. Among those, 129 patients (52%) with non-pCR were identified. Of those, 11 patients had a residual positive lymph node only. pCR was defined as absence of invasive tumor in breast and lymph node (ypT0/is; ypN0). According to German clinical guidelines, specimens were labeled hormone receptor positive, if ≥1% of tumor nuclei were reported estrogen receptor positive or ≥10% of tumor nuclei were reported progesterone receptor positive. Tumors were labeled HER2-positive if immunohistochemistry showed strong complete circular membrane staining of &gt;10% of invasive cells or if in-situ-hybridization showed HER2 positivity. Surgical specimens of patients with non-pCR were pathologically evaluated in order to 1) detect a receptor status switch compared to the analysis prior to neoadjuvant chemotherapy and 2) to see whether additional post neoadjuvant treatment options become available.

Results: The following results apply exclusively to non-pCR cases. Median age at diagnosis was 51 years, 27 patients were younger than 40. One male patient is included.A total of 36 cases (28%) switched either hormone- or HER2-status, including two cases of a simultaneous switch. In 19 cases, the hormone receptor status switched. 3 patients switched from hormone receptor negative to positive, while 16 switched from hormone receptor positive to negative. A total of 17 cases showed a switch in HER2 receptor status. 6 patients switched from HER2-negative to HER2-positive, while 11 switched from HER2-positive to HER2-negative. Due to technical limitations, HER2 status was not evaluable in two cases, and hormone receptor status in one case. See table below.

Conclusion: Our results illustrate, that a biomarker status switch after neoadjuvant treatment occurs in almost a third (28%) of cases. Reassessment of hormone- and HER2-receptor status subsequent to neoadjuvant treatment is still under discussion, with regard to post-neoadjuvant treatment. Nevertheless, it may have potential benefits for patients regarding individualization of treatment and potentially even patient outcome. At present, only gain of receptors should impact treatment concepts; in case of loss of receptors, treatment should not be changed as results in the residual tumor tissue may not reflect receptor status on disseminated tumor cells.

Biomarker status in patients with non-pCRBiomarrker status in patients with non-pCRStatus at initial diagnosisStatus in surgical non-pCR specimenCases with switch in biomarker status after NACHR positive99 (77%)85 (66%)3HR negative30 (23%)43 (34%)16HR total12912819 (15%)HER2 positive35 (27%)28 (22%)6HER2 negative94 (73%)99 (78%)11HER2 total12912717 (13%)Cases with switch in biomarker status36 (28%)

Citation Format: Moritz Dimpfl, Tom Degenhardt, Doris Mayr, Elisa Schmoeckel, Nadia Harbeck, Rachel Wuerstlein. Hormone- and HER2 receptor change in non-pCR breast cancer specimens after neoadjuvant treatment [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS13-32.