Frequent upregulation of HER2 protein in hormone-receptor-positive HER2-negative breast cancer after short-term neoadjuvant endocrine therapy. Breast Cancer Res Treat 2023 Oct;201(3):387-396
Date
07/18/2023Pubmed ID
37460683Pubmed Central ID
PMC10795510DOI
10.1007/s10549-023-07038-3Scopus ID
2-s2.0-85164922339 (requires institutional sign-in at Scopus site) 2 CitationsAbstract
BACKGROUND: Endocrine resistant metastatic disease develops in ~ 20-25% of hormone-receptor-positive (HR+) breast cancer (BC) patients despite endocrine therapy (ET) use. Upregulation of HER family receptor tyrosine kinases (RTKs) represent escape mechanisms in response to ET in some HR+ tumors. Short-term neoadjuvant ET (NET) offers the opportunity to identify early endocrine escape mechanisms initiated in individual tumors.
METHODS: This was a single arm, interventional phase II clinical trial evaluating 4 weeks (± 1 week) of NET in patients with early-stage HR+/HER2-negative (HER2-) BC. The primary objective was to assess NET-induced changes in HER1-4 proteins by immunohistochemistry (IHC) score. Protein upregulation was defined as an increase of ≥ 1 in IHC score following NET.
RESULTS: Thirty-seven patients with cT1-T3, cN0, HR+/HER2- BC were enrolled. In 35 patients with evaluable tumor HER protein after NET, HER2 was upregulated in 48.6% (17/35; p = 0.025), with HER2-positive status (IHC 3+ or FISH-amplified) detected in three patients at surgery, who were recommended adjuvant trastuzumab-based therapy. Downregulation of HER3 and/or HER4 protein was detected in 54.2% of tumors, whereas HER1 protein remained low and unchanged in all cases. While no significant volumetric reduction was detected radiographically after short-term NET, significant reduction in tumor proliferation rates were observed. No significant associations were identified between any clinicopathologic covariates and changes in HER1-4 protein expression on multivariable analysis.
CONCLUSION: Short-term NET frequently and preferentially upregulates HER2 over other HER family RTKs in early-stage HR+/HER2- BC and may be a promising strategy to identify tumors that utilize HER2 as an early endocrine escape pathway.
CLINICAL TRIAL REGISTRY: Trial registration number: NCT03219476.
Author List
Chaudhary LN, Jorns JM, Sun Y, Cheng YC, Kamaraju S, Burfeind J, Gonyo MB, Kong AL, Patten C, Yen T, Cortina CS, Carson E, Johnson N, Bergom C, Tsaih SW, Banerjee A, Wang Y, Chervoneva I, Weil E, Chitambar CR, Rui HAuthors
Anjishnu Banerjee PhD Associate Professor in the Institute for Health and Equity department at Medical College of WisconsinLubna N. Chaudhary MD Associate Professor in the Medicine department at Medical College of Wisconsin
Yee Chung Cheng MD Associate Professor in the Medicine department at Medical College of Wisconsin
Chandler S. Cortina MD Assistant Professor in the Surgery department at Medical College of Wisconsin
Mary Beth Gonyo MD Associate Professor in the Radiology department at Medical College of Wisconsin
Julie M. Jorns MD Professor in the Pathology department at Medical College of Wisconsin
Sailaja Kamaraju MD Associate Professor in the Medicine department at Medical College of Wisconsin
Amanda L. Kong MD, MS Professor in the Surgery department at Medical College of Wisconsin
Caitlin R. Patten MD, FACS Associate Professor in the Surgery department at Medical College of Wisconsin
Yunguang Sun MD, PhD Assistant Professor in the Pathology department at Medical College of Wisconsin
Shirng-Wern Tsaih Research Scientist II in the Obstetrics and Gynecology department at Medical College of Wisconsin
Tina W F Yen MD, MS Professor in the Surgery department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Antineoplastic Combined Chemotherapy ProtocolsBreast Neoplasms
Female
Humans
Neoadjuvant Therapy
Receptor, ErbB-2
Trastuzumab
Up-Regulation
