HER2 Assessment to Define Outcomes for Breast Cancer Patients Treated with Neoadjuvant Therapy
Huan Cheng1, Yalai Bai1, William Sikov3, Natalie Sinclair3, Maysa Abu-Khalaf2, Lyndsay N. Harris4, and David L. Rimm1
Departments of 1Pathology and 2Internal Medicine, Yale School of Medicine, New Haven, CT; 3Department of Medicine, Brown University, Providence, RI; 4Division of Hematology and Oncology, Seidman Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA
ABSTRACT (Updated)
Background:
Assessments for HER2 protein overexpression or gene amplification are established companion diagnostic tests in breast cancer. Only patients with HER2+ cancers benefit from targeted therapies like trastuzumab, but it is not known if level of HER2 expression influences response. In this study, we quantitatively assess HER2 expression prior to neoadjuvant chemotherapy and trastuzumab in the BrUOG BR-211B (NCT00617942) trial to determine whether the level of expression of the target (HER2 protein) correlates with achievement of pathologic complete response (PathCR). We also study whether brief exposure to either trastuzumab or chemotherapy affects the level of HER2 expression or its predictive value.
Methods:
We evaluated core biopsy samples from breast cancer patients enrolled in a preoperative clinical trial using trastuzumab, nab-paclitaxel, and carboplatin combination therapy. Tumor core biopsies were taken before and 9-13 days after “run-in” doses of either trastuzumab or nab-paclitaxel, after which patients received combination chemotherapy and trastuzumab for 6 cycles (18 weeks) followed by surgery. PathCR was defined as the absence of invasive cancer in the breast and axillary nodes. Auto-mated quantitative analysis (AQUA), a fluorescent-based method for analysis of in situ protein expres-sion, was used to assess HER2 and phospho-HER2 expression.
Results:
Of 20 evaluable patients, the 10 with a PathCR showed a mean HER2 level of 10214 compared with 4766 in patients without PathCR (p = 0.0021, power = 0.938). This is notable in that a HER2 score of 2000 is equivalent to HER2 2+ (usually considered HER2-negative) in previous studies. Measurement of phospho-HER2 showed no difference between the PathCR and Non-PathCR groups. In 9 patients with repeat biopsies taken after the single “run-in” dose of trastuzumab, no significant change in HER2 or phospho-HER2 expression levels was detected.
Conclusions:
High levels of HER2 are associated with an increased likelihood of achieving a PathCR with the combination of chemotherapy and trastuzumab in the neoadjuvant setting. Levels of phospho-HER2 are not associated with response. Further studies are underway to determine changes in levels of HER2 immediately after treatment.
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