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- Title
Predictive Markers of Treatment Response to Neoadjuvant Systemic Therapy with Dual HER2-Blockade.
- Authors
Bae, Soong June; Kim, Jee Hung; Lee, Min Ji; Baek, Seung Ho; Kook, Yoonwon; Ahn, Sung Gwe; Cha, Yoon Jin; Jeong, Joon
- Abstract
Simple Summary: In human epidermal growth factor receptor 2 (HER2)-positive breast cancer treated with neoadjuvant systemic therapy with docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP), estrogen receptor (ER) expression, HER2 protein expression, and tumor-infiltrating lymphocyte (TIL) levels are significantly associated with pathologic complete response (pCR). In ER-negative or low-ER (1–9%) breast cancer, treatment response is excellent, regardless of HER2 protein expression and TIL levels. Meanwhile, the pCR rate is notably lower in patients with ER-positive, HER2 immunohistochemistry (IHC) 2+ breast cancer, particularly in those with low TIL levels. Further investigation of novel treatment strategies for ER-positive breast cancer with HER2 IHC 2+ or low TIL levels is warranted. In patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer, achievement of pathologic complete response (pCR) is a known prognostic indicator after neoadjuvant systemic therapy (NAST). We investigated the clinicopathological factors associated with pCR in patients with HER2-positive breast cancer treated with dual HER2-blockade. In this retrospective study, 348 patients with HER2-positive breast cancer who received NAST with docetaxel and carboplatin, combined with trastuzumab and pertuzumab (TCHP), were included. Of the 348 patients with HER2 protein expression data, 278 (79.9%) had HER2 immunochemistry (IHC) 3+. Data on tumor-infiltrating lymphocyte (TIL) levels were available for 305 patients, showing a median TIL level of 20% (IQR 5–50), among which 121 (39.7%) had high TIL levels (≥30%). Estrogen receptor (ER) status (77.9% in ER-negative vs. 47.5% in ER-positive; p < 0.001), HER2 protein expression (71.6% in IHC 3+ vs. 34.3% in IHC 2+; p < 0.001), and TIL levels (71.9% in high vs. 57.6% in low; p = 0.011) were significantly associated with the pCR rate. In addition, we observed a significant link between numerical TIL levels (per 10% increment) and the pCR rate. After adjusting other clinicopathologic factors, ER status (low expression [defined as 1–9% expression] or negative), HER2 IHC 3+ and numerical TIL levels (per 10% increment), and high TIL levels (≥30%) were found to be independent predictors of pCR. Notably, in ER-negative breast cancer, the treatment response was excellent, irrespective of HER2 expression and TIL levels. Conversely, in ER-positive cases, low ER expression, HER2 IHC 3+, and numerical TIL levels or high TIL levels emerged as independent predictors of pCR. Our results suggest that ER expression, HER2 protein expression, and TIL levels serve as valuable predictors of the treatment response to neoadjuvant TCHP.
- Subjects
CARBOPLATIN; ONCOGENES; IMMUNOHISTOCHEMISTRY; MONOCLONAL antibodies; ANTINEOPLASTIC agents; RETROSPECTIVE studies; GENE expression; LYMPHOCYTES; DESCRIPTIVE statistics; DOCETAXEL; RESEARCH funding; COMBINED modality therapy; POLYMERASE chain reaction; BREAST tumors
- Publication
Cancers, 2024, Vol 16, Issue 4, p842
- ISSN
2072-6694
- Publication type
Article
- DOI
10.3390/cancers16040842