Predictive Markers of Treatment Response to Neoadjuvant Systemic Therapy with Dual HER2-Blockade
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 H...
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MDPI AG
2024-02-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/16/4/842 |
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| author | Soong June Bae Jee Hung Kim Min Ji Lee Seung Ho Baek Yoonwon Kook Sung Gwe Ahn Yoon Jin Cha Joon Jeong |
| author_facet | Soong June Bae Jee Hung Kim Min Ji Lee Seung Ho Baek Yoonwon Kook Sung Gwe Ahn Yoon Jin Cha Joon Jeong |
| author_sort | Soong June Bae |
| collection | DOAJ |
| description | 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; <i>p</i> < 0.001), HER2 protein expression (71.6% in IHC 3+ vs. 34.3% in IHC 2+; <i>p</i> < 0.001), and TIL levels (71.9% in high vs. 57.6% in low; <i>p</i> = 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. |
| first_indexed | 2024-03-07T22:38:33Z |
| format | Article |
| id | doaj.art-4c12c01553d041b4a338120cfe991857 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-07T22:38:33Z |
| publishDate | 2024-02-01 |
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| record_format | Article |
| series | Cancers |
| spelling | doaj.art-4c12c01553d041b4a338120cfe9918572024-02-23T15:11:24ZengMDPI AGCancers2072-66942024-02-0116484210.3390/cancers16040842Predictive Markers of Treatment Response to Neoadjuvant Systemic Therapy with Dual HER2-BlockadeSoong June Bae0Jee Hung Kim1Min Ji Lee2Seung Ho Baek3Yoonwon Kook4Sung Gwe Ahn5Yoon Jin Cha6Joon Jeong7Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Republic of KoreaInstitute for Breast Cancer Precision Medicine, Yonsei University College of Medicine, Seoul 06273, Republic of KoreaDepartment of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Republic of KoreaDepartment of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Republic of KoreaDepartment of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Republic of KoreaDepartment of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Republic of KoreaInstitute for Breast Cancer Precision Medicine, Yonsei University College of Medicine, Seoul 06273, Republic of KoreaDepartment of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Republic of KoreaIn 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; <i>p</i> < 0.001), HER2 protein expression (71.6% in IHC 3+ vs. 34.3% in IHC 2+; <i>p</i> < 0.001), and TIL levels (71.9% in high vs. 57.6% in low; <i>p</i> = 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.https://www.mdpi.com/2072-6694/16/4/842breast neoplasmneoadjuvant therapyHER2-targeted therapyHER2 expressiontumor-infiltrating lymphocyte |
| spellingShingle | Soong June Bae Jee Hung Kim Min Ji Lee Seung Ho Baek Yoonwon Kook Sung Gwe Ahn Yoon Jin Cha Joon Jeong Predictive Markers of Treatment Response to Neoadjuvant Systemic Therapy with Dual HER2-Blockade Cancers breast neoplasm neoadjuvant therapy HER2-targeted therapy HER2 expression tumor-infiltrating lymphocyte |
| title | Predictive Markers of Treatment Response to Neoadjuvant Systemic Therapy with Dual HER2-Blockade |
| title_full | Predictive Markers of Treatment Response to Neoadjuvant Systemic Therapy with Dual HER2-Blockade |
| title_fullStr | Predictive Markers of Treatment Response to Neoadjuvant Systemic Therapy with Dual HER2-Blockade |
| title_full_unstemmed | Predictive Markers of Treatment Response to Neoadjuvant Systemic Therapy with Dual HER2-Blockade |
| title_short | Predictive Markers of Treatment Response to Neoadjuvant Systemic Therapy with Dual HER2-Blockade |
| title_sort | predictive markers of treatment response to neoadjuvant systemic therapy with dual her2 blockade |
| topic | breast neoplasm neoadjuvant therapy HER2-targeted therapy HER2 expression tumor-infiltrating lymphocyte |
| url | https://www.mdpi.com/2072-6694/16/4/842 |
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