Impact of HER2 Overexpression and Co-expression of Hormonal Receptors on Pathological Response after Neoadjuvant Chemotherapy in HER2-Positive Breast Cancer

Moscoso LO1, Ruiz-Merino G2, Salazar LE3, Iborra-Lacal E4, de Romaní SE5, Jiménez-Lucas MD6, Sisó C5, Cabezas-Herrera J7, Ramón y Cajal S3,8,9, Piñero-Madrona A10,11* and Peg V3,8,9*

1Department of Pathology, National Oncology Institute “Dr. Juan Tanca Marengo” ION-SOLCA, Ecuador
2Department of Statistics, Fundación para la Formación e Investigación Biosanitaria (FFIS), Spain
3Department of Pathology, Vall d'Hebron University Hospital, Spain
4Department of Pathology, Hospital Clínico Universitario “Virgen de la Arrixaca”, Spain
5Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, Spain
6Department of Medical Oncology, Hospital Clínico Universitario “Virgen de la Arrixaca”, Murcia, Spain
7Department of Basic and Translational Research, Instituto Murciano de Investigación Biosanitaria (IMIB-Arrixaca), Spain
8Universidad Autónoma de Barcelona, Spain
9Spanish Biomedical Research Network Centre in Oncology (CIBERONC), Spain
10Department of Surgery, Breast Surgery Unit, Hospital Clínico Universitario “Virgen de la Arrixaca”, Spain
11Instituto Murciano de Investigación Biosanitaria (IMIB-Arrixaca), Spain

^*Correspondance to: Antonio Pi�ero-Madrona 

 PDF  Full Text DOI: 10.25107/2474-1647.3626

Abstract

Background: HER2 overexpression in Breast Carcinomas (BC) has been associated with poorer prognosis and higher aggressiveness. The development of targeted therapies has changed the behavior of this disease. Targeted therapies became the optimal Neoadjuvant Chemotherapy (NAC), achieving high rates of complete Pathologic Response (pCR). The ASCO/CAP guidelines classify HER2 positive tumors either by immunohistochemistry (3+) and/or in situ hybridization (HER2 amplification), but no correlation with response is addressed. In this study, we asked whether all HER2-positive cases (IHC 2+/ISH+ vs. IHC 3+) show the same response to NAC aiming at pCR rates, and whether this can be influenced hormone receptors co-expression. Design: A retrospective series of 207 HER2-positive BC treated with NAC at two institutions between 2011 and 2017 was reviewed. Age, histologic type, TNM staging, treatment received, and pathological response were evaluated. HER2 and hormone receptor assessment was performed according to ASCO/CAP guidelines. Bivariate comparative analysis for the categorized qualitative and quantitative variables and multivariate analysis using logistic regression were performed. Results: Mean age was 53.9 years. pCR was observed in 116 cases (56%). 94,2% were carcinomas of no special type, 72 cases were non-luminal HER2 (34.8%) and 135 cases were Luminal B-HER2 positive (65%). Tumors with IHC 3+ presented a pCR rate of 60% compared to 29.6% of the IHC 2+/ ISH+ group (p=0.003), and the risk of achieving a pCR was three times higher in this first group (OR: 3.07 (1.24-7.59), p=0.015) (Table 1). Furthermore, non-luminal HER2 tumors presented 75% pCR (54/72) compared to 45.9% of luminal HER2-positive tumors (62/135) (p=0.0001). No differences in pCR rates were observed depending on Ki67 (p=0.179) or type of surgery or anti- HER2 treatment received (p=0.503). Conclusion: Overall, not all tumors classified as "HER2 positive" respond equally to NAC. pCR rates after NAC were higher in tumors with complete immunohistochemical overexpression (IHC 3+) and without hormone receptor co-expression (HER2 positive (non-Luminal). In addition, progesterone receptor co-expression was associated with lower pCR.

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Cite the article

Moscoso LO, Ruiz-Merino G, Salazar LE, Iborra-Lacal E, de Romaní SE, Jiménez-Lucas MD, et al. Impact of HER2 Overexpression and Coexpression of Hormonal Receptors on Pathological Response after Neoadjuvant Chemotherapy in HER2- Positive Breast Cancer. Clin Surg. 2023; 8: 3626.