FGFR1 Amplification and Response to Neoadjuvant Anti-HER2 Treatment in Early HER2-Positive Breast Cancer

• Published in: Pharmaceutics 2022-01, Vol.14 (2), p.242
• Main Authors: Gaibar, María, Novillo, Apolonia, Romero-Lorca, Alicia, Malón, Diego, Antón, Beatriz, Moreno, Amalia, Fernández-Santander, Ana
• Format: Article
• Language: English
• Subjects: anti-HER2 treatment; Biopsy; Breast cancer; Cancer therapies; Cell cycle; Chemotherapy; CNVs; FGFR1 gene; Fibroblasts; Gene amplification; Gene expression; Growth factors; HER2-positive breast cancer; Kinases; Ligands; Lumpectomy; Medical prognosis; Miller–Payne grading; Monoclonal antibodies; pathological complete response; Patients; Surgery; Tumors
• ISSN: 1999-4923; 1999-4923
• DOI: 10.3390/pharmaceutics14020242

HER2-positive breast cancer (BC) is an aggressive subtype that affects 20-25% of BC patients. For these patients, neoadjuvant therapy is a good option that targets a pathological complete response (pCR) and more breast-conserving surgery. In effect, the outcomes of patients with HER2-positive BC have dramatically improved since the introduction of anti-HER2 antibodies such as trastuzumab (TZ) and/or pertuzumab (PZ) added to chemotherapy. This study sought to examine whether correlation exists between copy number variations (CNVs) in several genes related to the PI3K/AKT pathway ( and ) and the efficacy of anti-HER2 neoadjuvant treatment in patients with early HER2-positive BC. Forty-nine patients received TZ or PZ/TZ and chemotherapy as neoadjuvant treatment. Gene CNVs were determined by quantitative polymerase chain reaction on paraffin-embedded biopsy specimens. The response to 6 months of therapy was assessed by Miller-Payne grading of the tumor on surgical resection; grades 4 and 5, indicating >90% tumor reduction, were defined as a good response. A good response was shown by 64.5% and a pCR by 31.2% of patients. When stratified by anti-HER2 antibody received and gene CNV, it was found that patients with gene amplification or those with amplification treated with TZ alone showed a poor response ( = 0.024 and = 0.037, respectively). In the subset of patients treated with TZ/PZ combined, the pCR rate was significantly lower among those showing amplification ( = 0.021). Although based on a small sample size, our findings suggest that patients with amplification might benefit less from anti-HER2 antibody therapy.