<i>FGFR1</i> Amplification and Response to Neoadjuvant Anti-HER2 Treatment in Early HER2-Positive Breast Cancer
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 hav...
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MDPI AG
2022-01-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/2/242 |
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| author | María Gaibar Apolonia Novillo Alicia Romero-Lorca Diego Malón Beatriz Antón Amalia Moreno Ana Fernández-Santander |
| author_facet | María Gaibar Apolonia Novillo Alicia Romero-Lorca Diego Malón Beatriz Antón Amalia Moreno Ana Fernández-Santander |
| author_sort | María Gaibar |
| collection | DOAJ |
| description | 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 (<i>HER2, FGFR1, PIK3CA, AKT3</i> and <i>MDM2</i>) 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 <i>FGFR1</i> gene amplification or those with <i>FGFR1</i> amplification treated with TZ alone showed a poor response (<i>p</i> = 0.024 and <i>p</i> = 0.037, respectively). In the subset of patients treated with TZ/PZ combined, the pCR rate was significantly lower among those showing <i>FGFR1</i> amplification (<i>p</i> = 0.021). Although based on a small sample size, our findings suggest that patients with <i>FGFR1</i> amplification might benefit less from anti-HER2 antibody therapy. |
| first_indexed | 2024-03-09T21:14:45Z |
| format | Article |
| id | doaj.art-2b4348e3d6dc44aebcbca7300832cb98 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T21:14:45Z |
| publishDate | 2022-01-01 |
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| record_format | Article |
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| spelling | doaj.art-2b4348e3d6dc44aebcbca7300832cb982023-11-23T21:36:01ZengMDPI AGPharmaceutics1999-49232022-01-0114224210.3390/pharmaceutics14020242<i>FGFR1</i> Amplification and Response to Neoadjuvant Anti-HER2 Treatment in Early HER2-Positive Breast CancerMaría Gaibar0Apolonia Novillo1Alicia Romero-Lorca2Diego Malón3Beatriz Antón4Amalia Moreno5Ana Fernández-Santander6Health Sciences Faculty, Universidad Francisco de Vitoria, 28223 Madrid, SpainBiomedical and Health Sciences Faculty, Universidad Europea de Madrid, 28670 Madrid, SpainBiomedical and Health Sciences Faculty, Universidad Europea de Madrid, 28670 Madrid, SpainDepartment of Oncology, University Hospital of Fuenlabrada, 28942 Madrid, SpainDepartment of Oncology, University Hospital of Fuenlabrada, 28942 Madrid, SpainDepartment of Oncology, University Hospital of Fuenlabrada, 28942 Madrid, SpainBiomedical and Health Sciences Faculty, Universidad Europea de Madrid, 28670 Madrid, SpainHER2-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 (<i>HER2, FGFR1, PIK3CA, AKT3</i> and <i>MDM2</i>) 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 <i>FGFR1</i> gene amplification or those with <i>FGFR1</i> amplification treated with TZ alone showed a poor response (<i>p</i> = 0.024 and <i>p</i> = 0.037, respectively). In the subset of patients treated with TZ/PZ combined, the pCR rate was significantly lower among those showing <i>FGFR1</i> amplification (<i>p</i> = 0.021). Although based on a small sample size, our findings suggest that patients with <i>FGFR1</i> amplification might benefit less from anti-HER2 antibody therapy.https://www.mdpi.com/1999-4923/14/2/242HER2-positive breast canceranti-HER2 treatment<i>FGFR1</i> geneCNVspathological complete responseMiller–Payne grading |
| spellingShingle | María Gaibar Apolonia Novillo Alicia Romero-Lorca Diego Malón Beatriz Antón Amalia Moreno Ana Fernández-Santander <i>FGFR1</i> Amplification and Response to Neoadjuvant Anti-HER2 Treatment in Early HER2-Positive Breast Cancer Pharmaceutics HER2-positive breast cancer anti-HER2 treatment <i>FGFR1</i> gene CNVs pathological complete response Miller–Payne grading |
| title | <i>FGFR1</i> Amplification and Response to Neoadjuvant Anti-HER2 Treatment in Early HER2-Positive Breast Cancer |
| title_full | <i>FGFR1</i> Amplification and Response to Neoadjuvant Anti-HER2 Treatment in Early HER2-Positive Breast Cancer |
| title_fullStr | <i>FGFR1</i> Amplification and Response to Neoadjuvant Anti-HER2 Treatment in Early HER2-Positive Breast Cancer |
| title_full_unstemmed | <i>FGFR1</i> Amplification and Response to Neoadjuvant Anti-HER2 Treatment in Early HER2-Positive Breast Cancer |
| title_short | <i>FGFR1</i> Amplification and Response to Neoadjuvant Anti-HER2 Treatment in Early HER2-Positive Breast Cancer |
| title_sort | i fgfr1 i amplification and response to neoadjuvant anti her2 treatment in early her2 positive breast cancer |
| topic | HER2-positive breast cancer anti-HER2 treatment <i>FGFR1</i> gene CNVs pathological complete response Miller–Payne grading |
| url | https://www.mdpi.com/1999-4923/14/2/242 |
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