Top

Published in:

01-10-2021 | Breast Cancer | Brief Report

Is there a correlation between HER2 gene amplification level and response to neoadjuvant treatment with trastuzumab and chemotherapy in HER2-positive breast cancer?

Authors: Silvia Antolín, Lucía García-Caballero, Cristina Reboredo, Aurea Molina, Joaquín Mosquera, Ángel Vázquez-Boquete, Rosalía Gallego, Mari Paz Santiago, Ángel Concha, Eva Pérez, Lourdes Calvo, Tomás García-Caballero

Published in: Virchows Archiv | Issue 4/2021

Abstract

There are contradictory data regarding the correlation between HER2 amplification level determined by in situ hybridization and evolution after treatment with anti-HER2 therapies. The aim of this study was to correlate quantitative results of FISH (ratio HER2/CEP17 and number of HER2 signals/nucleus) with pathological response achieved after neoadjuvant treatment with trastuzumab and chemotherapy. For this purpose, we analysed 100 consecutive HER2-positive cases of breast carcinoma treated with neoadjuvant therapy. HER2 amplification determined by FISH was found in 92 of the 100 cases studied. pCR was obtained in 58% of the patients whose tumours presented amplification. In contrast, no pCR was obtained in the 8 patients with non-amplified tumours. A significant direct correlation between HER2 high amplification (HER2/CEP17 ratio > 5 or HER2 signals/nucleus > 10) and pCR was found. In conclusion, HER2 amplification levels are clinically relevant because they provide oncologists with valuable information on the possibilities of achieving pCR after neoadjuvant treatment.

Pegram MD, Lipton A, Hayes DF, Weber BL, Baselga JM, Tripathy D, Baly D, Baughman SA, Twaddell T, Glaspy JA, Slamon DJ (1998) Phase II study of receptor-enhanced chemosensitivity using recombinant humanized anti-p185HER2/neu monoclonal antibody plus cisplatin in patients with HER2/neu-overexpressing metastatic breast cancer refractory to chemotherapy treatment. J Clin Oncol 16:2659–2671. https://doi.org/10.1200/JCO.1998.16.8.2659CrossRefPubMed

Gianni L, Pienkowski T, Im YH, Roman L, Tseng LM, Liu MC, Lluch A, Staroslawska E, de la Haba-Rodriguez J, Im SA, Pedrini JL, Poirier B, Morandi P, Semiglazov V, Srimuninnimit V, Bianchi G, Szado T, Ratnayake J, Ross G, Valagussa P (2012) Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol 13:25–32. https://doi.org/10.1016/S1470-2045(11)70336-9CrossRefPubMed

Baselga J, Bradbury I, Eidtmann H, Di Cosimo S, de Azambuja E, Aura C, Gómez H, Dinh P, Fauria K, Van Dooren V, Aktan G, Goldhirsch A, Chang TW, Horváth Z, Coccia-Portugal M, Domont J, Tseng LM, Kunz G, Sohn JH, Semiglazov V, Lerzo G, Palacova M, Probachai V, Pusztai L, Untch M, Gelber RD, Piccart-Gebhart M, NeoALTTO Study Team (2012) Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet 379:633–640. https://doi.org/10.1016/S0140-6736(11)61847-3CrossRefPubMedPubMedCentral

Hurley J, Doliny P, Reis I, Silva O, Gomez-Fernandez C, Velez P, Pauletti G, Powell JE, Pegram MD, Slamon DJ (2006) Docetaxel, cisplatin, and trastuzumab as primary systemic therapy for human epidermal growth factor receptor 2-positive locally advanced breast cancer. J Clin Oncol 24:1831–1838. https://doi.org/10.1200/JCO.2005.02.8886CrossRefPubMed

Dowsett M, Procter M, McCaskill-Stevens W, de Azambuja E, Dafni U, Ruschoff J, Jordan B, Dolci S, Abramovitz M, Stoss O, Viale G, Gelber RD, Piccart-Gebhart M, Leyland-Jones B (2009) Disease-free survival according to degree of HER2 amplification for patients treated with adjuvant chemotherapy with or without 1 year of trastuzumab: the HERA Trial. J Clin Oncol 27:2962–2969. https://doi.org/10.1200/JCO.2008.19.7939CrossRefPubMedPubMedCentral

Perez EA, Reinholz MM, Hillman DW, Tenner KS, Schroeder MJ, Davidson NE, Martino S, Sledge GW, Harris LN, Gralow JR, Dueck AC, Ketterling RP, Ingle JN, Lingle WL, Kaufman PA, Visscher DW, Jenkins RB (2010) HER2 and chromosome 17 effect on patient outcome in the N9831 adjuvant trastuzumab trial. J Clin Oncol 28:4307–4315. https://doi.org/10.1200/JCO.2009.26.2154CrossRefPubMedPubMedCentral

Arnould L, Arveux P, Couturier J, Gelly-Marty M, Loustalot C, Ettore F, Sagan C, Antoine M, Penault-Llorca F, Vasseur B, Fumoleau P, Coudert BP (2007) Pathologic complete response to trastuzumab-based neoadjuvant therapy is related to the level of HER-2 amplification. Clin Cancer Res 13:6404–6409. https://doi.org/10.1158/1078-0432.CCR-06-3022CrossRefPubMed

Giuliani R, Durbecq V, Di Leo A, Paesmans M, Larsimont D, Leroy JY, Borms M, Vindevoghel A, Jerusalem G, D’Hondt V, Dirix L, Canon JL, Richard V, Cocquyt V, Majois F, Reginster M, Demol J, Kains JP, Delree P, Keppens C, Sotiriou C, Piccart MJ, Cardoso F (2007) Phosphorylated HER-2 tyrosine kinase and Her-2/neu gene amplification as predictive factors of response to trastuzumab in patients with HER-2 overexpressing metastatic breast cancer (MBC). Eur J Cancer 43:725–735. https://doi.org/10.1016/j.ejca.2006.11.019CrossRefPubMed

Fuchs EM, Köstler WJ, Horvat R, Hudelist G, Kubista E, Attems J, Zielinski CC, Singer CF (2014) High-level ERBB2 gene amplification is associated with a particularly short time-to-metastasis, but results in a high rate of complete response once trastuzumab-based therapy is offered in the metastatic setting. Int J Cancer 135:224–231. https://doi.org/10.1002/ijc.28660CrossRefPubMed

10.

Ogston KN, Miller D, Payne S, Hutcheon AW, Sarkar TK, Smith I, Schofield A, Heys SD (2003) A new histological grading system to assess response of breast cancers to primary chemotherapy: prognostic significance and survival. Breast 12:320–327. https://doi.org/10.1016/s0960-9776(03)00106-1CrossRefPubMed

11.

Meisel JL, Zhao J, Suo A, Zhang C, Wei Z, Taylor C, Aneja R, Krishnamurti U, Li Z, Nahta R, O’Regan R, Li X (2020) Clinicopathologic factors associated with response to neoadjuvant anti-HER2-directed chemotherapy in HER2-positive breast cancer. Clin Breast Cancer 20:19–24. https://doi.org/10.1016/j.clbc.2019.09.003CrossRefPubMed

12.

Singer CF, Tan YY, Fitzal F, Steger GG, Egle D, Reiner A, Rudas M, Moinfar F, Gruber C, Petru E, Bartsch R, Tendl KA, Fuchs D, Seifert M, Exner R, Balic M, Bago-Horvath Z, Filipits M, Gnant M, Austrian Breast and Colorectal Cancer Study Group (2017) Pathological complete response to neoadjuvant trastuzumab is dependent on HER2/CEP17 ratio in HER2-amplified early breast cancer. Clin Cancer Res 23:3676–3683. https://doi.org/10.1158/1078-0432.CCR-16-2373CrossRefPubMed

13.

Schneeweiss A, Chia S, Hegg R, Tausch C, Deb R, Ratnayake J, McNally V, Ross G, Kiermaier A, Cortés J (2014) Evaluating the predictive value of biomarkers for efficacy outcomes in response to pertuzumab- and trastuzumab-based therapy: an exploratory analysis of the TRYPHAENA study. Breast Cancer Res 16:R73. https://doi.org/10.1186/bcr3690CrossRefPubMedPubMedCentral

14.

Veeraraghavan J, Angelis C, Mao R, Wang T, Herrera S, Pavlick AC, Contreras A, Nuciforo P, Mayer IA, Forero A, Nanda R, Goetz MP, Chang JC, Wolff AC, Krop IE, Fuqua SAW, Prat A, Hilsenbeck SG, Weigelt B, Reis-Filho JS, Gutierrez C, Osborne CK, Rimawi MF, Schiff R (2019) A combinatorial biomarker predicts pathologic complete response to neoadjuvant lapatinib and trastuzumab without chemotherapy in patients with HER2+ breast cancer. Ann Oncol 30:927–933. https://doi.org/10.1093/annonc/mdz076CrossRefPubMedPubMedCentral

15.

Choi JH, Jeon CW, Kim YO, Jung S (2020) Pathological complete response to neoadjuvant trastuzumab and pertuzumab therapy is related to human epidermal growth factor receptor 2 (HER2) amplification level in HER2-amplified breast cancer. Medicine (Baltimore) 99:e23053. https://doi.org/10.1097/MD.0000000000023053CrossRef

Title: Is there a correlation between HER2 gene amplification level and response to neoadjuvant treatment with trastuzumab and chemotherapy in HER2-positive breast cancer?
Authors: Silvia Antolín
Lucía García-Caballero
Cristina Reboredo
Aurea Molina
Joaquín Mosquera
Ángel Vázquez-Boquete
Rosalía Gallego
Mari Paz Santiago
Ángel Concha
Eva Pérez
Lourdes Calvo
Tomás García-Caballero
Publication date: 01-10-2021
Publisher: Springer Berlin Heidelberg
Keywords: Breast Cancer
Breast Cancer
Anthracycline
Trastuzumab
Cytostatic Therapy
Published in: Virchows Archiv / Issue 4/2021
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI: https://doi.org/10.1007/s00428-021-03104-7

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Is there a correlation between HER2 gene amplification level and response to neoadjuvant treatment with trastuzumab and chemotherapy in HER2-positive breast cancer?

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 4/2021

Correction to: 33rd European Congress of Pathology – Abstracts

Concurrent epithelioid hemangioma and diffuse cavernous hemangioma in the rectum clinically mimicking a malignant tumor: a case report

Correction to: Keratin 7 expression in hepatic cholestatic diseases

Prognostic relevance and putative histogenetic role of cytokeratin 7 and MUC5AC expression in Crohn’s disease-associated small bowel carcinoma

Genome-wide copy number variations as molecular diagnostic tool for cutaneous intermediate melanocytic lesions: a systematic review and individual patient data meta-analysis

High-risk individuals for gastric cancer would be missed for surveillance without subtyping of intestinal metaplasia