Predictors of successful neoadjuvant treatment in HER2‑positive breast cancer

Hännikäinen,Elli-Noora; Mattson,Johanna; Karihtala,Peeter

doi:10.3892/ol.2023.14021

Predictors of successful neoadjuvant treatment in HER2‑positive breast cancer

Authors:
- Elli-Noora Hännikäinen
- Johanna Mattson
- Peeter Karihtala
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Affiliations: Department of Oncology, Helsinki University Hospital Comprehensive Cancer Centre and University of Helsinki, FI‑00029 Helsinki, Finland
Published online on: August 22, 2023 https://doi.org/10.3892/ol.2023.14021
Article Number: 434
Copyright: © Hännikäinen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The prognosis of local or locally advanced human epidermal growth factor receptor 2 (HER2)‑positive breast cancer after a complete response from neoadjuvant systemic treatment (NAT) is excellent. However, some of the patients succumb to their disease, so novel predictive factors to identify these patients at risk are needed. Retrospective data from 119 patients treated at the Helsinki University Hospital Comprehensive Cancer Centre (Helsinki, Finland) were collected. All patients had in situ hybridization‑confirmed HER2‑positive breast cancer and underwent NAT with a curative intention. The primary tumours were relatively large, most patients had cytologically confirmed lymph node metastases and the treatments used were current regimens. A total of 63 (52.1%) patients had a pathological complete response (pCR) to neoadjuvant therapy. Achieving pCR predicted longer disease‑free survival (DFS; P=0.0083) but not overall survival (P=0.061). The patients with a pCR had an estimated DFS rate of 96.8% at 5 years, compared with only 59.7% of the patients with non‑pCR. Radiological complete response (CR) was associated with pCR (P=0.00033), although imaging yielded 30.4% false‑negative and 36.9% false‑positive results. The association between the radiological CR and pCR was more obvious in oestrogen receptor‑negative tumours. Moderate (compared with strong) immunohistochemical HER2 expression predicted a lower chance of pCR (P=0.0078) and worse breast cancer‑specific survival (P=0.0015). In conclusion, pCR after NAT served as an important prognostic factor in women with high‑risk HER2‑positive breast cancer. The patients with only moderate immunohistochemical HER2 expression had a lower chance of reaching a pCR, as well as a shorter breast cancer‑specific survival.

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1	Loibl S, Poortmans P, Morrow M, Denkert C and Curigliano G: Breast cancer. Lancet. 397:1750–1769. 2021. View Article : Google Scholar : PubMed/NCBI
2	Cortazar P, Zhang L, Untch M, Mehta K, Costantino JP, Wolmark N, Bonnefoi H, Cameron D, Gianni L, Valagussa P, et al: Articles Pathological complete response and long-term clinical benefit in breast cancer: The CTNeoBC pooled analysis. Lancet. 384:164–172. 2014. View Article : Google Scholar : PubMed/NCBI
3	Davey MG, Browne F, Miller N, Lowery AJ and Kerin MJ: Pathological complete response as a surrogate to improved survival in human epidermal growth factor receptor-2-positive breast cancer: Systematic review and meta-analysis. BJS Open. 6:zrac0282022. View Article : Google Scholar : PubMed/NCBI
4	Liu H, Lv L, Gao H and Cheng M: Pathologic complete response and its impact on breast cancer recurrence and patient's survival after neoadjuvant therapy: A comprehensive meta-analysis. Comput Math Methods Med. 2021:75450912021. View Article : Google Scholar : PubMed/NCBI
5	Harbeck N: Neoadjuvant and adjuvant treatment of patients with HER2-positive early breast cancer. Breast. 62 (Suppl 1):S12–S16. 2022. View Article : Google Scholar : PubMed/NCBI
6	Broglio KR, Quintana M, Foster M, Olinger M, McGlothlin A, Berry SM, Boileau JF, Brezden-Masley C, Chia S, Dent S, et al: Association of pathologic complete response to neoadjuvant therapy in HER2-Positive breast cancer with long-term outcomes: A meta-analysis. JAMA Oncol. 2:751–760. 2016. View Article : Google Scholar : PubMed/NCBI
7	von Minckwitz G, Huang CS, Mano MS, Loibl S, Mamounas EP, Untch M, Wolmark N, Rastogi P, Schneeweiss A, Redondo A, et al: Trastuzumab emtansine for residual invasive HER2-Positive breast cancer. N Engl J Med. 380:617–628. 2019. View Article : Google Scholar : PubMed/NCBI
8	Pathak M, Dwivedi SN, Deo SVS, Thakur B, Sreenivas V and Rath GK: Effectiveness of added targeted therapies to neoadjuvant chemotherapy for breast cancer: A systematic review and meta-analysis. Clin Breast Cancer. 19:e690–e700. 2019. View Article : Google Scholar : PubMed/NCBI
9	Bria E, Carbognin L, Furlanetto J, Pilotto S, Bonomi M, Guarneri V, Vicentini C, Brunelli M, Nortilli R, Pellini F, et al: Impact of neoadjuvant single or dual HER2 inhibition and chemotherapy backbone upon pathological complete response in operable and locally advanced breast cancer: Sensitivity analysis of randomized trials. Cancer Treat Rev. 40:847–856. 2014. View Article : Google Scholar : PubMed/NCBI
10	Nakashoji A, Hayashida T, Yokoe T, Maeda H, Toyota T, Kikuchi M, Watanuki R, Nagayama A, Seki T, Takahashi M, et al: The updated network meta-analysis of neoadjuvant therapy for HER2-positive breast cancer. Cancer Treat Rev. 62:9–17. 2018. View Article : Google Scholar : PubMed/NCBI
11	Wolff AC, Hammond MEH, Allison KH, Harvey BE, Mangu PB, Bartlett JMS, Bilous M, Ellis IO, Fitzgibbons P, Hanna W, et al: Human epidermal growth factor receptor 2 testing in breast cancer: American society of clinical oncology/college of American pathologists clinical practice guideline focused update. Arch Pathol Lab Med. 142:1364–1382. 2018. View Article : Google Scholar : PubMed/NCBI
12	Takada M, Ishiguro H, Nagai S, Ohtani S, Kawabata H, Yanagita Y, Hozumi Y, Shimizu C, Takao S, Sato N, et al: Survival of HER2-positive primary breast cancer patients treated by neoadjuvant chemotherapy plus trastuzumab: A multicenter retrospective observational study (JBCRG-C03 study). Breast Cancer Res Treat. 145:143–153. 2014. View Article : Google Scholar : PubMed/NCBI
13	von Minckwitz G, Untch M, Nüesch E, Loibl S, Kaufmann M, Kümmel S, Fasching PA, Eiermann W, Blohmer JU, Costa SD, et al: Impact of treatment characteristics on response of different breast cancer phenotypes: Pooled analysis of the German neo-adjuvant chemotherapy trials. Breast Cancer Res Treat. 125:145–156. 2011. View Article : Google Scholar : PubMed/NCBI
14	Santamaría G, Bargalló X, Fernández PL, Farrús B, Caparrós X and Velasco M: Neoadjuvant systemic therapy in breast cancer: Association of Contrast-enhanced MR imaging findings, diffusion-weighted imaging findings, and tumor subtype with tumor response. Radiology. 283:663–672. 2017. View Article : Google Scholar : PubMed/NCBI
15	Mukhtar RA, Yau C, Rosen M, Tandon VJ and Hylton N: I-SPY 1 TRIAL and ACRIN 6657 Investigators; Hylton N and Esserman LJ: Clinically meaningful tumor reduction rates vary by prechemotherapy MRI phenotype and tumor subtype in the I-SPY 1 tRIAL (CALGB 150007/150012; ACRIN 6657). Ann Surg Oncol. 20:3828–3830. 2013. View Article : Google Scholar
16	van Ramshorst MS, Loo CE, Groen EJ, Winter-Warnars GH, Wesseling J, van Duijnhoven F, Peeters MTV and Sonke GS: MRI predicts pathologic complete response in HER2-positive breast cancer after neoadjuvant chemotherapy. Breast Cancer Res Treat. 164:99–106. 2017. View Article : Google Scholar : PubMed/NCBI
17	De Los Santos JF, Cantor A, Amos KD, Forero A, Golshan M, Horton JK, Hudis CA, Hylton NM, McGuire K, Meric-Bernstam F, et al: Magnetic resonance imaging as a predictor of pathologic response in patients treated with neoadjuvant systemic treatment for operable breast cancer. Translational breast cancer research consortium trial 017. Cancer. 119:1776–1783. 2013. View Article : Google Scholar : PubMed/NCBI
18	LeVasseur N, Sun J, Gondara L, Diocee R, Speers C, Lohrisch C and Chia S: Impact of pathologic complete response on survival after neoadjuvant chemotherapy in early-stage breast cancer: A population-based analysis. J Cancer Res Clin Oncol. 146:529–536. 2020. View Article : Google Scholar : PubMed/NCBI
19	van der Voort A, Liefaard MC, van Ramshorst MS, van Werkhoven E, Sanders J, Wesseling J, Scholten A, Vrancken Peeters MJTFD, de Munck L, Siesling S and Sonke GS: Efficacy of neoadjuvant treatment with or without pertuzumab in patients with stage II and III HER2-positive breast cancer: A nationwide cohort analysis of pathologic response and 5-year survival. Breast. 65:110–115. 2022. View Article : Google Scholar : PubMed/NCBI
20	Gianni L, Pienkowski T, Im YH, Tseng LM, Liu MC, Lluch A, Starosławska E, de la Haba-Rodriguez J, Im SA, Pedrini JL, et al: 5-year analysis of neoadjuvant pertuzumab and trastuzumab in patients with locally advanced, inflammatory, or early-stage HER2-positive breast cancer (NeoSphere): A multicentre, open-label, phase 2 randomised trial. Lancet Oncol. 17:791–800. 2016. View Article : Google Scholar : PubMed/NCBI
21	Chen HL, Chen Q and Deng YC: Pathologic complete response to neoadjuvant anti-HER2 therapy is associated with HER2 immunohistochemistry score in HER2-positive early breast cancer. Medicine (Baltimore). 100:e276322021. View Article : Google Scholar : PubMed/NCBI
22	Wang Y, Singh K, Dizon D, Graves T, Amin A and Yakirevich E: Immunohistochemical HER2 score correlates with response to neoadjuvant chemotherapy in HER2-positive primary breast cancer. Breast Cancer Res Treat. 186:667–676. 2021. View Article : Google Scholar : PubMed/NCBI
23	Andersson J, Linderholm B, Bergh J and Elmberger G: HER-2/neu (c-erbB-2) Evaluation in primary breast carcinoma by fluorescent in situ hybridization and immunohistochemistry with special focus on intratumor heterogeneity and comparison of invasive and in situ components. Appl Immunohistochem Mol Morphol. 12:14–20. 2004. View Article : Google Scholar : PubMed/NCBI
24	Öhlschlegel C, Zahel K, Kradolfer D, Hell M and Jochum W: HER2 genetic heterogeneity in breast carcinoma. J Clin Pathol. 64:1112–1116. 2011. View Article : Google Scholar : PubMed/NCBI
25	Seol H, Lee HJ, Choi Y, Lee HE, Kim YJ, Kim JH, Kang E, Kim SW and Park SY: Intratumoral heterogeneity of HER2 gene amplification in breast cancer: Its clinicopathological significance. Mod Pathol. 25:938–948. 2012. View Article : Google Scholar : PubMed/NCBI
26	Modi S, Jacot W, Yamashita T, Sohn J, Vidal M, Tokunaga E, Tsurutani J, Ueno NT, Prat A, Chae YS, et al: Trastuzumab deruxtecan in previously treated HER2-Low advanced breast cancer. N Engl J Med. 387:9–20. 2022. View Article : Google Scholar : PubMed/NCBI