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Impact of HER2 status on clinicopathological characteristics and pathological complete response to neoadjuvant chemotherapy in triple-negative breast cancer

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Abstract

Purpose

HER2-low triple-negative breast cancer (TNBC) accounted for up to 34%–39% of primary TNBC and 22.2%–32% of metastatic TNBC. Our study aims to explore the relationship between HER2 expression and clinicopathological characteristics, analyze the impact of HER2 expression on the pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in TNBC.

Methods

This study involved 191 patients with TNBC who underwent operation after NAC from October 2021 to August 2022. Clinicopathological characteristics and the frequency of pCR were compared between HER2-low and HER2-0 TNBC.

Results

42.2% (81/191) patients in our cohort were HER2-low. They exhibited differences in menopausal status, body mass index (BMI), androgen receptor (AR) expression, and histological grade (P < 0.05). Particularly, in HER2-low TNBC, AR was associated with tumor size, lymph node metastase, histological grade, and the incidence of multifocal disease (P < 0.05). The total pCR rate of entire cohor was 39.8%. Tumor size (P = 0.025), AR status (P = 0.033) and histological grade (P = 0.007) were significantly associated with the pCR rate of them, while the HER2 status did not exert a similar association. The multivariate analysis revealed that BMI (P = 0.004) and histological grade (P < 0.001) were associated with pCR of HER2-low TNBC, while tumor size (P = 0.034) and AR (P = 0.034) were associated with pCR of HER2-0 TNBC, respectively.

Conclusions

In our cohort, HER2-low TNBC patients exhibits specific clinical characteristics and response features to NAC.

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Data availability

Enquiries about data availability should be directed to the authors.

References

  1. Bianchini G, De Angelis C, Licata L, Gianni L (2022) Treatment landscape of triple-negative breast cancer—expanded options, evolving needs. Nat Rev Clin Oncol 19:91–113. https://doi.org/10.1038/s41571-021-00565-2

    Article  CAS  PubMed  Google Scholar 

  2. Corti C, Giugliano F, Nicolò E, Tarantino P, Criscitiello C, Curigliano G (2023) HER2-low breast cancer: a new subtype? Curr Treat Options Oncol 24:468–478. https://doi.org/10.1007/s11864-023-01068-1

    Article  PubMed  Google Scholar 

  3. Wolff AC, Hammond MEH, Allison KH, Harvey BE, Mangu PB, Bartlett JMS et al (2018) 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. https://doi.org/10.5858/arpa.2018-0902-SA

    Article  PubMed  Google Scholar 

  4. Tarantino P, Hamilton E, Tolaney SM, Cortes J, Morganti S, Ferraro E et al (2020) HER2-low breast cancer: pathological and clinical landscape. J Clin Oncol 38:1951–1962. https://doi.org/10.1200/JCO.19.02488

    Article  CAS  PubMed  Google Scholar 

  5. Denkert C, Seither F, Schneeweiss A, Link T, Blohmer JU, Just M et al (2021) Clinical and molecular characteristics of HER2-low-positive breast cancer: pooled analysis of individual patient data from four prospective, neoadjuvant clinical trials. Lancet Oncol 22:1151–1161. https://doi.org/10.1016/S1470-2045(21)00301-6

    Article  CAS  PubMed  Google Scholar 

  6. Gampenrieder SP, Dezentjé V, Lambertini M, De Nonneville A, Marhold M, Le Du F et al (2023) Influence of HER2 expression on prognosis in metastatic triple-negative breast cancer—results from an international, multicenter analysis coordinated by the AGMT Study Group. ESMO Open 8:100747. https://doi.org/10.1016/j.esmoop.2022.100747

    Article  CAS  PubMed  Google Scholar 

  7. Fehrenbacher L, Cecchini RS, Geyer CE, Rastogi P, Costantino JP, Atkins JN et al (2020) NSABP B-47/NRG oncology phase III randomized trial comparing adjuvant chemotherapy with or without trastuzumab in high-risk invasive breast cancer negative for HER2 by FISH and With IHC 1+ or 2+. J Clin Oncol 38:444–453. https://doi.org/10.1200/JCO.19.01455

    Article  CAS  PubMed  Google Scholar 

  8. Modi S, Jacot W, Yamashita T, Sohn J, Vidal M, Tokunaga E et al (2022) Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer. N Engl J Med 387:9–20. https://doi.org/10.1056/NEJMoa2203690

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Chick RC, Clifton GT, Hale DF, Vreeland TJ, Hickerson AT, Kemp Bohan PM et al (2021) Subgroup analysis of nelipepimut-S plus GM-CSF combined with trastuzumab versus trastuzumab alone to prevent recurrences in patients with high-risk, HER2 low-expressing breast cancer. Clin Immunol 225:108679. https://doi.org/10.1016/j.clim.2021.108679

    Article  CAS  PubMed  Google Scholar 

  10. Venema CM, Bense RD, Steenbruggen TG, Nienhuis HH, Qiu SQ, Van Kruchten M et al (2019) Consideration of breast cancer subtype in targeting the androgen receptor. Pharmacol Ther 200:135–147. https://doi.org/10.1016/j.pharmthera.2019.05.005

    Article  CAS  PubMed  Google Scholar 

  11. Cortazar P, Zhang L, Untch M, Mehta K, Costantino JP, Wolmark N et al (2014) Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet 384:164–172. https://doi.org/10.1016/S0140-6736(13)62422-8

    Article  PubMed  Google Scholar 

  12. Hu XE, Yang P, Chen S, Wei G, Yuan L, Yang Z et al (2023) Clinical and biological heterogeneities in triple-negative breast cancer reveals a non-negligible role of HER2-low. Breast Cancer Res 25:34. https://doi.org/10.1186/s13058-023-01639-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Ma Y, Jiao D, Zhang J, Lv M, Chen X, Liu Z (2023) HER2-low status was associated with better breast cancer-specific survival in early-stage triple-negative breast cancer. Oncologist. https://doi.org/10.1093/oncolo/oyad275

    Article  PubMed  PubMed Central  Google Scholar 

  14. Leon-Ferre RA, Goetz MP (2023) Advances in systemic therapies for triple negative breast cancer. BMJ 381:e071674. https://doi.org/10.1136/bmj-2022-071674

    Article  PubMed  Google Scholar 

  15. Thomas A, Teicher BA, Hassan R (2016) Antibody–drug conjugates for cancer therapy. Lancet Oncol 17:e254–e262. https://doi.org/10.1016/S1470-2045(16)30030-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. (2022) T-DXd: new standard for HER2-low breast cancer. Cancer Discov 12:1828. https://doi.org/10.1158/2159-8290.Cd-nb2022-0043

  17. Narayan P, Dilawari A, Osgood C, Feng Z, Bloomquist E, Pierce WF et al (2023) US Food and Drug Administration approval summary: fam-trastuzumab deruxtecan-nxki for human epidermal growth factor receptor 2-low unresectable or metastatic breast cancer. J Clin Oncol 41:2108–2116. https://doi.org/10.1200/JCO.22.02447

    Article  CAS  PubMed  Google Scholar 

  18. Schreiber AR, O’bryant CL, Kabos P, Diamond JR (2023) The emergence of targeted therapy for HER2-low triple-negative breast cancer: a review of fam-trastuzumab deruxtecan. Expert Rev Anticancer Ther 23:1061–1069. https://doi.org/10.1080/14737140.2023.2257885

    Article  CAS  PubMed  Google Scholar 

  19. Li Y, Tsang JY, Tam F, Loong T, Tse GM (2023) Comprehensive characterization of HER2-low breast cancers: implications in prognosis and treatment. EBioMedicine 91:104571. https://doi.org/10.1016/j.ebiom.2023.104571

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Jacot W, Maran-Gonzalez A, Massol O, Sorbs C, Mollevi C, Guiu S et al (2021) Prognostic value of HER2-low expression in non-metastatic triple-negative breast cancer and correlation with other biomarkers. Cancers 13:6059. https://doi.org/10.3390/cancers13236059

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Lehmann BD, Bauer JA, Chen X, Sanders ME, Chakravarthy AB, Shyr Y et al (2011) Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest 121:2750–2767. https://doi.org/10.1172/JCI45014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Choupani E, Gomari MM, Zanganeh S, Nasseri S, Haji-Allahverdipoor K, Rostami N et al (2023) Newly developed targeted therapies against the androgen receptor in triple-negative breast cancer: a review. Pharmacol Rev 75:309–327. https://doi.org/10.1124/pharmrev.122.000665

    Article  CAS  PubMed  Google Scholar 

  23. Wardley A, Cortes J, Provencher L, Miller K, Chien AJ, Rugo HS et al (2021) The efficacy and safety of enzalutamide with trastuzumab in patients with HER2+ and androgen receptor-positive metastatic or locally advanced breast cancer. Breast Cancer Res Treat 187:155–165. https://doi.org/10.1007/s10549-021-06109-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. De Moura LL, Cesca MG, Tavares MC, Santana DM, Saldanha EF, Guimarães PT et al (2021) HER2-low status and response to neoadjuvant chemotherapy in HER2 negative early breast cancer. Breast Cancer Res Treat 190:155–163. https://doi.org/10.1007/s10549-021-06365-7

    Article  CAS  Google Scholar 

  25. Domergue C, Martin E, Lemarié C, Jézéquel P, Frenel JS, Augereau P et al (2022) Impact of HER2 status on pathological response after neoadjuvant chemotherapy in early triple-negative breast cancer. Cancers 14:2509. https://doi.org/10.3390/cancers14102509

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Ergun Y, Akagunduz B, Karacin C, Turker S, Ucar G (2023) The effect of HER2-low status on pathological complete response and survival in triple-negative breast cancer: a systemic review and meta-analysis. Clin Breast Cancer 23:567–575. https://doi.org/10.1016/j.clbc.2023.05.015

    Article  CAS  PubMed  Google Scholar 

  27. Masuda N, Lee SJ, Ohtani S, Im YH, Lee ES, Yokota I et al (2017) Adjuvant capecitabine for breast cancer after preoperative chemotherapy. N Engl J Med 376:2147–2159. https://doi.org/10.1056/NEJMoa1612645

    Article  CAS  PubMed  Google Scholar 

  28. Sanomachi T, Okuma HS, Kitadai R, Kawachi A, Yazaki S, Tokura M et al (2023) Low HER2 expression is a predictor of poor prognosis in stage I triple-negative breast cancer. Front Oncol 13:1157789. https://doi.org/10.3389/fonc.2023.1157789

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Yi X, Hu S, Ma M, Huang D, Zhang Y (2023) Effect of HER2-low expression on neoadjuvant efficacy in operable breast cancer. Clin Transl Oncol. https://doi.org/10.1007/s12094-023-03318-y

    Article  PubMed  Google Scholar 

  30. Horisawa N, Adachi Y, Takatsuka D, Nozawa K, Endo Y, Ozaki Y et al (2022) The frequency of low HER2 expression in breast cancer and a comparison of prognosis between patients with HER2-low and HER2-negative breast cancer by HR status. Breast Cancer 29:234–241. https://doi.org/10.1007/s12282-021-01303-3

    Article  PubMed  Google Scholar 

  31. Wei T, Wang D, Gao S, Wang X, Yue J, Kang Y et al (2023) Clinicopathologic characteristics and prognostic significance of HER2-low expression in patients with early breast cancer: a systematic review and meta-analysis. Front Oncol 13:1100332. https://doi.org/10.3389/fonc.2023.1100332

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Funding

This article is funded by Education Department Foundation of Liaoning Province of China, LJKMZ20221227, Youth Science Program of the First Affiliated Hospital of **zhou Medical University, FYQKR-202201.

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Authors and Affiliations

  1. The First Affiliated Hospital of **zhou Medical University, **zhou, 110001, Liaoning, People’s Republic of China

    Yue Shi, Heng Lu & Yiqi Zhang

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  1. Yue Shi
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  2. Heng Lu
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Contributions

Yue Shi contributed to conceptualization, data curation, investigation, project administration, validation, writing-original draft. Heng Lu contributed to formal analysis, investigation, methodology, resources, visualization. Yiqi Zhang contributed to conceptualization, resources, supervision, funding acquisition, writing – review & editing.

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Correspondence to Yiqi Zhang.

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Shi, Y., Lu, H. & Zhang, Y. Impact of HER2 status on clinicopathological characteristics and pathological complete response to neoadjuvant chemotherapy in triple-negative breast cancer. Breast Cancer Res Treat 206, 387–395 (2024). https://doi.org/10.1007/s10549-024-07317-7

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