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Breast Cancer

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Open Access 21-06-2022 | Breast Cancer | Original Article

Prognostic values of clinical and molecular features in HER2 low-breast cancer with hormonal receptor overexpression: features of HER2-low breast cancer

Authors: Mengdi Chen, Weilin Chen, Deyue Liu, Weiguo Chen, Kunwei Shen, Jiayi Wu, Li Zhu

Published in: Breast Cancer | Issue 5/2022

Abstract

Background

Human epidermal growth factor receptor 2 (HER2) low breast cancer was considered as a distinct subtype different from HER2-zero breast cancer. Our study aimed to investigate the prognostic values of clinicopathological features and recurrence score (RS) in HER2-low and HER2-zero hormone receptor (HR)-positive breast cancer patients.

Methods

A total of 2099 HR + primary female breast cancer patients diagnosed between Jan 2009 and Jan 2019 were collected. Tumors with immunohistochemistry 1 + /2 + and negative in situ hybridization results were defined as HER2-low. We compared the clinical and genetical features of HER2-low (n = 1732) and HER2-zero (n = 367) breast cancer and their prognostic values.

Results

Estrogen receptor (ER) high expression (> 90%) was more common in HER2-low breast cancer than HER2-zero breast cancer (78.2% vs 58.6%, p < 0.01). Five-year disease-free survival (DFS) was similar between HER2-zero and HER2-low subgroups (92.3% vs 93.3%, p = 0.83). The predictive value of RS was only significant in HER2-zero patients (p = 0.03). The proliferation-related genes performed well in predicting DFS in HER2-zero patients, but not in HER2-low patients (p for interaction < 0.01). The higher HER2 module score was correlated with worse DFS only in HER2-low patients (p = 0.04).

Conclusion

We observed similar survival outcomes between HER2-low and HER2-zero HR + patients. HER2-low patients had a higher proportion of ER high expressed tumors than HER2-zero patients did. RS and its proliferation module might be less clinically meaningful to HER2-low patients.

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Cameron D, Piccart-Gebhart MJ, Gelber RD, Procter M, Goldhirsch A, de Azambuja E, et al. 11 years’ follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive early breast cancer: final analysis of the HERceptin Adjuvant (HERA) trial. Lancet. 2017;389:1195–205. https://doi.org/10.1016/S0140-6736(16)32616-2.CrossRefPubMedPubMedCentral

von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, et al. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017;377:122–31. https://doi.org/10.1056/NEJMoa1703643.CrossRef

Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, et al. Phase III, randomized study of dual human epidermal growth factor receptor 2 (HER2) blockade with lapatinib plus trastuzumab in combination with an aromatase inhibitor in postmenopausal women with HER2-positive, hormone receptor-positive metastatic breast cancer: alternative. J Clin Oncol. 2018;36:741–8. https://doi.org/10.1200/JCO.2017.74.7824.CrossRefPubMed

Tarantino P, Hamilton E, Tolaney SM, Cortes J, Morganti S, Ferraro E, et al. HER2-low breast cancer: pathological and clinical landscape. J Clin Oncol. 2020;38:1951–62. https://doi.org/10.1200/JCO.19.02488.CrossRefPubMed

Schalper KA, Kumar S, Hui P, Rimm DL, Gershkovich P. A retrospective population-based comparison of HER2 immunohistochemistry and fluorescence in situ hybridization in breast carcinomas: impact of 2007 American Society of Clinical Oncology/College of American Pathologists criteria. Arch Pathol Lab Med. 2014;138:213–9. https://doi.org/10.5858/arpa.2012-0617-OA.CrossRefPubMed

Eggemann H, Ignatov T, Burger E, Kantelhardt EJ, Fettke F, Thomssen C, et al. Moderate HER2 expression as a prognostic factor in hormone receptor positive breast cancer. Endocr Relat Cancer. 2015;22:725–33. https://doi.org/10.1530/ERC-15-0335.CrossRefPubMed

Agostinetto E, Rediti M, Fimereli D, Debien V, Piccart M, Aftimos P, et al. HER2-low breast cancer: molecular characteristics and prognosis. Cancers (Basel). 2021. https://doi.org/10.3390/cancers13112824.CrossRef

Schettini F, Chic N, Braso-Maristany F, Pare L, Pascual T, Conte B, et al. Clinical, pathological, and PAM50 gene expression features of HER2-low breast cancer. NPJ Breast Cancer. 2021;7:1. https://doi.org/10.1038/s41523-020-00208-2.CrossRefPubMedPubMedCentral

Kim MH, Kim GM, Kim JH, Kim JY, Park HS, Park S, et al. Intermediate HER2 expression is associated with poor prognosis in estrogen receptor-positive breast cancer patients aged 55 years and older. Breast Cancer Res Treat. 2020;179:687–97. https://doi.org/10.1007/s10549-019-05505-4.CrossRefPubMed

10.

Fehrenbacher L, Cecchini RS, Geyer CE Jr, Rastogi P, Costantino JP, Atkins JN, et al. 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. 2020;38:444–53. https://doi.org/10.1200/JCO.19.01455.CrossRefPubMed

11.

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

12.

Paik S, Shak S, Tang G, Kim C, Baker J, Cronin M, et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med. 2004;351:2817–26. https://doi.org/10.1056/NEJMoa041588.CrossRefPubMed

13.

Hammond ME, Hayes DF, Dowsett M, Allred DC, Hagerty KL, Badve S, et al. American Society of Clinical Oncology/College Of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Clin Oncol. 2010;28:2784–95. https://doi.org/10.1200/JCO.2009.25.6529.CrossRefPubMedPubMedCentral

14.

Wolff AC, Hammond MEH, Allison KH, Harvey BE, Mangu PB, Bartlett JMS, 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. J Clin Oncol. 2018;36:2105–22. https://doi.org/10.1200/JCO.2018.77.8738.CrossRefPubMed

15.

Lin C, Wu J, Lin L, Fei X, Chen X, Huang O, et al. A novel prognostic scoring system integrating gene expressions and clinicopathological characteristics to predict very early relapse in node-negative estrogen receptor-positive/HER2-negative breast cancer. Front Oncol. 2020;10:1335. https://doi.org/10.3389/fonc.2020.01335.CrossRefPubMedPubMedCentral

16.

Sparano JA, Gray RJ, Makower DF, Pritchard KI, Albain KS, Hayes DF, et al. Prospective validation of a 21-gene expression assay in breast cancer. N Engl J Med. 2015;373:2005–14. https://doi.org/10.1056/NEJMoa1510764.CrossRefPubMedPubMedCentral

17.

Lazar AA, Cole BF, Bonetti M, Gelber RD. Evaluation of treatment-effect heterogeneity using biomarkers measured on a continuous scale: subpopulation treatment effect pattern plot. J Clin Oncol. 2010;28:4539–44. https://doi.org/10.1200/JCO.2009.27.9182.CrossRefPubMedPubMedCentral

18.

Banerji U, van Herpen CML, Saura C, Thistlethwaite F, Lord S, Moreno V, et al. Trastuzumab duocarmazine in locally advanced and metastatic solid tumours and HER2-expressing breast cancer: a phase 1 dose-escalation and dose-expansion study. Lancet Oncol. 2019;20:1124–35. https://doi.org/10.1016/S1470-2045(19)30328-6.CrossRefPubMed

19.

Modi S, Park H, Murthy RK, Iwata H, Tamura K, Tsurutani J, et al. Antitumor activity and safety of trastuzumab deruxtecan in patients with HER2-Low-expressing advanced breast cancer: results from a phase ib study. J Clin Oncol. 2020;38:1887–96. https://doi.org/10.1200/JCO.19.02318.CrossRefPubMedPubMedCentral

20.

Pinhel I, Hills M, Drury S, Salter J, Sumo G, A’Hern R, et al. ER and HER2 expression are positively correlated in HER2 non-overexpressing breast cancer. Breast Cancer Res. 2012;14:R46. https://doi.org/10.1186/bcr3145.CrossRefPubMedPubMedCentral

21.

Loi S, Dafni U, Karlis D, Polydoropoulou V, Young BM, Willis S, et al. Effects of estrogen receptor and human epidermal growth factor receptor-2 levels on the efficacy of trastuzumab: a secondary analysis of the HERA trial. JAMA Oncol. 2016;2:1040–7. https://doi.org/10.1001/jamaoncol.2016.0339.CrossRefPubMed

22.

Lousberg L, Collignon J, Jerusalem G. Resistance to therapy in estrogen receptor positive and human epidermal growth factor 2 positive breast cancers: progress with latest therapeutic strategies. Ther Adv Med Oncol. 2016;8:429–49. https://doi.org/10.1177/1758834016665077.CrossRefPubMedPubMedCentral

23.

Rossi V, Sarotto I, Maggiorotto F, Berchialla P, Kubatzki F, Tomasi N, et al. Moderate immunohistochemical expression of HER-2 (2+) without HER-2 gene amplification is a negative prognostic factor in early breast cancer. Oncologist. 2012;17:1418–25. https://doi.org/10.1634/theoncologist.2012-0194.CrossRefPubMedPubMedCentral

24.

Selmani Z, Molimard C, Overs A, Bazan F, Chaigneau L, Dobi E, et al. Low correlation between Ki67 assessed by qRT-PCR in oncotype Dx score and Ki67 assessed by Immunohistochemistry. Sci Rep. 2022;12:3617. https://doi.org/10.1038/s41598-022-07593-7.CrossRefPubMedPubMedCentral

25.

Antonarelli G, Valenza C, Mayer EL, Loibl S, Curigliano G. Cyclin dependent kinase 4/6 inhibitors in early breast cancer: what is the role of Ki-67? Lancet Oncol. 2022;23:325–8. https://doi.org/10.1016/S1470-2045(21)00756-7.CrossRefPubMed

26.

Hicks D, O’Regan RM. Improving outcomes for high-risk hormone receptor-positive breast cancer With CDK inhibition. J Clin Oncol. 2022. https://doi.org/10.1200/JCO.21.02850.CrossRefPubMed

Title: Prognostic values of clinical and molecular features in HER2 low-breast cancer with hormonal receptor overexpression: features of HER2-low breast cancer
Authors: Mengdi Chen
Weilin Chen
Deyue Liu
Weiguo Chen
Kunwei Shen
Jiayi Wu
Li Zhu
Publication date: 21-06-2022
Publisher: Springer Nature Singapore
Keywords: Breast Cancer
Breast Cancer
Published in: Breast Cancer / Issue 5/2022
Print ISSN: 1340-6868
Electronic ISSN: 1880-4233
DOI: https://doi.org/10.1007/s12282-022-01364-y

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Abstract

Background

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