Analysis of clinicopathologic characteristics and prognosis in patients with HER2-low expressing triple-negative breast cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

YU Tong , ZHANG Min , ZHOU Lisha ,  WU Bin

Department of Breast Surgery, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P. R. China;

Corresponding author：

WU Bin, Email: wwbb129@sina.com

Keywords：

triple-negative breast cancer; human epidermal growth factor receptor 2; clinicopathologic characteristics; disease-free survival

DOI：

10.7507/1007-9424.202501032

Video：

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Objective To compare clinicopathologic characteristics and prognosis between HER2-low and HER2-negative with stage T1 and T2 triple-negative breast cancer (TNBC). Methods The patients with stage T1 and T2 TNBC treated at the Affiliated Hospital of Southwest Medical University from June 2019 to June 2021 were retrospectively collected. The clinicopathologic features were analyzed using two-sided Chi-square test. Multivariate binary logistic regression identified risk factors for 3-year postoperative recurrence/metastasis. Kaplan-Meier survival curves was used to compare 3-year disease-free survival (DFS) between the patients with HER2-low and HER2-negative. The statistical significance was defined as α=0.05. Results A total of 126 patients with stage T1 and T2 TNBC were enrolled, 63 were HER2-negative and 63 HER2-low. Compared with HER2-negative patients, HER2-low patients demonstrated significantly higher proportions of: Age ≥50 years old, postmenopausal status, lymphovascular invasion (P<0.05). HER2 expression level and axillary lymph node metastasis were the independent risk factors for 3-year postoperative recurrence/metastasis in the patients with stage T1 and T2 TNBC (P<0.05). The patients with HER2-low expressing demonstrated significantly inferior 3-year DFS compared to patients with HER2-negative (χ²=7.741, P=0.005). Conclusions Findings of this study suggest that among patients with stage T1 and T2 TNBC, HER2-low expression is associated with advanced age (≥50 years), menopausal status, and lymphovascular invasion. It may serve as an indicator of a distinct biologic subgroup or unfavorable pathologic characteristics. Patients with stage T1 and T2 TNBC who have HER2-low expression and positive lymph node metastasis require close monitoring for recurrence/metastasis within 3 years postoperatively.

1.	Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2021, 71(3): 209-249.
2.	Lehmann BD, Bauer JA, Chen X, et al. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest, 2011, 121(7): 2750-2767.
3.	Loibl S, Gianni L. HER2-positive breast cancer. Lancet, 2017, 389(10087): 2415-2429.
4.	Gilcrease MZ, Woodward WA, Nicolas MM, et al. Even low-level HER2 expression may be associated with worse outcome in node-positive breast cancer. Am J Surg Pathol, 2009, 33(5): 759-767.
5.	Rossi V, Sarotto I, Maggiorotto F, 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(11): 1418-1425.
6.	Dehghani M, Keshavarz P, Talei A, et al. The effects of low HER2/neu expression on the clinicopathological characteristics of triple-negative breast cancer patients. Asian Pac J Cancer Prev, 2020, 21(10): 3027-3032.
7.	Wolff AC, Somerfield MR, Dowsett M, et al. Human epidermal growth factor receptor 2 testing in breast cancer: ASCO-College of American Pathologists guideline update. J Clin Oncol, 2023, 41(22): 3867-3872.
8.	Tarantino P, Viale G, Press MF, et al. ESMO expert consensus statements (ECS) on the definition, diagnosis, and management of HER2-low breast cancer. Ann Oncol, 2023, 34(8): 645-659.
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10.	Safarpour D, Pakneshan S, Tavassoli FA. Androgen receptor (AR) expression in 400 breast carcinomas: Is routine AR assessment justified? Am J Cancer Res, 2014, 4(4): 353-368.
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12.	赵世阳, 王征, 张浩. 三阴性乳腺癌中HER2低表达与HER2不表达的新辅助化疗疗效评估. 医学研究杂志, 2024, 53(4): 86-90.
13.	高津, 张莉莉, 胡赛男, 等. HER2 表达强度对三阴性乳腺癌无病生存率的影响. 癌症进展, 2016, 14(12): 1221-1224.
14.	Schettini F, Chic N, Brasó-Maristany F, et al. Clinical, pathological, and PAM50 gene expression features of HER2-low breast cancer. NPJ Breast Cancer, 2021, 7(1): 1. doi: 10.1038/s41523-020-00208-2.
15.	中国医师协会肿瘤医师分会乳腺癌学组. 铂类药物晚期乳腺癌应用专家共识(2020版). 中国综合临床, 2021, 37(2): 97-105.
16.	Dent R, Trudeau M, Pritchard KI, et al. Triple-negative breast cancer: Clinical features and patterns of recurrence. Clin Cancer Res, 2007, 13(15 Pt 1): 4429-4434.
17.	连婧, 李若琪, 闫磊, 等. HER2低表达三阴性乳腺癌的生物学特征. 中华病理学杂志, 2024, 53(9): 898-904.
18.	Lehmann BD, Bauer JA, Chen X, et al. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest, 2011, 121(7): 2750-2767.
19.	Lehmann BD, Jovanović B, Chen X, et al. Refinement of triple-negative breast cancer molecular subtypes: Implications for neoadjuvant chemotherapy selection. PLoS One, 2016, 11(6): e0157368. doi: 10.1371/journal.pone.0157368.
20.	Gucalp A, Traina TA. Triple-negative breast cancer: role of the androgen receptor. Cancer J, 2010, 16(1): 62-65.
21.	Asghar US, Barr AR, Cutts R, et al. Single-cell dynamics determines response to CDK4/6 inhibition in triple-negative breast cancer. Clin Cancer Res, 2017, 23(18): 5561-5572.
22.	邢爱艳, 高鹏. 三阴性乳腺癌分子分型研究进展. 中华病理学杂志, 2022, 51(1): 82-86.
23.	Valenza C, Guidi L, Battaiotto E, et al. Targeting HER2 heterogeneity in breast and gastrointestinal cancers. Trends Cancer, 2024, 10(2): 113-123.
24.	Ogitani Y, Hagihara K, Oitate M, et al. Bystander killing effect of DS-8201a, a novel anti-human epidermal growth factor receptor 2 antibody-drug conjugate, in tumors with human epidermal growth factor receptor 2 heterogeneity. Cancer Sci, 2016, 107(7): 1039-1046.
25.	Van Raemdonck E, Floris G, Berteloot P, et al. Efficacy of anti-HER2 therapy in metastatic breast cancer by discordance of HER2 expression between primary and metastatic breast cancer. Breast Cancer Res Treat, 2021, 185(1): 183-194.
26.	Walter V, Fischer C, Deutsch TM, et al. Estrogen, progesterone, and human epidermal growth factor receptor 2 discordance between primary and metastatic breast cancer. Breast Cancer Res Treat, 2020, 183(1): 137-144.
27.	van de Ven S, Smit VT, Dekker TJ, et al. Discordances in ER, PR and HER2 receptors after neoadjuvant chemotherapy in breast cancer. Cancer Treat Rev, 2011, 37(6): 422-430.
28.	Curigliano G, Bagnardi V, Viale G, et al. Should liver metastases of breast cancer be biopsied to improve treatment choice?. Ann Oncol, 2011, 22(10): 2227-2233.

1. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2021, 71(3): 209-249.
2. Lehmann BD, Bauer JA, Chen X, et al. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest, 2011, 121(7): 2750-2767.
3. Loibl S, Gianni L. HER2-positive breast cancer. Lancet, 2017, 389(10087): 2415-2429.
4. Gilcrease MZ, Woodward WA, Nicolas MM, et al. Even low-level HER2 expression may be associated with worse outcome in node-positive breast cancer. Am J Surg Pathol, 2009, 33(5): 759-767.
5. Rossi V, Sarotto I, Maggiorotto F, 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(11): 1418-1425.
6. Dehghani M, Keshavarz P, Talei A, et al. The effects of low HER2/neu expression on the clinicopathological characteristics of triple-negative breast cancer patients. Asian Pac J Cancer Prev, 2020, 21(10): 3027-3032.
7. Wolff AC, Somerfield MR, Dowsett M, et al. Human epidermal growth factor receptor 2 testing in breast cancer: ASCO-College of American Pathologists guideline update. J Clin Oncol, 2023, 41(22): 3867-3872.
8. Tarantino P, Viale G, Press MF, et al. ESMO expert consensus statements (ECS) on the definition, diagnosis, and management of HER2-low breast cancer. Ann Oncol, 2023, 34(8): 645-659.
9. Nielsen TO, Leung SCY, Rimm DL, et al. Assessment of Ki67 in breast cancer: Updated recommendations from the International Ki67 in Breast Cancer Working Group. J Natl Cancer Inst, 2021, 113(7): 808-819.
10. Safarpour D, Pakneshan S, Tavassoli FA. Androgen receptor (AR) expression in 400 breast carcinomas: Is routine AR assessment justified? Am J Cancer Res, 2014, 4(4): 353-368.
11. Modi S, Jacot W, Yamashita T, et al. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer. N Engl J Med, 2022, 387(1): 9-20.
12. 赵世阳, 王征, 张浩. 三阴性乳腺癌中HER2低表达与HER2不表达的新辅助化疗疗效评估. 医学研究杂志, 2024, 53(4): 86-90.
13. 高津, 张莉莉, 胡赛男, 等. HER2 表达强度对三阴性乳腺癌无病生存率的影响. 癌症进展, 2016, 14(12): 1221-1224.
14. Schettini F, Chic N, Brasó-Maristany F, et al. Clinical, pathological, and PAM50 gene expression features of HER2-low breast cancer. NPJ Breast Cancer, 2021, 7(1): 1. doi: 10.1038/s41523-020-00208-2.
15. 中国医师协会肿瘤医师分会乳腺癌学组. 铂类药物晚期乳腺癌应用专家共识(2020版). 中国综合临床, 2021, 37(2): 97-105.
16. Dent R, Trudeau M, Pritchard KI, et al. Triple-negative breast cancer: Clinical features and patterns of recurrence. Clin Cancer Res, 2007, 13(15 Pt 1): 4429-4434.
17. 连婧, 李若琪, 闫磊, 等. HER2低表达三阴性乳腺癌的生物学特征. 中华病理学杂志, 2024, 53(9): 898-904.
18. Lehmann BD, Bauer JA, Chen X, et al. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest, 2011, 121(7): 2750-2767.
19. Lehmann BD, Jovanović B, Chen X, et al. Refinement of triple-negative breast cancer molecular subtypes: Implications for neoadjuvant chemotherapy selection. PLoS One, 2016, 11(6): e0157368. doi: 10.1371/journal.pone.0157368.
20. Gucalp A, Traina TA. Triple-negative breast cancer: role of the androgen receptor. Cancer J, 2010, 16(1): 62-65.
21. Asghar US, Barr AR, Cutts R, et al. Single-cell dynamics determines response to CDK4/6 inhibition in triple-negative breast cancer. Clin Cancer Res, 2017, 23(18): 5561-5572.
22. 邢爱艳, 高鹏. 三阴性乳腺癌分子分型研究进展. 中华病理学杂志, 2022, 51(1): 82-86.
23. Valenza C, Guidi L, Battaiotto E, et al. Targeting HER2 heterogeneity in breast and gastrointestinal cancers. Trends Cancer, 2024, 10(2): 113-123.
24. Ogitani Y, Hagihara K, Oitate M, et al. Bystander killing effect of DS-8201a, a novel anti-human epidermal growth factor receptor 2 antibody-drug conjugate, in tumors with human epidermal growth factor receptor 2 heterogeneity. Cancer Sci, 2016, 107(7): 1039-1046.
25. Van Raemdonck E, Floris G, Berteloot P, et al. Efficacy of anti-HER2 therapy in metastatic breast cancer by discordance of HER2 expression between primary and metastatic breast cancer. Breast Cancer Res Treat, 2021, 185(1): 183-194.
26. Walter V, Fischer C, Deutsch TM, et al. Estrogen, progesterone, and human epidermal growth factor receptor 2 discordance between primary and metastatic breast cancer. Breast Cancer Res Treat, 2020, 183(1): 137-144.
27. van de Ven S, Smit VT, Dekker TJ, et al. Discordances in ER, PR and HER2 receptors after neoadjuvant chemotherapy in breast cancer. Cancer Treat Rev, 2011, 37(6): 422-430.
28. Curigliano G, Bagnardi V, Viale G, et al. Should liver metastases of breast cancer be biopsied to improve treatment choice?. Ann Oncol, 2011, 22(10): 2227-2233.

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