Comparison of clinicopathological characteristics and prognosis of 1 560 breast cancer patients with different HER2 expression status_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

MA Ping ¹ , WANG Lijun ¹ , KONG Deguang ¹ , TANG Wei ² ,  SUN Shengrong ¹

1. Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, P. R. China;
2. Department of Pediatrics, Renmin Hospital of Wuhan University, Wuhan 430060, P. R. China;

Corresponding author：

SUN Shengrong, Email: sun137@sina.com

Keywords：

breast cancer; human epidermal growth factor receptor 2; clinicopathological characteristic; prognostic analysis

DOI：

10.7507/1007-9424.202211052

Video：

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Objective To investigate the differences in clinicopathological characteristics and prognostic survival of human epidermal growth factor receptor 2 (HER2) high expression, HER2 low expression and HER2 negative breast cancer. Method We retrospectively collected 1 560 female breast cancer patients who underwent surgical treatment at the Department of Breast and Thyroid Surgery in Renmin Hospital of Wuhan University between January 8, 2010 and December 31, 2015, and divided them into high expression group, low expression group and negative group according to HER2 expression, to compare the differences in clinicopathological characteristics among the three groups of breast cancer patients and to explore the factors influencing prognosis. Results The proportions of histological grade Ⅲ, tumor diameter >2 cm, lymph node metastasis, TNM stage Ⅲ, Ki67 high expression, and hormone receptor negative expression were higher in the high expression group than those in the low expression group and negative group (P<0.050); the proportions of histological grade Ⅲ, tumor diameter >2 cm, lymph node metastasis, and TNM stage Ⅲ were higher in the low expression group than those in the negative group (P<0.050). However, the proportions of Ki67 high expression and hormone receptor negative expression were lower than those of the negative group (P<0.050). The 5-year disease-free survival rate were 85.6%, 80.3% and 74.5% for the high expression, low expression and negative group, respectively, and the 5-year overall survival rate were 90.4%, 86.0% and 80.7%, respectively. The results of multivariate Cox proportional hazard model showed that patients with high histological grade, late TNM stage, Ki67 high expression and weaker HER2 expression intensity had worse 5-year disease-free survival (P<0.050); patients with older age, high histological grade, lymph node metastasis, late TNM stage, Ki67 high expression and weaker HER2 expression intensity had worse 5-year overall survival (P<0.050). Conclusions The intensity of HER2 expression affects the 5-year disease-free survival and overall survival of breast cancer patients, and the higher the intensity of HER2 expression, the better the 5-year disease-free survival and overall survival, while the weaker the HER2 expression, the worse the 5-year disease-free survival and overall survival.

Citation： MA Ping, WANG Lijun, KONG Deguang, TANG Wei, SUN Shengrong. Comparison of clinicopathological characteristics and prognosis of 1 560 breast cancer patients with different HER2 expression status. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2023, 30(5): 554-560. doi: 10.7507/1007-9424.202211052 Copy

1.	Cao W, Chen HD, Yu YW, et al. Changing profiles of cancer burden worldwide and in China: a secondary analysis of the global cancer statistics 2020. Chin Med J (Engl), 2021, 134(7): 783-791.
2.	Tarantino P, Hamilton E, Tolaney SM, et al. HER2-low breast cancer: pathological and clinical landscape. J Clin Oncol, 2020, 38(17): 1951-1962.
3.	Choong GM, Cullen GD, O’Sullivan CC. Evolving standards of care and new challenges in the management of HER2-positive breast cancer. CA Cancer J Clin, 2020, 70(5): 355-374.
4.	Denkert C, Seither F, Schneeweiss A, 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, 22(8): 1151-1161.
5.	Wolff AC, Hammond MEH, Allison KH, 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(20): 2105-2122.
6.	Pernas S, Tolaney SM. HER2-positive breast cancer: new therapeutic frontiers and overcoming resistance. Ther Adv Med Oncol, 2019, 11: 1758835919833519. doi:10.1177/1758835919833519.
7.	刘荫华, 刘真真, 王翔, 等. 乳腺癌改良根治术专家共识及手术操作指南 (2018版). 中国实用外科杂志, 2018, 38(8): 851-854.
8.	Zhang A, Wang X, Fan C, et al. The role of Ki67 in evaluating neoadjuvant endocrine therapy of hormone receptor-positive breast cancer. Front Endocrinol (Lausanne), 2021, 12: 687244. doi: 10.3389/fendo.2021.687244.
9.	Conforti F, Pala L, Sala I, et al. Evaluation of pathological complete response as surrogate endpoint in neoadjuvant randomised clinical trials of early stage breast cancer: systematic review and meta-analysis. BMJ, 2021, 375: e066381. doi: 10.1136/bmj-2021-066381.
10.	Shui R, Liang X, Li X, et al. Hormone receptor and human epidermal growth factor receptor 2 detection in invasive breast carcinoma: a retrospective study of 12,467 patients from 19 Chinese Representative Clinical Centers. Clin Breast Cancer, 2020, 20(1): e65-e74.
11.	Holloway RW, Marignani PA. Targeting mTOR and glycolysis in HER2-positive breast cancer. Cancers (Basel), 2021, 13(12): 2922. doi: 10.3390/cancers13122922.
12.	Jin J, Tao Z, Cao J, et al. DNA damage response inhibitors: an avenue for TNBC treatment. Biochim Biophys Acta Rev Cancer, 2021, 1875(2): 188521. doi: 10.1016/j.bbcan.2021.188521.
13.	Manjunath M, Choudhary B. Triple-negative breast cancer: a run-through of features, classification and current therapies. Oncol Lett, 2021, 22(1): 512. doi: 10.3892/ol.2021.12773.
14.	Horimoto Y, Terao T, Tsutsumi Y, et al. Estrogen receptor-positive ductal carcinoma in situ frequently overexpresses HER2 protein without gene amplification. Am J Surg Pathol, 2019, 43(9): 1221-1228.
15.	胡莺菡, 吴云秋, 邓建, 等. 三阳性与HER2过表达型乳腺癌患者新辅助化学药物治疗的疗效对比. 中国普外基础与临床杂志, 2022, 29(12): 1605-1610.
16.	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.
17.	Eggemann H, Ignatov T, Burger E, et al. Moderate HER2 expression as a prognostic factor in hormone receptor positive breast cancer. Endocr Relat Cancer, 2015, 22(5): 725-733.
18.	Marchiò C, Annaratone L, Marques A, et al. Evolving concepts in HER2 evaluation in breast cancer: heterogeneity, HER2-low carcinomas and beyond. Semin Cancer Biol, 2021, 72: 123-135.
19.	von Minckwitz G, Huang CS, Mano MS, et al. Trastuzumab emtansine for residual invasive HER2-positive breast cancer. N Engl J Med, 2019, 380(7): 617-628.
20.	Modi S, Saura C, Yamashita T, et al. Trastuzumab deruxtecan in previously treated HER2-positive breast cancer. N Engl J Med, 2020, 382(7): 610-621.
21.	Goutsouliak K, Veeraraghavan J, Sethunath V, et al. Towards personalized treatment for early stage HER2-positive breast cancer. Nat Rev Clin Oncol, 2020, 17(4): 233-250.
22.	Banerji U, van Herpen CML, Saura C, 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(8): 1124-1135.
23.	Ferraro E, Drago JZ, Modi S. Implementing antibody-drug conjugates (ADCs) in HER2-positive breast cancer: state of the art and future directions. Breast Cancer Res, 2021, 23(1): 84. doi: 10.1186/s13058-021-01459-y.
24.	Agostinetto E, Rediti M, Fimereli D, et al. HER2-low breast cancer: molecular characteristics and prognosis. Cancers (Basel), 2021, 13(11): 2824. doi: 10.3390/cancers13112824.
25.	Dieci MV, Miglietta F, Griguolo G, et al. Biomarkers for HER2-positive metastatic breast cancer: beyond hormone receptors. Cancer Treat Rev, 2020, 88: 102064. doi: 10.1016/ j.ctrv.2020.102064.
26.	Modi S, Park H, Murthy RK, 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(17): 1887-1896.
27.	Siena S, Di Bartolomeo M, Raghav K, et al. Trastuzumab deruxtecan (DS-8201) in patients with HER2-expressing metastatic colorectal cancer (DESTINY-CRC01): a multicentre, open-label, phase 2 trial. Lancet Oncol, 2021, 22(6): 779-789.

1. Cao W, Chen HD, Yu YW, et al. Changing profiles of cancer burden worldwide and in China: a secondary analysis of the global cancer statistics 2020. Chin Med J (Engl), 2021, 134(7): 783-791.
2. Tarantino P, Hamilton E, Tolaney SM, et al. HER2-low breast cancer: pathological and clinical landscape. J Clin Oncol, 2020, 38(17): 1951-1962.
3. Choong GM, Cullen GD, O’Sullivan CC. Evolving standards of care and new challenges in the management of HER2-positive breast cancer. CA Cancer J Clin, 2020, 70(5): 355-374.
4. Denkert C, Seither F, Schneeweiss A, 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, 22(8): 1151-1161.
5. Wolff AC, Hammond MEH, Allison KH, 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(20): 2105-2122.
6. Pernas S, Tolaney SM. HER2-positive breast cancer: new therapeutic frontiers and overcoming resistance. Ther Adv Med Oncol, 2019, 11: 1758835919833519. doi:10.1177/1758835919833519.
7. 刘荫华, 刘真真, 王翔, 等. 乳腺癌改良根治术专家共识及手术操作指南 (2018版). 中国实用外科杂志, 2018, 38(8): 851-854.
8. Zhang A, Wang X, Fan C, et al. The role of Ki67 in evaluating neoadjuvant endocrine therapy of hormone receptor-positive breast cancer. Front Endocrinol (Lausanne), 2021, 12: 687244. doi: 10.3389/fendo.2021.687244.
9. Conforti F, Pala L, Sala I, et al. Evaluation of pathological complete response as surrogate endpoint in neoadjuvant randomised clinical trials of early stage breast cancer: systematic review and meta-analysis. BMJ, 2021, 375: e066381. doi: 10.1136/bmj-2021-066381.
10. Shui R, Liang X, Li X, et al. Hormone receptor and human epidermal growth factor receptor 2 detection in invasive breast carcinoma: a retrospective study of 12,467 patients from 19 Chinese Representative Clinical Centers. Clin Breast Cancer, 2020, 20(1): e65-e74.
11. Holloway RW, Marignani PA. Targeting mTOR and glycolysis in HER2-positive breast cancer. Cancers (Basel), 2021, 13(12): 2922. doi: 10.3390/cancers13122922.
12. Jin J, Tao Z, Cao J, et al. DNA damage response inhibitors: an avenue for TNBC treatment. Biochim Biophys Acta Rev Cancer, 2021, 1875(2): 188521. doi: 10.1016/j.bbcan.2021.188521.
13. Manjunath M, Choudhary B. Triple-negative breast cancer: a run-through of features, classification and current therapies. Oncol Lett, 2021, 22(1): 512. doi: 10.3892/ol.2021.12773.
14. Horimoto Y, Terao T, Tsutsumi Y, et al. Estrogen receptor-positive ductal carcinoma in situ frequently overexpresses HER2 protein without gene amplification. Am J Surg Pathol, 2019, 43(9): 1221-1228.
15. 胡莺菡, 吴云秋, 邓建, 等. 三阳性与HER2过表达型乳腺癌患者新辅助化学药物治疗的疗效对比. 中国普外基础与临床杂志, 2022, 29(12): 1605-1610.
16. 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.
17. Eggemann H, Ignatov T, Burger E, et al. Moderate HER2 expression as a prognostic factor in hormone receptor positive breast cancer. Endocr Relat Cancer, 2015, 22(5): 725-733.
18. Marchiò C, Annaratone L, Marques A, et al. Evolving concepts in HER2 evaluation in breast cancer: heterogeneity, HER2-low carcinomas and beyond. Semin Cancer Biol, 2021, 72: 123-135.
19. von Minckwitz G, Huang CS, Mano MS, et al. Trastuzumab emtansine for residual invasive HER2-positive breast cancer. N Engl J Med, 2019, 380(7): 617-628.
20. Modi S, Saura C, Yamashita T, et al. Trastuzumab deruxtecan in previously treated HER2-positive breast cancer. N Engl J Med, 2020, 382(7): 610-621.
21. Goutsouliak K, Veeraraghavan J, Sethunath V, et al. Towards personalized treatment for early stage HER2-positive breast cancer. Nat Rev Clin Oncol, 2020, 17(4): 233-250.
22. Banerji U, van Herpen CML, Saura C, 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(8): 1124-1135.
23. Ferraro E, Drago JZ, Modi S. Implementing antibody-drug conjugates (ADCs) in HER2-positive breast cancer: state of the art and future directions. Breast Cancer Res, 2021, 23(1): 84. doi: 10.1186/s13058-021-01459-y.
24. Agostinetto E, Rediti M, Fimereli D, et al. HER2-low breast cancer: molecular characteristics and prognosis. Cancers (Basel), 2021, 13(11): 2824. doi: 10.3390/cancers13112824.
25. Dieci MV, Miglietta F, Griguolo G, et al. Biomarkers for HER2-positive metastatic breast cancer: beyond hormone receptors. Cancer Treat Rev, 2020, 88: 102064. doi: 10.1016/ j.ctrv.2020.102064.
26. Modi S, Park H, Murthy RK, 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(17): 1887-1896.
27. Siena S, Di Bartolomeo M, Raghav K, et al. Trastuzumab deruxtecan (DS-8201) in patients with HER2-expressing metastatic colorectal cancer (DESTINY-CRC01): a multicentre, open-label, phase 2 trial. Lancet Oncol, 2021, 22(6): 779-789.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Comparison of clinicopathological characteristics and prognosis of 1 560 breast cancer patients with different HER2 expression status

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