<trans-title xml:lang="en"/>_West China Medical Journal

Authors：

, , 

四川大学华西医院甲状腺乳腺外科（成都 610041）;

Corresponding author：

, Email: wangj889@163.com

Keywords：

三阴性乳腺癌; 分子分型; 治疗; 研究进展

DOI：

10.7507/1002-0179.201505036

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三阴性乳腺癌（triple-negative breast cancer，TNBC）是乳腺癌中的一种特殊免疫组织化学亚型，以雌激素受体、孕激素受体及人类表皮生长因子受体 2 阴性表达为特征。TNBC 具有高度异质性且通常发病早、临床分期较晚、组织学级别高、易于局部复发、转移并且预后差等特点。由于其不表达雌激素受体、孕激素受体和人类表皮生长因子受体 2，不能从内分泌治疗和抗人类表皮生长因子受体 2 靶向治疗中受益，故其治疗手段相对于其他类型乳腺癌亦受到相应的限制。自 TNBC 的概念提出后已成为乳腺癌研究和关注的焦点。该文对 TNBC 临床病理特征、分子生物学特点及治疗最新进展作了综述。

Citation： 李稳, 陈玉娟, 汪静. . West China Medical Journal, 2017, 32(2): 267-270. doi: 10.7507/1002-0179.201505036 Copy

1.	Fan L, Strasser-Weippl K, Li JJ, et al. Breast cancer in China. Lancet Oncol, 2014, 15(7): e279-e289.
2.	Siegel R, Ward E, Brawley O, et al. Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin, 2011, 61(4): 212-236.
3.	Dawood S. Triple-negative breast cancer: epidemiology and management options. Drugs, 2010, 70(17): 2247-2258.
4.	Perou CM, Sorlie T, Eisen MB, et al. Molecular portraits of human breast tumours. Nature, 2000, 406(6797): 747-752.
5.	Hennessy BT, Gonzalez-Angulo AM, Stemke-Hale K, et al. Characterization of a naturally occurring breast cancer subset enriched in epithelial-to-mesenchymal transition and stem cell characteristics. Cancer Res, 2009, 69(10): 4116-4124.
6.	Penault-Llorca F, Viale G. Pathological and molecular diagnosis of triple-negative breast cancer: a clinical perspective. Ann Oncol, 2012, 23(Suppl 6): vi19-vi22.
7.	Brenton JD, Carey LA, Ahmed AA, et al. Molecular classification and molecular forecasting of breast cancer: ready for clinical application?. J Clin Oncol, 2005, 23(29): 7350-7360.
8.	Badve S, Dabbs DJ, Schnitt SJ, et al. Basal-like and triple-negative breast cancers: a critical review with an emphasis on the implications for pathologists and oncologists. Mod Pathol, 2011, 24(2): 157-167.
9.	Rakha EA, El-Sayed ME, Green AR, et al. Prognostic markers in triple-negative breast cancer. Cancer, 2007, 109(1): 25-32.
10.	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.
11.	Gusterson A, Ross T, Heath J, et al. Basal cytokeratins and their relationship to the cellular origin and functional classification of breast cancer. Breast Cancer Res, 2005, 7(4): 143-148.
12.	Kim MJ, Ro JY, Ahn SH, et al. Clinicopathologic significance of the basal-like subtype of breast cancer: a comparison with hormone receptor and Her2/neu-overexpressing phenotypes. Hum Pathol, 2006, 37(9): 1217-1226.
13.	Cleator S, Heller W, Coombes RC. Triple-negative breast cancer: therapeutic options. Lancet Oncol, 2007, 8(3): 235-244.
14.	Turner C, Reis-Filho S, Russell M, et al. BRCA1 dysfunction in sporadic basal-like breast cancer. Oncogene, 2007, 26(14): 2126-2132.
15.	Abd El-Rehim DM, Ball G, Pinder SE, et al. High-throughput protein expression analysis using tissue microarray technology of a large well-characterised series identifies biologically distinct classes of breast cancer confirming recent cDNA expression analyses. Int J Cancer, 2005, 116(3): 340-350.
16.	Gangi A, Chung A, Mirocha J, et al. Breast-conserving therapy for triple-negative breast cancer. JAMA Surg, 2014, 149(3): 252-258.
17.	Moran MS. Radiation therapy in the locoregional treatment of triple-negative breast cancer. Lancet Oncology, 2015, 16(3): E113-E122.
18.	Pilewskie M, Ho A, Orell E, et al. Effect of margin width on local recurrence in triple-negative breast cancer patients treated with Breast-Conserving therapy. Ann Surg Oncol, 2014, 21(4): 1209-1214.
19.	Gangi A, Mirocha J, Leong T, et al. Triple-negative breast cancer is not associated with increased likelihood of nodal metastases. Ann Surg Oncol, 2014, 21(13): 4098-4103.
20.	Carey LA, Dees EC, Sawyer L, et al. The triple negative paradox: primary tumor chemosensitivity of breast cancer subtypes. Clin Cancer Res, 2007, 13(8): 2329-2334.
21.	Liedtke C, Mazouni C, Hess KR, et al. Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. J Clin Oncol, 2008, 26(8): 1275-1281.
22.	Symmans F, Peintinger F, Hatzis C, et al. Measurement of residual breast cancer burden to predict survival after neoadjuvant chemotherapy. J Clin Oncol, 2007, 25(28): 4414-4422.
23.	Hugh J, Hanson J, Cheang MC, et al. Breast cancer subtypes and response to docetaxel in node-positive breast cancer: use of an immunohistochemical definition in the BCIRG 001 trial. J Clin Oncol, 2009, 27(8): 1168-1176.
24.	Isakoff SJ. Triple-negative breast cancer role of specific chemotherapy agents. Cancer J, 2010, 16(1): 53-61.
25.	Printz C. I-SPY2 trial yields first results on combination therapy for triple-negative breast cancer. Cancer, 2014, 120(6): 773.
26.	Sikov M, Berry A, Perou M, et al. Impact of the addition of carboplatin and/or bevacizumab to neoadjuvant once-per-week paclitaxel followed by dose-dense doxorubicin and cyclophosphamide on pathologic complete response rates in stage Ⅱ to Ⅲ triple-negative breast cancer: CALGB 40603 (Alliance) . J Clin Oncol, 2015, 33(1): 13-21.
27.	Von Minckwitz G, Schneeweiss A, Loibl S, et al. Neoadjuvant carboplatin in patients with triple-negative and HER2-positive early breast cancer (GeparSixto; GBG 66): a randomised phase 2 trial. Lancet Oncol, 2014, 15(7): 747-756.
28.	Koshy N, Quispe D, Shi R, et al. Cisplatin-gemcitabine therapy in metastatic breast cancer: improved outcome in triple negative breast cancer patients compared to non-triple negative patients. Breast, 2010, 19(3): 246-248.
29.	Zhang J, Wang ZH, Hu XC, et al. Cisplatin and gemcitabine as the first line therapy in metastatic triple negative breast cancer. Int J Cancer, 2015, 136(1): 204-211.
30.	Kotsori AA, Dolly S, Sheri A, et al. Is capecitabine efficacious in triple negative metastatic breast cancer?. Oncology, 2010, 79(5/6): 331-336.
31.	Rivera E, Lee J, Davies A. Clinical development of ixabepilone and other epothilones in patients with advanced solid tumors. Oncologist, 2008, 13(12): 1207-1223.
32.	Perez A, Patel T, Moreno-Aspitia A. Efficacy of ixabepilone in ER/PR/HER2-negative (triple-negative) breast cancer. Breast Cancer Res Treat, 2010, 121(2): 261-271.
33.	Tredan O, Campone M, Jassem J, et al. Ixabepilone alone or with cetuximab as First-Line treatment for advanced/metastatic triple-negative breast cancer. Clin Breast Cancer, 2015, 15(1): 8-15.
34.	Telli ML, Jensen KC, Vinayak S, et al. Phase Ⅱ study of gemcitabine, carboplatin, and iniparib as neoadjuvant therapy for triple-negative and BRCA1/2 mutation-associated breast cancer with assessment of a tumor-based measure of genomic instability: PrECOG 0105. J Clin Oncol, 2015, 33(17): 1895-1901.
35.	O’shaughnessy J, Osborne C, Pippen JE, et al. Iniparib plus chemotherapy in metastatic triple-negative breast cancer. N Engl J Med, 2011, 364(3): 205-214.
36.	O’shaughnessy J, Schwartzberg L, Danso A, et al. Phase Ⅲ study of iniparib plus gemcitabine and carboplatin versus gemcitabine and carboplatin in patients with metastatic triple-negative breast cancer. J Clin Oncol, 2014, 32(34): 3840-3847.
37.	Corkery B, Crown J, Clynes M, et al. Epidermal growth factor receptor as a potential therapeutic target in triple-negative breast cancer. Ann Oncol, 2009, 20(5): 862-867.
38.	Perez EA, Spano JP. Current and emerging targeted therapies for metastatic breast cancer. Cancer, 2012, 118(12): 3014-3025.
39.	Cameron D, Brown J, Dent R, et al. Adjuvant bevacizumab-containing therapy in triple-negative breast cancer (Beatrice): primary results of a randomised, phase 3 trial. Lancet Oncol, 2013, 14(10): 933-942.

1. Fan L, Strasser-Weippl K, Li JJ, et al. Breast cancer in China. Lancet Oncol, 2014, 15(7): e279-e289.
2. Siegel R, Ward E, Brawley O, et al. Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin, 2011, 61(4): 212-236.
3. Dawood S. Triple-negative breast cancer: epidemiology and management options. Drugs, 2010, 70(17): 2247-2258.
4. Perou CM, Sorlie T, Eisen MB, et al. Molecular portraits of human breast tumours. Nature, 2000, 406(6797): 747-752.
5. Hennessy BT, Gonzalez-Angulo AM, Stemke-Hale K, et al. Characterization of a naturally occurring breast cancer subset enriched in epithelial-to-mesenchymal transition and stem cell characteristics. Cancer Res, 2009, 69(10): 4116-4124.
6. Penault-Llorca F, Viale G. Pathological and molecular diagnosis of triple-negative breast cancer: a clinical perspective. Ann Oncol, 2012, 23(Suppl 6): vi19-vi22.
7. Brenton JD, Carey LA, Ahmed AA, et al. Molecular classification and molecular forecasting of breast cancer: ready for clinical application?. J Clin Oncol, 2005, 23(29): 7350-7360.
8. Badve S, Dabbs DJ, Schnitt SJ, et al. Basal-like and triple-negative breast cancers: a critical review with an emphasis on the implications for pathologists and oncologists. Mod Pathol, 2011, 24(2): 157-167.
9. Rakha EA, El-Sayed ME, Green AR, et al. Prognostic markers in triple-negative breast cancer. Cancer, 2007, 109(1): 25-32.
10. 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.
11. Gusterson A, Ross T, Heath J, et al. Basal cytokeratins and their relationship to the cellular origin and functional classification of breast cancer. Breast Cancer Res, 2005, 7(4): 143-148.
12. Kim MJ, Ro JY, Ahn SH, et al. Clinicopathologic significance of the basal-like subtype of breast cancer: a comparison with hormone receptor and Her2/neu-overexpressing phenotypes. Hum Pathol, 2006, 37(9): 1217-1226.
13. Cleator S, Heller W, Coombes RC. Triple-negative breast cancer: therapeutic options. Lancet Oncol, 2007, 8(3): 235-244.
14. Turner C, Reis-Filho S, Russell M, et al. BRCA1 dysfunction in sporadic basal-like breast cancer. Oncogene, 2007, 26(14): 2126-2132.
15. Abd El-Rehim DM, Ball G, Pinder SE, et al. High-throughput protein expression analysis using tissue microarray technology of a large well-characterised series identifies biologically distinct classes of breast cancer confirming recent cDNA expression analyses. Int J Cancer, 2005, 116(3): 340-350.
16. Gangi A, Chung A, Mirocha J, et al. Breast-conserving therapy for triple-negative breast cancer. JAMA Surg, 2014, 149(3): 252-258.
17. Moran MS. Radiation therapy in the locoregional treatment of triple-negative breast cancer. Lancet Oncology, 2015, 16(3): E113-E122.
18. Pilewskie M, Ho A, Orell E, et al. Effect of margin width on local recurrence in triple-negative breast cancer patients treated with Breast-Conserving therapy. Ann Surg Oncol, 2014, 21(4): 1209-1214.
19. Gangi A, Mirocha J, Leong T, et al. Triple-negative breast cancer is not associated with increased likelihood of nodal metastases. Ann Surg Oncol, 2014, 21(13): 4098-4103.
20. Carey LA, Dees EC, Sawyer L, et al. The triple negative paradox: primary tumor chemosensitivity of breast cancer subtypes. Clin Cancer Res, 2007, 13(8): 2329-2334.
21. Liedtke C, Mazouni C, Hess KR, et al. Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. J Clin Oncol, 2008, 26(8): 1275-1281.
22. Symmans F, Peintinger F, Hatzis C, et al. Measurement of residual breast cancer burden to predict survival after neoadjuvant chemotherapy. J Clin Oncol, 2007, 25(28): 4414-4422.
23. Hugh J, Hanson J, Cheang MC, et al. Breast cancer subtypes and response to docetaxel in node-positive breast cancer: use of an immunohistochemical definition in the BCIRG 001 trial. J Clin Oncol, 2009, 27(8): 1168-1176.
24. Isakoff SJ. Triple-negative breast cancer role of specific chemotherapy agents. Cancer J, 2010, 16(1): 53-61.
25. Printz C. I-SPY2 trial yields first results on combination therapy for triple-negative breast cancer. Cancer, 2014, 120(6): 773.
26. Sikov M, Berry A, Perou M, et al. Impact of the addition of carboplatin and/or bevacizumab to neoadjuvant once-per-week paclitaxel followed by dose-dense doxorubicin and cyclophosphamide on pathologic complete response rates in stage Ⅱ to Ⅲ triple-negative breast cancer: CALGB 40603 (Alliance) . J Clin Oncol, 2015, 33(1): 13-21.
27. Von Minckwitz G, Schneeweiss A, Loibl S, et al. Neoadjuvant carboplatin in patients with triple-negative and HER2-positive early breast cancer (GeparSixto; GBG 66): a randomised phase 2 trial. Lancet Oncol, 2014, 15(7): 747-756.
28. Koshy N, Quispe D, Shi R, et al. Cisplatin-gemcitabine therapy in metastatic breast cancer: improved outcome in triple negative breast cancer patients compared to non-triple negative patients. Breast, 2010, 19(3): 246-248.
29. Zhang J, Wang ZH, Hu XC, et al. Cisplatin and gemcitabine as the first line therapy in metastatic triple negative breast cancer. Int J Cancer, 2015, 136(1): 204-211.
30. Kotsori AA, Dolly S, Sheri A, et al. Is capecitabine efficacious in triple negative metastatic breast cancer?. Oncology, 2010, 79(5/6): 331-336.
31. Rivera E, Lee J, Davies A. Clinical development of ixabepilone and other epothilones in patients with advanced solid tumors. Oncologist, 2008, 13(12): 1207-1223.
32. Perez A, Patel T, Moreno-Aspitia A. Efficacy of ixabepilone in ER/PR/HER2-negative (triple-negative) breast cancer. Breast Cancer Res Treat, 2010, 121(2): 261-271.
33. Tredan O, Campone M, Jassem J, et al. Ixabepilone alone or with cetuximab as First-Line treatment for advanced/metastatic triple-negative breast cancer. Clin Breast Cancer, 2015, 15(1): 8-15.
34. Telli ML, Jensen KC, Vinayak S, et al. Phase Ⅱ study of gemcitabine, carboplatin, and iniparib as neoadjuvant therapy for triple-negative and BRCA1/2 mutation-associated breast cancer with assessment of a tumor-based measure of genomic instability: PrECOG 0105. J Clin Oncol, 2015, 33(17): 1895-1901.
35. O’shaughnessy J, Osborne C, Pippen JE, et al. Iniparib plus chemotherapy in metastatic triple-negative breast cancer. N Engl J Med, 2011, 364(3): 205-214.
36. O’shaughnessy J, Schwartzberg L, Danso A, et al. Phase Ⅲ study of iniparib plus gemcitabine and carboplatin versus gemcitabine and carboplatin in patients with metastatic triple-negative breast cancer. J Clin Oncol, 2014, 32(34): 3840-3847.
37. Corkery B, Crown J, Clynes M, et al. Epidermal growth factor receptor as a potential therapeutic target in triple-negative breast cancer. Ann Oncol, 2009, 20(5): 862-867.
38. Perez EA, Spano JP. Current and emerging targeted therapies for metastatic breast cancer. Cancer, 2012, 118(12): 3014-3025.
39. Cameron D, Brown J, Dent R, et al. Adjuvant bevacizumab-containing therapy in triple-negative breast cancer (Beatrice): primary results of a randomised, phase 3 trial. Lancet Oncol, 2013, 14(10): 933-942.

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