三阴乳腺癌抗血管生成治疗进展及影像学评价_West China Medical Journal

Authors：

 朱鹏晋 ,  邹立群

四川大学华西医院肿瘤中心（成都 610041）;

Corresponding author：

邹立群, Email: zliqun@hotmail.com

Keywords：

三阴乳腺癌; 抗血管生成分子靶向治疗; 影像学评价; 磁共振成像

DOI：

10.7507/1002-0179.20150454

Video：

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Abstract Full text Figures/Tables Video References Cited by

三阴乳腺癌（TNBC）是乳腺癌中一个特殊的类型，具有特殊的分子表达类型和生物学特性，内分泌治疗和曲妥珠单抗靶向治疗无效且无明确治疗靶点，复发早、进展快、生存期短、早期易发生远处转移等特点。此类型乳腺癌对常规放射、化学治疗不敏感，导致其预后较其他类型乳腺癌差。对TNBC靶向治疗的深入研究，有助于人们采取更有效的治疗手段来提高疗效。在实体瘤的恶性生长及转移中，肿瘤的新生血管生成起着至关重要的作用，针对新生血管生成靶向治疗的研究成为热点。MRI技术是诊断乳腺癌的最准确的影像学方法，有助于肿瘤诊断、治疗方案制定、治疗反应及预后评估，并能加深对其生物学行为的理解。现对TNBC抗血管生成靶向治疗进展及MRI影像学疗效评价进行综述。

Citation： 朱鹏晋, 邹立群. 三阴乳腺癌抗血管生成治疗进展及影像学评价. West China Medical Journal, 2015, 30(8): 1587-1592. doi: 10.7507/1002-0179.20150454 Copy

1.	Carey LA, Perou CM, Livasy CA, et al. Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study[J]. JAMA, 2006, 295(21):2492-2502.
2.	Lund MJ, Butler EN, Bumpers HL, et al. High prevalence of triple-negative tumors in an urban cancer center[J]. Cancer, 2008, 113(3):608-615.
3.	Reis-Filho JS, Tutt A. Triple negative tumours:a critical review[J]. Histopathology, 2008, 52(1):108-118.
4.	Yoon JK, Kim DH, Koo JS. Implications of differences in expression of sarcosine metabolism-related proteins according to the molecular subtype of breast cancer[J]. J Transl Med, 2014, 12:149.
5.	Liedtke C, Mazouni C, Hess KR, et al. Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer[J]. J Clin Oncol, 2008, 26(8):1275-1281.
6.	Millar EK, Graham PH, O'toole SA, et al. Prediction of local recurrence, distant metastases, and death after breast-conserving therapy in early-stage invasive breast cancer using a five-biomarker panel[J]. J Clin Oncol, 2009, 27(28):4701-4708.
7.	Solin LJ, Hwang WT, Vapiwala N. Outcome after breast conservation treatment with radiation for women with triple-negative early-stage invasive breast carcinoma[J]. Clin Breast Cancer, 2009, 9(2):96-100.
8.	Voduc KD, Cheang MC, Tyldesley S, et al. Breast cancer subtypes and the risk of local and regional relapse[J]. J Clin Oncol, 2010, 28(10):1684-1691.
9.	陈玉娟, 王晓东, 汪静. 三阴乳腺癌的特征及治疗现状[J]. 中国普外基础与临床杂志, 2012, 19(9):1024-1027.
10.	Rakha EA, El-Sayed ME, Green AR, et al. Prognostic markers in triple-negative breast cancer[J]. Cancer, 2007, 109(1):25-32.
11.	Greenberg S, Rugo HS. Challenging clinical scenarios:treatment of patients with triple-negative or basal-like metastatic breast cancer[J]. Clin Breast Cancer, 2010, 10(Suppl 2):S20-S29.
12.	Irshad S, Ellis P, Tutt A. Molecular heterogeneity of triple-negative breast cancer and its clinical implications[J]. Curr Opin Oncol, 2011, 23(6):566-577.
13.	Bayraktar S, Glück S. Molecularly targeted therapies for metastatic triple-negative breast cancer[J]. Breast Cancer Res Treat, 2013, 138(1):21-35.
14.	Conlin AK, Seidman AD. Beyond cytotoxic chemotherapy for the first-line treatment of HER2-negative, hormone-insensitive metastatic breast cancer:current status and future opportunities[J]. Clin Breast Cancer, 2008, 8(3):215-223.
15.	Burstein HJ, Elias AD, Rugo HS, et al. Phase Ⅱ study of sunitinib malate, an oral multitargeted tyrosine kinase inhibitor, in patients with metastatic breast cancer previously treated with an anthracycline and a taxane[J]. J Clin Oncol, 2008, 26(11):1810-1816.
16.	Fan XJ, Krieg S, Kuo CJ, et al. VEGF blockade inhibits angiogenesis and reepithelialization of endometrium[J]. FASEB J, 2008, 22(10):3571-3580.
17.	Crown J, O'Shaughnessy J, Gullo G. Emerging targeted therapies in triple-negative breast cancer[J]. Ann Oncol, 2012, 23(Suppl 6):vi56-vi65.
18.	Carey LA. Directed therapy of subtypes of triple-negative breast cancer[J]. Oncologist, 2010, 15(Suppl 5):49-56.
19.	Carey LA, Rugo HS, Marcom PK, et al. TBCRC 001:randomized phase Ⅱ study of cetuximab in combination with carboplatin in stage Ⅳ triple-negative breast cancer[J]. J Clin Oncol, 2012, 30(21):2615-2623.
20.	Jain RK, Duda DG, Clark JW, et al. Lessons from phase Ⅲ clinical trials on anti-VEGF therapy for cancer[J]. Nat Clin Pract Oncol, 2006, 3(1):24-40.
21.	Damasceno M. Bevacizumab for the first-line treatment of human epidermal growth factor receptor 2-negative advanced breast cancer[J]. Curr Opin Oncol, 2011, 23(Suppl):S3-S9.
22.	江冠铭, 袁领勤, 张爱玲, 等. 贝伐单抗联合白蛋白结合型紫杉醇治疗难治三阴性乳腺癌的初步临床观察[J]. 中华肿瘤防治杂志, 2012, 19(10):783-785.
23.	Miller K, Wang ML, Gralow J, et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer[J]. N Engl J Med, 2007, 357(26):2666-2676.
24.	Gelmon K, Dent R, Mackey JR, et al. Targeting triple-negative breast cancer:optimising therapeutic outcomes[J]. Ann Oncol, 2012, 23(9):2223-2234.
25.	Robert NJ, Diéras V, Glaspy J, et al. RIBBON-1:randomized, double-blind, placebo-controlled, phase Ⅲ trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer[J]. J Clin Oncol, 2011, 29(10):1252-1260.
26.	Brufsky A, Valero V, Tiangco B, et al. Second-line bevacizumab-containing therapy in patients with triple-negative breast cancer:subgroup analysis of the RIBBON-2 trial[J]. Breast Cancer Res Treat, 2012, 133(3):1067-1075.
27.	Thomssen C, Pierga JY, Pritchard KI, et al. First-line bevacizumab-containing therapy for triple-negative breast cancer:analysis of 585 patients treated in the Athena study[J]. Oncology, 2012, 82(4):218-227.
28.	王升晔, 杜向慧. 贝伐单抗在乳腺癌治疗中的疗效和风险评估[J]. 中国临床药理学与治疗学, 2013, 18(1):115-120.
29.	Mackey J, Gelmon K, Martin M, et al. TRIO-012:a multicenter, multinational, randomized, double-blind phase Ⅲ study of IMC-1121B plus docetaxel versus placebo plus docetaxel in previously untreated patients with HER2-negative, unresectable, locally recurrent or metastatic breast cancer[J]. Clinical breast cancer, 2009, 9(4):258-261.
30.	Baselga J, Segalla JGM, Roché H, et al. 3LBA SOLTI-0701:a double-blind, randomized phase 2b study evaluating the efficacy and safety of sorafenib (SOR) compared to placebo (PL) when administered in combination with capecitabine (CAP) in patients (pts) with locally advanced (adv) or metastatic (met) breast cancer (BC)[J]. Cancer Research, 2009, 7(3):3-4.
31.	Barrios CH, Liu MC, Lee SC, et al. Phase Ⅲ randomized trial of sunitinib versus capecitabine in patients with previously treated HER2-negative advanced breast cancer[J]. Breast Cancer Res Treat, 2010, 121(1):121-131.
32.	Bergh J, Bondarenko IM, Lichinitser MR, et al. First-line treatment of advanced breast cancer with sunitinib in combination with docetaxel versus docetaxel alone:results of a prospective, randomized phase Ⅲ study[J]. J Clin Oncol, 2012, 30(9):921-929.
33.	Crown JP, Diéras V, Staroslawska E, et al. Phase Ⅲ trial of sunitinib in combination with capecitabine versus capecitabine monotherapy for the treatment of patients with pretreated metastatic breast cancer[J]. J Clin Oncol, 2013, 31(23):2870-2878.
34.	Curigliano G, Pivot X, Cortés J, et al. Randomized phase Ⅱ study of sunitinib versus standard of care for patients with previously treated advanced triple-negative breast cancer[J]. Breast, 2013, 22(5):650-656.
35.	Bianchi G, Loibl S, Zamagni C, et al. Phase Ⅱ multicenter, uncontrolled trial of sorafenib in patients with metastatic breast cancer[J]. Anticancer Drugs, 2009, 20(7):616-624.
36.	Baselga J, Costa F, Gomez H, et al. A phase 3 tRial comparing capecitabinE in combination with Sorafenib or placebo for treatment of locally advanced or metastatic HER2-Negative breast CancEr (the RESILIENCE study):study protocol for a randomized controlled trial[J]. Trials, 2013, 14:228-235.
37.	Hudis CTW, Hermann RC, Makari-Judson GC, et al. Sorafenib (SOR) plus chemotherapy (CRx) for patients (pts) with advanced (adv) breast cancer (BC) previously treated with bevacizumab (BEV)[J]. J Clin Oncol, 2011 ASCO Annual Meeting Abstracts Part1, 29(Suppl 15):1009.
38.	Gradishar WJ, Kaklamani V, Sahoo TP, et al. A double-blind, randomised, placebo-controlled, phase 2b study evaluating sorafenib in combination with paclitaxel as a first-line therapy in patients with HER2-negative advanced breast cancer[J]. Eur J Cancer, 2013, 49(2):312-322.
39.	刘勇, 汤光宇, 顾伟中. 动态增强MRI对乳腺癌血管生成的评价[J]. 国外医学:临床放射学分册, 2005, 28(6):413-416.
40.	刘丽. 肿瘤血管生成的影像学评价及新进展[J]. 医学研究生学报, 2012, 25(10):1102-1108.
41.	陈波. 肿瘤血管生成的影像学评价[J]. 医学研究生学报, 2011, 24(2):196-202.
42.	马凤华, 赵泽华, 李莉, 等. 乳腺癌的动态增强MRI及DWI鉴别诊断[J]. 中国医学计算机成像杂志, 2011, 17(4):317-322.
43.	丁爽, 贾文霄, 许永华, 等. DCE-MRI联合DWI评价肿瘤血管生成的实验研究[J]. 中国医学计算机成像杂志, 2012, 18(6):542-547.
44.	Cyran CC, Paprottka PM, Eisenblätter M, et al. Visualization, imaging and new preclinical diagnostics in radiation oncology[J]. Radiat Oncol, 2014, 9:3.
45.	Viel T, Boehm-Sturm P, Rapic S, et al. Non-invasive imaging of glioma vessel size and densities in correlation with tumour cell proliferation by small animal PET and MRI[J]. Eur J Nucl Med Mol Imaging, 2013, 40(10):1595-1606.
46.	Rieger J, Bähr O, Müller K, et al. Bevacizumab-induced diffusion-restricted lesions in malignant glioma patients[J]. J Neurooncol, 2010, 99(1):49-56.
47.	李子园, 史大鹏, 李海婷, 等. ASL与DSC技术在颅内肿瘤鉴别中的对比研究[J]. 医药论坛杂志, 2011, 32(6):3-4, 6.
48.	车英玉, 杨子涛, 程敬亮. 3D ASL与DSC灌注技术在脑肿瘤的对比研究[J]. 临床放射学杂志, 2014, 33(5):770-774.

1. Carey LA, Perou CM, Livasy CA, et al. Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study[J]. JAMA, 2006, 295(21):2492-2502.
2. Lund MJ, Butler EN, Bumpers HL, et al. High prevalence of triple-negative tumors in an urban cancer center[J]. Cancer, 2008, 113(3):608-615.
3. Reis-Filho JS, Tutt A. Triple negative tumours:a critical review[J]. Histopathology, 2008, 52(1):108-118.
4. Yoon JK, Kim DH, Koo JS. Implications of differences in expression of sarcosine metabolism-related proteins according to the molecular subtype of breast cancer[J]. J Transl Med, 2014, 12:149.
5. Liedtke C, Mazouni C, Hess KR, et al. Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer[J]. J Clin Oncol, 2008, 26(8):1275-1281.
6. Millar EK, Graham PH, O'toole SA, et al. Prediction of local recurrence, distant metastases, and death after breast-conserving therapy in early-stage invasive breast cancer using a five-biomarker panel[J]. J Clin Oncol, 2009, 27(28):4701-4708.
7. Solin LJ, Hwang WT, Vapiwala N. Outcome after breast conservation treatment with radiation for women with triple-negative early-stage invasive breast carcinoma[J]. Clin Breast Cancer, 2009, 9(2):96-100.
8. Voduc KD, Cheang MC, Tyldesley S, et al. Breast cancer subtypes and the risk of local and regional relapse[J]. J Clin Oncol, 2010, 28(10):1684-1691.
9. 陈玉娟, 王晓东, 汪静. 三阴乳腺癌的特征及治疗现状[J]. 中国普外基础与临床杂志, 2012, 19(9):1024-1027.
10. Rakha EA, El-Sayed ME, Green AR, et al. Prognostic markers in triple-negative breast cancer[J]. Cancer, 2007, 109(1):25-32.
11. Greenberg S, Rugo HS. Challenging clinical scenarios:treatment of patients with triple-negative or basal-like metastatic breast cancer[J]. Clin Breast Cancer, 2010, 10(Suppl 2):S20-S29.
12. Irshad S, Ellis P, Tutt A. Molecular heterogeneity of triple-negative breast cancer and its clinical implications[J]. Curr Opin Oncol, 2011, 23(6):566-577.
13. Bayraktar S, Glück S. Molecularly targeted therapies for metastatic triple-negative breast cancer[J]. Breast Cancer Res Treat, 2013, 138(1):21-35.
14. Conlin AK, Seidman AD. Beyond cytotoxic chemotherapy for the first-line treatment of HER2-negative, hormone-insensitive metastatic breast cancer:current status and future opportunities[J]. Clin Breast Cancer, 2008, 8(3):215-223.
15. Burstein HJ, Elias AD, Rugo HS, et al. Phase Ⅱ study of sunitinib malate, an oral multitargeted tyrosine kinase inhibitor, in patients with metastatic breast cancer previously treated with an anthracycline and a taxane[J]. J Clin Oncol, 2008, 26(11):1810-1816.
16. Fan XJ, Krieg S, Kuo CJ, et al. VEGF blockade inhibits angiogenesis and reepithelialization of endometrium[J]. FASEB J, 2008, 22(10):3571-3580.
17. Crown J, O'Shaughnessy J, Gullo G. Emerging targeted therapies in triple-negative breast cancer[J]. Ann Oncol, 2012, 23(Suppl 6):vi56-vi65.
18. Carey LA. Directed therapy of subtypes of triple-negative breast cancer[J]. Oncologist, 2010, 15(Suppl 5):49-56.
19. Carey LA, Rugo HS, Marcom PK, et al. TBCRC 001:randomized phase Ⅱ study of cetuximab in combination with carboplatin in stage Ⅳ triple-negative breast cancer[J]. J Clin Oncol, 2012, 30(21):2615-2623.
20. Jain RK, Duda DG, Clark JW, et al. Lessons from phase Ⅲ clinical trials on anti-VEGF therapy for cancer[J]. Nat Clin Pract Oncol, 2006, 3(1):24-40.
21. Damasceno M. Bevacizumab for the first-line treatment of human epidermal growth factor receptor 2-negative advanced breast cancer[J]. Curr Opin Oncol, 2011, 23(Suppl):S3-S9.
22. 江冠铭, 袁领勤, 张爱玲, 等. 贝伐单抗联合白蛋白结合型紫杉醇治疗难治三阴性乳腺癌的初步临床观察[J]. 中华肿瘤防治杂志, 2012, 19(10):783-785.
23. Miller K, Wang ML, Gralow J, et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer[J]. N Engl J Med, 2007, 357(26):2666-2676.
24. Gelmon K, Dent R, Mackey JR, et al. Targeting triple-negative breast cancer:optimising therapeutic outcomes[J]. Ann Oncol, 2012, 23(9):2223-2234.
25. Robert NJ, Diéras V, Glaspy J, et al. RIBBON-1:randomized, double-blind, placebo-controlled, phase Ⅲ trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer[J]. J Clin Oncol, 2011, 29(10):1252-1260.
26. Brufsky A, Valero V, Tiangco B, et al. Second-line bevacizumab-containing therapy in patients with triple-negative breast cancer:subgroup analysis of the RIBBON-2 trial[J]. Breast Cancer Res Treat, 2012, 133(3):1067-1075.
27. Thomssen C, Pierga JY, Pritchard KI, et al. First-line bevacizumab-containing therapy for triple-negative breast cancer:analysis of 585 patients treated in the Athena study[J]. Oncology, 2012, 82(4):218-227.
28. 王升晔, 杜向慧. 贝伐单抗在乳腺癌治疗中的疗效和风险评估[J]. 中国临床药理学与治疗学, 2013, 18(1):115-120.
29. Mackey J, Gelmon K, Martin M, et al. TRIO-012:a multicenter, multinational, randomized, double-blind phase Ⅲ study of IMC-1121B plus docetaxel versus placebo plus docetaxel in previously untreated patients with HER2-negative, unresectable, locally recurrent or metastatic breast cancer[J]. Clinical breast cancer, 2009, 9(4):258-261.
30. Baselga J, Segalla JGM, Roché H, et al. 3LBA SOLTI-0701:a double-blind, randomized phase 2b study evaluating the efficacy and safety of sorafenib (SOR) compared to placebo (PL) when administered in combination with capecitabine (CAP) in patients (pts) with locally advanced (adv) or metastatic (met) breast cancer (BC)[J]. Cancer Research, 2009, 7(3):3-4.
31. Barrios CH, Liu MC, Lee SC, et al. Phase Ⅲ randomized trial of sunitinib versus capecitabine in patients with previously treated HER2-negative advanced breast cancer[J]. Breast Cancer Res Treat, 2010, 121(1):121-131.
32. Bergh J, Bondarenko IM, Lichinitser MR, et al. First-line treatment of advanced breast cancer with sunitinib in combination with docetaxel versus docetaxel alone:results of a prospective, randomized phase Ⅲ study[J]. J Clin Oncol, 2012, 30(9):921-929.
33. Crown JP, Diéras V, Staroslawska E, et al. Phase Ⅲ trial of sunitinib in combination with capecitabine versus capecitabine monotherapy for the treatment of patients with pretreated metastatic breast cancer[J]. J Clin Oncol, 2013, 31(23):2870-2878.
34. Curigliano G, Pivot X, Cortés J, et al. Randomized phase Ⅱ study of sunitinib versus standard of care for patients with previously treated advanced triple-negative breast cancer[J]. Breast, 2013, 22(5):650-656.
35. Bianchi G, Loibl S, Zamagni C, et al. Phase Ⅱ multicenter, uncontrolled trial of sorafenib in patients with metastatic breast cancer[J]. Anticancer Drugs, 2009, 20(7):616-624.
36. Baselga J, Costa F, Gomez H, et al. A phase 3 tRial comparing capecitabinE in combination with Sorafenib or placebo for treatment of locally advanced or metastatic HER2-Negative breast CancEr (the RESILIENCE study):study protocol for a randomized controlled trial[J]. Trials, 2013, 14:228-235.
37. Hudis CTW, Hermann RC, Makari-Judson GC, et al. Sorafenib (SOR) plus chemotherapy (CRx) for patients (pts) with advanced (adv) breast cancer (BC) previously treated with bevacizumab (BEV)[J]. J Clin Oncol, 2011 ASCO Annual Meeting Abstracts Part1, 29(Suppl 15):1009.
38. Gradishar WJ, Kaklamani V, Sahoo TP, et al. A double-blind, randomised, placebo-controlled, phase 2b study evaluating sorafenib in combination with paclitaxel as a first-line therapy in patients with HER2-negative advanced breast cancer[J]. Eur J Cancer, 2013, 49(2):312-322.
39. 刘勇, 汤光宇, 顾伟中. 动态增强MRI对乳腺癌血管生成的评价[J]. 国外医学:临床放射学分册, 2005, 28(6):413-416.
40. 刘丽. 肿瘤血管生成的影像学评价及新进展[J]. 医学研究生学报, 2012, 25(10):1102-1108.
41. 陈波. 肿瘤血管生成的影像学评价[J]. 医学研究生学报, 2011, 24(2):196-202.
42. 马凤华, 赵泽华, 李莉, 等. 乳腺癌的动态增强MRI及DWI鉴别诊断[J]. 中国医学计算机成像杂志, 2011, 17(4):317-322.
43. 丁爽, 贾文霄, 许永华, 等. DCE-MRI联合DWI评价肿瘤血管生成的实验研究[J]. 中国医学计算机成像杂志, 2012, 18(6):542-547.
44. Cyran CC, Paprottka PM, Eisenblätter M, et al. Visualization, imaging and new preclinical diagnostics in radiation oncology[J]. Radiat Oncol, 2014, 9:3.
45. Viel T, Boehm-Sturm P, Rapic S, et al. Non-invasive imaging of glioma vessel size and densities in correlation with tumour cell proliferation by small animal PET and MRI[J]. Eur J Nucl Med Mol Imaging, 2013, 40(10):1595-1606.
46. Rieger J, Bähr O, Müller K, et al. Bevacizumab-induced diffusion-restricted lesions in malignant glioma patients[J]. J Neurooncol, 2010, 99(1):49-56.
47. 李子园, 史大鹏, 李海婷, 等. ASL与DSC技术在颅内肿瘤鉴别中的对比研究[J]. 医药论坛杂志, 2011, 32(6):3-4, 6.
48. 车英玉, 杨子涛, 程敬亮. 3D ASL与DSC灌注技术在脑肿瘤的对比研究[J]. 临床放射学杂志, 2014, 33(5):770-774.

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三阴乳腺癌抗血管生成治疗进展及影像学评价

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