三陰乳腺癌抗血管生成治療進展及影像學評價_West China Medical Journal

Authors：

 朱鵬晉 ,  鄒立群

四川大學華西醫院腫瘤中心（成都 610041）;

Corresponding?author：

鄒立群, Email: zliqun@hotmail.com

Keywords：

三陰乳腺癌; 抗血管生成分子靶向治療; 影像學評價; 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

三陰乳腺癌（TNBC）是乳腺癌中一個特殊的類型，具有特殊的分子表達類型和生物學特性，內分泌治療和曲妥珠單抗靶向治療無效且無明確治療靶點，復發早、進展快、生存期短、早期易發生遠處轉移等特點。此類型乳腺癌對常規放射、化學治療不敏感，導致其預后較其他類型乳腺癌差。對TNBC靶向治療的深入研究，有助于人們采取更有效的治療手段來提高療效。在實體瘤的惡性生長及轉移中，腫瘤的新生血管生成起著至關重要的作用，針對新生血管生成靶向治療的研究成為熱點。MRI技術是診斷乳腺癌的最準確的影像學方法，有助于腫瘤診斷、治療方案制定、治療反應及預后評估，并能加深對其生物學行為的理解。現對TNBC抗血管生成靶向治療進展及MRI影像學療效評價進行綜述。

Citation： 朱鵬晉, 鄒立群. 三陰乳腺癌抗血管生成治療進展及影像學評價. 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.	陳玉娟, 王曉東, 汪靜. 三陰乳腺癌的特征及治療現狀[J]. 中國普外基礎與臨床雜志, 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.	江冠銘, 袁領勤, 張愛玲, 等. 貝伐單抗聯合白蛋白結合型紫杉醇治療難治三陰性乳腺癌的初步臨床觀察[J]. 中華腫瘤防治雜志, 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.	王升曄, 杜向慧. 貝伐單抗在乳腺癌治療中的療效和風險評估[J]. 中國臨床藥理學與治療學, 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.	劉勇, 湯光宇, 顧偉中. 動態增強MRI對乳腺癌血管生成的評價[J]. 國外醫學:臨床放射學分冊, 2005, 28(6):413-416.
40.	劉麗. 腫瘤血管生成的影像學評價及新進展[J]. 醫學研究生學報, 2012, 25(10):1102-1108.
41.	陳波. 腫瘤血管生成的影像學評價[J]. 醫學研究生學報, 2011, 24(2):196-202.
42.	馬鳳華, 趙澤華, 李莉, 等. 乳腺癌的動態增強MRI及DWI鑒別診斷[J]. 中國醫學計算機成像雜志, 2011, 17(4):317-322.
43.	丁爽, 賈文霄, 許永華, 等. DCE-MRI聯合DWI評價腫瘤血管生成的實驗研究[J]. 中國醫學計算機成像雜志, 2012, 18(6):542-547.
44.	Cyran CC, Paprottka PM, Eisenbl?tter 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, B?hr O, Müller K, et al. Bevacizumab-induced diffusion-restricted lesions in malignant glioma patients[J]. J Neurooncol, 2010, 99(1):49-56.
47.	李子園, 史大鵬, 李海婷, 等. ASL與DSC技術在顱內腫瘤鑒別中的對比研究[J]. 醫藥論壇雜志, 2011, 32(6):3-4, 6.
48.	車英玉, 楊子濤, 程敬亮. 3D ASL與DSC灌注技術在腦腫瘤的對比研究[J]. 臨床放射學雜志, 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. 陳玉娟, 王曉東, 汪靜. 三陰乳腺癌的特征及治療現狀[J]. 中國普外基礎與臨床雜志, 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. 江冠銘, 袁領勤, 張愛玲, 等. 貝伐單抗聯合白蛋白結合型紫杉醇治療難治三陰性乳腺癌的初步臨床觀察[J]. 中華腫瘤防治雜志, 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. 王升曄, 杜向慧. 貝伐單抗在乳腺癌治療中的療效和風險評估[J]. 中國臨床藥理學與治療學, 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. 劉勇, 湯光宇, 顧偉中. 動態增強MRI對乳腺癌血管生成的評價[J]. 國外醫學:臨床放射學分冊, 2005, 28(6):413-416.
40. 劉麗. 腫瘤血管生成的影像學評價及新進展[J]. 醫學研究生學報, 2012, 25(10):1102-1108.
41. 陳波. 腫瘤血管生成的影像學評價[J]. 醫學研究生學報, 2011, 24(2):196-202.
42. 馬鳳華, 趙澤華, 李莉, 等. 乳腺癌的動態增強MRI及DWI鑒別診斷[J]. 中國醫學計算機成像雜志, 2011, 17(4):317-322.
43. 丁爽, 賈文霄, 許永華, 等. DCE-MRI聯合DWI評價腫瘤血管生成的實驗研究[J]. 中國醫學計算機成像雜志, 2012, 18(6):542-547.
44. Cyran CC, Paprottka PM, Eisenbl?tter 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, B?hr O, Müller K, et al. Bevacizumab-induced diffusion-restricted lesions in malignant glioma patients[J]. J Neurooncol, 2010, 99(1):49-56.
47. 李子園, 史大鵬, 李海婷, 等. ASL與DSC技術在顱內腫瘤鑒別中的對比研究[J]. 醫藥論壇雜志, 2011, 32(6):3-4, 6.
48. 車英玉, 楊子濤, 程敬亮. 3D ASL與DSC灌注技術在腦腫瘤的對比研究[J]. 臨床放射學雜志, 2014, 33(5):770-774.

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West China Medical Journal

三陰乳腺癌抗血管生成治療進展及影像學評價

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