Антиангиогенная терапия при раке молочной железы с тройным негативным фенотипом

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Аннотация

Терапия рака молочной железы с тройным негативным фенотипом является трудной клинической задачей. С одной стороны, высокая пролиферативная активность опухоли, характерная для этой когорты больных, обусловливает относительно высокую чувствительность к химиотерапии, с другой стороны – агрессивное течение с быстрой диссеминацией процесса и высокой смертностью. До настоящего времени химиотерапия остается основным методом лечения больных раком молочной железы с тройным негативным фенотипом. Однако результаты ее применения неудовлетворительны и существует острая потребность в поиске новых терапевтических мишеней, воздействие на которые могло бы увеличить эффективность лечения этой прогностически крайне неблагоприятной подгруппы больных. Антиангиогенная терапия позволяет несколько улучшить результаты лечения, однако до сих пор мы не имеем ни одного маркера, позволяющего предсказывать эффективность антиангиогенных препаратов. В связи с этим в настоящее время усилия исследователей должны быть направлены на поиск предсказательных факторов, позволяющих выявлять больных с чувствительными к антиангиогенным препаратам опухолями.

Ключевые слова: рак молочной железы, рак молочной железы с тройным негативным фенотипом, антиангиогенная терапия, бевацизумаб.

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The treatment for triple-negative breast cancer is a difficult clinical task. On the one hand, a high tumor proliferative activity, typical for this cohort, results in a relatively high sensitivity to chemotherapy; on the other hand, there is an aggressive clinical behavior with rapid dissemination and high mortality. To date, chemotherapy remains the principal treatment option for triple-negative breast cancer. However, its results are unsatisfactory and there is a critical need for new therapeutic targets, hitting which might increase the treatment efficacy in this extremely challenging patient subpopulation. Antiangiogenic therapy allows some improvement of treatment results; however, to date, we do not have any markers to predict the efficacy of antiangiogenic drugs. Therefore, the investigators’ efforts should be currently focused on searching for predictors of tumor susceptibility to antiangiogenic drugs, and hence eligible patients.

Key words: breast cancer, triple-negative breast cancer, antiangiogenic therapy, bevacizumab

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Список литературы

1. Prat A, Parker JS, Karginova O et al. Phenotypic and molecular characterization of the claudin-low intrinsic subtype of breast cancer. Breast Cancer Research 2010; 12: R68.
2. William D, Foulkes IE, Smith JS, Reis-Filho. Triple-Negative Breast Cancer. N Engl J Med 2010; 363: 1938–48.
3. Maggie CU, Cheang DV, Bajdik Ch et al. Basal-Like Breast Cancer Defined by Five Biomarkers Has Superior Prognostic Value than Triple-Negative Phenotype. Clin Cancer Res 2008; 14: 1368–76.
4. Oakman C, Viale G, Di Leo A. Management of triple negative breast cancer. Breast 2010; 19 (5): 312–21.
5. Carey L, Dees E, Sawyer et al. The triple negative paradox: primary tumor chemosensitivity of breast cancer subtypes. Clinical Cancer Research 2007; 8 (13): 2329–34.
6. Стенина М., Фролова М., Скрыпникова М. Базальноподобный (тройной негативный) рак молочной железы: молекулярные особенности, течение и возможные терапевтические подходы. Врач. 2010; 3: 24–8.
7. Torrisi R, Balduzzi A, Ghisini R et al. Tailored preoperative treatment of locally advanced triple negative (hormone receptor negative and HER2 negative) breast cancer with epirubicin, cisplatin, and infusional fluorouracil followed by weekly paclitaxel. Cancer Chemother Pharmacol 2008; 62: 667–72.
8. Rakha EA, El-Sayed ME, Green AR et al. Prognostic markers in triple-negative breast cancer. Cancer 2007; 109: 25–32.
9. Haffty BG, Yang Q, Reiss M et al. Locoregional Relapse and Distant Metastasis in Conservatively Managed Triple Negative Early-Stage Breast Cancer. J Clin Oncol 2006; 36 (24): 5652–7.
10. Dent R, Trudeau M, Pritchard K et al. Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res 2007; 15 (13): 4429–34.
11. Dent R, Hanna WM, Trudeau M et al. Pattern of metastatic spread in triple-negative breast cancer. Breast Cancer Res Treat 2009; 115 (2): 423–8.
12. Семиглазов В.Ф., Дашян Г.А., Семиглазов В.В. и др. Лечение «трижды негативного» рака молочной железы. Фарматека. 2009; 18: 14–7.
13. Gluz O, Nitz UA, Harbeck N et al. Triple-negative high-risk breast cancer derives particular benefit from dose intensification of adjuvant chemotherapy: Results of WSG AM-01 trial. Ann Oncol 2008; 19: 861–70.
14. Di Leo A, Isola J, Piette F et al. A meta-analysis of phase III trials evaluating the predictive value of HER-2 and topoisomerase II alpha in early breast cancer patients treated with CMF or anthracycline-based adjuvant therapy. Breast Cancer Res Treat 2008; 107: 24.
15. Bidard FC, Matthieu MC, Chollet P et al. p53 status and efficacy of primary anthracyclines/alkylating agent-based regimen according to breast cancer molecular classes. Ann Oncol 2008; 19: 1261–5.
16. Pivot XB, Li RK, Thomas ES et al. Activity of ixabepilone in oestrogen receptor-negative and oestrogen receptor-progesterone receptor-human epidermal growth factor receptor 2-negative metastatic breast cancer. Eur J Cancer 2009; 45 (17): 2940–6.
17. Baselga J, Zambetti M, Llombart-Cussac A et al. Phase II genomics study of ixabepilone as neoadjuvant treatment for breast cancer. J Clin Oncol 2009; 27 (4): 526–34.
18. Di Leo A, Isola J, Piette F, et al. A meta-analysis of phase III trials evaluating the predictive value of HER-2 and topoisomerase II alpha in early breast cancer patients treated with CMF or anthracycline-based adjuvant therapy. Breast Cancer Res Treat 2008; 107: 24.
19. Genentech, Inc. US Prescribing Information for Avastin 2011.
20. Hoffmann-La Roche F Ltd. Avastin Summary of Product Characteristics 2009; http://www. emea.europa.eu/humandocs/PDFs/EPAR/avastin/emea-combinedh582en.pdf (11 March 2010 date last accessed).
21. Miller K, Wang M, Gralow J et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med 2007; 357: 2666–76.
22. Miles DW, Chan A, Dirix LY et al. Phase III study of bevacizumab plus docetaxel compared with placebo plus docetaxel for the first-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol 2010; 28: 3239–47.
23. Fumoleau P, Greil R, Rayson D et al. Bevacizumab maintenance therapy significantly delays disease progression or death compared with placebo in the AVADO trial. SABCS 2008. post. 903.
24. Robert NJ, Die´ras 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 Clin Oncol 2011; 29: 1252–60.
25. O'Shaughnessy J, Miles D, Gray RJ. A meta-analysis of overall survival data from three randomized trials of bevacizumab (BV) and first-line chemotherapy as treatment for patients with metastatic breast cancer (MBC). J Clin Oncol 2010; 28 (Suppl. Abstr. 1005): 15s.
26. Brufsky A, Bondarenko I, Smirnov V et al. RIBBON-2: A Randomized, Double-Blind, Placebo-Controlled, Phase III Trial Evaluating the Efficacy and Safety of Bevacizumab In Combination with Chemotherapy for Second-Line Treatment of HER2-Negative Metastatic Breast Cancer. SABCS 2009.
27. Brufsky A, Valero V, Tiangco B et al. Impact of bevacizumab (BEV) on efficacy of second-line chemotherapy (CT) for triple-negative breast cancer (TNBC): Analysis of RIBBON-2. Аbstr. 1010. ASCO 2011.
28. Frasci G, D’Aiuto G, Comella P et al. Southern Italy Cooperative Oncology Group (SICOG). Weekly cisplatin, epirubicin, and paclitaxel with granulocyte colonystimulating factor support vs triweekly epirubicin and paclitaxel in locally advanced breast cancer: ﬁnal analysis of a SICOG phase III study. Br J Cancer 2006; 95: 1005–12.
29. Frasci G, D’Aiuto G, Comella P et al. Preoperative weekly cisplatin, epirubicin, and paclitaxel (PET) improves prognosis in locally advanced breast cancer patients: an update of the Southern Italy Cooperative Oncology Group (SICOG) randomised trial 9908. Ann Oncol 2010; 21: 707–16.
30. Ryan PD, Tung NM, Isakoff SJ et al. Neoadjuvant cisplatin and bevacizumab in triple negative breast cancer (TNBC): Safety and efficacy. J Clin Oncol 2009; 27 (Suppl): 15s. Abstr 551.
31. Gerber B, Eidtmann H, Rezai M et al. Neoadjuvant bevacizumab and anthracycline–taxane-based chemotherapry in 686 triple-negative primary breast cancers: Seconday endpoint analysis of the Gepar-Quinto study (GBG 44). ASCO 2011. Abstr 1006.
32. Cortes J, Calvo V, Ramirez-Merino N et al. Adverse events risk associated with Bevacizumab addition to breast cancer chemotherapy: A Meta-Analysis Ann Oncol 2011.
33. Жуков Н. В. Современное состояние антиангиогенной терапии. Целевая терапия без мишени? Практическая онкология. 2007; 3 (8): 164–72.
34. Moreno-Aspitia A et al. BAY43-9006 as single oral agent in patients with metastatic breast cancer previously exposed to anthracycline and/or taxane. J Clin Oncol 2006; 24 (Suppl. 18S): abstr. 577.

Авторы

Л.Г.Жукова

ФГБУ Российский онкологический научный центр им. Н.Н.Блохина РАМН

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L.G.Zhukova

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