Ganshina IP, Ivanova KA, Gordeeva OO, Arkhipov AV, Zhukova LG. Antiangiogenic therapy for breast cancer with triple negative phenotype Journal of Modern Oncology. 2021; 23 (1): 88–92.
DOI: 10.26442/18151434.2021.1.200763
Антиангиогенная терапия при раке молочной железы с тройным негативным фенотипом
Ganshina IP, Ivanova KA, Gordeeva OO, Arkhipov AV, Zhukova LG. Antiangiogenic therapy for breast cancer with triple negative phenotype Journal of Modern Oncology. 2021; 23 (1): 88–92.
DOI: 10.26442/18151434.2021.1.200763
Трижды негативный рак молочной железы (ТНРМЖ) составляет 10–24% всех случаев рака молочной железы (РМЖ), характеризуется отсутствием в опухоли рецепторов к эстрогенам, прогестерону и HER-2. Терапия данного заболевания является трудной клинической задачей. В отличие от гормонопозитивного и HER-2-позитивного РМЖ, при которых мы успешно применяем таргетные препараты (антиэстрогены и анти-HER-2-препараты), при ТНРМЖ мы долгое время не имели таких мишеней. Так, несмотря на впечатляющие результаты иммунотерапии метастатического ТНРМЖ, остается достаточно большая группа пациенток с отрицательным PD-L1-статусом, для которых необходимо разрабатывать иные стратегии лечения. Один из подходов в лечении злокачественных опухолей предусматривает воздействие не на опухолевые клетки, а на процесс новообразования сосудов в опухоли – ангиогенез. Антиангиогенные препараты положительно зарекомендовали себя при лечении большого количества злокачественных опухолей, но являются недооцененными для РМЖ (в том числе для тройного негативного фенотипа). Применение бевацизумаба в комбинации с цитостатиками на различных этапах лечения пациенток с РМЖ изучалось в многочисленных клинических исследованиях и продемонстрировало обнадеживающие результаты, в том числе и для ТНРМЖ, однако из-за отозванной регистрации Управлением по контролю пищевых продуктов и лекарств в США было незаслуженно забыто в ряде стран. В данном обзоре представлена роль бевацизумаба в терапии пациенток с ТНРМЖ и предложены условия, при которых назначение этого препарата было бы оправданным и приводило к лучшим результатам.
Triple-negative breast cancer is 10–24% of all cases of breast cancer and is characterized by the absence of estrogen, progesterone, and HER-2 receptors in the tumor. The therapy of this illness is a difficult clinical case. In contrast to hormone-positive and HER-2-positive phenotypes, in which we successfully use targeted drugs (antiestrogens and anti-HER-2 drugs), for triple-negative breast cancer we have not had such targets for a long time. Thus, despite the impressive results of immunotherapy of triple-negative breast cancer, there remains a fairly large group of patients with negative PD-L1 status, for whom it is necessary to develop other treatment strategies. One of the approaches in the treatment of malignant tumors includes not the impact on tumor cells, but the process of angiogenesis. Antiangiogenic drugs have positively proven themselves in the treatment of a large number of malignant tumors but are underestimated for breast cancer (including triple-negative phenotype). The use of bevacizumab in combinations with cytostatic drugs in breast cancer therapy (including triple-negative breast cancer) has been studied in a large number of clinical trials but was undeservedly forgotten in some countries due to the revoked FDA registration. This review presents the role of bevacizumab in the treatment of patients with triple-negative breast cancer and suggests the conditions when the administration of this drug is justified and leads to better results.
Keywords: triple-negative breast cancer, angiogenesis, bevacizumab, antiangiogenic therapy
1. Folkman J. Tumor Angiogenesis: Therapeutic Implications. N Engl J Med 1971; 285 (21): 1182–6. DOI: 10.1056/nejm197111182852108
2. Jain RK. Normalizing tumor vasculature with anti-angiogenic therapy: A new paradigm for combination therapy. Nat Med 2001; 7 (9): 987–9.
3. Jain RK. Normalization of tumor vasculature: An emerging concept in antiangiogenic therapy. Science 2005; 307 (5706): 58–62.
4. Duda DG, Jain RK, Willett CG. Antiangiogenics: The potential role of integrating this novel treatment modality with chemoradiation for solid cancers. J Clin Oncol 2007; 25 (26): 4033–42.
5. Gray R, Bhattacharya S, Bowden C, et al. Independent review of E2100: a phase III trial of bevacizumab plus paclitaxel versus paclitaxel in women with metastatic breast cancer. J Clin Oncol 2009; 27 (30): 4966–72.
6. Miles DW, Chan A, Romieu G, et al. Randomized, double-blind, placebo-controlled, phase III study of bevacizumab with docetaxel or docetaxel with placebo as first-line therapy for patients with locally recurrent or metastatic breast cancer (mBC): AVADO. J Clin Oncol 2008; 26 (43s).
7. 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 Clin Oncol 2011; 29 (10): 1252–60.
8. O'Shaughnessy J, Miles D, Gray RJ, et al. 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. 15): 1005.
9. Smith IE, Pierga JY, Biganzoli L, et al. First-line bevacizumab plus taxane-based chemotherapy for locally recurrent or metastatic breast cancer: Safety and efficacy in an open-label study in 2251 patients Ann Oncol [epub ahead of print on September 5, 2010].
10. Smith I, Pierga JY, Biganzoli L, et al. Final overall survival results and effect of prolonged (≥1 year) first-line bevacizumab-containing therapy for metastatic breast cancer in the ATHENA trial. Breast Cancer Res Treat 2011; 130: 133.
11. Gligorov J, Doval D, Bines J, et al. Maintenance capecitabine and bevacizumab versus bevacizumab alone after initial first-line bevacizumab and docetaxel for patients with HER2-negative metastatic breast cancer. Lancet Oncol 2014; 15 (12): 1351–60.
12. Brufsky AM, Hurvitz S, Perez E, 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 Human Epidermal Growth Factor Receptor 2–Negative Metastatic Breast Cancer. J Clin Oncol 2011; 29 (32): 4286–93. DOI: 10.1200/jco.2010.34.1255
13. O’Shaughnessy JA, Brufsky AM. RiBBON 1 and RiBBON 2: Phase III Trials of Bevacizumab with Standard Chemotherapy for Metastatic Breast Cancer. Clin Breast Cancer 2008. 8(4); 370–3. DOI: 10.3816/cbc.2008.n.045
14. Nahleh Z, Botrus G, Dwivedi A, et al. Bevacizumab in the neoadjuvant treatment of human epidermal growth factor receptor 2-negative breast cancer: A meta-analysis of randomized controlled trials. Mol Clin Oncol 2019; 10: 357–65.
15. Hardy-Bessard AC, Brocard F, Clatot F, et al. First-line bevacizumab and eribulin combination therapy for HER2-negative metastatic breast cancer: Efficacy and safety in the GINECO phase II ESMERALDA study. Breast 2020; 54: 256–63. DOI: 10.1016/j.breast.2020.09.011
16. De Angelis C, Bruzzese D, Bernardo A, et al. Eribulin in combination with bevacizumab as second-line treatment for HER2-negative metastatic breast cancer progressing after first-line therapy with paclitaxel and bevacizumab: a multicenter, phase II, single arm trial (GIM11-BERGI). ESMO Open 2021; 6 (2): 100054. DOI: 10.1016/j.esmoop.2021.100054. PMID: 33601296.
17. Hirai T, Nemoto A, Ito Y, et al. Meta-analyses on progression-free survival as a surrogate endpoint for overall survival in triple-negative breast cancer. Breast Cancer Res Treat 2020; 181: 189–98. DOI: 10.1007/s10549-020-05615-4
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1. Folkman J. Tumor Angiogenesis: Therapeutic Implications. N Engl J Med 1971; 285 (21): 1182–6. DOI: 10.1056/nejm197111182852108
2. Jain RK. Normalizing tumor vasculature with anti-angiogenic therapy: A new paradigm for combination therapy. Nat Med 2001; 7 (9): 987–9.
3. Jain RK. Normalization of tumor vasculature: An emerging concept in antiangiogenic therapy. Science 2005; 307 (5706): 58–62.
4. Duda DG, Jain RK, Willett CG. Antiangiogenics: The potential role of integrating this novel treatment modality with chemoradiation for solid cancers. J Clin Oncol 2007; 25 (26): 4033–42.
5. Gray R, Bhattacharya S, Bowden C, et al. Independent review of E2100: a phase III trial of bevacizumab plus paclitaxel versus paclitaxel in women with metastatic breast cancer. J Clin Oncol 2009; 27 (30): 4966–72.
6. Miles DW, Chan A, Romieu G, et al. Randomized, double-blind, placebo-controlled, phase III study of bevacizumab with docetaxel or docetaxel with placebo as first-line therapy for patients with locally recurrent or metastatic breast cancer (mBC): AVADO. J Clin Oncol 2008; 26 (43s).
7. 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 Clin Oncol 2011; 29 (10): 1252–60.
8. O'Shaughnessy J, Miles D, Gray RJ, et al. 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. 15): 1005.
9. Smith IE, Pierga JY, Biganzoli L, et al. First-line bevacizumab plus taxane-based chemotherapy for locally recurrent or metastatic breast cancer: Safety and efficacy in an open-label study in 2251 patients Ann Oncol [epub ahead of print on September 5, 2010].
10. Smith I, Pierga JY, Biganzoli L, et al. Final overall survival results and effect of prolonged (≥1 year) first-line bevacizumab-containing therapy for metastatic breast cancer in the ATHENA trial. Breast Cancer Res Treat 2011; 130: 133.
11. Gligorov J, Doval D, Bines J, et al. Maintenance capecitabine and bevacizumab versus bevacizumab alone after initial first-line bevacizumab and docetaxel for patients with HER2-negative metastatic breast cancer. Lancet Oncol 2014; 15 (12): 1351–60.
12. Brufsky AM, Hurvitz S, Perez E, 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 Human Epidermal Growth Factor Receptor 2–Negative Metastatic Breast Cancer. J Clin Oncol 2011; 29 (32): 4286–93. DOI: 10.1200/jco.2010.34.1255
13. O’Shaughnessy JA, Brufsky AM. RiBBON 1 and RiBBON 2: Phase III Trials of Bevacizumab with Standard Chemotherapy for Metastatic Breast Cancer. Clin Breast Cancer 2008. 8(4); 370–3. DOI: 10.3816/cbc.2008.n.045
14. Nahleh Z, Botrus G, Dwivedi A, et al. Bevacizumab in the neoadjuvant treatment of human epidermal growth factor receptor 2-negative breast cancer: A meta-analysis of randomized controlled trials. Mol Clin Oncol 2019; 10: 357–65.
15. Hardy-Bessard AC, Brocard F, Clatot F, et al. First-line bevacizumab and eribulin combination therapy for HER2-negative metastatic breast cancer: Efficacy and safety in the GINECO phase II ESMERALDA study. Breast 2020; 54: 256–63. DOI: 10.1016/j.breast.2020.09.011
16. De Angelis C, Bruzzese D, Bernardo A, et al. Eribulin in combination with bevacizumab as second-line treatment for HER2-negative metastatic breast cancer progressing after first-line therapy with paclitaxel and bevacizumab: a multicenter, phase II, single arm trial (GIM11-BERGI). ESMO Open 2021; 6 (2): 100054. DOI: 10.1016/j.esmoop.2021.100054. PMID: 33601296.
17. Hirai T, Nemoto A, Ito Y, et al. Meta-analyses on progression-free survival as a surrogate endpoint for overall survival in triple-negative breast cancer. Breast Cancer Res Treat 2020; 181: 189–98. DOI: 10.1007/s10549-020-05615-4
1 ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава России, Москва, Россия;
2 ФГАУ «Национальный медицинский исследовательский центр ”Лечебно-реабилитационный центр”» Минздрава России, Москва, Россия;
3 ГБУЗ «Московский клинический научно-практический центр им. А.С. Логинова» Департамента здравоохранения г. Москвы, Москва, Россия
*ganshinainna77@mail.ru
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Inna P. Ganshina*1, Kristina A. Ivanova1, Olga O. Gordeeva1, Aleksandr V. Arkhipov2, Liudmila G. Zhukova3
1 Blokhin National Medical Research Center of Oncology, Moscow, Russia;
2 National Medical Research Center "Treatment and Rehabilitation Center", Moscow, Russia;
3 Loginov Moscow Clinical Scientific and Practical Center, Moscow, Russia
*ganshinainna77@mail.ru