Иммунотерапия в комбинации с химиотерапией при раке молочной железы с тройным негативным фенотипом – первая «таргетная» терапия, но только для «таргетной» популяции

Гречухина К.С., Жукова Л.Г. Иммунотерапия в комбинации с химиотерапией при раке молочной железы с тройным негативным фенотипом – первая «таргетная» терапия, но только для «таргетной» популяции. Современная Онкология. 2019; 21 (3): 33–37. DOI: 10.26442/18151434.2019.3.190655

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Grechukhina K.S., Zhukova L.G. Immunotherapy in combination with chemotherapy in triple-negative breast cancer – the first “target” therapy for the “target” patients’ population. Journal of Modern Oncology. 2019; 21 (3): 33–37. DOI: 10.26442/18151434.2019.3.190655

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Аннотация

До последнего времени единственным вариантом системной терапии при раке молочной железы (РМЖ) с тройным негативным фенотипом (тройной негативный РМЖ – ТНРМЖ) являлась химиотерапия, причем единый стандарт лечения метастатических форм так и не определен, поэтому подход к лечению остается на усмотрение врача и является эмпирическим, заключаясь в искусном подборе различных комбинаций препаратов. ТНРМЖ печально известен как наименее прогностически благоприятный подтип. Отсутствие при данном виде опухоли экспрессии рецепторов эстрогенов, прогестерона и амплификации гена HER2 делало невозможным применение таргетной терапии, определяющей успехи в лечении люминальных и HER2-позитивного подтипов РМЖ. Полученные данные о потенциальной иммуногенности опухоли при ТНРМЖ позволили начать изучение эффективности иммунотерапии и при этом виде рака. Международное клиническое исследование IMpassion130 не только положило основу развития этого направления в лечении ТНРМЖ, но и позволило определить выигрывающую («таргетную») популяцию больных в отношении одной из самых главных целей нашей терапии – общей выживаемости, увеличение которой так важно для пациенток с этим подтипом РМЖ.

Ключевые слова: рак молочной железы, тройной негативный фенотип, иммунотерапия, PD-L1.

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The only option of systemic therapy for triple-negative breast cancer (TNBC) was cytotoxic chemotherapy until recently, moreover the unitary standard of care for metastatic forms was not strictly defined. That is why paradigm of the treatment remains at the discretion of the doctor and it is empirical, consisting of precise combination of drugs. TNBC is infamous as the worst prognostic subtype. The absence of estrogen and progesterone receptors expression and HER2 amplification in this subtype of tumors made the usage of target therapy impossible, which is essential for successful treatment of luminal and HER2 positive breast cancer subtypes. The data about potential immunogenicity of tumor in TNBC launched the investigation of immunotherapy efficacy in this subtype of breast cancer. International clinical trial Impassion130 has not only created the basis in this field of TNBC treatment but also identified and determined the “benefiters”-cohort of patients concerning one of the most important goals – improving overall survival, that is so significant for patients with this subtype of breast cancer.

Key words: breast cancer, triple-negative, immunotherapy, PD-L1.

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Список литературы

1. Garrido-Castro AС, Lin NU, Polyak K. Insights into molecular classifications of triple-negative breast cancer: improving patient selection for treatment. Cancer Discov 2019; 9 (2): 176–98.
2. Carey L, Dees E, Sawyer L et al. The triple-negative paradox: primary tumor chemosensitivity of breast cancer subtypes. Clin Cancer Res 2007; 13: 2329–334.
3. Patel SP, Kurzrock R. PD-L1 expression as a predictive biomarker in cancer immunotherapy. Mol Cancer Ther 2015; 14: 847–56.
4. Gibney GT, Weiner LM, Atkins MB. Predictive biomarkers for checkpoint inhibitor-based immunotherapy. Lancet Oncol 2016; 17: e542–51.
5. Reck M, Rodriguez-Abreu D, Robinson A et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med 2016; 375: 1823–3.
6. Criscitiello C, Esposito A, Trapani D et al. Prognostic and predictive value of tumor infiltrating lymphocytes in early breast cancer. Cancer Treat Rev 2016; 50: 205–7.
7. Loi S, Drubay D, Adams S et al. Tumor-infiltrating lymphocytes and prognosis: a pooled individual patient analysis of early-stage triple-negative breast cancers. J Clin Oncol 2019; 37 (7): 559–69.
8. Gu-Trantien C, Loi S, Garaud S et al. CD4⁺ follicular helper T cell infiltration predicts breast cancer survival. J Clin Invest 2013; 123 (7): 2873–92.
9. Melichar B, Studentova H, Kalabova H et al. Predictive and Prognostic Significance of Tumor-infiltrating Lymphocytes in Patients with Breast Cancer Treated with Neoadjuvant Systemic Therapy Anticancer Res March 2014; 34 (3): 1115–25.
10. Ali H, Provenzano E, Dawson S et al. Association between CD8+ T-cell infiltration and breast cancer survival in 12 439 patients. Ann Oncol 2014; 25 (8): 1536–43.
11. Miyashita M, Sasano H, Tamaki K et al. Prognostic significance of tumor-infiltrating CD8+ and FOXP3+ lymphocytes in residual tumors and alterations in these parameters after neoadjuvant chemotherapy in triple- negative breast cancer: a retrospective multicenter study. Breast Cancer Res 2015; 17: 124.
12. Adams S, Gray R, Demaria S et al. Prognostic value of tumor-infiltrating lymphocytes in triple-negative breast cancers fr om two phase III randomized adjuvant breast cancer trials: ECOG 2197 and ECOG 1199. J Clin Oncol 2014; 32 (27): 2959–66.
13. Loi S, Drubay D, Adams S et al. Tumor-Infiltrating Lymphocytes and Prognosis: A Pooled Individual Patient Analysis of Early-Stage Triple-Negative Breast Cancers. J Clin Oncol 2019; 37: 559–69.
14. Ruffel B, Au A, Rugo H et al. Leukocyte composition of human breast cancer. Proc Natl Acad Sci USA 2012; 109: 2796–801.
15. Andre F, Dieci M, Dubsky P et al. Molecular pathways: involvement of immune pathways in the therapeutic response and outcome in breast cancer. Clin Cancer Res 2013; 19 (1): 28–33.
16. Beckers RK, Selinger CI, Vilain R et al. Programmed death ligand 1 expression in triple-negative breast cancer is associated with tumour-infiltrating lymphocytes and improved outcome. Histopathology 2016; 69: 25–34.
17. Mittendorf EA, Philips AV, Meric-Bernstam F et al. PD-L1 expression in triple- negative breast cancer. Cancer Immunol Res 2014; 2: 361–70.
18. Cimino-Mathews А, Thompson E, Taube JM et al. PD-L1 (B7-H1) expression and the immune tumor microenvironment in primary and metastatic breast carcinomas. Hum Pathol 2016; 47: 52–63.
19. Kwa MJ, Adams S. Checkpoint inhibitors in triple-negative breast cancer (TNBC): wh ere to go from here. Cancer 2018; 124: 2086–103.
20. Marra A, Viale G, Curigliano G. Recent advances in triple negative breast cancer: the immunotherapy era. BMC Med 2019; 17 (1): 90.
21. Emens L, Braiteh F, Cassier P et al. Inhibition of PD-L1 by MPDL3280A leads to clinical activity in patients with metastatic triple-negative breast cancer. Presented at San Antonio Breast Cancer Symposium. December 9–13, 2014. San Antonio, TX.
22. Loi S. Host Antitumor Immunity Plays a Role in the Survival of Patients With Newly Diagnosed Triple-Negative Breast Cancer. J Clin Oncol 2014; 32 (27): 2935–7.
23. Nanda R, Chow L, Dees E et al. A phase Ib study of pembrolizumab (MK-3475) in patients with advanced triple-negative breast cancer. 2014; San Antonio, TX: 2014 San Antonio Breast Cancer Symposium.
24. Emens L, Braiteh F, Cassier P et al. Inhibition of PD-L1 by MPDL3280A leads to clinical activity in patients with metastatic triple-negative breast cancer. Cancer Res 2015; 75 (Suppl. 9): abstr PD1–6.
25. Emens L. Breast Cancer Immunotherapy: Facts and Hopes. Clin Cancer Res 2018; 24 (3): 511–20.
26. Schmid P, Adams S, Rugo HS et al. Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. N Engl J Med 2018; 379: 2108–21.
27. Schmid P, Adams S, Rugo H et al. IMpassion130: updated overall survival (OS) from a global, randomized, double-blind, placebo-controlled, Phase III study of atezolizumab (atezo) + nab-paclitaxel (nP) in previously untreated locally advanced or metastatic triple-negative breast cancer (mTNBC). J Clin Oncol 2019; 27 (suppl; abstr 1003).
28. Emens L, Loi S, Rugo H et al. Abstract GS1-04: IMpassion130: efficacy in immune biomarker subgroups from the global, randomized, double-blind, placebo-controlled, phase III study of atezolizumab + nab-paclitaxel in patients with treatment-naïve, locally advanced or metastatic triple-negative breast cancer. Cancer Res 2019; 79: GS1–04.
29. Ribas A, Hu-Lieskovan S. What does PD-L1 positive or negative mean? J Exp Med 2016; 213: 2835–40.
30. Schmidt P, Cruz C, Braiteh F et al. Abstract 2986: Atezolizumab in metastatic TNBC (mTNBC): Long-term clinical outcomes and biomarker analyses. Cancer Res 2017 (77; 13 Suppl.): 2986.

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Авторы

К.С. Гречухина*, Л.Г. Жукова

ГБУЗ «Московский клинический научный центр им. А.С. Логинова», Москва, Россия
*dr.grechukhina@gmail.com

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Katerina S. Grechukhina*, Ludmila G. Zhukova

Loginov Moscow Clinical Scientific Center, Moscow, Russia
*dr.grechukhina@gmail.com

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