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Современный подход к адъювантной терапии рака молочной железы (обзор)
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Аннотация
В настоящее время подходы к терапии рака молочной железы (РМЖ) основаны на определении наличия или отсутствия основных маркеров – рецепторов эстрогенов, рецепторов прогестерона и HER2-рецепторов. Современные научные данные позволяют предполагать, что процесс подразделения РМЖ на более мелкие, но четкие подгруппы будет продолжаться, а подходы к лечению – совершенствоваться. Значимость скрининга и ранней диагностики в улучшении результатов лечения и снижении уровня смертности от РМЖ несомненна, однако появляется все больше данных, свидетельствующих о преимущественном значении адъювантной химиотерапии (ХТ). Данные клинических исследований показывают, что включение трастузумаба в адъювантные схемы ХТ HER2-положительного РМЖ существенно улучшает отдаленные результаты лечения, уменьшает частоту рецидивов и снижает вероятность летального исхода. Особый интерес вызывают возможности двойного ингибирования HER2-рецепторов препаратами с разными механизмами действия. Использование таргетной терапии, в частности трастузумаба, позволило кардинально изменить прогноз в прошлом абсолютно летального варианта РМЖ, а применение комбинированной таргетной терапии еще больше приблизит эру персонализированной медицины.
Ключевые слова: рак молочной железы, адъювантная терапия, таргетная терапия, трастузумаб.
Ключевые слова: рак молочной железы, адъювантная терапия, таргетная терапия, трастузумаб.
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The current approaches to therapy for breast cancer (BC) are based on whether the major markers, such as estrogen receptors, progesterone receptors, and HER2 receptors, are present or absent. Scientific update suggests that subdividing BC into more minor, but distinct subgroups will be continued and treatment approaches will be improved. There is no question that screening and early diagnosis are important in improving treatment results and reducing BC mortality; however, there is increasing evidence for the precedence of adjuvant chemotherapy. Clinical trials show that incorporation of trastuzumab in adjuvant treatment regimens for HER2-positive BC improves substantially long-term results and reduces recurrence rates and the likelihood of a fatal outcome. Of particular interest is the fact that the drugs having different modes of action can produce double inhibition of HER2 receptor. Targeted therapy with trastuzumab in particular could change dramatically the prognosis of the previously absolutely fatal variant of BC, and combination targeted therapy will bring the era of personalized medicine closer.
Key words: breast cancer, adjuvant therapy, targeted therapy, trastuzumab.
Полный текст
Список литературы
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20. Goldhirsch A et al. ESMO 2012.
21. NCCN Сlinical Practice Guidelines in Oncology (NCCN Guidelines). Breast Cancer 2013; 2.
22. Ismael G et al. Subcutaneous versus intravenous administration of (neo) adjuvant trastuzumab in patients with HER2-positive, clinical stage I–III breast cancer (HannaH study): a phase 3, open-label, multicentre, randomised trial. Lancet Oncol 2013; 13 (9): 869–78.
23. SafeHer NCT 01566721. A phase III prospective, two-cohort non-randomized, multi-centre, multinational, open label study to assess the safety of assisted and self-administered subcutaneous trastuzumab as adjuvant therapy in patients with operable HER2-positive early breast cancer. http://clinicaltrials.gov/show/NCT01566721
24. Pivot X et al. Patient preference for subcutaneous vs intravenous adjuvant trastuzumab: results of the PrefHer Study. SG-BCC 2013; p. 207.
2. Статистика злокачественных новообразований в России и странах СНГ в 2010 г. Под ред. акад. РАН и РАМН М.И.Давыдова, д-ра биол. наук Е.М.Аксель. М., 2012.
3. Autier P et al. Breast cancer mortality in neighbouring European countries with different levels of screening but similar access to treatment: trend analysis of WHO mortality database. BMJ 2011; 343: d4411.
4. Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100 000 women in 123 randomised trials EBCTCG. Lancet 2012; 379: 432–44.
5. Dowsett M, Cuzick J, Ingle J et al. Meta-Analysis of Breast Cancer Outcomes in Adjuvant Trials of Aromatase Inhibitors Versus Tamoxifen. JCO, 2010; 28 (3): 509–18.6. Mouridsen H et al. Letrozole therapy alone or in sequence with tamoxifen in women with breast cancer. The BIG 1–98 Collaborative Group. N Engl J Med 2009; 361: 766–76.
7. Goss P et al. A randomized trial of letrozole in postmenopausal women after five years of tamoxifen therapy for early-stage breast cancer. N Engl J Med 2003; 349: 1793–802.
8. Piccart-Gebhart М. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 2005; 353: 1659–72.
9. Romond ЕН. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 2005; 353 (16): 1673–84.
10. Slamon SABCS 2006.
11. Smith I. 2-Year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial. Lancet 2007; 369: 29–36.
12. Perez Е. ASCO 2005.
13. Joensuu Н. Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer. N Engl J Med 2006; 354: 809–20.
14. Spielmann SABCS 2007.
15. Moja L et al. Trastuzumab containing regimens for early breast cancer. The Cochrane Library 2012; Is. 4.
16. Keefe DL. Trastuzumab-associated cardiotoxicity. Cancer 2002; 95 (7): 1592.
17. Perez EA, Rodeheffer R. Clinical cardiac tolerability of trastuzumab. J Clin Oncol 2004; 22 (2): 322.
18. Fiúza M. Cardiotoxicity associated with trastuzumab treatment of HER2+-breast cancer. Adv Ther 2009; 26 (Suppl. 1): s9.
19. Pivot X, Romieu G, Bonnefori H et al. PHARE trial results comparing 6 to 12 months of trastuzumab in adjuvant early breast cancer. 2012 ESMO Congress. Abstr. LBA5 2012.
20. Goldhirsch A et al. ESMO 2012.
21. NCCN Сlinical Practice Guidelines in Oncology (NCCN Guidelines). Breast Cancer 2013; 2.
22. Ismael G et al. Subcutaneous versus intravenous administration of (neo) adjuvant trastuzumab in patients with HER2-positive, clinical stage I–III breast cancer (HannaH study): a phase 3, open-label, multicentre, randomised trial. Lancet Oncol 2013; 13 (9): 869–78.
23. SafeHer NCT 01566721. A phase III prospective, two-cohort non-randomized, multi-centre, multinational, open label study to assess the safety of assisted and self-administered subcutaneous trastuzumab as adjuvant therapy in patients with operable HER2-positive early breast cancer. http://clinicaltrials.gov/show/NCT01566721
24. Pivot X et al. Patient preference for subcutaneous vs intravenous adjuvant trastuzumab: results of the PrefHer Study. SG-BCC 2013; p. 207.
Авторы
ПьерФранко Конте, Валентина Гварнери
Университетская клиника г. Падуя, Италия
Университетская клиника г. Падуя, Италия
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PierFranco Conte, Valentina Guarneri
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