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Неоадъювантная лекарственная терапия при HER2-позитивном раке молочной железы
Фролова М.А. Неоадъювантная лекарственная терапия при HER2-позитивном раке молочной железы. Современная Онкология. 2015; 17 (4): 22–25.
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Frolova M.A. Neoadjuvant systemic therapy of HER2-positive breast cancer. Journal of Modern Oncology. 2015; 17 (4): 22–25.
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Аннотация
Рак молочной железы (РМЖ) с гиперэкспрессией рецептора HER2 встречается в 15–20% случаев и характеризуется агрессивным характером течения заболевания. Внедрение в клиническую практику трастузумаба кардинальным образом изменило прогноз больных ранним и метастатическим HER2-позитивным РМЖ. Однако около 40% больных имеют либо первичную, либо приобретенную в процессе лечения резистентность к трастузумабу. Двойная блокада HER2-рецептора трастузумабом в сочетании с другими препаратами анти-HER2-направленного действия показала преимущество перед монотерапией трастузумабом. Неоадъювантная лекарственная терапия приобретает все большую популярность при раннем РМЖ и служит моделью для изучения новых противоопухолевых препаратов, режимов лечения, а также поиска предиктивных биомаркеров.
В статье анализируются наиболее важные исследования последних лет при HER2-позитивном РМЖ, посвященные неоадъювантной терапии и оказавших непосредственное влияние на повседневную клиническую практику.
Ключевые слова: рак молочной железы, неоадъювантная терапия, HER2, трастузумаб, лапатиниб, пертузумаб.
В статье анализируются наиболее важные исследования последних лет при HER2-позитивном РМЖ, посвященные неоадъювантной терапии и оказавших непосредственное влияние на повседневную клиническую практику.
Ключевые слова: рак молочной железы, неоадъювантная терапия, HER2, трастузумаб, лапатиниб, пертузумаб.
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HER2 overexpression is evaluated in 15–20% of breast tumors and associated with aggressive type of the disease. Introduction of trastuzumab in clinical practice significantly improve the prognosis of patients with metastatic and early HER2-positive breast cancer. However, up to 40% of patients have a resistance to trastuzumab therapy (de novo or acquired resistance). Dual anti-HER2 blockade of trastuzumab in combination with other anti-HER2 targeted agents is more effective then trastuzumab monotherapy. Neoadjuvant systemic therapy has become very useful in early breast cancer and serves as a model for research of new antitumor agents, treatment regimens and predictive biomarkers. In current review the most important recent neoadjuvant trials in HER2-positive breast cancer and their impact on clinical practice are being analysed.
Key words: breast cancer, neoadjuvant therapy, HER2, trastuzumab, lapatinib, pertuzumab.
Полный текст
Список литературы
1. Cortazar P, Zhang L, Untch M et al. Pathological complete response and long-term clinical benefi t in breast cancer: the CTNeoBC pooled analysis. Lancet 2014; 384: 164–72.
2. Gianni L, Eiermann W, Semiglazov V et al. Neoadjuvant and adjuvant trastuzumab in patients with HER2-positive locally advanced breast cancer (NOAH): follow-up of a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet Oncol 2014; 15: 640–7.
3. Baselga J, Bradbury I, Eidtmann H et al. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet 2012; 379: 633–40.
4. De Azambuja E, Holmes AP, Piccart-Gebhart M et al. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): survival outcomes of a randomised, open-label, multicentre, phase 3 trial and their association with pathological complete response. Lancet Oncol 2014; 15: 1137–46.
5. Piccart-Gebhart M, Holmes E, Baselga J et al. Adjuvant Lapatinib and Trastuzumab for Early Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer: Results From the Randomized Phase III Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization Trial. Published online ahead of print at www.jco.org on November 23, 2015.
6. DeMichele A, Yee D, Berry DA et al. The neoadjuvant model is still the future for drug development in breast cancer. Clin Cancer Res 2015; 21 (13): 2911–5.
7. Gianni L, Pienkowski T, Im YH et al. Effi cacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, infl ammatory, or early HER2-positive breast cancer (NeoSpHERe): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol 2012; 13: 25–32.
8. Gianni L, Pienkowski T, Im YH et al. Five-year analysis of the phase II NeoSpHERe trial evaluating four cycles of neoadjuvant docetaxel (D) and/or trastuzumab (T) and/or pertuzumab (P). JCO May 2015; 33 (15), Suppl. 505.
9. Schneeweiss A, Chia S, Hickish T et al. Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotHERapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol 2013; 24: 2278–84.
10. Rimawi MF, Niravath PA, Wang T et al. TBCRC023: A randomized multicenter phase II neoadjuvant trial of lapatinib plus trastuzumab, with endcorine tHERapy and without chemotHERapy, for 12 vs. 24 weeks in patients with HER2 overexpressing breast cancer. SABCS 2014; Abstr S6–02.
11. Harbeck N, Gluz O, Christgen M et al. Final analysis of WSG-ADAPT HER2+/HR+ phase II trial: Efficacy, safety, and predictive markers for 12-weeks of neoadjuvant TDM1 with or without endocrine tHERapy versus trastuzumab+endocrine tHERapy in HER2-positive hormone-receptor-positive early breast cancer. SABCS 2015; Abstr S5–03.
2. Gianni L, Eiermann W, Semiglazov V et al. Neoadjuvant and adjuvant trastuzumab in patients with HER2-positive locally advanced breast cancer (NOAH): follow-up of a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet Oncol 2014; 15: 640–7.
3. Baselga J, Bradbury I, Eidtmann H et al. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet 2012; 379: 633–40.
4. De Azambuja E, Holmes AP, Piccart-Gebhart M et al. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): survival outcomes of a randomised, open-label, multicentre, phase 3 trial and their association with pathological complete response. Lancet Oncol 2014; 15: 1137–46.
5. Piccart-Gebhart M, Holmes E, Baselga J et al. Adjuvant Lapatinib and Trastuzumab for Early Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer: Results From the Randomized Phase III Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization Trial. Published online ahead of print at www.jco.org on November 23, 2015.
6. DeMichele A, Yee D, Berry DA et al. The neoadjuvant model is still the future for drug development in breast cancer. Clin Cancer Res 2015; 21 (13): 2911–5.
7. Gianni L, Pienkowski T, Im YH et al. Effi cacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, infl ammatory, or early HER2-positive breast cancer (NeoSpHERe): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol 2012; 13: 25–32.
8. Gianni L, Pienkowski T, Im YH et al. Five-year analysis of the phase II NeoSpHERe trial evaluating four cycles of neoadjuvant docetaxel (D) and/or trastuzumab (T) and/or pertuzumab (P). JCO May 2015; 33 (15), Suppl. 505.
9. Schneeweiss A, Chia S, Hickish T et al. Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotHERapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol 2013; 24: 2278–84.
10. Rimawi MF, Niravath PA, Wang T et al. TBCRC023: A randomized multicenter phase II neoadjuvant trial of lapatinib plus trastuzumab, with endcorine tHERapy and without chemotHERapy, for 12 vs. 24 weeks in patients with HER2 overexpressing breast cancer. SABCS 2014; Abstr S6–02.
11. Harbeck N, Gluz O, Christgen M et al. Final analysis of WSG-ADAPT HER2+/HR+ phase II trial: Efficacy, safety, and predictive markers for 12-weeks of neoadjuvant TDM1 with or without endocrine tHERapy versus trastuzumab+endocrine tHERapy in HER2-positive hormone-receptor-positive early breast cancer. SABCS 2015; Abstr S5–03.
________________________________________________
1. Cortazar P, Zhang L, Untch M et al. Pathological complete response and long-term clinical benefi t in breast cancer: the CTNeoBC pooled analysis. Lancet 2014; 384: 164–72.
2. Gianni L, Eiermann W, Semiglazov V et al. Neoadjuvant and adjuvant trastuzumab in patients with HER2-positive locally advanced breast cancer (NOAH): follow-up of a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet Oncol 2014; 15: 640–7.
3. Baselga J, Bradbury I, Eidtmann H et al. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet 2012; 379: 633–40.
4. De Azambuja E, Holmes AP, Piccart-Gebhart M et al. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): survival outcomes of a randomised, open-label, multicentre, phase 3 trial and their association with pathological complete response. Lancet Oncol 2014; 15: 1137–46.
5. Piccart-Gebhart M, Holmes E, Baselga J et al. Adjuvant Lapatinib and Trastuzumab for Early Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer: Results From the Randomized Phase III Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization Trial. Published online ahead of print at www.jco.org on November 23, 2015.
6. DeMichele A, Yee D, Berry DA et al. The neoadjuvant model is still the future for drug development in breast cancer. Clin Cancer Res 2015; 21 (13): 2911–5.
7. Gianni L, Pienkowski T, Im YH et al. Effi cacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, infl ammatory, or early HER2-positive breast cancer (NeoSpHERe): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol 2012; 13: 25–32.
8. Gianni L, Pienkowski T, Im YH et al. Five-year analysis of the phase II NeoSpHERe trial evaluating four cycles of neoadjuvant docetaxel (D) and/or trastuzumab (T) and/or pertuzumab (P). JCO May 2015; 33 (15), Suppl. 505.
9. Schneeweiss A, Chia S, Hickish T et al. Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotHERapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol 2013; 24: 2278–84.
10. Rimawi MF, Niravath PA, Wang T et al. TBCRC023: A randomized multicenter phase II neoadjuvant trial of lapatinib plus trastuzumab, with endcorine tHERapy and without chemotHERapy, for 12 vs. 24 weeks in patients with HER2 overexpressing breast cancer. SABCS 2014; Abstr S6–02.
11. Harbeck N, Gluz O, Christgen M et al. Final analysis of WSG-ADAPT HER2+/HR+ phase II trial: Efficacy, safety, and predictive markers for 12-weeks of neoadjuvant TDM1 with or without endocrine tHERapy versus trastuzumab+endocrine tHERapy in HER2-positive hormone-receptor-positive early breast cancer. SABCS 2015; Abstr S5–03.
Авторы
М.А.Фролова*
ФГБУ Российский онкологический научный центр им. Н.Н..Блохина Минздрава России. 115478, Россия, Москва, Каширское ш., д. 23
*drfrolova@yandex.ru
ФГБУ Российский онкологический научный центр им. Н.Н..Блохина Минздрава России. 115478, Россия, Москва, Каширское ш., д. 23
*drfrolova@yandex.ru
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M.A.Frolova*
N.N.Blokhin Russian Cancer Research Center of the Ministry of Health of the Russian Federation. 115478, Russian Federation, Moscow, Kashirskoe sh., d. 23
*drfrolova@yandex.ru
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