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Метастазы рака молочной железы в парастернальные лимфоузлы: нужна ли морфологическая верификация?
Триголосов А.В., Уйманов В.А., Черных М.В. и др. Метастазы рака молочной железы в парастернальные лимфоузлы: нужна ли морфологическая верификация? Современная Онкология. 2017; 19 (2): 22–27.
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Trigolosov A.V., Uimanov V.A., Chernikh M.V. et al. Internal mammary nodes metastases for breast cancer: whether the morphological verification is necessary? Journal of Modern Oncology. 2017; 19 (2): 22–27.
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Аннотация
Предпосылка. Метастатическое поражение парастернальных лимфоузлов (ПЛУ) ассоциируется с плохим прогнозом рака молочной железы (РМЖ). Однако проведение лучевой терапии на парастернальную зону все еще является предметом дискуссии.
Методы. Ретроспективно изучены результаты 1144 последовательно пролеченных больных первичным РМЖ, перенесших одномоментную видеоторакоскопическую парастернальную лимфаденэктомию в период с 1998 по 2009 г.
Результаты. Осложнения, связанные с эндоскопическим этапом, не превысили 2%. Метастазы в ПЛУ выявлены у 211 (18,4%) больных, в 6,0% случаев отсутствовала аксиллярная инвазия. При многомерном анализе на частоту поражения статистически значимое влияние оказывали: локализация опухоли, отличная от наружной, критерий Т, степень поражения аксиллярных лимфоузлов и лимфоваскулярная инвазия. Метастазы в ПЛУ достоверно ухудшали показатели отдаленных исходов и 5-летнюю общую – ОВ и безрецидивную выживаемость – БРВ (ОВ 79,0±3,1% против 91,4±1,0%, р<0,001; БРВ 69,0±3,4% против 86,0±1,2%, р<0,001, соответственно) у больных как с метастазами, так и без метастазов в аксиллярные лимфоузлы. Метастазы в ПЛУ наряду с размерами опухоли и аксиллярным поражением оказывали независимое прогностическое негативное влияние на показатели БРВ и ОВ (отношение шансов 2,24 [1,45–3,46] и 2,50 [1,41–4,43] соответственно).
Заключение. Состояние ПЛУ является значимым компонентом регионарного распространения РМЖ, способным влиять на тактику адъювантного лечения. Проведение рандомизированных клинических исследований относительно лучевой терапии на ПЛУ с морфологически подтвержденным поражением представляется целесообразным.
Ключевые слова: рак молочной железы, парастернальные лимфоузлы, видеоторакоскопическая парастернальная лимфаденэктомия.
Методы. Ретроспективно изучены результаты 1144 последовательно пролеченных больных первичным РМЖ, перенесших одномоментную видеоторакоскопическую парастернальную лимфаденэктомию в период с 1998 по 2009 г.
Результаты. Осложнения, связанные с эндоскопическим этапом, не превысили 2%. Метастазы в ПЛУ выявлены у 211 (18,4%) больных, в 6,0% случаев отсутствовала аксиллярная инвазия. При многомерном анализе на частоту поражения статистически значимое влияние оказывали: локализация опухоли, отличная от наружной, критерий Т, степень поражения аксиллярных лимфоузлов и лимфоваскулярная инвазия. Метастазы в ПЛУ достоверно ухудшали показатели отдаленных исходов и 5-летнюю общую – ОВ и безрецидивную выживаемость – БРВ (ОВ 79,0±3,1% против 91,4±1,0%, р<0,001; БРВ 69,0±3,4% против 86,0±1,2%, р<0,001, соответственно) у больных как с метастазами, так и без метастазов в аксиллярные лимфоузлы. Метастазы в ПЛУ наряду с размерами опухоли и аксиллярным поражением оказывали независимое прогностическое негативное влияние на показатели БРВ и ОВ (отношение шансов 2,24 [1,45–3,46] и 2,50 [1,41–4,43] соответственно).
Заключение. Состояние ПЛУ является значимым компонентом регионарного распространения РМЖ, способным влиять на тактику адъювантного лечения. Проведение рандомизированных клинических исследований относительно лучевой терапии на ПЛУ с морфологически подтвержденным поражением представляется целесообразным.
Ключевые слова: рак молочной железы, парастернальные лимфоузлы, видеоторакоскопическая парастернальная лимфаденэктомия.
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Background. Metastatic involvement of the internal mammary chain lymph nodes (IMN) is associated with poor prognosis for breast cancer (BC) patients. However, parasternal radiation therapy is still a subject for debate.
Methods. Results of 1144 consecutively treated patients with primary BC, who underwent one-stage videothoracoscopic (VATS) parasternal lymphadenectomy from 1998 to 2009, were retrospectively studied.
Results. Surgical complications associated with thoracoscopic procedure did not exceed 2%. IMN metastases were detected in 211 (18.4%) patients, 6.0% of these cases did not have axillary invasion. In a wide analysis, the frequency of metastasis was statistically more influenced by: tumor localization (different from external quadrants), primary tumor size (T), level of involved axillary lymph nodes (N) and lymphovascular invasion. Patients with IMN metastases showed significantly poorer long-term outcomes: 5-year overall – OS and disease-free survival – DFS (OS 79.0±3.1% vs 91.4±1.0%, p<0.001; DFS 69.0±3.4% vs 86.0±1.2%, p<0.001, respectively) both in the whole group and in the subgroups with and without axillary lymph node metastases. IMN metastases along with tumor size and axillary nodes showed a negative independent prognostic influence on the DFS and OS (hazard ratio 2.24 [1.45–3.46]; 2.50 [1.41–4.43], respectively).
Conclusions. IMN status is an important criterion which may influence on the prognosis and adjuvant treatment strategy in BC. Our study is in favor of conducting randomized clinical studies supporting the impact of radiotherapy treatment for involved IMN.
Key words: breast cancer, internal mammary nodes, videothoracoscopic parasternal lymphadenectomy.
Полный текст
Список литературы
1. Taghian A, Jagsi R, Makris A et al. Results of a survey regarding irradiation of internal mammary chain in patients with breast cancer: Practice is culture driven rather than evidence based. Int J Radiat Oncol Biol Phys 2004; 60: 706–14.
2. Coates S, Winer EP, Goldhirsch A et al. Tailoring therapies – improving the management of early breast cancer: St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2015. Ann Oncol 2015; 26 (8): 1533–46.
3. NCCN Clinical Practice Guidelines in Oncology. Breast cancer. v. 2.2016// http://www.nccn.org/professionals/physician_gls/pdf/breast.pdf
4. Senkus E, Kyriakides S, Ohno S et al. Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2015; 26 (5): 8–30.
5. Dutch national guideline for the treatment of breast cancer, v. 2.0; http://www.oncoline.nl/mammacarcinoom
6. Chang JS, Park W, Kim YB et al. Long-term survival outcomes following internal mammary node irradiation in stage II–III breast cancer: results of a large retrospective study with 12-year follow-up. Int J Radiat Oncol Biol Phys 2013; 86 (5): 867–72.
7. Hennequin C, Bossard N, Servagi-Vernat S et al. Ten-year survival results of a randomized trial of irradiation of internal mammary nodes after mastectomy. Int J Radiat Oncol Biol Phys 2013; 86 (5): 860–6.
8. Overgaard M. Evaluation of radiotherapy in high risk breast cancer patients given adjuvant systemic therapy. A 25-year update of the Danish breast cancer cooperative group DBCG 82B&C trial. Radiother Oncol 2011; 99 (1): S81.
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10. Clarke M, Collins R, Darby S et al. Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: An overview of the randomized trials. Lancet 2005; 366: 2087–106.
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13. Leidenius MHK, Krogerus LA, Toivonen TS et al. The clinical value of parasternal sentinel node biopsy in breast cancer. Ann Surg Oncol 2006; 13 (3): 321–6.
14. Madsen E, Gobardhan P, Bongers V et al. The impact on post-surgical treatment of sentinel lymph node biopsy of internal mammary lymph nodes in patients with breast cancer. Ann Surg Oncol 2007; 14 (4): 1486–92.
15. Veronesi U, Arnone P, Veronesi P. The value of radiotherapy on metastatic internal mammary nodes in breast cancer. Results on a large series. Ann Oncol 2008; 19: 1553–60.
16. Bourre JC, Payan R, Collomb D et al. Can the sentinel lymph node technique affect decisions to offer internal mammary chain irradiation? Eur J Nucl Med Mol Imag 2009; 36 (5): 758–64.
17. Coombs NJ, Boyages J, French JR et al. Internal mammary sentinel nodes: ignore, irradiate or operate? Eur J Cancer 2009; 45 (5): 789–94.
18. Heuts EM, Van der Ent FWC, Von Meyenfeldt MF, Voogd AC. Internal mammary lymph drainage and sentinel node biopsy in breast cancer – A study on 1008 patients. Eur J Surg Oncol 2009; 35: 252–7.
19. Postma EL, van Wieringen S, Hobbelink MG et al. Sentinel lymph node biopsy of the internal mammary chain in breast cancer. Breast Cancer Res Treat 2012; 134 (2): 735–41.
20. Gnerlich JL, Barreto-Andrade JC, Czechura T et al. Accurate Staging with Internal Mammary Chain Sentinel Node Biopsy for Breast Cancer. Ann Surg Oncol 2014; 21 (2): 368–74.
21. Caudle AS, Yi M, Hoffman KE et al. Impact of Identification of Internal Mammary Sentinel Lymph Node Metastasis in Breast Cancer Patients. Ann Surg Oncol 2014; 21 (1): 60–5.
22. Poortmans PM, Collette S, Kirkove C et al. Internal mammary and medial supraclavicular irradiation in breast cancer. N Engl J Med 2015; 373: 317–27.
23. Whelan TJ, Olivotto IA, Parulekar WR et al. Regional nodal irradiation in early-stage breast cancer. N Engl J Med 2015; 373: 307–16.
24. Thorsen LBJ, Thomsen MS, Berg M et al. CT-planned internal mammary node radiotherapy in the DBCG-IMN study: benefit versus potentially harmful effects. Acta Oncol 2014; 53: 1027–34.
25. Thorsen LBJ, Offersen BV, Dano H et al. DBCG-IMN: A population-based cohort study on the effect of internal mammary node irradiation in early node-positive breast cancer. J Clin Oncol 2016; 34: 314–20.
2. Coates S, Winer EP, Goldhirsch A et al. Tailoring therapies – improving the management of early breast cancer: St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2015. Ann Oncol 2015; 26 (8): 1533–46.
3. NCCN Clinical Practice Guidelines in Oncology. Breast cancer. v. 2.2016// http://www.nccn.org/professionals/physician_gls/pdf/breast.pdf
4. Senkus E, Kyriakides S, Ohno S et al. Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2015; 26 (5): 8–30.
5. Dutch national guideline for the treatment of breast cancer, v. 2.0; http://www.oncoline.nl/mammacarcinoom
6. Chang JS, Park W, Kim YB et al. Long-term survival outcomes following internal mammary node irradiation in stage II–III breast cancer: results of a large retrospective study with 12-year follow-up. Int J Radiat Oncol Biol Phys 2013; 86 (5): 867–72.
7. Hennequin C, Bossard N, Servagi-Vernat S et al. Ten-year survival results of a randomized trial of irradiation of internal mammary nodes after mastectomy. Int J Radiat Oncol Biol Phys 2013; 86 (5): 860–6.
8. Overgaard M. Evaluation of radiotherapy in high risk breast cancer patients given adjuvant systemic therapy. A 25-year update of the Danish breast cancer cooperative group DBCG 82B&C trial. Radiother Oncol 2011; 99 (1): S81.
9. Ragaz J, Olivotto IA, Spinelli JJ et al. Locoregional radiation therapy in patients with high-risk breast cancer receiving adjuvant chemotherapy: 20-year results of the British Columbia randomized trial. J Natl Cancer Inst 2005; 97: 116–26.
10. Clarke M, Collins R, Darby S et al. Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: An overview of the randomized trials. Lancet 2005; 366: 2087–106.
11. EBCTCG (Early Breast Cancer Trialists' Collaborative Group). Effect of radiotherapy after mastectomy and axillary surgery on 10-year recurrence and 20-year breast cancer mortality: meta-analysis of individual patient data for 8135 women in 22 randomised trials. Lancet 2014; 383 (9935): 2127–35.
12. Estourgie SH, Tanis PJ, Nieweg OE et al. Should the hunt for internal mammary chain sentinel nodes begin? An evaluation of 150 breast cancer patients. Ann Surg Oncol 2004; 10 (8): 935–41.
13. Leidenius MHK, Krogerus LA, Toivonen TS et al. The clinical value of parasternal sentinel node biopsy in breast cancer. Ann Surg Oncol 2006; 13 (3): 321–6.
14. Madsen E, Gobardhan P, Bongers V et al. The impact on post-surgical treatment of sentinel lymph node biopsy of internal mammary lymph nodes in patients with breast cancer. Ann Surg Oncol 2007; 14 (4): 1486–92.
15. Veronesi U, Arnone P, Veronesi P. The value of radiotherapy on metastatic internal mammary nodes in breast cancer. Results on a large series. Ann Oncol 2008; 19: 1553–60.
16. Bourre JC, Payan R, Collomb D et al. Can the sentinel lymph node technique affect decisions to offer internal mammary chain irradiation? Eur J Nucl Med Mol Imag 2009; 36 (5): 758–64.
17. Coombs NJ, Boyages J, French JR et al. Internal mammary sentinel nodes: ignore, irradiate or operate? Eur J Cancer 2009; 45 (5): 789–94.
18. Heuts EM, Van der Ent FWC, Von Meyenfeldt MF, Voogd AC. Internal mammary lymph drainage and sentinel node biopsy in breast cancer – A study on 1008 patients. Eur J Surg Oncol 2009; 35: 252–7.
19. Postma EL, van Wieringen S, Hobbelink MG et al. Sentinel lymph node biopsy of the internal mammary chain in breast cancer. Breast Cancer Res Treat 2012; 134 (2): 735–41.
20. Gnerlich JL, Barreto-Andrade JC, Czechura T et al. Accurate Staging with Internal Mammary Chain Sentinel Node Biopsy for Breast Cancer. Ann Surg Oncol 2014; 21 (2): 368–74.
21. Caudle AS, Yi M, Hoffman KE et al. Impact of Identification of Internal Mammary Sentinel Lymph Node Metastasis in Breast Cancer Patients. Ann Surg Oncol 2014; 21 (1): 60–5.
22. Poortmans PM, Collette S, Kirkove C et al. Internal mammary and medial supraclavicular irradiation in breast cancer. N Engl J Med 2015; 373: 317–27.
23. Whelan TJ, Olivotto IA, Parulekar WR et al. Regional nodal irradiation in early-stage breast cancer. N Engl J Med 2015; 373: 307–16.
24. Thorsen LBJ, Thomsen MS, Berg M et al. CT-planned internal mammary node radiotherapy in the DBCG-IMN study: benefit versus potentially harmful effects. Acta Oncol 2014; 53: 1027–34.
25. Thorsen LBJ, Offersen BV, Dano H et al. DBCG-IMN: A population-based cohort study on the effect of internal mammary node irradiation in early node-positive breast cancer. J Clin Oncol 2016; 34: 314–20.
________________________________________________
1. Taghian A, Jagsi R, Makris A et al. Results of a survey regarding irradiation of internal mammary chain in patients with breast cancer: Practice is culture driven rather than evidence based. Int J Radiat Oncol Biol Phys 2004; 60: 706–14.
2. Coates S, Winer EP, Goldhirsch A et al. Tailoring therapies – improving the management of early breast cancer: St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2015. Ann Oncol 2015; 26 (8): 1533–46.
3. NCCN Clinical Practice Guidelines in Oncology. Breast cancer. v. 2.2016// http://www.nccn.org/professionals/physician_gls/pdf/breast.pdf
4. Senkus E, Kyriakides S, Ohno S et al. Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2015; 26 (5): 8–30.
5. Dutch national guideline for the treatment of breast cancer, v. 2.0; http://www.oncoline.nl/mammacarcinoom
6. Chang JS, Park W, Kim YB et al. Long-term survival outcomes following internal mammary node irradiation in stage II–III breast cancer: results of a large retrospective study with 12-year follow-up. Int J Radiat Oncol Biol Phys 2013; 86 (5): 867–72.
7. Hennequin C, Bossard N, Servagi-Vernat S et al. Ten-year survival results of a randomized trial of irradiation of internal mammary nodes after mastectomy. Int J Radiat Oncol Biol Phys 2013; 86 (5): 860–6.
8. Overgaard M. Evaluation of radiotherapy in high risk breast cancer patients given adjuvant systemic therapy. A 25-year update of the Danish breast cancer cooperative group DBCG 82B&C trial. Radiother Oncol 2011; 99 (1): S81.
9. Ragaz J, Olivotto IA, Spinelli JJ et al. Locoregional radiation therapy in patients with high-risk breast cancer receiving adjuvant chemotherapy: 20-year results of the British Columbia randomized trial. J Natl Cancer Inst 2005; 97: 116–26.
10. Clarke M, Collins R, Darby S et al. Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: An overview of the randomized trials. Lancet 2005; 366: 2087–106.
11. EBCTCG (Early Breast Cancer Trialists' Collaborative Group). Effect of radiotherapy after mastectomy and axillary surgery on 10-year recurrence and 20-year breast cancer mortality: meta-analysis of individual patient data for 8135 women in 22 randomised trials. Lancet 2014; 383 (9935): 2127–35.
12. Estourgie SH, Tanis PJ, Nieweg OE et al. Should the hunt for internal mammary chain sentinel nodes begin? An evaluation of 150 breast cancer patients. Ann Surg Oncol 2004; 10 (8): 935–41.
13. Leidenius MHK, Krogerus LA, Toivonen TS et al. The clinical value of parasternal sentinel node biopsy in breast cancer. Ann Surg Oncol 2006; 13 (3): 321–6.
14. Madsen E, Gobardhan P, Bongers V et al. The impact on post-surgical treatment of sentinel lymph node biopsy of internal mammary lymph nodes in patients with breast cancer. Ann Surg Oncol 2007; 14 (4): 1486–92.
15. Veronesi U, Arnone P, Veronesi P. The value of radiotherapy on metastatic internal mammary nodes in breast cancer. Results on a large series. Ann Oncol 2008; 19: 1553–60.
16. Bourre JC, Payan R, Collomb D et al. Can the sentinel lymph node technique affect decisions to offer internal mammary chain irradiation? Eur J Nucl Med Mol Imag 2009; 36 (5): 758–64.
17. Coombs NJ, Boyages J, French JR et al. Internal mammary sentinel nodes: ignore, irradiate or operate? Eur J Cancer 2009; 45 (5): 789–94.
18. Heuts EM, Van der Ent FWC, Von Meyenfeldt MF, Voogd AC. Internal mammary lymph drainage and sentinel node biopsy in breast cancer – A study on 1008 patients. Eur J Surg Oncol 2009; 35: 252–7.
19. Postma EL, van Wieringen S, Hobbelink MG et al. Sentinel lymph node biopsy of the internal mammary chain in breast cancer. Breast Cancer Res Treat 2012; 134 (2): 735–41.
20. Gnerlich JL, Barreto-Andrade JC, Czechura T et al. Accurate Staging with Internal Mammary Chain Sentinel Node Biopsy for Breast Cancer. Ann Surg Oncol 2014; 21 (2): 368–74.
21. Caudle AS, Yi M, Hoffman KE et al. Impact of Identification of Internal Mammary Sentinel Lymph Node Metastasis in Breast Cancer Patients. Ann Surg Oncol 2014; 21 (1): 60–5.
22. Poortmans PM, Collette S, Kirkove C et al. Internal mammary and medial supraclavicular irradiation in breast cancer. N Engl J Med 2015; 373: 317–27.
23. Whelan TJ, Olivotto IA, Parulekar WR et al. Regional nodal irradiation in early-stage breast cancer. N Engl J Med 2015; 373: 307–16.
24. Thorsen LBJ, Thomsen MS, Berg M et al. CT-planned internal mammary node radiotherapy in the DBCG-IMN study: benefit versus potentially harmful effects. Acta Oncol 2014; 53: 1027–34.
25. Thorsen LBJ, Offersen BV, Dano H et al. DBCG-IMN: A population-based cohort study on the effect of internal mammary node irradiation in early node-positive breast cancer. J Clin Oncol 2016; 34: 314–20.
Авторы
А.В.Триголосов*, В.А.Уйманов, М.В.Черных, А.В.Петровский, Е.А.Никитина, М.И.Нечушкин
ФГБУ «Российский онкологический научный центр им. Н.Н.Блохина» Минздрава России. 115478, Россия, Москва, Каширское ш., д. 23
*trigolosov@mail.ru
ФГБУ «Российский онкологический научный центр им. Н.Н.Блохина» Минздрава России. 115478, Россия, Москва, Каширское ш., д. 23
*trigolosov@mail.ru
________________________________________________
A.V.Trigolosov*, V.A.Uimanov, M.V.Chernikh, A.V.Petrovskiy, E.A.Nikitina, M.I.Nechushkin
N.N.Blokhin Russian Cancer Research Center of the Ministry of Health of the Russian Federation. 115478, Russian Federation, Moscow, Kashirskoe sh., d. 23
*trigolosov@mail.ru
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