Tumors of female reproductive systemTumors of female reproductive systemОпухоли женской репродуктивной системы1994-40981999-8627Publishing House ABV Press70210.17650/1994-4098-2020-16-1-43-54MAMMOLOGY. REVIEWSМАММОЛОГИЯ. ОБЗОРНЫЕ СТАТЬИStrategy of post-neoadjuvant treatment of patients with residual breast cancerСтратегия постнеоадъювантного лечения пациенток с резидуальным раком молочной железыhttps://orcid.org/0000-0002-8825-5221SemiglazovV. V.СемиглазовВ. В.
Russian Federation

Владислав Владимирович Семиглазов

oncology.spbgmu@mail.ruNatopkinA. A.НатопкинА. А.
Russian Federation
N.N. Petrov National Medical Research Center of Oncology, Ministry of Health of RussiaФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Петрова» Минздрава РоссииPavlov First Saint Petersburg State Medical University, Ministry of Health of RussiaФГБОУ ВО «Первый Санкт-Петербургский государственный медицинский университет им. И.П. Павлова» Минздрава России0906202016143540806202008062020https://ojrs.abvpress.ru/ojrs/article/view/702

The article considers the aspects of selection of post-neoadjuvant therapy for patients with residual breast cancer depending on biological subtype and molecular profile of the tumor. Analysis of morphological and molecular markers allowing to evaluate sensitivity of malignant breast tumors with high recurrence risk to new types of systemic treatment is presented.

В статье освещены аспекты выбора постнеоадъювантной терапии больных с резидуальным раком молочной железы в зависимости от биологического подтипа и молекулярного профиля опухоли. Дан анализ морфологических и молекулярных маркеров, позволяющих оценить чувствительность злокачественных опухолей молочной железы высокого риска рецидива к новым видам системного лечения.

 

residual breast cancerpost-neoadjuvant treatmentadjuvant treatmentHER2-positive breast cancertriple negative breast cancerendocrine sensitive breast cancerKi-67tumor-infiltrating lymphocytesmolecular profileрезидуальный рак молочной железыпостнеоадъювантное лечениеадъювантное лечениеHER2-положительный рак молочной железытрижды негативный рак молочной железыэндокриночувствительный рак молочной железыKi-67опухоль-инфильтрирующие лимфоцитымолекулярный профильMauri D., Pavlidis N., Ioannidis J.P. Neoadjuvant versus adjuvant systemic treatment in breast cancer: a metaanalysis. J Natl Cancer Inst 2005;97: 188–94. DOI: 10.1093/jnci/dji021.Gianni L., Pienkowski T., Im Y.H. et al. 5-year analysis of neoadjuvant pertuzumab and trastuzumab in patients with locally advanced, inflammatory, or early-stage HER2-positive breast cancer (NeoSphere): a multicentre, openlabel, phase 2 randomised trial. Lancet Oncol 2016;17:791–800.Schneeweiss A., Chia S., Hickish T. et al. Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracyclinecontaining 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. DOI: 10.1093/annonc/mdt182.Cortazar P., Zhang L., Untch M. et al. Pathological complete response and longterm clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet 2014;384:164–72.Esserman L.J., Berry D.A., DeMichele A. et al. Pathologic complete response predicts recurrence-free survival more effectively by cancer subset: results from the I-SPY 1 TRIAL–CALGB 150007/150012, ACRIn 6657. J Clin Oncol 2012;30(26):3242–9.Von Minckwitz G., Untch M., Blohmer J.U. et al. Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol 2012;30:1796–804. DOI: 10.1200/JCO.2011.38.8595.Masuda N., Lee S.J., Ohtani S. et al. Adjuvant capecitabine for breast cancer after preoperative chemotherapy. N Engl J Med 2017;376:2147–59.Natori A., Ethier J.L., Amir E. et al. Capecitabine in early breast cancer: a meta-analysis of randomised controlled trials. Eur J Cancer 2017;77:40–7.Zhang Z.C., Xu Q.N., Lin S.L. et al. Capecitabine in combination with standard (Neo) adjuvant regimens in early breast cancer: survival outcome from a meta-analysis of randomized controlled trials. PLoS One 2016;11:e0164663. DOI: 10.1371/journal.pone.0164663.Burstein H.J., Curigliano G., Loibl S. et al. Estimating the benefits of therapy for early-stage breast cancer: the St. Gallen International Consensus Guidelines for the primary therapy of early breast cancer 2019. Ann Oncol 2019;30(10):1541–57. DOI: 10.1093/annonc/mdz235.Semiglazov V.V., Krivorotko P.V., Semiglazov V.F. et al. International guidelines for the treatment of breast cancer. Moscow: SIMK, 2020. 272 p. (In Russ.).Семиглазов В.В., Криворотько П.В., Семиглазов В.Ф. и др. Международные рекомендации по лечению рака молочной железы. Под ред. проф. В.Ф. Семиглазова. М.: СИМК, 2020. 272 с.Platinum based chemotherapy or capecitabine in treating patients with residual triple-negative basal-like breast cancer following neoadjuvant chemotherapy. Available at: https://clinicaltrials.gov/ct2/show/NCT02445391.Miller K., Tong Y., Jones D.R. et al. Cisplatin with or without rucaparib after preoperative chemotherapy in patients with triple negative breast cancer: final efficacy results of Hoosier Oncology Group BRE09-146. J Clin Oncol 2015;33:1082.Olaparib as adjuvant treatment in patients with germline BRCA mutated high risk HER2 negative primary breast cancer(OLYMPIA). Available at: https:// clinicaltrials.gov/ct2/show/NCT02032823?term=02032823&draw=2&rank=1.Olaparib as adjuvant treatment in patients with germline BRCA mutated high risk HER2 negative primary breast cancer(OLYMPIA). Available at: https://clinicaltrials.gov/ct2/show/NCT02032823?term=02032823&draw=2&rank=1.Martin M., Holmes F.A., Ejlertsen B. et al. Neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer(ExteNET): 5-year analysis of a randomised, double-blind, placebocontrolled, phase 3 trial. Lancet Oncol 2017;18:1688–700. DOI: 10.1016/S1470-2045(17)30717-9.Von Minckwitz G., Huang C.S., Mano M.S. et al. Trastuzumab emtansine for residual invasive HER2-positive breast cancer. N Engl J Med 2019;380(7):617–28.Mano M.S., Loibl S, Mamounas E.P. et al. Adjuvant trastuzumab emtansine (T-DM1) vs trastuzumab (H) in patients with residual invasive disease after neoadjuvant therapy for HER2-positive breast cancer: KATHERINE subgroup analysis. San Antonio Breast Cancer Symposium, December 10–14, 2019. Available at: https://www.abstractsonline.com/pp8/#!/7946/presentation/1101.Cristofanilli M., Turner N.C., Bondarenko I. et al. Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptorpositive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phase 3 randomised controlled trial. Lancet Oncol 2016;17(4):425–39. DOI: 10.1016/S1470-2045(15)00613-0.Hortobagyi G.N., Stemmer S.M., Burris H.A. et al. Updated results from MONALEESA-2, a phase 3 trial of firstline ribociclib + letrosol in hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) advanced breast cancer (ABC). ASCO-2017. Abstr. 1038.Sledge G.W., Toi M., Neven P. et al. MONARCH-2: abemaciclib in combination with fulvestrant in women with HR+/HER2– advanced breast cancer who had progressed while receiving endocrine therapy. J Clin Oncol 2017;(25):2874–84. DOI: 10.1200/JCO.2017.73.7585.A study of palbociclib in addition to standard endocrine treatment in hormone receptor positive HER2 normal patients with residual disease after neoadjuvant chemotherapy and surgery(PENELOPE-B). Available at: https://clinicaltrials.gov/ct2/show/NCT01864746?term= NCT01864746&draw=2&rank=1.Palbociclib collaborative adjuvant study(PALLAS). Available at: https://clinicaltrials.gov/ct2/show/study/NCT02513394.Palbociclib collaborative adjuvant study(PALLAS). Available at: https://clinicaltrials.gov/ct2/show/study/ NCT02513394.Semiglazov V.F., Semiglazov V.V., Dashyan G.A. et al. Phase 2 randomized trial of primary endocrine therapy versus chemotherapy in postmenopausal patients with estrogen receptor-positive breast cancer. Cancer 2007;110(2):244–54. DOI: 10.1002/cncr.22789.Symmans W.F., Peintinger F., Hatzis C. et al. Measurement of residual breast cancer burden to predict survival after neoadjuvant chemotherapy. J Clin Oncol 2007;25:4414–22. DOI:10.1200/JCO.2007.10.6823.Symmans W.F., Wei C., Gould R. et al. Long-term prognostic risk after neoadjuvant chemotherapy associated with residual cancer burden and breast cancer subtype. J Clin Oncol 2017;35:1049–60. DOI: 10.1200/JCO.2015.63.1010.Perez E.A., Ballman K.V., Tenner K.S. et al. Association of stromal tumor-infiltrating lymphocytes with recurrence-free survival in the N9831 Adjuvant Trial in patients with early-stage HER2-positive breast cancer. AMA Oncol 2016;2(1):56–64. DOI: 10.1001/jamaoncol.2015.3239.Miglietta F., Tsvetkova V., Dieci1 M.V. et al. Validation of residual proliferative cancer burden(RPCB) as a predictor of long-term outcome following neoadjuvant chemotherapy in hormonereceptor positive/HER2 negative breast cancer patients. San Antonio Breast Cancer Symposium, December 10–14, 2019. Available at: https://www.abstractsonline.com/pp8/#!/7946/presentation/1430.Balko J.M., Nixon M., GonzalezEricsson P.I. et al. Immunologic correlates of long-term outcome in the residual disease of triple-negative breast cancer after neoadjuvant chemotherapy San Antonio Breast Cancer Symposium, December 10–14, 2019. Available at: https://www.abstractsonline.com/pp8/#!/7946/presentation/977.Prihantono P., Hatta M., Binekada C. et al. Ki-67 expression by immunohistochemistry and quantitative real-time polymerase chain reaction as predictor of clinical response to neoadjuvant chemotherapy in locally advanced breast cancer. J Oncol 2017;2017:6209849. DOI: 10.1155/2017/6209849.Sinn H.P., Schneeweiss A., Keller M. et al. Comparison of immunohistochemistry with PCR for assessment of ER, PR, and Ki-67 and prediction of pathological complete response in breast cancer. BMC Cancer 2017;17:124.Ellis M.J., Suman V.J., Hoog J. et al. Ki-67 proliferation index as a tool for chemotherapy decisions during and after neoadjuvant aromatase inhibitor treatment of breast cancer: Results from the American College of Surgeons Oncology Group Z1031 trial (Alliance). J Clin Oncol 2017;35:1061–9.Savas P., Salgado R., Denkert C. et al. Clinical relevance of host immunity in breast cancer: from TILs to the clinic. Nat Rev Clin Oncol 2016;13:228–41. DOI: 10.1038/nrclinonc.2015.215.Kochi M., Iwamoto T., Niikura N. et al. Tumour-infiltrating lymphocytes (TILs)- related genomic signature predicts chemotherapy response in breast cancer. Breast Cancer Res Treat 2018;167:39–47. DOI: 10.1007/s10549-017-4502-3.Wang Y., Waters J., Leung M.L. et al. Clonal evolution in breast cancer revealed by single nucleus genome sequencing. Nature 2014;512:155–60. DOI: 10.1038/nature13600.Salgado R., Denkert C., Campbell C. et al. Tumor-infiltrating lymphocytes and associations with pathological complete response and event-free survival in HER2-positive early-stage breast cancer treated with lapatinib and trastuzumab: a secondary analysis of the NeoALTTO Trial. JAMA Oncol 2015;1(4):448–54. DOI: 10.1001/jamaoncol.2015.0830.Hamy A.S., Pierga J.Y., Sabaila A. et al. Stromal lymphocyte infiltration after neoadjuvantchemotherapy is associated with aggressive residual disease and lower disease-free in HER2-positive breast cancer. Ann Oncol 2017;28:2233–40.Miyashita M., Sasano H., Tamaki K. et al. Prognostic significance of tumorinfiltrating CD8+ and FOXP3+ lymphocytes in residual tumors and alterations in these parameters after neoadjuvant chemotherapy in triplenegative breast cancer: a retrospective multicenter study. Breast Cancer Res BCR 2015;17:124. DOI: 10.1186/s13058-015-0632-x.Liu F., Li Y., Ren M. et al. Peritumoral FOXP3+ regulatory T cell is sensitive to chemotherapy while intratumoral FOXP3+ regulatory T cell is prognostic predictor of breast cancer patients. Breast Cancer Res Treat 2012;135:459–67. DOI: 10.1007/s10549-012-2132-3.Ladoire S., Mignot G., Dabakuyo S. et al. In situ immune response after neoadjuvant chemotherapy for breast cancer predicts survival. J Pathol 2011;224:389–400.Asano Y., Kashiwagi S., Goto W. et al. Prediction of survival after neoadjuvant chemotherapy for breast cancer by evaluation of tumor-infiltrating lymphocytes and residual cancer burden. BMC Cancer 2017;17:888. DOI: 10.1186/s12885-017-3927-8.Luen S.J., Salgado R., Dieci M.V. et al. Prognostic implications of residual disease tumor-infiltrating lymphocytes and residual cancer burden in triple-negative breast cancer patients after neoadjuvant chemotherapy. Ann Oncol 2019;30(2):236–42. DOI: 10.1093/annonc/mdy547.Dieci M.V., Radosevic-Robin N., Fineberg S. et al. Update on tumorinfiltrating lymphocytes (TILs) in breast cancer, including recommendations to assess TILs in residual disease after neoadjuvant therapy and in carcinoma in situ: a report of the International Immuno-Oncology Biomarker Working Group on Breast Cancer. Semin Cancer Biol 2018;52(Pt 2):16–25. DOI: 10.1016/j.semcancer.2017.10.003.Chen S., Wang R.X., Liu Y. et al. PD-L1 expression of the residual tumor serves as a prognostic marker in local advanced breast cancer after neoadjuvant chemotherapy. Int J Cancer 2017;140(6): 1384–95. DOI: 10.1002/ijc.30552.Nanda R., Chow L.Q., Dees E.C. et al. Pembrolizumab in patients with advanced triple-negative breast cancer: Phase Ib KEYNOTE-012 Study. J Clin Oncol 2016;34:2460–7.Pascual T., Villagrasa P., Vidal M.J. et al. Combination of talimogene laherparepvec(T-VEC) with atezolizumab in patients with residual breast cancer after standard neoadjuvant multi-agent chemotherapy. San Antonio Breast Cancer Symposium, December 10–14, 2019. Available at: https://www.abstractsonline.com/pp8/#!/7946/presentation/1792.Pembrolizumab in treating patients with triple-negative breast cancer. Available at: https://clinicaltrials.gov/ct2/show/NCT02954874?term=SWOG+S1418&draw= 2&rank=1.Beitsch P., Whitworth P., Baron P. et al. Genomic impact of neoadjuvant therapy on breast cancer: incomplete response is associated with altered diagnostic gene signatures. Ann Surg Oncol 2016;23:3317–23. DOI: 10.1245/s10434-016-5329-6.Jiang Y.Z., Yu K.D., Bao J. et al. Favorable prognostic impact in loss of TP53 and PIK3CA mutations after neoadjuvant chemotherapy in breast cancer. Cancer Res 2014;74:3399–407.Hattori M., Huo D. et al. Comparative analysis of genomic landscape reveals heterogeneity in HER2-positive primary breast cancers and residual disease following neoadjuvant therapy. San Antonio Breast Cancer Symposium, December 10–14, 2019.Balko J.M., Giltnane J.M., Wang K. et al. Molecular profiling of the residual disease of triplenegative breast cancers after neoadjuvant chemotherapy identifies actionable therapeutic targets. Cancer Discov 2014;4.2:232e45.Denkert C., Liedtke C., Tutt A., von Minckwitz G. Molecular alterations in triplenegative breast cancer-the road to new treatment strategies. Lancet 2017;389(10087):2430e42. DOI: 10.1016/S0140-6736(16)32454-0.The Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours. Nature 2012;490:61e70.Brasó-Maristany F., Filosto S., Catchpole S. et al. PIM1 kinase regulates cell death, tumor growth and chemotherapy response in triple-negative breast cancer. Nat Med 2016;22(11):1303e13.Wein L., Loi S. Mechanisms of resistance of chemotherapy in early-stage triple negative breast cancer (TNBC). Breast 2017;34(Suppl 1):S27–30.Garcia-Murillas I., Schiavon G., Weigelt B. et al. Mutation tracking in circulating tumor DNA predicts relapse in early breast cancer. Sci Transl Med 2015;7:302ra133. DOI: 10.1126/scitranslmed.aab0021. 56. Riva F., Bidard F.-C., Houy A. et al. Patient-specific circulating tumor DNA detection during neoadjuvant chemotherapy in triple-negative breast cancer. Clin Chem 2017;63:691–9.Chen Y.H., Hancock B.A., Solzak J.P. et al. Nextgeneration sequencing of circulating tumor DNA to predict recurrence in triple-negative breast cancer patients with residual disease after neoadjuvant chemotherapy. NPJ Breast Cancer 2017;3:24. DOI: 10.1038/s41523-017-0028-4.