Advances in Molecular OncologyAdvances in Molecular OncologyУспехи молекулярной онкологии2313-805X2413-3787Publishing House ABV Press27110.17650/2313-805X-2020-7-2-20-28REVIEW ARTICLESОБЗОРНЫЕ СТАТЬИThe modern views of the clinical, morphological and molecular biological predictors of breast cancer sensitivity to chemotherapyСовременные представления о клинических, морфологических и молекулярно-биологических предикторах чувствительности рака молочной железы к химиотерапииhttps://orcid.org/0000-0001-7025-0206ZubarevaE. Yu.ЗубареваЕ. Ю.
Russian Federation

11 Prospekt Gagarina, Orenburg 460021

6 Sovetskaya St., Orenburg 460000

Евгения Юрьевна Зубарева

460021 Оренбург, проспект Гагарина, 11

460000 Оренбург, ул. Советская, 6

tishkova_evgeniy@mail.ruhttps://orcid.org/0000-0001-8371-740XSen’chukovaM. A.СеньчуковаМ. А.
Russian Federation

11 Prospekt Gagarina, Orenburg 460021

6 Sovetskaya St., Orenburg 460000

460021 Оренбург, проспект Гагарина, 11

460000 Оренбург, ул. Советская, 6

Orenburg Regional Clinical Oncology DispensaryГБУЗ «Оренбургский областной клинический онкологический диспансер»Orenburg State Medical University, Ministry of Health of RussiaФГБОУ ВО «Оренбургский государственный медицинский университет» Минздрава России150520207220280609202006092020Copyright ©; 2020, Zubareva E.Y., Sen’chukova M.A.Copyright ©; 2020, Зубарева Е.Ю., Сеньчукова М.А.2020Zubareva E.Y., Sen’chukova M.A.Зубарева Е.Ю., Сеньчукова М.А.https://creativecommons.org/licenses/by/4.0https://umo.abvpress.ru/jour/article/view/271

In the treatment of breast cancer, the neoadjuvant chemotherapy is vitally important and the evaluation of its effectiveness is crucial for determining the further therapy treatment, as well as the prognosis of the disease. This review provides current data of the physical, instrumental, morphological, molecular biology and genetics analysis used for the estimation of the neoadjuvant treatment effectiveness. Thus, review discusses the data concerning association of the disease peculiarities with the efficient therapeutic response to neoadjuvant chemotherapy including characteristics of patients (age, status of regional lymph nodes, presence of the lymphovascular invasion) and tumors (size, histological type, degree of differentiation, severity of the lymphoid tumor infiltration, molecular biological and genetic peculiarities). Particular attention is paid to such a promising predictive marker of the breast cancer response to chemotherapy as the level of tissue hypoxia. This section discusses the currently known mechanisms that might enable the effect of tissue hypoxia on the sensitivity of the tumor to drug treatment. The prospects for the use of a comprehensive analysis of predictive markers of the effectiveness of chemotherapeutic treatment are discussed.

В лечении рака молочной железы особое место занимает неоадъювантная химиотерапия, оценка эффективности которой имеет ключевое значение для коррекции проводимой терапии, а также для определения прогноза заболевания. В настоящем обзоре приведены современные данные о физикальных, инструментальных и морфологических методах исследования, используемых для оценки эффективности неоадъювантного лечения. Мы рассмотрели данные об ассоциации различных характеристик развития опухолевого процесса с ответом на неоадъювантную химиотерапию, среди них характеристики пациенток (возраст, статус регионарных лимфатических узлов, лимфоваскулярная инвазия, молекулярно-генетические особенности) и опухоли (размер, гистологический тип, степень дифференцировки, выраженность лимфоидной инфильтрации, молекулярно-биологические и молекулярно-генетические особенности). Один из разделов статьи посвящен такому перспективному предиктивному маркеру ответа опухоли на проводимое лечение, как уровень тканевой гипоксии. В данном разделе рассмотрены известные в настоящее время механизмы, которые обеспечивают влияние тканевой гипоксии на чувствительность опухоли к лекарственному лечению. Обсуждены перспективы применения комплексного анализа предиктивных маркеров эффективности химиотерапевтического лечения.

breast cancerneoadjuvant chemotherapypredictive markertissue hypoxiahypoxia-inducible factorangiogenesisepithelial-mesenchymal transformationрак молочной железынеоадъювантная химиотерапияпредиктивный маркертканевая гипоксияиндуцированный гипоксией факторангиогенезэпителиально-мезенхимальный переход1. Злокачественные новообразования в России в 2018 году (заболеваемость и смертность). Под ред. А.Д. Каприна, В.В. Старинского, Г.В. Петровой. М.: МНИОИ им. П.А. Герцена – филиал ФГБУ «НМИЦ радиологии» Минздрава России, 2019. 250 с. [Malignant tumors in Russia in 2018(morbidity and mortality). Eds.: А.D. Kaprin, V.V. Starinskiy, G.V. Petrova. Moscow: MNIOI im. P.A. Gertsen – filial FGBU “NMITS radiologii” Minzdrava Rossii, 2019. 250 p. (In Russ.)].Злокачественные новообразования в России в 2018 году (заболеваемость и смертность). Под ред. А.Д. Каприна, В.В. Старинского, Г.В. Петровой. М.: МНИОИ им. П.А. Герцена – филиал ФГБУ «НМИЦ радиологии» Минздрава России, 2019. 250 с. [Malignant tumors in Russia in 2018(morbidity and mortality). Eds.: А.D. Kaprin, V.V. Starinskiy, G.V. Petrova. Moscow: MNIOI im. P.A. Gertsen – filial FGBU “NMITS radiologii” Minzdrava Rossii, 2019. 250 p. (In Russ.)].2. Состояние онкологической помощи населению России в 2018 году. Под ред. А.Д. Каприна, В.В. Старинского, Г.В. Петровой. М.: МНИОИ им. П.А. Герцена – филиал ФГБУ «НМИЦ радиологии» Минздрава России, 2019. 236 с. [State of oncological care in Russia in 2018. Eds.: А.D. Kaprin, V.V. Starinskiy, G.V. Petrova. Moscow: MNIOI im. P.A. Gertsena – filial FGBU “NMITS radiologii” Minzdrava Rossii, 2019. 236 p. (In Russ.)].Состояние онкологической помощи населению России в 2018 году. Под ред. А.Д. Каприна, В.В. Старинского, Г.В. Петровой. М.: МНИОИ им. П.А. Герцена – филиал ФГБУ «НМИЦ радиологии» Минздрава России, 2019. 236 с. [State of oncological care in Russia in 2018. Eds.: А.D. Kaprin, V.V. Starinskiy, G.V. Petrova. Moscow: MNIOI im. P.A. Gertsena – filial FGBU “NMITS radiologii” Minzdrava Rossii, 2019. 236 p. (In Russ.)].3. Семиглазов В.Ф., Семиглазов В.В., Палтуев Р.М. и др. Неоадъювантное лечение рака молочной железы. Опухоли женской репродуктивной системы 2014;(2):30–6. [Semiglazov V.F., Semiglazov V.V., Paltuev R.M. et al. Neoadjuvant treatment for breast cancer. Opukholi zhenskoy reproduktivnoi sistemy = Tumors of Female Reproductive System 2014;(2):30–6. (In Russ.)].Семиглазов В.Ф., Семиглазов В.В., Палтуев Р.М. и др. Неоадъювантное лечение рака молочной железы. Опухоли женской репродуктивной системы 2014;(2):30–6. [Semiglazov V.F., Semiglazov V.V., Paltuev R.M. et al. Neoadjuvant treatment for breast cancer. Opukholi zhenskoy reproduktivnoi sistemy = Tumors of Female Reproductive System 2014;(2):30–6. (In Russ.)].4. Колядина И.В., Поддубная И.В., Павликова О.А. и др. Эволюция неоадъювантного подхода при первично-операбельном раке молочной железы в последнюю декаду: модный тренд или реальная клиническая практика? Современная онкология 2017;19(1):9–16. [Kolyadina I.V., Poddubnaya I.V., Pavlikova O.A. et al. The evolution of neoadjuvant approach in primary operable breast cancer last decade: modern trend or a real clinical practice? Sovremennaya onkologiya = Modern Oncology 2017;19(1):9–16. (In Russ.)].Колядина И.В., Поддубная И.В., Павликова О.А. и др. Эволюция неоадъювантного подхода при первично-операбельном раке молочной железы в последнюю декаду: модный тренд или реальная клиническая практика? Современная онкология 2017;19(1):9–16. [Kolyadina I.V., Poddubnaya I.V., Pavlikova O.A. et al. The evolution of neoadjuvant approach in primary operable breast cancer last decade: modern trend or a real clinical practice? Sovremennaya onkologiya = Modern Oncology 2017;19(1):9–16. (In Russ.)].5. Игнатьева В.И., Грецова О.П., Стенина М.Б. и др. Социально-экономическое бремя рака молочной железы в РФ. Медицинские технологии. Оценка и выбор 2016;4(26):32–49. [Ignatyeva V.I., Gretsova O.P., Stenina M.B. et al. Social and economic burden of breast cancer in the Russian Federation. Medical technologies. Otsenka i vybor = Assessment and Choice 2016;4(26):32–49. (In Russ.)].Игнатьева В.И., Грецова О.П., Стенина М.Б. и др. Социально-экономическое бремя рака молочной железы в РФ. Медицинские технологии. Оценка и выбор 2016;4(26):32–49. [Ignatyeva V.I., Gretsova O.P., Stenina M.B. et al. Social and economic burden of breast cancer in the Russian Federation. Medical technologies. Otsenka i vybor = Assessment and Choice 2016;4(26):32–49. (In Russ.)].6. Авксентьева М.В., Горкавенко Ф.В., Никитина А.В. и др. Оценка социально-экономического бремени рака легкого в Российской Федерации. Медицинские технологии. Оценка и выбор 2018;4(34):63–75. DOI: 10.31556/2219-0678.2018.34.4.063-075. Avksent’eva M.V., Gorkavenko F. V., Nikitina A.V. et al. Assessing the socioeconomic burden of lung cancer in the Russian Federation. Medical technology. Otsenka i vybor = Assessment and Choice 2018;4(34):63–75. (In Russ.)].Авксентьева М.В., Горкавенко Ф.В., Никитина А.В. и др. Оценка социально-экономического бремени рака легкого в Российской Федерации. Медицинские технологии. Оценка и выбор 2018;4(34):63–75. DOI: 10.31556/2219-0678.2018.34.4.063-075. Avksent’eva M.V., Gorkavenko F. V., Nikitina A.V. et al. Assessing the socioeconomic burden of lung cancer in the Russian Federation. Medical technology. Otsenka i vybor = Assessment and Choice 2018;4(34):63–75. (In Russ.)].7. Стенина М.Б., Жукова Л.Г., Королева И.А. и др. Практические рекомендации по лекарственному лечению инвазивного рака молочной железы. Злокачественные опухоли. Российское общество клинической онкологии 2019;9(3):145–9. DOI: 10.18027/2224-5057-2019-9-3s2- 128-163. [Stenina M.B., Zhukova L.G., Koroleva I.A. et al. Practical guidelines for the drug treatment of invasive breast cancer. Malignant tumors. Rossiyskoe obshchestvo klinicheskoy onkologii = Russian Society of Clinical Oncology 2019;9(3):145–9. (In Russ.)].Стенина М.Б., Жукова Л.Г., Королева И.А. и др. Практические рекомендации по лекарственному лечению инвазивного рака молочной железы. Злокачественные опухоли. Российское общество клинической онкологии 2019;9(3):145–9. DOI: 10.18027/2224-5057-2019-9-3s2- 128-163. [Stenina M.B., Zhukova L.G., Koroleva I.A. et al. Practical guidelines for the drug treatment of invasive breast cancer. Malignant tumors. Rossiyskoe obshchestvo klinicheskoy onkologii = Russian Society of Clinical Oncology 2019;9(3):145–9. (In Russ.)].8. Лисаева А.А., Вишневская Я.В., Рощин Е.М. и др. Лечебный патоморфоз злокачественных опухолей: клинические и морфологические критерии. Классификации. Прогностическое значение лечебного патоморфоза при раке молочной железы и других опухолях. Опухоли женской репродуктивной системы 2011;(4):19–23. [Lisaeva A.A., Vishnevskaya Ya.V., Roshchin E.M. et al. Therapeutic pathomorphism of malignancies: Clinical and morphological criteria. Classifications. Prognostic value of therapeutic pathomorphism in breast cancer and other tumors. Opukholi zhenskoy reproduktivnoi sistemy = Tumors of Female Reproductive System 2011;(4):19–23. (In Russ.)].Лисаева А.А., Вишневская Я.В., Рощин Е.М. и др. Лечебный патоморфоз злокачественных опухолей: клинические и морфологические критерии. Классификации. Прогностическое значение лечебного патоморфоза при раке молочной железы и других опухолях. Опухоли женской репродуктивной системы 2011;(4):19–23. [Lisaeva A.A., Vishnevskaya Ya.V., Roshchin E.M. et al. Therapeutic pathomorphism of malignancies: Clinical and morphological criteria. Classifications. Prognostic value of therapeutic pathomorphism in breast cancer and other tumors. Opukholi zhenskoy reproduktivnoi sistemy = Tumors of Female Reproductive System 2011;(4):19–23. (In Russ.)].9. Павликова О.А., Поддубная И.В., Колядина И.В. и др. Клинико-рентгенологическая оценка эффективности предоперационной лекарственной терапии при различных биологических подтипах рака молочной железы стадий T1–3N0–1M0. Современная онкология 2017;19(4):16–21. [Pavlikova O.A., Poddubnaya I.V., Kolyadina I.V. et al. Clinical and radiological evaluation the effectiveness of preoperative systemic therapy in different biological subtypes of breast cancer stages T1–3N0–1M0. Sovremennaya onkologiya = Modern Oncology 2017;19(4):16–21. (In Russ.)].Павликова О.А., Поддубная И.В., Колядина И.В. и др. Клинико-рентгенологическая оценка эффективности предоперационной лекарственной терапии при различных биологических подтипах рака молочной железы стадий T1–3N0–1M0. Современная онкология 2017;19(4):16–21. [Pavlikova O.A., Poddubnaya I.V., Kolyadina I.V. et al. Clinical and radiological evaluation the effectiveness of preoperative systemic therapy in different biological subtypes of breast cancer stages T1–3N0–1M0. Sovremennaya onkologiya = Modern Oncology 2017;19(4):16–21. (In Russ.)].10. Лавникова Г.А. Гистологический метод количественной оценки терапевтического повреждения опухоли. М.: Методические рекомендации, 1979. 13 с. [Lavnikova G.A. Histological method for quantifying therapeutic tumor damage Moscow: Metodicheskie rekomendacii, 1979. 13 p. (In Russ.)].Лавникова Г.А. Гистологический метод количественной оценки терапевтического повреждения опухоли. М.: Методические рекомендации, 1979. 13 с. [Lavnikova G.A. Histological method for quantifying therapeutic tumor damage Moscow: Metodicheskie rekomendacii, 1979. 13 p. (In Russ.)].11. Loibl S., Jackisch C., Lederer B. et al. Outcome after neoadjuvant chemotherapy in young breast cancer patients: a pooled analysis of individual patient data from eight prospectively randomized controlled trials. Breast Cancer Res Treat 2015;152(2):377–87. DOI: 10.1007/s10549-015-3479-z.Loibl S., Jackisch C., Lederer B. et al. Outcome after neoadjuvant chemotherapy in young breast cancer patients: a pooled analysis of individual patient data from eight prospectively randomized controlled trials. Breast Cancer Res Treat 2015;152(2):377–87. DOI: 10.1007/s10549-015-3479-z.12. Von Waldenfels G., Loibl S., Furlanetto J. et al. Outcome after neoadjuvant chemotherapy in elderly breast cancer patients – a pooled analysis of individual patient data from eight prospectively randomized controlled trials. Oncotarget 2018;9(20): 15168–79. DOI: 10.18632/oncotarget.24586.Von Waldenfels G., Loibl S., Furlanetto J. et al. Outcome after neoadjuvant chemotherapy in elderly breast cancer patients – a pooled analysis of individual patient data from eight prospectively randomized controlled trials. Oncotarget 2018;9(20): 15168–79. DOI: 10.18632/oncotarget.24586.13. Sasanpour P., Sandoughdaran S., Mosavi-Jarrahi A., Malekzadeh M. Predictors of pathological complete response to neoadjuvant chemotherapy in Iranian breast cancer patients. Asian Pac J Cancer Prev 2018;19(9):2423–7. DOI: 10.22034/APJCP.2018.19.9.2423.Sasanpour P., Sandoughdaran S., Mosavi-Jarrahi A., Malekzadeh M. Predictors of pathological complete response to neoadjuvant chemotherapy in Iranian breast cancer patients. Asian Pac J Cancer Prev 2018;19(9):2423–7. DOI: 10.22034/APJCP.2018.19.9.2423.14. Павликова О.А., Колядина И.В., Комов Д.В. и др. Факторы-предикторы достижения полного лекарственного патоморфоза при неоадъювантной химиотерапии первично-операбельного рака молочной железы. Современная онкология 2017;19(1):24–9. [Pavlikova O.A., Kolyadina I.V., Komov D.V. et al. Predictive factors of achievement pathological complete response at neoadjuvant chemotherapy of primary operable breast cancer. Sovremennaya onkologiya = Modern Oncology 2017;19(1):24–9. (In Russ.)].Павликова О.А., Колядина И.В., Комов Д.В. и др. Факторы-предикторы достижения полного лекарственного патоморфоза при неоадъювантной химиотерапии первично-операбельного рака молочной железы. Современная онкология 2017;19(1):24–9. [Pavlikova O.A., Kolyadina I.V., Komov D.V. et al. Predictive factors of achievement pathological complete response at neoadjuvant chemotherapy of primary operable breast cancer. Sovremennaya onkologiya = Modern Oncology 2017;19(1):24–9. (In Russ.)].15. Рощин Е.М., Зубанова А.А, Колядина И.В. Лечебный патоморфоз как критерий эффективности лечения и прогноза рака молочной железы. Медицинский альманах 2010;12(3):48–53. [Roshchin E.M., Zubanova A.A, Kolyadina I.V. Therapeutic pathomorphosis as a criterion for the effectiveness of treatment and prognosis of breast cancer. Meditsinskiy al’manakh = Medical Almanac 2010;12(3):48–53. (In Russ.)].Рощин Е.М., Зубанова А.А, Колядина И.В. Лечебный патоморфоз как критерий эффективности лечения и прогноза рака молочной железы. Медицинский альманах 2010;12(3):48–53. [Roshchin E.M., Zubanova A.A, Kolyadina I.V. Therapeutic pathomorphosis as a criterion for the effectiveness of treatment and prognosis of breast cancer. Meditsinskiy al’manakh = Medical Almanac 2010;12(3):48–53. (In Russ.)].16. Hwang H.W., Jung H., Hyeon J. et al. A nomogram to predict pathologic complete response (pCR) and the value of tumor-infiltrating lymphocytes (TILs) for prediction of response to neoadjuvant chemotherapy (NAC) in breast cancer patients. Breast Cancer Res Treat 2019;173(2):255–66. DOI: 10.1007/s10549-018-4981-x.Hwang H.W., Jung H., Hyeon J. et al. A nomogram to predict pathologic complete response (pCR) and the value of tumor-infiltrating lymphocytes (TILs) for prediction of response to neoadjuvant chemotherapy (NAC) in breast cancer patients. Breast Cancer Res Treat 2019;173(2):255–66. DOI: 10.1007/s10549-018-4981-x.17. Uematsu T., Kasami M., Watanabe J. et al. Is lymphovascular invasion degree one of the important factors to predict neoadjuvant chemotherapy efficacy in breast cancer? Breast Cancer 2011;18(4):309–13. DOI: 10.1007/s12282-010-0211-z.Uematsu T., Kasami M., Watanabe J. et al. Is lymphovascular invasion degree one of the important factors to predict neoadjuvant chemotherapy efficacy in breast cancer? Breast Cancer 2011;18(4):309–13. DOI: 10.1007/s12282-010-0211-z.18. Yang L., Ye F., Bao L. et al. Somatic alterations of TP53, ERBB2, PIK3CA and CCND1 are associated with chemosensitivity for breast cancers. Cancer Sci 2019;110(4):1389–400. DOI: 10.1111/cas.13976.Yang L., Ye F., Bao L. et al. Somatic alterations of TP53, ERBB2, PIK3CA and CCND1 are associated with chemosensitivity for breast cancers. Cancer Sci 2019;110(4):1389–400. DOI: 10.1111/cas.13976.19. Dave R.V., Millican-Slater R., Dodwell D. et al. Neoadjuvant chemotherapy with MRI monitoring for breast cancer. Br J Surg 2017;104(9):1177–87. DOI: 10.1002/bjs.10544.Dave R.V., Millican-Slater R., Dodwell D. et al. Neoadjuvant chemotherapy with MRI monitoring for breast cancer. Br J Surg 2017;104(9):1177–87. DOI: 10.1002/bjs.10544.20. Shiraishi Y., Kataoka K., Chiba K. et al. A comprehensive characterization of cis-acting splicing-associated variants in human cancer. Genome Res 2017. DOI: http://dx.doi.org/10.1101/162560.Shiraishi Y., Kataoka K., Chiba K. et al. A comprehensive characterization of cis-acting splicing-associated variants in human cancer. Genome Res 2017. DOI: http://dx.doi.org/10.1101/162560.21. Brooks D.L., Luciana P.S., Krutilina R. et al. ITGA6 is directly regulated by hypoxia-inducible factors and enriches for cancer stem cell activity and invasion in metastatic breast cancer models. Mol Cancer 2016;15:26. DOI: 10.1186/s12943-016-0510-x.Brooks D.L., Luciana P.S., Krutilina R. et al. ITGA6 is directly regulated by hypoxia-inducible factors and enriches for cancer stem cell activity and invasion in metastatic breast cancer models. Mol Cancer 2016;15:26. DOI: 10.1186/s12943-016-0510-x.22. Zhang C., Samanta D., Lu H. et. al. Hypoxia induces the breast cancer stem cell phenotype by HIF-dependent and ALKBH5-mediated m6A-demethylation of NANOG mRNA. Proc Natl Acad Sci USA 2016;113(14):E2047–56. DOI: 10.1073/pnas.1602883113.Zhang C., Samanta D., Lu H. et. al. Hypoxia induces the breast cancer stem cell phenotype by HIF-dependent and ALKBH5-mediated m6A-demethylation of NANOG mRNA. Proc Natl Acad Sci USA 2016;113(14):E2047–56. DOI: 10.1073/pnas.1602883113.23. Schlotter C.M., Tietze L., Vogt U. et al. Ki-67 and lymphocytes in the pretherapeutic core biopsy of primary invasive breast cancer: positive markers of therapy response prediction and superior survival. Horm Mol Biol Clin Investig 2017;32(2). DOI: 10.1515/hmbci-2017-0022.Schlotter C.M., Tietze L., Vogt U. et al. Ki-67 and lymphocytes in the pretherapeutic core biopsy of primary invasive breast cancer: positive markers of therapy response prediction and superior survival. Horm Mol Biol Clin Investig 2017;32(2). DOI: 10.1515/hmbci-2017-0022.24. 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.2015.0830Salgado 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.2015.083025. Solinas C., Ceppi M., Lambertini M. et al. Tumor-infiltrating lymphocytes in patients with HER2-positive breast cancer treated with neoadjuvant chemotherapy plus trastuzumab, lapatinib or their combination: a meta-analysis of randomized controlled trials. Cancer Treat Rev 2017; 57:8–15. DOI: 10.1016/j.ctrv.2017.04.005.Solinas C., Ceppi M., Lambertini M. et al. Tumor-infiltrating lymphocytes in patients with HER2-positive breast cancer treated with neoadjuvant chemotherapy plus trastuzumab, lapatinib or their combination: a meta-analysis of randomized controlled trials. Cancer Treat Rev 2017; 57:8–15. DOI: 10.1016/j.ctrv.2017.04.005.26. Yoshioka T., Hosoda M., Yamamoto M. et al. Prognostic significance of pathologic complete response and Ki-67 expression after neoadjuvant chemotherapy in breast cancer. Breast Cancer 2015;22(2):185–91. DOI: 10.1007/s12282-013-0474-2.Yoshioka T., Hosoda M., Yamamoto M. et al. Prognostic significance of pathologic complete response and Ki-67 expression after neoadjuvant chemotherapy in breast cancer. Breast Cancer 2015;22(2):185–91. DOI: 10.1007/s12282-013-0474-2.27. Kurozumi S., Inoue K., Takei H. et al. ER, PgR, Ki-67, p27(Kip1), and histological grade as predictors of pathological complete response in patients with HER2-positive breast cancer receiving neoadjuvant chemotherapy using taxanes followed by fluorouracil, epirubicin, and cyclophosphamide concomitant with trastuzumab. BMC Cancer 2015;15:622. DOI: 10.1186/s12885-015-1641-y.Kurozumi S., Inoue K., Takei H. et al. ER, PgR, Ki-67, p27(Kip1), and histological grade as predictors of pathological complete response in patients with HER2-positive breast cancer receiving neoadjuvant chemotherapy using taxanes followed by fluorouracil, epirubicin, and cyclophosphamide concomitant with trastuzumab. BMC Cancer 2015;15:622. DOI: 10.1186/s12885-015-1641-y.28. Bottini A., Berruti A., Brizzi M.P. et al. Single agent epirubicin versus the combination epirubicin plus tamoxifen as primary chemotherapy in breast cancer patients. A single institution phase III trial. Proc Am Soc Clin Oncol 2003;22:abstract 80.Bottini A., Berruti A., Brizzi M.P. et al. Single agent epirubicin versus the combination epirubicin plus tamoxifen as primary chemotherapy in breast cancer patients. A single institution phase III trial. Proc Am Soc Clin Oncol 2003;22:abstract 80.29. Smirnоva О.V., Bоrisоv V.I., Guens G.P. The evоlutiоn оf knоwledge оf triplnegative breast cancer: frоm biоlоgy tо nоvel drug treatment. Malig Tumоrs 2017;1:5–17. DОI: 10.18027/2224-5057-207-1-5-17.Smirnоva О.V., Bоrisоv V.I., Guens G.P. The evоlutiоn оf knоwledge оf triplnegative breast cancer: frоm biоlоgy tо nоvel drug treatment. Malig Tumоrs 2017;1:5–17. DОI: 10.18027/2224-5057-207-1-5-17.30. Burstein M.D., Tsimelzоn A., Pоage G.M. et al. Соmprehensive genоmnic analysis identifies nоvel subtypes and targents оf tripl-negative breast cancer. Clin Cancer Res 2015;21(7):1688–9. DOI: 10.1158/1078-0432.CCR-14-0432.Burstein M.D., Tsimelzоn A., Pоage G.M. et al. Соmprehensive genоmnic analysis identifies nоvel subtypes and targents оf tripl-negative breast cancer. Clin Cancer Res 2015;21(7):1688–9. DOI: 10.1158/1078-0432.CCR-14-0432.31. Lehmann B.D., Bauer J.A., Chen X. et al. Identificatiоn оf human tripl-negative breast cancer subtypes and preclinical mоdels fоr selectiоn оf targeted therapies. J Clin Invest 2011:121:2750–67. DOI: 10.1172/JCI45014.Lehmann B.D., Bauer J.A., Chen X. et al. Identificatiоn оf human tripl-negative breast cancer subtypes and preclinical mоdels fоr selectiоn оf targeted therapies. J Clin Invest 2011:121:2750–67. DOI: 10.1172/JCI45014.32. Masuda H., Baggerly K.A., Wang Y. et al. Differential response to neoadjuvant chemotherapy among 7 triple-negative breast cancer molecular subtypes. Clin Cancer Res 2013;19(19):5533–40. DOI: 10.1158/1078-0432.CCR-13-0799.Masuda H., Baggerly K.A., Wang Y. et al. Differential response to neoadjuvant chemotherapy among 7 triple-negative breast cancer molecular subtypes. Clin Cancer Res 2013;19(19):5533–40. DOI: 10.1158/1078-0432.CCR-13-0799.33. Gucalp A., Tоlaney S., Isakоff S.J. et al. Phase II trial оf bicalutamide in pacients with andrоgen receptоr pоsitive, estrоgen receptоr negative metastatic breast cancer. Clin Cancer Res 2013;19(19):5505–12. DOI: 10.1158/1078-0432.CCR-12-3327.Gucalp A., Tоlaney S., Isakоff S.J. et al. Phase II trial оf bicalutamide in pacients with andrоgen receptоr pоsitive, estrоgen receptоr negative metastatic breast cancer. Clin Cancer Res 2013;19(19):5505–12. DOI: 10.1158/1078-0432.CCR-12-3327.34. Tan Q.X., Qin Q.H., Yang W.P. et al. Prognostic value of Ki-67 expression in HR-negative breast cancer before and after neoadjuvant chemotherapy. Int J Clin Exp Pathol 2014;7(10):6862–70.Tan Q.X., Qin Q.H., Yang W.P. et al. Prognostic value of Ki-67 expression in HR-negative breast cancer before and after neoadjuvant chemotherapy. Int J Clin Exp Pathol 2014;7(10):6862–70.35. Имянитов Е.Н. Наследственный рак молочной железы. Практическая онкология 2010;11(4):258–66. [Imyanitov E.N. Hereditary breast cancer. Prakticheskaya onkologiya = Practical Oncology 2010;11(4):258–66. (In Russ.)].Имянитов Е.Н. Наследственный рак молочной железы. Практическая онкология 2010;11(4):258–66. [Imyanitov E.N. Hereditary breast cancer. Prakticheskaya onkologiya = Practical Oncology 2010;11(4):258–66. (In Russ.)].36. Chacón R.D., Costanzo M.V. Triplenegative breast cancer. Breast Cancer Res 2010;12(Suppl 2):S3. DOI: 10.1186/bcr2574.Chacón R.D., Costanzo M.V. Triplenegative breast cancer. Breast Cancer Res 2010;12(Suppl 2):S3. DOI: 10.1186/bcr2574.37. Byrski T., Gronwald J., Huzarski T. et al. Pathologic complete response rates in young women with BRCA-positive breast cancers after neoadjuvant chemotherapy. J Clin Oncol 2010;28:375–9. DOI: 10.1200/JCO.2008.20.7019.Byrski T., Gronwald J., Huzarski T. et al. Pathologic complete response rates in young women with BRCA-positive breast cancers after neoadjuvant chemotherapy. J Clin Oncol 2010;28:375–9. DOI: 10.1200/JCO.2008.20.7019.38. Foedermayr M., Sebesta M., Rudas M. et al. BRCA-1 methylation and TP53 mutation in triple-negative breast cancer patients without pathological complete response to taxane-based neoadjuvant chemotherapy. Cancer Chemother Pharmacol 2014;73(4):771–8. DOI: 10.1007/s00280-014-2404-1.Foedermayr M., Sebesta M., Rudas M. et al. BRCA-1 methylation and TP53 mutation in triple-negative breast cancer patients without pathological complete response to taxane-based neoadjuvant chemotherapy. Cancer Chemother Pharmacol 2014;73(4):771–8. DOI: 10.1007/s00280-014-2404-1.39. Von Minckwitz G., Blohmer J.U., Costa S.D. et al. Response-guided neoadjuvant chemotherapy for breast cancer. J Clin Oncol 2013;31(29):3623–30. DOI: 10.1200/JCO.2012.45.0940.Von Minckwitz G., Blohmer J.U., Costa S.D. et al. Response-guided neoadjuvant chemotherapy for breast cancer. J Clin Oncol 2013;31(29):3623–30. DOI: 10.1200/JCO.2012.45.0940.40. Hahnen E., Lederer B., Hauke J. et al. Germline mutation status, pathological complete response, and disease-free survival in triple-negative breast cancer. JAMA Oncol 2017;3:1378. DOI: 10.1001/jamaoncol.2017.1007.Hahnen E., Lederer B., Hauke J. et al. Germline mutation status, pathological complete response, and disease-free survival in triple-negative breast cancer. JAMA Oncol 2017;3:1378. DOI: 10.1001/jamaoncol.2017.1007.41. Tutt A., Tovey H., Chon M. et al. A randomised phase III trial of carboplatin compared with docetaxel in BRCA1/2 mutated and pre-specified triple negative breast cancer “BRCAness” subgroups: the TNT Trial. Nat Med 2018; 24(5):628–37. DOI: 10.1038/s41591-018-0009-7.Tutt A., Tovey H., Chon M. et al. A randomised phase III trial of carboplatin compared with docetaxel in BRCA1/2 mutated and pre-specified triple negative breast cancer “BRCAness” subgroups: the TNT Trial. Nat Med 2018; 24(5):628–37. DOI: 10.1038/s41591-018-0009-7.42. Caramelo O., Silva C., Caramelo F. et al. The effect of neoadjuvant platinum-based chemotherapy in BRCA mutated triple negative breast cancers –systematic review and meta-analysis. Hered Cancer Clin Pract 2019;17:11. DOI: 10.1186/s13053-019-0111-y.Caramelo O., Silva C., Caramelo F. et al. The effect of neoadjuvant platinum-based chemotherapy in BRCA mutated triple negative breast cancers –systematic review and meta-analysis. Hered Cancer Clin Pract 2019;17:11. DOI: 10.1186/s13053-019-0111-y.43. Sikov W.M., Berry D.A., Perou C.M. et al. Impact of the addition of carboplatin and/ or bevacizumab to neoadjuvant once-perweek paclitaxel followed by dose-dense doxorubicin and cyclophosphamide on pathologic complete response rates in stage II to III triple-negative breast cancer: CALGB 40603 (Alliance). J Clin Oncol 2015;33(1):13–21. DOI: 10.1200/JCO.2014.57.0572.Sikov W.M., Berry D.A., Perou C.M. et al. Impact of the addition of carboplatin and/ or bevacizumab to neoadjuvant once-perweek paclitaxel followed by dose-dense doxorubicin and cyclophosphamide on pathologic complete response rates in stage II to III triple-negative breast cancer: CALGB 40603 (Alliance). J Clin Oncol 2015;33(1):13–21. DOI: 10.1200/JCO.2014.57.0572.44. Sporikova Z., Koudelakova V., Trojanec R., Hajduch M. Genetic markers in triplenegative breast cancer. Clin Breast Cancer 2018;18(5):e841–50. DOI: 10.1016/j.clbc.2018.07.023.Sporikova Z., Koudelakova V., Trojanec R., Hajduch M. Genetic markers in triplenegative breast cancer. Clin Breast Cancer 2018;18(5):e841–50. DOI: 10.1016/j.clbc.2018.07.023.45. Darb-Esfahani S., Denkert C., Stenzinger A. et al. et al. Role of TP53 mutations in triple negative and HER2-positive breast cancer treated with neoadjuvant anthracycline/taxane-based chemotherapy. Oncotarget 2016;7(42):67686–98. DOI: 10.18632/oncotarget.11891.Darb-Esfahani S., Denkert C., Stenzinger A. et al. et al. Role of TP53 mutations in triple negative and HER2-positive breast cancer treated with neoadjuvant anthracycline/taxane-based chemotherapy. Oncotarget 2016;7(42):67686–98. DOI: 10.18632/oncotarget.11891.46. Wang Y., Xu Y., Chen J. et al. TP53 mutations are associated with higher rates of pathologic complete response to anthracycline/cyclophosphamide-based neoadjuvant chemotherapy in operable primary breast cancer. Int J Cancer 2016;138(2):489–96. DOI: 10.1002/ijc.29715.Wang Y., Xu Y., Chen J. et al. TP53 mutations are associated with higher rates of pathologic complete response to anthracycline/cyclophosphamide-based neoadjuvant chemotherapy in operable primary breast cancer. Int J Cancer 2016;138(2):489–96. DOI: 10.1002/ijc.29715.47. Филипенко М.Л., Оськина Н.А., Оскорбин И.А. и др. Соматические мутации гена PIK3CA в опухолях больных раком молочной железы. Вопросы биологической, медицинской и фармацевтической химии 2016;19(12):28–33. [Filipenko M.L., Os’kina N.A., Oskorbin I.A. et al. Somatic mutations of the PIK3CA gene in tumors of patients with breast cancer. Voprosy biologicheskoy, medicinskoy i farmacevticheskoy khimii = Biological, Medical and Pharmaceutical Chemistry Issues 2016;19(12):28–33. (In Russ.)].Филипенко М.Л., Оськина Н.А., Оскорбин И.А. и др. Соматические мутации гена PIK3CA в опухолях больных раком молочной железы. Вопросы биологической, медицинской и фармацевтической химии 2016;19(12):28–33. [Filipenko M.L., Os’kina N.A., Oskorbin I.A. et al. Somatic mutations of the PIK3CA gene in tumors of patients with breast cancer. Voprosy biologicheskoy, medicinskoy i farmacevticheskoy khimii = Biological, Medical and Pharmaceutical Chemistry Issues 2016;19(12):28–33. (In Russ.)].48. Alqahtani A., Ayesh H.S.K., Halawani H. PIK3CA Gene mutations in solid malignancies: association with clinicopathological parameters and prognosis. Cancers 2020;12(1):93. DOI: 10.3390/cancers12010093.Alqahtani A., Ayesh H.S.K., Halawani H. PIK3CA Gene mutations in solid malignancies: association with clinicopathological parameters and prognosis. Cancers 2020;12(1):93. DOI: 10.3390/cancers12010093.49. Barbareschi M., Buttitta F., Felicioni L., Cotrupi S. Different prognostic roles of mutations in the helical and kinase domains of the PIK3CA gene in breast carcinomas. Clin Cancer Res 2007;13(20):6064–9. DOI: 10.1158/1078-0432.CCR-07-0266.Barbareschi M., Buttitta F., Felicioni L., Cotrupi S. Different prognostic roles of mutations in the helical and kinase domains of the PIK3CA gene in breast carcinomas. Clin Cancer Res 2007;13(20):6064–9. DOI: 10.1158/1078-0432.CCR-07-0266.50. Goel S., Krop I.E. PIK3CA mutations in HER2-positive breast cancer: an ongoing conundrum. Annal Oncol 2016;27:1368–72. DOI: 10.1093/annonc/mdw246.Goel S., Krop I.E. PIK3CA mutations in HER2-positive breast cancer: an ongoing conundrum. Annal Oncol 2016;27:1368–72. DOI: 10.1093/annonc/mdw246.51. Fan H., Li C., Xiang Q. et al. PIK3CA mutations and their response to neoadjuvant treatment in early breast cancer: a systematic review and meta-analysis. Thorac Cancer 2018;9(5):571–9. DOI: 10.1111/1759-7714.12618.Fan H., Li C., Xiang Q. et al. PIK3CA mutations and their response to neoadjuvant treatment in early breast cancer: a systematic review and meta-analysis. Thorac Cancer 2018;9(5):571–9. DOI: 10.1111/1759-7714.12618.52. Seo Y., Park Y.H., Ahn J.S. et al. PIK3CA mutations and neoadjuvant therapy outcome in patients with human epidermal growth factor receptor 2-positive breast cancer: a sequential analysis. J Breast Cancer 2018;21(4):382–90. DOI: 10.4048/jbc.2018.21.e48.Seo Y., Park Y.H., Ahn J.S. et al. PIK3CA mutations and neoadjuvant therapy outcome in patients with human epidermal growth factor receptor 2-positive breast cancer: a sequential analysis. J Breast Cancer 2018;21(4):382–90. DOI: 10.4048/jbc.2018.21.e48.53. Liedtke C., Cardone L., Tordai A. et al. PIK3CA-activating mutations and chemotherapy sensitivity in stage II–III breast cancer. Breast Cancer Res 2008;10(2):R27. DOI: 10.1186/bcr1984.Liedtke C., Cardone L., Tordai A. et al. PIK3CA-activating mutations and chemotherapy sensitivity in stage II–III breast cancer. Breast Cancer Res 2008;10(2):R27. DOI: 10.1186/bcr1984.54. Brown K.K., Toker A. The phosphoinositide 3-kinase pathway and therapy resistance in cancer. F1000Prime Rep 2015;7:13. DOI: 10.12703/P7-13.Brown K.K., Toker A. The phosphoinositide 3-kinase pathway and therapy resistance in cancer. F1000Prime Rep 2015;7:13. DOI: 10.12703/P7-13.55. Ellis M.J., Lin L., Crowder R. et al. Phosphatidyl-inositol-3-kinase alpha catalytic subunit mutation and response to neoadjuvant endocrine therapy for estrogen receptor positive breast cancer. Breast Cancer Res Treat 2010;119(2):379–90. DOI: 10.1007/s10549-009-0575-y.Ellis M.J., Lin L., Crowder R. et al. Phosphatidyl-inositol-3-kinase alpha catalytic subunit mutation and response to neoadjuvant endocrine therapy for estrogen receptor positive breast cancer. Breast Cancer Res Treat 2010;119(2):379–90. DOI: 10.1007/s10549-009-0575-y.56. Guarneri V., Generali D.G., Frassoldati A. et al. Double-blind, placebo-controlled, multicenter, randomized, phase IIb neoadjuvant study of letrozole-lapatinib in postmenopausal hormone receptorpositive, human epidermal growth factor receptor 2-negative, operable breast cancer. J Clin Oncol 2014;32(10):1050–7. DOI: 10.1200/JCO.2013.51.4737.Guarneri V., Generali D.G., Frassoldati A. et al. Double-blind, placebo-controlled, multicenter, randomized, phase IIb neoadjuvant study of letrozole-lapatinib in postmenopausal hormone receptorpositive, human epidermal growth factor receptor 2-negative, operable breast cancer. J Clin Oncol 2014;32(10):1050–7. DOI: 10.1200/JCO.2013.51.4737.57. Dang C.V. MYC on the path to cancer. Cell 2012;149(1):22–35. DOI: 10.1016/j.cell.2012.03.003.Dang C.V. MYC on the path to cancer. Cell 2012;149(1):22–35. DOI: 10.1016/j.cell.2012.03.003.58. Pereira C.B.L., Lea M.F., Souza C.R.T. et al. Prognostic and predictive significance of MYC and KRAS Alterations in breast cancer from women treated with neoadjuvant chemotherapy. PLoS One 2013;8(3):e60576. DOI: 10.1371/journal.pone.0060576Pereira C.B.L., Lea M.F., Souza C.R.T. et al. Prognostic and predictive significance of MYC and KRAS Alterations in breast cancer from women treated with neoadjuvant chemotherapy. PLoS One 2013;8(3):e60576. DOI: 10.1371/journal.pone.006057659. Naab T.J., Gautam A., Ricks-Santi L. et al. MYC amplification in subtypes of breast cancers in African American women. BMC Cancer 2018;18(1):274. DOI: 10.1186/s12885-018-4171-6.Naab T.J., Gautam A., Ricks-Santi L. et al. MYC amplification in subtypes of breast cancers in African American women. BMC Cancer 2018;18(1):274. DOI: 10.1186/s12885-018-4171-6.60. Fallah Y., Brundage J., Allegakoen P., Shajahan-Haq A.N. MYC-driven pathways in breast cancer subtypes. Biomolecules 2017;7(3):53. DOI: 10.3390/biom7030053.Fallah Y., Brundage J., Allegakoen P., Shajahan-Haq A.N. MYC-driven pathways in breast cancer subtypes. Biomolecules 2017;7(3):53. DOI: 10.3390/biom7030053.61. Li C.Y., Su W., Zhang S. et al. Effects of cell cycle regulatory genes on breast cancer neo-adjuvant chemotherapy by M-FISH. Zhonghua Yi Xue Za Zhi 2017;97(34):2682–6. DOI: 10.3760/cma.j. issn.0376-2491.2017.34.009.Li C.Y., Su W., Zhang S. et al. Effects of cell cycle regulatory genes on breast cancer neo-adjuvant chemotherapy by M-FISH. Zhonghua Yi Xue Za Zhi 2017;97(34):2682–6. DOI: 10.3760/cma.j. issn.0376-2491.2017.34.009.62. Yasojima H., Shimomura A., Naoi Y. et al. Association between C-MYC amplification and pathological complete response to neoadjuvant chemotherapy in breast cancer. Eur J Cancer 2011;47(12):1779–88. DOI: 10.1016/j.ejca.2011.06.017.Yasojima H., Shimomura A., Naoi Y. et al. Association between C-MYC amplification and pathological complete response to neoadjuvant chemotherapy in breast cancer. Eur J Cancer 2011;47(12):1779–88. DOI: 10.1016/j.ejca.2011.06.017.63. Пожилова Е.В., Новиков В.Е. Роль фактора адаптации к гипоксии в развитии опухолей. Вестник Смоленской государственной медицинской академии 2015;14(3):16–20. [Pozhilova E.V., Novikov V.E. The role of the factor of adaptation to hypoxia in the development of tumors. Vestnik Smolenskoy gosudarstvennoy medicinskoy akademii = Bulletin of the Smolensk State Medical Academy 2015;14(3):16–20. (In Russ.)].Пожилова Е.В., Новиков В.Е. Роль фактора адаптации к гипоксии в развитии опухолей. Вестник Смоленской государственной медицинской академии 2015;14(3):16–20. [Pozhilova E.V., Novikov V.E. The role of the factor of adaptation to hypoxia in the development of tumors. Vestnik Smolenskoy gosudarstvennoy medicinskoy akademii = Bulletin of the Smolensk State Medical Academy 2015;14(3):16–20. (In Russ.)].64. Bao B., Azmi A.S., Ali S. et al. The biological kinship of hypoxia with CSC and EMT and their relationship with deregulated expression of miRNAs and tumor aggressiveness. Biochim Biophys Acta 2012;1826(2):272–96. DOI: 10.1016/j.bbcan.2012.04.008.Bao B., Azmi A.S., Ali S. et al. The biological kinship of hypoxia with CSC and EMT and their relationship with deregulated expression of miRNAs and tumor aggressiveness. Biochim Biophys Acta 2012;1826(2):272–96. DOI: 10.1016/j.bbcan.2012.04.008.65. Liu Z.J., Semenza G.L., Zhang H.F. Hypoxia-inducible factor 1 and breast cancer metastasis. J Zhejiang Univ Sci B 2015;16(1):32–43. DOI: 10.1631/jzus.B1400221.Liu Z.J., Semenza G.L., Zhang H.F. Hypoxia-inducible factor 1 and breast cancer metastasis. J Zhejiang Univ Sci B 2015;16(1):32–43. DOI: 10.1631/jzus.B1400221.66. Zonneville J., Safina A., Truskinovsky A.M. et al. TGF-β signaling promotes tumor vasculature by enhancing the pericyte-endothelium association. BMC Cancer 2018;18(1):670. DOI: 10.1186/s12885-018-4587-z.Zonneville J., Safina A., Truskinovsky A.M. et al. TGF-β signaling promotes tumor vasculature by enhancing the pericyte-endothelium association. BMC Cancer 2018;18(1):670. DOI: 10.1186/s12885-018-4587-z.67. Li S., Zhang Q., Zhou L. et al. Inhibitory effects of compound DMBT on hypoxiainduced vasculogenic mimicry in human breast cancer. Biomed Pharmacother 2017;96:982–92. DOI: 10.1016/j.biopha.2017.11.137.Li S., Zhang Q., Zhou L. et al. Inhibitory effects of compound DMBT on hypoxiainduced vasculogenic mimicry in human breast cancer. Biomed Pharmacother 2017;96:982–92. DOI: 10.1016/j.biopha.2017.11.137.68. Zhang J., Zhang J., Xu S. et al. Hypoxiainduced TPM2 methylation is associated with chemoresistance and poor prognosis in breast cancer. Cell Physiol Biochem 2018;45(2):692–705. DOI: 10.1159/000487162.Zhang J., Zhang J., Xu S. et al. Hypoxiainduced TPM2 methylation is associated with chemoresistance and poor prognosis in breast cancer. Cell Physiol Biochem 2018;45(2):692–705. DOI: 10.1159/000487162.69. Bharti R., Dey G., Das A.K., Mandal M. Differential expression of IL-6/IL-6R and MAO-A regulates invasion/angiogenesis in breast cancer. Br J Cancer 2018;118(11):1442–52. DOI: 10.1038/s41416-018-0078-x.Bharti R., Dey G., Das A.K., Mandal M. Differential expression of IL-6/IL-6R and MAO-A regulates invasion/angiogenesis in breast cancer. Br J Cancer 2018;118(11):1442–52. DOI: 10.1038/s41416-018-0078-x.70. Milani M., Venturini S., Bonardi S. et al. Hypoxia-related biological markers as predictors of epirubicin-based treatment responsiveness and resistance in locally advanced breast cancer. Oncotarget 2017;8(45):78870–81. DOI: 10.18632/oncotarget.20239.Milani M., Venturini S., Bonardi S. et al. Hypoxia-related biological markers as predictors of epirubicin-based treatment responsiveness and resistance in locally advanced breast cancer. Oncotarget 2017;8(45):78870–81. DOI: 10.18632/oncotarget.20239.71. Rundqvist H., Johnson R.S. Tumour oxygenation: implications for breast cancer prognosis. J Intern Med 2013;274(2):105–12. DOI: 10.1111/joim.12091.Rundqvist H., Johnson R.S. Tumour oxygenation: implications for breast cancer prognosis. J Intern Med 2013;274(2):105–12. DOI: 10.1111/joim.12091.72. Nie C., Lv H., Bie L. et al. Hypoxiainducible factor 1-alpha expression correlates with response to neoadjuvant chemotherapy in women with breast cancer. Medicine (Baltimore) 2018;97(51):e13551. DOI: 10.1097/MD.0000000000013551.Nie C., Lv H., Bie L. et al. Hypoxiainducible factor 1-alpha expression correlates with response to neoadjuvant chemotherapy in women with breast cancer. Medicine (Baltimore) 2018;97(51):e13551. DOI: 10.1097/MD.0000000000013551.73. Padró M., Louie R.J., Lananna B.V. et al. Genome-independent hypoxic repression of estrogen receptor alpha in breast cancer cells. BMC Cancer 2017;17(1):203. DOI: 10.1186/s12885-017-3140-9.Padró M., Louie R.J., Lananna B.V. et al. Genome-independent hypoxic repression of estrogen receptor alpha in breast cancer cells. BMC Cancer 2017;17(1):203. DOI: 10.1186/s12885-017-3140-9.74. Badowska-Kozakiewicz A., Sobol M., Patera J. Expression of hypoxia-inducible factor 1α in invasive breast cancer with metastasis to lymph nodes: correlation with steroid receptors, HER2 and EPO-R. Adv Clin Exp Med 2016;25(4):741–50. DOI: 10.17219/acem/63143.Badowska-Kozakiewicz A., Sobol M., Patera J. Expression of hypoxia-inducible factor 1α in invasive breast cancer with metastasis to lymph nodes: correlation with steroid receptors, HER2 and EPO-R. Adv Clin Exp Med 2016;25(4):741–50. DOI: 10.17219/acem/63143.