tumorsMalignant tumoursMalignant tumours2224-50572587-6813Rosoncoweb10.18027/2224-5057-2023-13-3-29-36tumors-1166Research ArticleОБЗОРЫ И АНАЛИТИКАREVIEWS AND ANALYSISВозможности де-эскалации неоадъювантной терапии у больных с HER2-позитивным раком молочной железыDe-escalation of neoadjuvant therapy as an option for patients with HER2 positive breast cancerДешкинаТ. И.DeshkinaT.  I.

Татьяна И. Дешкина, к. м. н., врач-онколог, старший научный сотрудник

Москва

Tatiana I. Deshkina, Oncologist, Senior Researcher

Moscow

БолотинаЛ. В.BolotinaL.  V.

Лариса В. Болотина, д. м. н., заведующая отделением химиотерапии

Москва

Larisa V. Bolotina, MD, PhD, DSc, Head of the Chemotherapy Department

Moscow

ГолубевП. В.GolubevP.  V.

Анна Л. Корниецкая, к. м. н., врач-онколог, ведущий научный сотрудник отделения химиотерапии

Москва

Pavel V. Golubev, Graduate Student

Moscow

ГабунияИ. Э.GabuniyaI.  E.

Ирина Э. Габуния, клинический ординатор

Москва

Irina E. Gabunia, Сlinical Resident

Moscow

РубанМ. С.RubanM.  S.

Максим С. Рубан, клинический ординатор

Москва

Maksim S. Ruban, Сlinical Resident

Moscow

ФеденкоА. А.FedenkoA.  A.

Александр А. Феденко, д. м. н., заведующий отделом лекарственного лечения опухолей

Москва

Aleksandr A. Fedenko, MD, PhD, DSc, Head of the Department of Drug Treatment of Tumors

Мoscow

КапринА. Д.KaprinA.  D.

Андрей Д. Каприн, д. м. н., профессор, академик РАН и РАО, главный онколог РФ, директор; генеральный директор

Москва

Andrey D. Kaprin, MD, PhD, DSc, Professor, Academician of the Russian Academy of Sciences, Director;  Director of the National Medical Research Radiological Centre of the Ministry of Health of the Russia, Head of the Department of Oncology and Radiology, V. P. Kharchenko Medical Institute, Medical Faculty

Obninsk; Moscow

МНИОИ им. П.А. Герцена — филиал ФГБУ «НМИЦ радиологии» Минздрава РоссииРоссияP. A. Hertsen Moscow Oncology Research Institute — Branch of the National Medical Research Radiological CentreRussian FederationМНИОИ им. П.А. Герцена — филиал ФГБУ «НМИЦ радиологии» Минздрава России; ФГБУ «НМИЦ радиологии» Минздрава России; ФГАОУ ВО «Российский университет дружбы народов»РоссияP. A. Hertsen Moscow Oncology Research Institute — Branch of the National Medical Research Radiological Centre; National Medical Research Radiological Centre; Peoples’ Friendship University of RussiaRussian Federation2023081120231332936Copyright © Дешкина Т.И., Болотина Л.В., Голубев П.В., Габуния И.Э., Рубан М.С., Феденко А.А., Каприн А.Д., 20232023Дешкина Т.И., Болотина Л.В., Голубев П.В., Габуния И.Э., Рубан М.С., Феденко А.А., Каприн А.Д.Deshkina T.I., Bolotina L.V., Golubev P. ., Gabuniya I.E., Ruban M.S., Fedenko A.A., Kaprin A.D.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.malignanttumors.org/jour/article/view/1166

Возможности де-эскалации неоадъювантной терапии у больных с HER2-Рак молочной железы занимает лидирующее позиции в структуре онкологической заболеваемости и смертности у женщин во всем мире. В каждом пятом случае выявляется гиперэкспрессия HER2/neu, что является неблагоприятным прогностическим маркером и ассоциируется с более агрессивным течением опухолевого процесса. Однако активное внедрение таргетной терапии за последние 20 лет позволило изменить естественную историю этого заболевания. В тоже время общепринятые режимы неоадъювантной химиотерапии в комбинации с таргетной терапией сложно назвать оптимальными в виду их неудовлетворительной переносимости. Очевидно, что существует определенная категория пациенток, не нуждающаяся в назначении столь токсичных схем лечения. В данной обзорной статье мы хотим представить свой взгляд на возможность де-эскалации объема неоадъювантной терапии у больных с HER2-позитивным раком молочной железы.

Breast cancer is the most common female cancer and cause of death from cancer in women worldwide. Overexpression of HER2 / neu, which is an unfavorable predictor associated with a more aggressive course of the disease, is detected in every 5th breast cancer patient. Over the past 20 years, targeted therapy has changed the natural course of breast cancer. However, standard neoadjuvant chemotherapy regimens in combination with targeted therapy are poorly tolerated and, therefore, are considered suboptimal. Evidently, not all patients require such toxic treatment regimens. In this review article, we present our view whether neoadjuvant therapy can be de-escalated in patients with HER2‑positive breast cancer.

рак молочной железынеоадъювантная терапияHER2-позитивный статусде-эскалацияbreast cancerneoadjuvant therapyHER2‑positive statusde-escalationReferencesСостояние онкологической помощи населению России в 2021 г, под редакцией А. Д. Каприна, В. В. Старинского, А. О. Шахзадовой. Москва 2022 г, с. 23–25.Состояние онкологической помощи населению России в 2021 г, под редакцией А. Д. Каприна, В. В. Старинского, А. О. Шахзадовой. Москва 2022 г, с. 23–25.Cronin KA, Harlan LC, Dodd KW, Abrams JS, Ballard-Barbash R. Population-based estimate of the prevalence of HER-2 positive breast cancer tumors for early stage patients in the US. Cancer Invest. 2010 Nov ; 28 (9) : 963–8. doi: 10.3109/07357907.2010.496759. PMID: 20690807 ; PMCID: PMC5094051.Cronin KA, Harlan LC, Dodd KW, Abrams JS, Ballard-Barbash R. Population-based estimate of the prevalence of HER-2 positive breast cancer tumors for early stage patients in the US. Cancer Invest. 2010 Nov ; 28 (9) : 963–8. doi: 10.3109/07357907.2010.496759. PMID: 20690807 ; PMCID: PMC5094051.Slamon, D. J. ; Clark, G. M. ; Wong, S. G. ; Levin, W. J. ; Ullrich, A. ; McGuire, W. L. Human breast cancer : Correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 1987, 235, 177–182.Slamon, D. J. ; Clark, G. M. ; Wong, S. G. ; Levin, W. J. ; Ullrich, A. ; McGuire, W. L. Human breast cancer : Correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 1987, 235, 177–182.Slamon, D. J. ; Leyland-Jones, B. ; Shak, S. ; Fuchs, H. ; Paton, V. ; Bajamonde, A. ; Fleming, T. ; Eiermann, W. ; Wolter, J. ; Pegram, M. ; et al. Use of Chemotherapy plus a Monoclonal Antibody against HER2 for Metastatic Breast Cancer That Overexpresses HER2. New Engl. J. Med. 2001, 344, 783–792.Slamon, D. J. ; Leyland-Jones, B. ; Shak, S. ; Fuchs, H. ; Paton, V. ; Bajamonde, A. ; Fleming, T. ; Eiermann, W. ; Wolter, J. ; Pegram, M. ; et al. Use of Chemotherapy plus a Monoclonal Antibody against HER2 for Metastatic Breast Cancer That Overexpresses HER2. New Engl. J. Med. 2001, 344, 783–792.Клинические рекомендации «Рак молочной железы» Общероссийский национальный союз «Ассоциация онкологов России» • Общероссийская общественная организация «Российское общество клинической онкологии» • Общероссийская общественная организация «Российское общество онкомаммологов», 2021 г.Клинические рекомендации «Рак молочной железы» Общероссийский национальный союз «Ассоциация онкологов России» • Общероссийская общественная организация «Российское общество клинической онкологии» • Общероссийская общественная организация «Российское общество онкомаммологов», 2021 г.Тюляндин С. А., Жукова Л. Г., Королева И. А., Пароконная А. А., Семиглазова Т. Ю., Стенина М. Б. и соавт. Практические рекомендации по лекарственному лечению рака молочной железы. Злокачественные опухоли : Практические рекомендации RUSSCO #3s2, 2021 (том 11). 09.Тюляндин С. А., Жукова Л. Г., Королева И. А., Пароконная А. А., Семиглазова Т. Ю., Стенина М. Б. и соавт. Практические рекомендации по лекарственному лечению рака молочной железы. Злокачественные опухоли : Практические рекомендации RUSSCO #3s2, 2021 (том 11). 09.Cortazar P, Zhang L, Untch M, et al. Pathological complete response and long-term clinical benefit in breast cancer : the CTNeoBC pooled analysis [published correction appears in Lancet. 2019 Mar 9 ; 393 (10175) : 986]. Lancet. 2014 ; 384 (9938) : 164–172. doi: 10.1016/S0140-6736(13)62422-8.Cortazar P, Zhang L, Untch M, et al. Pathological complete response and long-term clinical benefit in breast cancer : the CTNeoBC pooled analysis [published correction appears in Lancet. 2019 Mar 9 ; 393 (10175) : 986]. Lancet. 2014 ; 384 (9938) : 164–172. doi: 10.1016/S0140-6736(13)62422-8.von Minckwitz G, Untch M, Blohmer JU, 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 (15) : 1796–1804. doi: 10.1200/JCO. 2011.38.8595.von Minckwitz G, Untch M, Blohmer JU, 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 (15) : 1796–1804. doi: 10.1200/JCO. 2011.38.8595.Untch M, Fasching PA, Konecny GE, et al. Pathologic complete response after neoadjuvant chemotherapy plus trastuzumab predicts favorable survival in human epidermal growth factor receptor 2-overexpressing breast cancer : results from the TECHNO trial of the AGO and GBG study groups. J Clin Oncol. 2011 ; 29 (25) : 3351–3357. doi: 10.1200/ JCO.2010.31.4930.Untch M, Fasching PA, Konecny GE, et al. Pathologic complete response after neoadjuvant chemotherapy plus trastuzumab predicts favorable survival in human epidermal growth factor receptor 2-overexpressing breast cancer : results from the TECHNO trial of the AGO and GBG study groups. J Clin Oncol. 2011 ; 29 (25) : 3351–3357. doi: 10.1200/ JCO.2010.31.4930.Broglio KR, Quintana M, Foster M, et al. Association of Pathologic Complete Response to Neoadjuvant Therapy in HER2-Positive Breast Cancer With Long-Term Outcomes : A Meta-Analysis. JAMA Oncol. 2016 ; 2 (6) : 751–760. doi: 10.1001/jamaoncol. 2015.6113.Broglio KR, Quintana M, Foster M, et al. Association of Pathologic Complete Response to Neoadjuvant Therapy in HER2-Positive Breast Cancer With Long-Term Outcomes : A Meta-Analysis. JAMA Oncol. 2016 ; 2 (6) : 751–760. doi: 10.1001/jamaoncol. 2015.6113.von Minckwitz G, Huang CS, Mano MS, et al. Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer. N Engl J Med. 2019 ; 380 (7) : 617–628. doi: 10.1056/NEJMoa1814017.von Minckwitz G, Huang CS, Mano MS, et al. Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer. N Engl J Med. 2019 ; 380 (7) : 617–628. doi: 10.1056/NEJMoa1814017.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 [published correction appears in Lancet Oncol. 2018 Dec ; 19 (12) : e667]. Lancet Oncol. 2014 ; 15 (6) : 640–647. doi: 10.1016/S1470-2045(14)70080-4.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 [published correction appears in Lancet Oncol. 2018 Dec ; 19 (12) : e667]. Lancet Oncol. 2014 ; 15 (6) : 640–647. doi: 10.1016/S1470-2045(14)70080-4.Cortazar P, Zhang L, Untch M, et al. Pathological complete response and long-term clinical benefit in breast cancer : the CTNeoBC pooled analysis [published correction appears in Lancet. 2019 Mar 9 ; 393 (10175) : 986]. Lancet. 2014 ; 384 (9938) : 164–172. doi: 10.1016/S0140-6736(13)62422-8.Cortazar P, Zhang L, Untch M, et al. Pathological complete response and long-term clinical benefit in breast cancer : the CTNeoBC pooled analysis [published correction appears in Lancet. 2019 Mar 9 ; 393 (10175) : 986]. Lancet. 2014 ; 384 (9938) : 164–172. doi: 10.1016/S0140-6736(13)62422-8.Gianni L, Pienkowski T, Im YH, et al. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere) : a randomised multicentre, open-label, phase 2 trial. Lancet Oncol. 2012 ; 13 (1) : 25–32. doi: 10.1016/S1470-2045(11)70336-9.Gianni L, Pienkowski T, Im YH, et al. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere) : a randomised multicentre, open-label, phase 2 trial. Lancet Oncol. 2012 ; 13 (1) : 25–32. doi: 10.1016/S1470-2045(11)70336-9.Untch M, Jackisch C, Schneeweiss A, et al. NAB-Paclitaxel Improves Disease-Free Survival in Early Breast Cancer : GBG 69-GeparSepto. J Clin Oncol. 2019 ; 37 (25) : 2226–2234. doi: 10.1200/JCO. 18.01842.Untch M, Jackisch C, Schneeweiss A, et al. NAB-Paclitaxel Improves Disease-Free Survival in Early Breast Cancer : GBG 69-GeparSepto. J Clin Oncol. 2019 ; 37 (25) : 2226–2234. doi: 10.1200/JCO. 18.01842.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 (9) : 2278–2284. doi: 10.1093/ annonc/mdt182.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 (9) : 2278–2284. doi: 10.1093/ annonc/mdt182.van Ramshorst MS, van der Voort A, van Werkhoven ED, et al. Neoadjuvant chemotherapy with or without anthracyclines in the presence of dual HER2 blockade for HER2-positive breast cancer (TRAIN-2) : a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2018 ; 19 (12) : 1630–1640. doi: 10.1016/S1470-2045(18)30570-9.van Ramshorst MS, van der Voort A, van Werkhoven ED, et al. Neoadjuvant chemotherapy with or without anthracyclines in the presence of dual HER2 blockade for HER2-positive breast cancer (TRAIN-2) : a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2018 ; 19 (12) : 1630–1640. doi: 10.1016/S1470-2045(18)30570-9.Rimawi MF, Mayer IA, Forero A, et al. Multicenter phase II study of neoadjuvant lapatinib and trastuzumab with hormonal therapy and without chemotherapy in patients with human epidermal growth factor receptor 2-overexpressing breast cancer : TBCRC 006. J Clin Oncol. 2013 ; 31 (14) : 1726–1731. doi: 10.1200/JCO. 2012.44.8027.Rimawi MF, Mayer IA, Forero A, et al. Multicenter phase II study of neoadjuvant lapatinib and trastuzumab with hormonal therapy and without chemotherapy in patients with human epidermal growth factor receptor 2-overexpressing breast cancer : TBCRC 006. J Clin Oncol. 2013 ; 31 (14) : 1726–1731. doi: 10.1200/JCO. 2012.44.8027.Rimawi MF, Niravath P, Wang T, Rexer BN, Forero A, et al. ; Translational Breast Cancer Research Consortium. TBCRC023 : A Randomized Phase II Neoadjuvant Trial of Lapatinib Plus Trastuzumab Without Chemotherapy for 12 versus 24 Weeks in Patients with HER2-Positive Breast Cancer. Clin Cancer Res. 2020 Feb 15 ; 26 (4) : 821–827. doi: 10.1158/1078-0432.CCR-19-0851. Epub 2019 Oct 29. PMID: 31662331.Rimawi MF, Niravath P, Wang T, Rexer BN, Forero A, et al. ; Translational Breast Cancer Research Consortium. TBCRC023 : A Randomized Phase II Neoadjuvant Trial of Lapatinib Plus Trastuzumab Without Chemotherapy for 12 versus 24 Weeks in Patients with HER2-Positive Breast Cancer. Clin Cancer Res. 2020 Feb 15 ; 26 (4) : 821–827. doi: 10.1158/1078-0432.CCR-19-0851. Epub 2019 Oct 29. PMID: 31662331.Llombart-Cussac A, Cortés J, Paré L, Galván P, Bermejo B, Martínez N, Vidal M, Pernas S, López R, Muñoz M, Nuciforo P, Morales S, Oliveira M, de la Peña L, Peláez A, Prat A. HER2-enriched subtype as a predictor of pathological complete response following trastuzumab and lapatinib without chemotherapy in early-stage HER2-positive breast cancer (PAMELA) : an open-label, single-group, multicentre, phase 2 trial. Lancet Oncol. 2017 Apr ; 18 (4) : 545–554. doi: 10.1016/S1470-2045(17)30021-9. Epub 2017 Feb 24. PMID: 28238593.Llombart-Cussac A, Cortés J, Paré L, Galván P, Bermejo B, Martínez N, Vidal M, Pernas S, López R, Muñoz M, Nuciforo P, Morales S, Oliveira M, de la Peña L, Peláez A, Prat A. HER2-enriched subtype as a predictor of pathological complete response following trastuzumab and lapatinib without chemotherapy in early-stage HER2-positive breast cancer (PAMELA) : an open-label, single-group, multicentre, phase 2 trial. Lancet Oncol. 2017 Apr ; 18 (4) : 545–554. doi: 10.1016/S1470-2045(17)30021-9. Epub 2017 Feb 24. PMID: 28238593.Guarneri V, Dieci MV, Bisagni G, et al. De-escalated therapy for HR + / HER2 + breast cancer patients with Ki67 response after 2-week letrozole : results of the PerELISA neoadjuvant study. Ann Oncol. 2019 ; 30 (6) : 921–926. doi: 10.1093/annonc/mdz055.Guarneri V, Dieci MV, Bisagni G, et al. De-escalated therapy for HR + / HER2 + breast cancer patients with Ki67 response after 2-week letrozole : results of the PerELISA neoadjuvant study. Ann Oncol. 2019 ; 30 (6) : 921–926. doi: 10.1093/annonc/mdz055.Gianni L, Bisagni G, Colleoni M, Del Mastro L, Zamagni C, Mansutti M, Zambetti M, Frassoldati A, De Fato R, Valagussa P, Viale G. Neoadjuvant treatment with trastuzumab and pertuzumab plus palbociclib and fulvestrant in HER2-positive, ER-positive breast cancer (NA-PHER2) : an exploratory, open-label, phase 2 study. Lancet Oncol. 2018 Feb ; 19 (2) : 249–256. doi: 10.1016/S1470-2045(18)30001-9. Epub 2018 Jan 8. PMID: 29326029.Gianni L, Bisagni G, Colleoni M, Del Mastro L, Zamagni C, Mansutti M, Zambetti M, Frassoldati A, De Fato R, Valagussa P, Viale G. Neoadjuvant treatment with trastuzumab and pertuzumab plus palbociclib and fulvestrant in HER2-positive, ER-positive breast cancer (NA-PHER2) : an exploratory, open-label, phase 2 study. Lancet Oncol. 2018 Feb ; 19 (2) : 249–256. doi: 10.1016/S1470-2045(18)30001-9. Epub 2018 Jan 8. PMID: 29326029.Hurvitz SA, Martin M, Symmans WF, et al. Neoadjuvant trastuzumab, pertuzumab, and chemotherapy versus trastuzumab emtansine plus pertuzumab in patients with HER2-positive breast cancer (KRISTINE) : a randomised, open-label, multicentre, phase 3 trial. Lancet Oncol. 2018 ; 19 (1) : 115–126. doi: 10.1016/S1470-2045(17) 30716–7.Hurvitz SA, Martin M, Symmans WF, et al. Neoadjuvant trastuzumab, pertuzumab, and chemotherapy versus trastuzumab emtansine plus pertuzumab in patients with HER2-positive breast cancer (KRISTINE) : a randomised, open-label, multicentre, phase 3 trial. Lancet Oncol. 2018 ; 19 (1) : 115–126. doi: 10.1016/S1470-2045(17) 30716–7.Hurvitz SA, Martin M, Jung KH, et al. Neoadjuvant Trastuzumab Emtansine and Pertuzumab in Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer : Three-Year Outcomes From the Phase III KRISTINE Study. J Clin Oncol. 2019 ; 37 (25) : 2206–2216. doi: 10.1200/JCO. 19.00882.Hurvitz SA, Martin M, Jung KH, et al. Neoadjuvant Trastuzumab Emtansine and Pertuzumab in Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer : Three-Year Outcomes From the Phase III KRISTINE Study. J Clin Oncol. 2019 ; 37 (25) : 2206–2216. doi: 10.1200/JCO. 19.00882.Nitz UA, Gluz O, Christgen M, et al. De-escalation strategies in HER2-positive early breast cancer (EBC) : final analysis of the WSG-ADAPT HER2 +/HR- phase II trial : efficacy, safety, and predictive markers for 12 weeks of neoadjuvant dual blockade with trastuzumab and pertuzumab ± weekly paclitaxel [published correction appears in Ann Oncol. 2022 Mar ; 33 (3) : 355]. Ann Oncol. 2017 ; 28 (11) : 2768–2772. doi: 10.1093/annonc/mdx494.Nitz UA, Gluz O, Christgen M, et al. De-escalation strategies in HER2-positive early breast cancer (EBC) : final analysis of the WSG-ADAPT HER2 +/HR- phase II trial : efficacy, safety, and predictive markers for 12 weeks of neoadjuvant dual blockade with trastuzumab and pertuzumab ± weekly paclitaxel [published correction appears in Ann Oncol. 2022 Mar ; 33 (3) : 355]. Ann Oncol. 2017 ; 28 (11) : 2768–2772. doi: 10.1093/annonc/mdx494.Nitz U, Gluz O, Graeser M, et al. De-escalated neoadjuvant pertuzumab plus trastuzumab therapy with or without weekly paclitaxel in HER2-positive, hormone receptor-negative, early breast cancer (WSG-ADAPT-HER2 + / HR-) : survival outcomes from a multicentre, open-label, randomised, phase 2 trial. Lancet Oncol. 2022 ; 23 (5) : 625–635. doi: 10.1016/S1470-2045(22)00159-0.Nitz U, Gluz O, Graeser M, et al. De-escalated neoadjuvant pertuzumab plus trastuzumab therapy with or without weekly paclitaxel in HER2-positive, hormone receptor-negative, early breast cancer (WSG-ADAPT-HER2 + / HR-) : survival outcomes from a multicentre, open-label, randomised, phase 2 trial. Lancet Oncol. 2022 ; 23 (5) : 625–635. doi: 10.1016/S1470-2045(22)00159-0.Pérez-García JM, Gebhart G, Ruiz Borrego M, et al. Chemotherapy de-escalation using an 18F-FDG-PET-based pathological response-adapted strategy in patients with HER2-positive early breast cancer (PHERGain) : a multicentre, randomised, open-label, non-comparative, phase 2 trial. Lancet Oncol. 2021 ; 22 (6) : 858–871. doi: 10.1016/S1470- 2045 (21) 00122-4.Pérez-García JM, Gebhart G, Ruiz Borrego M, et al. Chemotherapy de-escalation using an 18F-FDG-PET-based pathological response-adapted strategy in patients with HER2-positive early breast cancer (PHERGain) : a multicentre, randomised, open-label, non-comparative, phase 2 trial. Lancet Oncol. 2021 ; 22 (6) : 858–871. doi: 10.1016/S1470- 2045 (21) 00122-4.

The authors declare that there are no conflicts of interest present.