Journal of Modern OncologyJournal of Modern Oncology1815-14341815-1442LLC Obyedinennaya Redaktsiya10004610.26442/18151434.2021.4.201297Research ArticleFeatures of response to modern neoadjuvant chemotherapy with dual anti-HER2 blockade (trastuzumab and pertuzumab) in the patients with HER2-positive breast cancer stage II–IIIMorozovDmitriy A.<p>Graduate Student</p>emulator2008@rambler.ruKolyadinaIrina V.<p>D. Sci. (Med.), Prof.</p>irinakolyadina@yandex.ruhttps://orcid.org/0000-0002-1124-6802PoddubnayaIrina V.<p>D. Sci. (Med.), Prof., Acad. RAS</p>ivprectorat@inbox.ruhttps://orcid.org/0000-0002-0995-1801GanshinaInna P.<p>Cand. Sci. (Med.)</p>ganshinainna77@mail.ruhttps://orcid.org/0000-0002-0105-9376KhokhlovaSvetlana V.<p>D. Sci. (Med.)</p>svkhokhlova@mail.ruKоmetovaVlada V.<p>Cand. Sci. (Med.)</p>vladakometova@gmail.comhttps://orcid.org/0000-0001-9666-6875RodionovValery V.<p>D. Sci. (Med.)</p>dr.valery.rodionov@gmail.comhttps://orcid.org/0000-0003-0096-7126Russian Medical Academy of Continuous Professional EducationKulakov National Medical Research Center for Obstetrics, Gynecology and PerinatologyBlokhin National Medical Research Center of Oncology151220212346036090102202201022022Copyright © 2021, Consilium Medicum2021<p><strong>Background. </strong>Neoadjuvant chemotherapy (NACT) with dual anti-HER2 blockade has become a priority in the treatment of patients with HER2+ breast cancer (BC) stages IIIII. However, the question of the accordance of various systems for assessing tumor response to NACT, as well as identifying predictor factors for achieving a complete pathomorphological response (pCR) in HER2+ BC remains open.</p>
<p><strong>Aim. </strong>To assess the accordance of various systems for assessing tumor response to neoadjuvant chemotherapy (NACT) in patients with HER2+ BC and to identify predictor factors for achieving pCR and residual cancer burden.</p>
<p><strong>Materials and methods. </strong>The study included 49 women with HER2+ BC stage IIIII, who underwent NACT with anti-HER2 blockade, followed by surgical treatment and morphological analysis of the results. The median age of the patients was 47 years; 91.8% had tumor size T2, N+ status 71.4%; tumor grade G3 73.5%, luminal and non-luminal HER2+ subtype 44.9 and 55.1% of patients, respectively. Ki6730% was observed in 93.9% of cases, the level of TILs in the tumor was 10%, 1020% and 20% in 38.1, 9.5 and 52.4% of cases, respectively. The patients received combinations of anthracyclines and taxanes or the anthracycline-free regimen of docetaxel + carboplatin; 87.8% of patients received a dual blockade of trastuzumab + pertuzumab, and 12.2% trastuzumab. After the end of NACT, all patients underwent a radical surgery (mastectomy or breast-conserving) with an assessment of the pathomorphological response, the pathomorphological stage of ypTN, and the residual cancer burden according to the RCB system.</p>
<p><strong>Results. </strong>The rate of complete pathomorphological response (tpCR/RCB-0/ypT0N0) in HER2+ BC was 61.2%; significant predictors of achieving tpCR were only 3 factors: primary operable BC stages (T13N01) the rate of tpCR was 71.4%, the level of TILs20% the proportion of tpCR reached 95.5%, and the dual anti-HER2 therapy (trastuzumab + pertuzumab) tpCR was 65.1%. Residual tumor was presented by classes RCB-I, RCB-II, RCB-III in 10.2, 24.5, 4.1%. The RCB-I class included of patients with a residual tumor less than 1.0 cm in the absence of regional lymph node involvement (80% of cases); class RCB-II was represented by the presence of a residual tumor less than 2.0 cm in combination with the absence or presence of residual metastases in 13 lymph nodes (83.4%), and class RCB-III was presented the residual tumors 2.0 cm and N12 status in 100% of cases (<em>p</em>0.0001).</p>
<p><strong>Conclusion. </strong>Modern NACT with dual anti-HER2 blockade (trastuzumab + pertuzumab) are highly effective the rate of tpCR is 61.2%, and in the presence of high TILs20% reaches 95.5%. Residual tumor in most cases was presented by class RCB-I or RCB-II, only 4% of patients had massive residual tumor load (class RCB-III).</p>HER2+ breast cancer stage II–IIIneoadjuvant chemotherapydual anti-HER2 blockade (trastuzumab + pertuzumab)pCRRCBresidual pathomorphological stage ypTNTILspredictor factors for achieving pCRHER2-положительный рак молочной железы II–III стадиинеоадъювантная химиотерапиядвойная анти-HER2-блокада (трастузумаб + пертузумаб)pCRRCBостаточная патоморфологическая стадия ypTNTILsфакторы-предикторы достижения pCR[Burstein HJ, Curigliano G, Thürlimann B, et al. Customizing local and systemic therapies for women with early breast cancer: the St. Gallen International Consensus Guidelines for treatment of early breast cancer 2021. Ann Oncol. 2021;32(10):1216-35. 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