HER2 cluster amplification as a factor of an especial sensitivity for anti-HER2 neoadjuvant therapy with biosimilar of trastuzumab in Russian women with breast cancer stage II-III.

Irina Vladimirovna Kolyadina Federal State Budgetary Institution “N.N. Blokhin National Medical Research Center of Oncology”оf the Ministry of Health of the Russian Federation, Moscow, Russian Federation info_outline Irina Vladimirovna Kolyadina, Olga Gordeeva, Inna Ganshina, Larisa Zavalishina, Yulia Andreeva, Georgy Frank, Nikita Savelov, Elena Tuzova, Lyudmila Zhukova, Yana Vishnevskaya, Aleksandr Arkhipov, Vahan Yurikovich Bokhian, Dmitry Komov, Irina Poddubnaya

Authors Irina Vladimirovna Kolyadina Federal State Budgetary Institution “N.N. Blokhin National Medical Research Center of Oncology”оf the Ministry of Health of the Russian Federation, Moscow, Russian Federation info_outline Irina Vladimirovna Kolyadina, Olga Gordeeva, Inna Ganshina, Larisa Zavalishina, Yulia Andreeva, Georgy Frank, Nikita Savelov, Elena Tuzova, Lyudmila Zhukova, Yana Vishnevskaya, Aleksandr Arkhipov, Vahan Yurikovich Bokhian, Dmitry Komov, Irina Poddubnaya Organizations Federal State Budgetary Institution “N.N. Blokhin National Medical Research Center of Oncology”оf the Ministry of Health of the Russian Federation, Moscow, Russian Federation, Russian Medical Academy of Continuous Professional Education, Moscow, Russian Federation, Moscow State Oncology Hospital #62, Moscow, Russian Federation, The Loginov Moscow Clinical Scientific Centre MHD, Moscow, Russian Federation, Federal State Autonomus Institution "Treatment and Rehabilitation Centre" of the Ministry of Health of Russian Federation, Moscow, Russian Federation Abstract Disclosures Research Funding Other Background: Effect of neoadjuvant chemotherapy (NACT) is extremely important for patients with HER2-positive breast cancer stage II-III as it correlates with long-term outcomes. However, predictive factors for achieving complete pathologic response (pCR) remain unclear. Aim of the study: Assess an impact of clinical, morphological and genetic factors on pCR achievement in patients with HER2-positive breast cancer stage II-III treated by biosimilar of trastuzumab. Methods: We studied treatment results in 73 patients with HER2-positive breast cancer (BC) stage II-III (aged 29-71, median – 51 years), treated with NACT with anti-HER2 therapy and radical surgery in “N.N. Blokhin National Medical Research Center of Oncology”оf the Ministry of Health of the Russian Federation in 2015-2018. After radical surgery pathologic response was assessed. Initially operable tumors were observed in 45,2% patients, locally advanced - in 53,4%. Luminal HER2-positive BC was diagnosed in 41,1%, non-luminal HER2-positive in 58,9%. Ki67 was high (≥ 20%) in 91,5%. NACT included anthracycline and non-antracycline regimens with addition of biosimilar of trastuzumab ± pertuzumab. Radical mastectomy was performed in 78,8% patients, 21,2% had breast-conserving surgery. We studied biopsies obtained before the start of treatment in all women, HER2 amplification was detected by HER2 IQFISH pharmDx (DAKO) kit in accordance with ASCO/CAP 2018 guidelines. In 87,1% HER2+ status was defined as ASCO/CAP 2018 category 1; cluster amplification was detected in 30,1% patients. We analyzed the rate of bpCR и tpCR achievement depending on clinical, pathological data and amplification of HER2. Results: Pathologic complete response in primary tumor (bpCR) was achieved in 57,4%, both in primary tumor and lymph nodes (tpCR) – in 48,9% patients; bpCR achievement depended on age, NACT regimen, addition of pertuzumab and HER2 copy number ( < 0,05). The highest rate of bpCR was noted in women aged 50 and older (71,9%, p = 0,026); in patients received TCH±Р regimen (80,0%, p = 0,045); with addition of pertuzumab (88,9%, p = 0,049); and if cluster amplification was detected (81%, p = 0,013). Cluster amplification was the only one significant predictive factor for achieving tpCR: with cluster amplification - 68,8%, without - 38,7% (p = 0,049). Conclusions: Cluster amplification of HER2 is the most significant factor of especial sensitivity for NACT with biosimilar of trastuzumab in HER2-positive BC stage II-III.