Search for new prognostic and predictive markers of sensitivity to endocrine therapy, chemotherapy and immunotherapy of breast cancer


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Abstract

The decrease in mortality from breast cancer (BC) observed in recent years in Europe, North America and Russia is largely associated with the wider use of neoadjuvant and adjuvant systemic therapy, including endocrine therapy (ET), chemotherapy (CT), targeted therapy and immunotherapy. Planning systemic therapy based only on stage, age and pathomorphology (histological type and grade) appears to be insufficient. More accurate prognostic and predictive markers of sensitivity to current and new types of drugs are required. Recently, it is believed that the ER expression from 1 to 10% justifies the appointment of ET. At the EBCC-12 conference, the use of adjuvant chemotherapy was declared inappropriate for the majority of patients with luminal A-subtype breast cancer and metastatic lymph nodes. At the same time, it is known that a significant number of patients with ER+ BC develop late (delayed) relapse 5 or more years after surgery. How to prevent the development of endocrine therapy (ET) resistance? Many markers of resistance are already known. CDK 4/6 inhibitors (palbociclib, abemacyclib, ribociclib) are the most studied. Their high efficiency has been proven in metastatic ER+ breast cancer. An interim assessment of the adjuvant use of CDK 4/6 inhibitors showed contradicting results: significant improvement in 2-year DFS in the MonarchE trial and negative results in the PALLAS trial. The MonarchE trial enrolled patients with resectable high-risk breast cancer. In addition, the mean follow-up period (15 to 28 months) is insufficient for a final conclusion on the effectiveness of adjuvant treatment. In women with residual invasive HER2- positive breast cancer after neoadjuvant systemic therapy (NAST), adjuvant therapy with trastuzumab-emtansine (TD-M) significantly reduces the risk of recurrence. Patients with residual triple negative breast cancer (TNBC) benefit from post-neoadjuvant therapy with capecitabine. Prognostic biomarkers (TILs, PD1, PDL-1 ligand) are the main regulators of the immune response to a growing tumor. In recent years, monoclonal antibodies blocking immune checkpoint proteins have been developed. In breast cancer, the most studied drug is atezolizumab (anti-PDL1 antibody). In the Impassion-130 study, the use of atezolizumab (PDL1 ligand inhibitor) in combination with nab-paclitaxel in metastatic TNBC increased 2-year progression-free survival (PDL1 positive arm). The NeoTrip PD-L1 trial showed that the combination of atezolizumab, carboplatin, and nab-paclitaxel increased the rate of reaching pCR by 10% or more.

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About the authors

V. F Semiglazov

N.N. Petrov National Medical Research Center of Oncology; North-Western State Medical University n.a. I. I. Mechnikov

Email: vsemiglazov@mail.ru
St. Petersburg, Russia

R. S Pesotsky

N.N. Petrov National Medical Research Center of Oncology

St. Petersburg, Russia

A. I Tseluiko

N.N. Petrov National Medical Research Center of Oncology

St. Petersburg, Russia

M. A Dzhelyalova

N.N. Petrov National Medical Research Center of Oncology

St. Petersburg, Russia

V. S Apollonova

N.N. Petrov National Medical Research Center of Oncology

St. Petersburg, Russia

V. V Semiglazov

N.N. Petrov National Medical Research Center of Oncology; Pavlov University

St. Petersburg, Russia

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