Neoadjuvant endocrine therapy of breast cancer: history and modern views of the problem
Summary. The purpose of the review was to study the history of neoadjuvant hormone therapy, its effectiveness in comparison with neoadjuvant chemotherapy, and the possibility and safety of its use in patients with luminal B breast cancer. As can be seen from the analysis of 51 foreign sources (one of them an English-language textbook translated into Ukrainian) and 5 domestic publications, the history of adjuvant therapy for breast cancer dates back to 1958, when P. Carbone’s team at the US National Cancer Institute began research in В-01, in which the effect of additional alkylating drug thiotepa in breast cancer was evaluated. M. De Lena has been studying the possibilities of chemotherapy in the preoperative mode since the 70’s of the last century. In 1990, G. Bonadonna and his co-authors published the results of the first non-randomized clinical trial, which showed that 81% of women receiving neoadjuvant chemotherapy managed to perform organ-sparing surgeries. Іn 1988, B. Fisher began a clinical study of B18 with the participation of 1523 patients, 747 of whom received 4 courses of doxorubicin with cyclophosphamide before surgery, the rest received 4 courses of chemotherapy after surgery. Lumpectomy was performed in 67% of patients in the neoadjuvant treatment group versus 60% in the group without preoperative exposure. In both groups, patients older than 50 years continued tamoxifen treatment (in the neoadjuvant treatment group — after surgery). After organ-sparing operations, all patients received radiation therapy. One of the conclusions of the study, which still has its practical significance, indicates a significant increase in the chances of organ-preserving treatment as a result of neoadjuvant treatment. Subsequent studies of neoadjuvant chemotherapy have shown better treatment efficacy in hormone receptor-negative patients compared to hormone-dependent patients. In 2001, for the first time, J.C. Gazet and colleagues published the results of a study in which the overall response rate to neoadjuvant treatment in patients with hormone-dependent breast tumors was 60% in the MMM chemotherapy group, 58.3% in the goserelin group, and 58.3% in the formestane group — 35%. Further studies of neoadjuvant hormone therapy were conducted primarily in postmenopausal women with hormone-dependent cancer. They demonstrated almost the same effectiveness as chemotherapy, but with a significantly better toxicity profile, which allowed to preserve the quality of life of patients, or at least to minimize the impact of treatment on this indicator. At the same time, the possibilities of using organ-sparing surgery practically do not differ depending on the use of chemotherapy or endocrinotherapy. In the ACOSOG-Z1031 study, which was conducted from 2006 to 2019, the Ki-67 proliferation index was used for the first time as a prognostic primary marker of the effectiveness of endocrine therapy, which demonstrably responds to treatment already after 2 weeks of taking a hormonal drug. The results of the study, like all previous ones, indicate the importance of studying the response to treatment in predicting the further course of the disease and contribute to the choice of additional treatment. Today, a significant number of clinical studies of neoadjuvant endocrine therapy are being conducted in the world, both with the use of exclusively endocrine agents and in combination with modern drugs of targeted, immune, cytostatic action, antitumor vaccines, sugar-lowering drugs, etc. Studying the effectiveness of neoadjuvant hormone therapy for breast cancer is a topical topic of today’s oncology science, which is actively studied through clinical research.
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