Efficacy analysis of neoadjuvant chemotherapy regimens in patients with HER2/neunegative locally advanced breast cancer: A nonrandomized comparative study

Background. In present times, no unified standard for selecting a neoadjuvant chemotherapy regimen for breast cancer exists. Although the efficacy of neoadjuvant chemotherapy has been confirmed by numerous clinical studies, tumor drug resistance develops in some cases, which reduces the expected effect of neoadjuvant chemotherapy. Currently, drug resistance to neoadjuvant chemotherapy is a major cause of treatment failure and one of the most challenging problems in the therapy of metastatic and locally advanced breast cancer. Objectives. To evaluate the efficacy of neoadjuvant chemotherapy in HER2/neu-negative locally advanced breast cancer. Methods. A nonrandomized comparative study involving 187 women with a verified diagnosis of HER2/neu-negative (human epidermal growth factor receptor) primary locally advanced (T3N2, T4N0-3) breast cancer was conducted. From 2020 to 2024, these women (mean age of 53.6 ± 7.8 years) underwent therapy, follow-up, and examination in the Crimean Republican Oncological Clinical Dispensary named after V.M. Efetov, Republic of Crimea. At the first stage of neoadjuvant chemotherapy, all patients received a combination of doxorubicin and cyclophosphamide intravenously once every 21 days within four courses; the effect was evaluated. At the next stage, taking into account the immunohistochemical subtype and prescribed cytostatics, the studied cohort of patients was divided into subgroups. Patients with luminal breast cancer (n = 130) received standard (175 mg/m² once every 21 days within four courses — 96 patients) and dose-intensive (paclitaxel 80 mg/m² once a week, 12 administrations — 34 patients) chemotherapies. Patients with triple-negative breast cancer (n = 57) received standard (paclitaxel 175 mg/m² once every 21 days within four courses — 42 patients) and dose-intensive (paclitaxel 80 mg/m² in combination with carboplatin AUC2 (Area under Curve) once a week, 12 administrations — 15 patients) chemotherapies. The results of neoadjuvant chemotherapy were analyzed by calculating the overall objective response rate and tumor pathologic complete response. Statistical analysis was performed using Microsoft Office Excel 2007 (Microsoft, USA), IBM SPSS Statistics, version 23.0 (IBM, USA), and both parametric and nonparametric statistical methods. To analyze the differences in two independent groups, Pearson’s χ² test or Fisher’s exact test (for comparison of very small samples) were used. Differences were considered statistically significant at p ≤ 0.05. Results. During neoadjuvant chemotherapy of HER2/neu-negative locally advanced luminal breast cancer, weekly administration of taxanes after anthracycline therapy does not statistically significantly increase the overall objective response rate and tumor pathologic complete response. The detection rate of resistant forms of locally advanced breast cancer affected by ongoing taxane therapy (paclitaxel 175 mg/m² once every 21 days) is higher in comparison with anthracycline therapy (p = 0.005). Weekly administration of taxanes in combination with platinum-based drugs after anthracycline therapy in locally advanced triple-negative breast cancer does not significantly increase the overall objective response rate and tumor pathologic complete response. The detection rate of resistant forms of locally advanced breast cancer affected by ongoing taxane therapy (paclitaxel 175 mg/m² once every 21 days within 4 courses) is statistically significantly higher compared to neoadjuvant chemotherapy based on anthracycline cytostatics (p = 0.02). Conclusion. The applied regimens of neoadjuvant chemotherapy are characterized by a high incidence of post-cytotoxic complications in the studied subgroups. In the group of triple-negative breast cancer, the combination of weekly paclitaxel and carboplatin administrations is accompanied by marked asthenization. In this regard, priority at the beginning of treatment should be given to anthracycline antitumor drugs.

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