ABSTRACT
BACKGROUND: Conventionally, breast cancer (BC) prognosis and prediction of response to therapy are based on TNM staging, histological and molecular subtype, as well as genetic alterations. The role of various epigenetic factors has been elucidated in carcinogenesis. However, it is still unknown to what extent miRNAs affect the response to neoadjuvant chemotherapy (NACT). This pilot study is focused on evaluating the role of miR-34a, miR-124a, miR-155, miR-137 and miR-373 in response to NACT. METHODS: That was a prospective study enrolling 34 patients with histologically confirmed BC of II-III stages. The median age of patients was 53 (47-59.8) years old, 70.6% of whom were HR-positive. MiRs levels were measured in the primary tumor before and after NACT. The response to therapy was assessed after surgery using the Miller-Payne scoring system. To establish the role of miRs in modulating response to NACT the Cox model was applied for analysis. RESULTS: BC demonstrated a great variability of miRs expression before and after NACT with no strong links to tumor stage and molecular subtype. Only miR-124a and miR-373 demonstrated differential expression between malignant and normal breast tissues before and after therapy though these distinctions did not impact response to NACT. Besides miR-124a and miR-137 levels after NACT were found to be dependent on HR status. While miR-124a levels increased (p = 0.021) in the tumor tissue, the expression of miR-137 was downregulated (p = 0.041) after NACT in HR positive BC. CONCLUSIONS: The study revealed differences in miR-124a and miR-373 expression after NACT in primary BC tissues. Although miRs levels did not impact the response to NACT, we found miR-124a and miR-137 levels to be related to hormonal sensitivity of BC.
ABSTRACT
PURPOSE: To evaluate the efficacy of neoadjuvant chemotherapy in combination with regional inductive moderate hyperthermia for patients with locally advanced breast cancer. PATIENTS AND METHODS: 200 patients with stage IIB-IIIA breast cancer received neoadjuvant chemotherapy (control group, n = 97) or chemotherapy combined with hyperthermia (experimental group, n = 103). Inductive hyperthermia was set at 27.12 ± 0.16 MHz and the 50 W output power. RESULTS: Thermal and color Doppler ultrasound imaging demonstrated that hyperthermia increased the surface temperature on the breasts to < 4°Ð¡ while the mean values for systolic blood flow were 3.5 times as high as those prior to treatment. Assessment of tumor size and response found a (31.24 ± 3.85)% reduction in the size of the primary tumor in patients receiving chemotherapy + hyperthermia, while chemotherapy alone showed a (22.95 ± 3.61)% decrease on average (p = 0.034). The rate of objective response increased by 15.9% in the experimental group (Ñ = 0.034) compared with the control group. The patients in the experimental group also had axillary lymph node regression of 14.17% greater than in the control group (p = 0.011). Moreover, the combination treatment allowed to increase the proportion of women eligible for breast-conserving and reconstructive surgery by 13.63% in the experimental group. The viable tumor volume was lower in patients receiving neoadjuvant chemotherapy + hyperthermia (24.4 ± 0.2)% compared with those given chemotherapy alone (30.4 ± 0.25)%. The 10-year overall survival rates were higher (log-rank: p = 0.009) in breast cancer patients who underwent chemotherapy combined with hyperthermia than in patients receiving chemotherapy only. CONCLUSION: The combination neoadjuvant chemotherapy and the technology of regional inductive moderate hyperthermia improved the efficacy of treatment for patients with locally advanced breast cancer staged IIB-IIIA.
