Connections of serum and tumor ferritin levels with sensitivity to neoadjuvant chemotherapy in breast cancer patients

Shepil A.V., Lukianova N.Y., Chekhun V.F.

A.V. Shepil, N.Yu. Lukianova, V.F. Chekhun

R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, Kyiv, Ukraine

shepilalex@gmail.com

Introduction: Design of new strategies for breast cancer (BC) treatment is still one of the actual problems in oncology. The main phase of complex therapy of locally disseminated BC stage II–III is neoadjuvant chemotherapy. Nowadays different prognostic values are being used in clinical practice, but objective criteria of BC sensitivity to neoadjuvant chemotherapy, which could give data about answer to chemotherapy on organism and tumor levels, are still unclear. Aim: To study connections between ferritin levels in serum and tumor tissue with sensitivity to neoadjuvant chemotherapy in BC patients. Patients and Methods: We studied 168 women with BC stage IIА–IIIB. Age of patients ranged from 28 to 69 years. Serum ferritin was measured by solid-phase immunoenzyme assay after histological verification of diagnosis before the first cycle of neoadjuvant chemotherapy. Patients received FAC, AC chemotherapy (2–6 cycles) every 21 days. Neoadjuvant chemotherapy efficacy was evaluated every 2 cycles by mammography according to RECIST criteria. Ferritin expression studies were performed on operation material of BC patients by standard immunohistochemical assay with specific monoclonal antibodies. Statistical analysis was performed using STATISTICA 6.0 software. Results: Patients were divided into 2 groups according to the degree of the clinical effect after neoadjuvant chemotherapy. The first group consisted of 79 BC patients with positive reaction on chemotherapy: complete tumor regression was observed in 8, partial — in 71 patients from this group. The second group consisted of 89 women with tumors resistant to chemotherapy. Among them 61 patients showed stabilization of tumor growth and 28 — tumor progression after neoadjuvant chemotherapy. The highest levels of serum and tumor ferritin were registered in group of patients with tumors resistant to neoadjuvant chemotherapy. In particular at the beginning of the therapy before the first cycle of neoadjuvant treatment average ferritin concentration in serum of these patients was 226.2 ± 5.7 ng/ml (213.4 ± 4.8 ng/ml — in patients with stabilization and 254.2 ±6.2 ng/ml — in patients with progression of tumor growth). At the end of treatment patients with resistant tumors showed significant (p < 0.05) elevation of serum ferritin levels (to 294.7 ± 7.3 ng/ml in patients with stabilization and to 351.9 ± 5.5 ng/ml — in patients with tumor progression). Most part (87%) of tumors from the resistant group of patients showed elevated levels of ferritin expression in operation material. The highest levels of expression of this protein (more then 92% of positive cells) was observed in tumors with progression after neoadjuvant treatment. Patients with tumors sensitive to neoadjuvant therapy had slightly elevated average concentration of serum ferritin before the first cycle of neoadjuvant chemotherapy (93.1 ± 2.8 ng/ml: 56.8 ± 4.0 ng/ml in patients with full and 97.2 ± 3.1 ng/ml in patients with partial tumor regression). After treatment patients with sensitive tumors showed significantly (p < 0.05) lower serum ferritin levels (4.3 and 3.2 times for patients with full and partial tumor regression, respectively). Average and low levels of ferritin expression were observed only in 18% of tumors with partial regression, although tumors with full regression showed absence of this protein expression. Correlation analysis showed reverse correlation between levels of serum and tumor ferritin and sensitivity of BC patients to FAC and AC neoadjuvant chemotherapy (r = -0.39; p < 0.05). Conclusions: So, we found relations between levels of ferritinin in serum and tumor tissue with sensitivity to neoadjuvant chemotherapy of BC patients. High serum and tumor ferritin levels point on resistance of BC patients to neoadjuvant chemotherapy. The acquired data showed that ferritin level should be used as objective criteria for determination of BC sensitivity to neoadjuvant chemotherapy on both organism and tumor levels.

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