HFE Gene Variants' Impact on Anthracycline-Based Chemotherapy-Induced Subclinical Cardiotoxicity.

Progress in oncology has allowed to improve outcomes in many breast cancer patients. The core stone of breast cancer chemotherapy is anthracycline-based chemotherapy. Unfortunately, anthracyclines cause cardiotoxicity which is a limiting factor of its use and lifetime cumulative dose of anthracyclines is the major risk factor for cardiotoxicity. With evolution of echocardiography subclinical damage is identified, and more sensitive evaluation can be performed. This leads to understanding the heart damage beyond cumulative dose in early phase and importance of other risk factors. There are many risk factors for anthracycline-based chemotherapy cardiotoxicity (ABCC) like arterial hypertension, obesity, diabetes, genetic predisposition, etc. One of possible pathophysiological pathways is iron metabolism, especially HFE gene-regulated iron metabolism pathway. Pre-existing genetic iron metabolism dysregulation increases risk for ABCC. Clinical studies and experimental models in mice have shown potential impact of HFE gene SNP on ABCC. The main objective of our study was to identify the impact of HFE C282Y and H63D SNP on the development of subclinical heart damage during and/or after doxorubicin-based chemotherapy in breast cancer patients. Data of 81 women with breast cancer treated with doxorubicin-based chemotherapy in the outpatient clinic were analyzed and SNP RT-PCR tests were performed. Statistically significant association between H63D and ABCC after completion of chemotherapy was observed (p < 0.005). Consequently, our study demonstrated that H63D SNP has an important role in the development of ABCC. HFE SNP mutation status could be used as one of important tools to identify high-risk patients for ABCC.

Preoperative Axillary Ultrasound versus Sentinel Lymph Node Biopsy in Patients with Early Breast Cancer.

Background and objectives: With improved diagnostic means of early breast cancer, the percentage of cases with metastasis in axillary lymph nodes has decreased from 50%-75% to 15%-30%. Lymphadenectomy and sentinel lymph node biopsy are not treatment procedures, as they aim at axillary nodal staging in breast cancer. Being surgical interventions, they can lead to various complications. Therefore, recently much attention has been paid to the identification of non-invasive methods for axillary nodal staging. In many countries, ultrasound is a first-line method to evaluate axillary lymph node status. The aim of this study was to evaluate the prognostic value of ultrasound in detecting intact axillary lymph nodes and to assess the accuracy of ultrasound in detecting a heavy nodal disease burden. The additional objective was to evaluate patients' and tumor characteristics leading to false-negative results. Materials and Methods: A total of 227 women with newly diagnosed pT1 breast cancer were included to this prospective study conducted at the Breast Surgery Unit, Clinic of Surgery, Hospital of Lithuanian University of Health Sciences Kauno Klinikos, between May 1, 2016, and May 31, 2018. All patients underwent preoperative axillary ultrasound examination. Ultrasound data were compared with the results of histological examination. The accuracy and true-negative rate of ultrasound were calculated. The reasons of false-negative results were analyzed. Results: Of the 189 patients who had normally appearing axillary lymph nodes on preoperative ultrasound (PAUS-negative), 173 (91.5%) patients were also confirmed to have intact axillary lymph nodes (node-negative) by histological examination after surgery. The accuracy and the negative predictive value of ultrasound examination were 84.1% and 91.5%, respectively. In ≥3 node-positive cases, the accuracy and the negative predictive value increased to 88.7% and 98.3%, respectively. In total, false-negative results were found in 8.5% of the cases (n = 16); in the PAUS-negative group, false-negative results were recorded only in 1.6% of the cases (n = 3). The results of PAUS and pathological examination differed significantly between patients without and with lymphovascular invasion (LV0 vs. LV1, p < 0.001) as well as those showing no human epidermal growth factor receptor 2 (HER2) expression and patients with weakly or strongly expressed HER2 (HER2(0) vs. HER2(1), p = 0.024). Paired comparisons revealed that the true-negative rate was significantly different between the LV0 and LV1 groups (91% vs. 66.7%, p < 0.05), and the false-negative rate was statistically significant different between the HER2(0) and HER2(1) groups (10.5% vs. 1.2%, p < 0.05). Evaluation of other characteristics showed both the groups to be homogenous. Conclusions: Negative axillary ultrasound excluded axillary metastatic disease in 91.5% of the patients. PAUS had an accuracy of 88.7% in detecting a heavy nodal disease burden. With the absence of lymphovascular invasion (LV0), we can rely on PAUS examination that axillary lymph nodes are intact (PAUS-negative), and this patients' group could avoid sentinel lymph node biopsy. Patients without HER2 expression are at a greater likelihood of false-negative results; therefore, the findings of ultrasound that axillary lymph nodes are intact (PAUS-negative results) should be interpreted with caution.

The integrated evaluation of the results of oncoplastic surgery for locally advanced breast cancer.

The optimal surgical management of locally advanced breast cancer (LABC) remains undefined. The aim of the study was to obtain long-term results of oncoplastic surgery in terms of overall survival, loco-regional recurrence, and quality of life in case of LABC. Prospective cohort study enrolled 60 patients with stage III breast cancer. Forty-two (70%) patients received neo-adjuvant chemotherapy, 28 patients were considered suitable for surgery as initial treatment option. Type II oncoplastic surgery was performed for all patients: hemimastectomy and breast reconstruction with latissimus dorsi flap - for 29 (48.3%), lumpectomy - 31 (51.7%), and reconstruction with subaxillary flap for four (6.7%), with bilateral reduction mammoplasty - 14 (23.3%) and with J-plastic - 13 (21.7%) patients. Adjuvant chemotherapy and hormonal therapy followed surgery for all, except one, patients. Sequential radiotherapy was administered for all patients. The mean period of follow-up was 86 months. Postoperative morbidity rate was 5%. Local-regional recurrence was detected in six (10%) patients. After reoperation no local relapse was diagnosed. However, three of these patients had systemic dissemination of the disease. Distant metastasis was detected in 23 (38.3%) patients. Distant metastasis-free survival at 5 years was 61.7%. Fourteen patients died (23.3%). A total of 87.2% of the patients had good and excellent esthetic outcome. Oncoplastic breast-conserving surgery can be proposed for selected patients with LABC with acceptable complication, local recurrence rate, and good esthetic results.

Quality of life after sentinel lymph node biopsy versus complete axillary lymph node dissection in early breast cancer: a 3-year follow-up study.

BACKGROUND AND OBJECTIVES: The rating of life quality may belong to the method of surgical treatment: after the axillary lymph node dissection patients may suffer from arm symptoms; after sentinel lymph node biopsy women may highlight the anxiety about the success of radical treatment. The aim was to assess the influence of sentinel lymph node biopsy on the quality of life of the patients with early stage breast cancer compared with total axillary lymph node dissection. MATERIAL AND METHODS: In a prospective case-control study, 48 patients with early invasive breast cancer and no evidence of lymph nodes involvement underwent breast conserving surgery with sentinel lymph node biopsy. They were grouped as matched pairs with the patients who underwert axillary lymph node dissection, according to the age, TNM stage, localization, hormonal receptor status, and surgical characteristics. Quality of life was evaluated using the QLQ-C30 and QLQ-BR-23 questionnaires before surgery and after 1, 3, 6, 12, and 36 months. RESULTS: The patients who underwent sentinel lymph node biopsy scored better on the emotional functioning, pain, sexual functioning, and future perspective scales in comparison with those who underwent axillary lymph node dissection. The score on the arm symptom scale remained significantly better in the sentinel lymph node biopsy group than the axillary lymph node dissection group within the overall follow-up period. CONCLUSIONS: The women who underwent sentinel lymph node biopsy experienced better quality of life than the patients who underwent axillary lymph node dissection.