Circulating proteins hold a potential benefit as biomarkers for precision medicine. Previously, we showed that systemic levels of neuropilin-1 (NRP-1) and its associated molecules correlated with poor-prognosis breast cancer. To further identify the role of NRP-1 and its interacting molecules in correspondence with patients' response to neoadjuvant chemotherapy (NAC), we conducted a comparative study on blood and tissue samples collected from a cohort of locally advanced breast cancer patients, before and after neoadjuvant chemotherapy (NAC). From a panel of tested proteins and genes, we found that the levels of plasma NRP-1, placenta growth factor (PlGF) and immune cell expression of the transcription factor SNAI1 before and after NAC were significantly different. Paired t -test analysis of 22 locally advanced breast cancer patients showed that plasma NRP-1 levels were increased significantly ( p = 0.018) post-NAC in patients with pathological partial response (pPR). Kaplan–Meier analysis indicated that patients who received NAC cycles and their excised tumors remained with high levels of NRP-1 had a lower overall survival compared with patients whose tissue NRP-1 decreased post-NAC (log-rank p = 0.049). In vitro validation of the former result showed an increase in the secreted and cellular NRP-1 levels in resistant MDA-MB-231 cells to the most common NAC regimen Adriyamicin/cyclophosphamide+Paclitaxel (AC+PAC). In addition, NRP-1 knockdown in MDA-MB-231 cells sensitized the cells to AC and more profoundly to PAC treatment and the cells sensitivity was proportional to the expressed levels of NRP-1. Unlike NRP-1, circulating PlGF was significantly increased ( p = 0.014) in patients with a pathological complete response (pCR). SNAI1 expression in immune cells showed a significant increase ( p = 0.018) in patients with pCR, consistent with its posited protective role. We conclude that increased plasma and tissue NRP-1 post-NAC correlate with pPR and shorter overall survival, respectively. These observations support the need to consider anti-NRP-1 as a potential targeted therapy for breast cancer patients who are identified with high NRP-1 levels. Meanwhile, the increase in both PlGF and SNAI1 in pCR patients potentially suggests their antitumorigenic role in breast cancer that paves the way for further mechanistic investigation to validate their role as potential predictive markers for pCR in breast cancer.

Trastuzumab, a monoclonal antibody targeting the human epidermal growth factor receptor 2 (HER2), is used to treat breast cancers harboring amplification of the HER2 locus. Cardiotoxicity is a common side effect of trastuzumab that leads to discontinuation of treatment in a significant proportion of cancer patients. In our retrospective study, we evaluate the prevalence and identify the risk factors for cardiotoxicity associated with trastuzumab in HER2-positive breast cancer patients attending to Sultan Qaboos University Hospital between 10/2012 and 10/2017. Using patient records, we collected patients’ characteristics (age, menopausal status, lymph nodal status, distant metastasis at presentation, grade of tumor, comorbidities (diabetes mellitus, hypertension, coronary artery disease diseases)), chemotherapy received and total dose of trastuzumab as well as cardiotoxicity (including timing). Cardiotoxicity was defined based on the ejection fraction dropping by 10% of the original value or a drop in the ejection fraction below the normal value. Among the 146 patients included in the study, 35 showed trastuzumab-induced cardiotoxicity (24%). Twenty-nine (83%) of those patients stopped trastuzumab temporarily. Risk of trastuzumab-induced cardiotoxicity was not altered by common cardiac risk factors such as history of coronary artery disease, hypertension and diabetes. Previous anthracyclines therapy exposure increased the risk of trastuzumab-induced cardiotoxicity significantly ( p =  0.009). None of the other covariates influenced the incidence of trastuzumab-induced cardiotoxicity, which may be related to the relatively small sample size. Further studies are warranted to establish ways to predict, prevent, and treat trastuzumab-induced cardiotoxicity to provide patients with maximal therapeutic benefit.

Background: Our study aimed to assess the risk of endometrial pathologies after tamoxifen and aromatase inhibitors (AIs) adjuvant treatment for female breast cancer patients treated at Sultan Qaboos University Hospital in Oman.Materials and Methods: A total of 457 patients diagnosed with estrogen positive breast cancer between January 2011 and December 2018 were screened. Two hundred and four patients met the inclusion criteria, and their detailed clinicopathological and endometrial surveillance data were collected from their electronic health records.Results: All patients underwent endometrial assessment during tamoxifen or letrozole therapy. The mean diagnostic age of breast cancer patients is 43.6 years, ranging from 27-84 years. Eighty-three percent of those patients are premenopausal, and 17% are postmenopausal. The mean tamoxifen use duration was 33 months. The majority of patients, 123 (60.3%), have had tamoxifen for three years or less, 47 (23.1%) for 3-5 years, and only 22 (10.8%) were on tamoxifen for more than five years. Increased endometrial thickness was reported in 8% of the premenopausal and 14% of the postmenopausal group. Other endometrial pathologies that were detected are inactive endometrium three (1.47%), atrophic endometrium three (1.47%), serous carcinoma one (0.50%), endometrial cancer two (0.98%), and chronic endometritis one (0.50%), which were not significantly associated with tamoxifen or letrozole therapy duration. Two patients have developed endometrial cancer, and both are postmenopausal and > 60 years old.Conclusions: Tamoxifen and letrozole did not increase the risk of endometrial cancer in premenopausal patients. Breast Cancer (BC) patients on tamoxifen or letrozole might need a pre-treatment endometrial evaluation and explanation of alarming symptoms to guide further endometrial surveillance.

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