Improved Survival of Young Patients With Breast Cancer 40 Years and Younger at Diagnosis.

PURPOSE: Around 50% of patients with breast cancer in low- or middle-income countries are younger than 50 years, a poor prognostic variable. We report the outcome of patients with breast cancer 40 years and younger. METHODS: We reviewed 386 patients with breast cancer 40 years and younger and retrieved demographic, clinicopathologic, treatment-related, disease progression, and survival data from electronic medical records. RESULTS: The median age at diagnosis was 36 years, and infiltrating ductal carcinoma was present in 94.3% of patients, infiltrating lobular carcinoma in 1.3%, and ductal carcinoma in situ in 4.4%. Grade 1 disease was present in 8.5% of patients, grade 2 in 35.5%, and grade 3 in 53.4%; 25.1% had human epidermal growth factor receptor 2 (HER2)-positive, 74.6% had hormone receptor (HR)+, and 16.6% had triple-negative breast cancer. Early breast cancer (EBC) constituted 63.6% (stage I, 22.4%; stage II, 41.2%) of patients, whereas 23.2% had stage III, and 13.2% had metastatic disease at diagnosis. Of patients with EBC, 51% had partial mastectomy and 49.0% had total mastectomy. And 77.1% had chemotherapy with or without anti-HER2 therapy. All HR+ patients received adjuvant hormonal therapy. The disease-free survival at 5 years was 72.5% and 55.9% at 10 years. The overall survival (OS) was 89.4% at 5 years and 76% at 10 years. Patients with stages I/II had an OS of 96.0% at 5 years and 87.1% at 10 years. Patients with stage III had an OS of 88.3% at 5 years and 68.7% at 10 years. The OS of patients with stage IV was 64.5% at 5 years and 48.4% at 10 years. CONCLUSION: We report survival rates of 89% at 5 years and 76% at 10 years with modern multidisciplinary management. Best results were seen in EBC: OS rates of 96% and 87% at 5 years and 10 years.

Genetic Counseling, Screening and Risk-Reducing Surgery in Patients with Primary Breast Cancer and Germline BRCA Mutations: Unmet Needs in Low- and Middle-Income Countries.

OBJECTIVE: Worldwide genetic counseling practices are variable and often not reported in low- and middle-income countries (LMICs). We present the follow-up genetic counseling, breast screening, risk-reducing salpingo-oophorectomy (RRSO) and contralateral prophylactic mastectomy (CPM) in a cohort of study patients with either BRCA pathogenic mutations or BRCA variant of unknown significance (VUS). MATERIALS AND METHODS: Chart review and phone calls for the collection of information. Out of a cohort of 250 patients, 14 had deleterious mutations and 31 had a VUS, of whom 19 had primary early breast cancer. We collected information about genetic counseling, screening, CPM and RRSO. RESULTS: Fourteen patients with deleterious mutations (7 BRCA1 and 7 BRCA2) and 19 patients with VUS mutations (20 VUS, 4 BRCA1, 16 BRCA2; 1 patient had both) were surveyed. Of 14 patients with deleterious BRCA mutations, 57.14% (8/14 patients) received genetic counseling from their oncologist. Subsequently 85.71% (12/14) are undergoing mammography screening and 35.71% (5/14) breast screening magnetic resonance imaging (MRI). Furthermore, 50% of them underwent CPM and 57.14% underwent RRSO. Of 19 patients with VUS mutations, 10.5% received genetic counseling from their oncologist; 78.9% were undergoing regular screening mammogram and 31.5% were undergoing breast MRI; one patient underwent CPM and two patients RRSO. CONCLUSION: Within three years from knowing they have a mutation, 50% of patients with germline BRCA mutations had undergone CPM and 60% RRSO, the majority of them had screening mammography surveillance but only 50% had screening MRI. Follow-up of patients with VUS with mammography was 78% but MRI was only 31%. Lack of MRI surveillance reflects both limited resources and insufficient counseling. Genetic counseling was done by medical oncologists, which reflects a trend in LMIC. Our Data shows the importance of the need for professional genetic counselors and optimal surveillance in Lebanon and other LMICs.

Malignant carcinoma and skin melanoma neoplasms concomitantly in the thyroid.

Malignant melanomas metastatic to the thyroid gland are uncommon. Based on microscopy and DNA methylation profile, we report a rare coexistence of neoplasms in the thyroid, presumably in our case, with relapse-free condition on adjuvant therapy.

Metronomic chemotherapy for patients with metastatic breast cancer: Review of effectiveness and potential use during pandemics.

Metronomic chemotherapy (M-CT) is defined as dose dense administration of chemotherapy at lower doses than maximum tolerated dose but at shorter free intervals, to obtain a near continuous exposure of cancer cells to those potentially effective drugs. M-CT is a useful strategy to obtain response, overcome resistance and reduce side effects, with low costs. This review will focus on the use of M-CT in advanced breast cancer (ABC). Cytostatic and cytotoxic effect on cancer cells, the anti-angiogenic and the immunomodulatory effects are its main mechanisms of actions. Many clinical trials proved the efficacy and tolerability of different monotherapies and combinations of chemotherapeutic agents administered in metronomic doses and frequencies in ABC. M-CT is a reasonable option for second and later lines of chemotherapy in metastatic breast cancer including those with prior anthracycline or taxane exposure, older patients and patients with comorbidities, and even as first-line in certain groups of patients. The acceptable efficacy and low toxicity of oral metronomic chemotherapy makes it a reasonable option during COVID-19 pandemic as well as in the post-COVID era which is projected to last for some time.

Impact of Merit-Based Immigration Policies on Brain Drain From Low- and Middle-Income Countries.

PURPOSE: Brain drain is the migration of educated and skilled individuals from a less developed region or country to a more economically established one. The Trump administration proposed a merit-based immigration plan. This article addresses its potential impact on health care delivery in low- and middle-income countries (LMICs) and their preparedness to deal with it. MATERIALS AND METHODS: Data on immigration policies, numbers of international medical graduates practicing in high-income countries (HICs), various scientific exchange methods, and efforts for capacity building in LMICs. RESULTS: Talented individuals seek to advance their knowledge and skills, and may stay in HICs because of greater rewards and opportunities. HICs also rely on immigrant international medical graduates to supplement their physician workforces. CONCLUSION: Ambitious individuals from LMICs need and should have opportunities to advance their education and training in more advanced countries. LMICs should increase their educational efforts, research capabilities, infrastructures, and living conditions to better serve their own populations and reduce their brain drain phenomenon.

Overview, prevention and management of chemotherapy extravasation.

Chemotherapy extravasation remains an accidental complication of chemotherapy administration and may result in serious damage to patients. We review in this article the clinical aspects of chemotherapy extravasation and latest advances in definitions, classification, prevention, management and guidelines. We review the grading of extravasation and tissue damage according to various chemotherapeutic drugs and present an update on treatment and new antidotes including dexrazoxane for anthracyclines extravasation. We highlight the importance of education and training of the oncology team for prevention and prompt pharmacological and non-pharmacological management and stress the availability of new antidotes like dexrazoxane wherever anthracyclines are being infused.

Reactive oxygen species mediate thymoquinone-induced apoptosis and activate ERK and JNK signaling.

Thymoquinone (TQ), a component of black seed essential oil, is known to induce apoptotic cell death and oxidative stress, however, the direct involvement of oxidants in TQ-induced cell death has not been established yet. Here, we show that TQ inhibited the proliferation of a panel of human colon cancer cells (Caco-2, HCT-116, LoVo, DLD-1 and HT-29), without exhibiting cytotoxicity to normal human intestinal FHs74Int cells. Further investigation in DLD-1 revealed that apoptotic cell death is the mechanism for TQ-induced growth inhibition as confirmed by flow cytometry, M30 cytodeath and caspase-3/7 activation. Apoptosis was induced via the generation of reactive oxygen species (ROS) as evidenced by the abrogation of TQ apoptotic effect in cells preincubated with the strong antioxidant N-acetyl cysteine (NAC). TQ increased the phosphorylation states of the mitogen-activated protein kinases (MAPK) JNK and ERK, but not of p38. Their activation was completely abolished in the presence of NAC. Using PD98059 and SP600125, specific ERK and JNK inhibitors, the two kinases were found to possess pro-survival activities in TQ-induced cell death. These data present evidence linking the pro-oxidant effects of TQ with its apoptotic effects in colon cancer and prove a protective role of MAPK.