2020 consensus guideline for optimal approach to the diagnosis and treatment of HER2-positive breast cancer in Bosnia and Herzegovina.

The HERe2Cure project, which involved a group of breast cancer experts, members of multidisciplinary tumor boards from healthcare institutions in Bosnia and Herzegovina, was initiated with the aim of defining an optimal approach to the diagnosis and treatment of HER2 positive breast cancer. After individual multidisciplinary consensus meetings were held in all oncology centers in Bosnia and Herzegovina, a final consensus meeting was held in order to reconcile the final conclusions discussed in individual meetings. Guidelines were adopted by consensus, based on the presentations and suggestions of experts, which were first discussed in a panel discussion and then agreed electronically between all the authors mentioned. The conclusions of the panel discussion represent the consensus of experts in the field of breast cancer diagnosis and treatment in Bosnia and Herzegovina. The objectives of the guidelines include the standardization, harmonization and optimization of the procedures for the diagnosis, treatment and monitoring of patients with HER2-positive breast cancer, all of which should lead to an improvement in the quality of health care of mentioned patients. The initial treatment plan for patients with HER2-positive breast cancer must be made by a multidisciplinary tumor board comprised of at least: a medical oncologist, a pathologist, a radiologist, a surgeon, and a radiation oncologist/radiotherapist.

Proliferation, apoptosis and expression of matrix metalloproteinase-9 in human fetal lung.

Expression pattern of the Ki-67, caspase-3 and matrix metalloproteinases-9 (MMP-9) factors were immunohistochemically analyzed in 48 human fetal lungs from 12 to 40 weeks of gestation. The number of Ki-67 positive cells in the epithelium of canaliculare (88cells/mm(2)) and sacculare stage (93cells/mm(2)) were significantly higher than in the epithelium of pseudoglandular stage (12cells/mm(2)) (p=0.0008 vs. p=0.003). The number of Ki-67 positive cells in the mesenchyme of canaliculare stage (132cells/mm(2)) was significantly higher than in the mesenchyme of pseudoglandular stage (37cells/mm(2)) (p=0.001). The proliferation of mesenchymal cells was higher than the epithelial cells in all developmental stages, especially in the canaliculare stage (p=0.007). Similarly, the number of caspase-3 positive cells in the epithelium of canalicular stage (13cells/mm(2)) was significantly higher than in the epithelium of pseudoglandular stage (6cells/mm(2)) (p=0.002) with peaks in the conductive epithelium of canalicular stage. The number of caspase-3 positive cells in the mesenchyme of canaliculare stage (3cells/mm(2)) was significantly higher than in the mesenchyme of saccular stage (0cells/mm(2)) (p=0.05). There were no caspase-3 positive cells in the mesenchyme of pseudoglandular stage. However, unlike the Ki-67 expression, mesenchymal cells in comparison to epithelial cells express substantially less caspase-3 in all developmental stages. Up to the saccular stage, the expression of MMP-9 in mesenchymal cells showed a linear increase with most pronounced expression in that stage. The number of MMP-9 positive cells in the mesenchyme of canaliculare (20cells/mm(2)) and sacculare (39cells/mm(2)) stage were significantly higher than in the mesenchyme of pseudoglandular stage (12cells/mm(2)) (p=0.04 vs. p=0.004). The first epithelial cells that express MMP-9 were present only at the alveolar stage. Increased proliferation and apoptosis of the mesenchymal cells of canalicular stage is important for formation of definite structures within the stroma of the lung parenchyma. Although apoptosis in the epithelium is not pronounced as proliferation, it is important for thinning of the epithelium and consequent spread of respiratory tract. However in the saccular stage when mesenchyme disappears, MMP-9 expression is more important for primitive alveoli differentiation.

ZAP-70 expression and proliferative activity in chronic lymphocytic leukemia.

The expression of 70 kDa protein zeta-associated protein (ZAP-70) in chronic lymphocytic leukemia (CLL) has been used to detect those patients with more aggressive disease. The aim of this study was to determine the proliferative activity of ZAP-70(+) leukemic cells by immunocytochemical methods. The study was undertaken on native blood marrow (BM) and peripheral blood (PB) smears from 65 patients with CLL. ZAP-70 was expressed in leukemic cells of 35 patients (54%). We demonstrated that ZAP-70 immunoreactivity correlated with Rai 0-IV (p = 0.002) and Binet A-C stages (p < 0.001), total tumor mass (TTM score) (p < 0.001), ß2-microglobulin (p = 0.006), atypical lymphocytes (p < 0.001) and proliferative activity in bone marrow and peripheral blood (p = 0.014, p = 0.002, respectively) using χ(2) test and Mann-Whitney test. ZAP-70 protein expression is in direct correlation with the poorer prognostic parameters, which additionally confirms the successful method of detection of ZAP-70 expression. Higher Ki-67 expression in BM and PB smears of patients with ZAP-70(+) disease indicates higher proliferating compartments, which may contribute to poorer prognosis.

An unusual case of advanced bilateral male breast cancer.

BACKGROUND: Breast cancer in men is an uncommon disease. Little is known about its etiology, clinical behavior, treatment, and outcome. Retrospective data indicate that stage- and age-matched male and female breast cancer is similar in presentation. The aim is to find an adequate treatment for male breast cancer, which is not just extrapolated from its female counterpart. CASE REPORT: We present the history of a 41-year-old man who was diagnosed with pT2 (3 cm) breast cancer in 2001. After mastectomy without axillary dissection, 4 cycles of adjuvant epirubicin and cyclophosphamide and radiation therapy were performed followed by hormonal treatment with tamoxifen until 2003. In 2003, 2004, 2005, and 2006, there were relapses with skin metastases, treated with several courses of chemotherapy. In 2006, an inflammatory carcinoma in the contralateral breast was revealed during the course of epirubicin chemotherapy. In May 2007, the patient passed away from extensive tumor progression despite numerous attempts of local and systemic chemotherapeutic treatment. CONCLUSION: Here, an unusual case of male breast cancer is reported. It was first diagnosed at the age of 41 years, which is relatively young for male breast cancer. Although the treatment was started at an early stage, several relapses and contralateral breast cancer occurred within 5 years and could no be controlled.