Background ER-α36 is a novel 36 kDa isoform of the full-length oestrogen receptor alpha (ER-α66). ER-α36 primarily localises to the cytoplasm and the plasma membrane, and responds to membrane-initiated oestrogen and antioestrogen signalling pathways. Aim To examine the expression of ER-α36 in apocrine and adenoid cystic carcinoma of the breast, both of which are consistently ER-α66 negative and currently lack effective targeted therapeutic options. Methods 19 pure apocrine carcinomas (17 invasive and two in-situ carcinomas) and 11 adenoid cystic carcinomas of the breast were evaluated for ER-α36 expression, along with expressions of ER-α66, progesterone receptor (PR) and androgen receptor (AR) using immunohistochemical methods. Results All pure apocrine carcinomas showed a characteristic steroid receptor expression profile (ER-α66 and PR negative, AR strongly positive). ER-α36 expression was detected in 18/19 pure apocrine carcinomas (94.7%, 95% CI 75.1 to 98.7) in predominantly membranous and cytoplasmic distribution. When positive, pure apocrine carcinomas uniformly (100% of cells) expressed ER-α36. All adenoid cystic carcinomas were uniformly negative for all three classic steroid receptors, but ER-α36 was detected in 8/11 cases (72.7%, 95% CI 42.8 to 90) with the similar sub-cellular pattern of expression as in the pure apocrine carcinomas. When positive, adenoid cystic carcinomas expressed ER-α36 in the majority of cells (average 76%). Conclusion ER-α36, a novel isoform of ER-α66, is frequently over-expressed in apocrine and adenoid cystic carcinomas of the breast. These results indicate a potential for a novel targeted treatment in these cancers.

Abstract:  Management of patients at high risk for hereditary breast cancer (HBC) must critically assess its phenotypic and genotypic heterogeneity, particularly evidenced by the varying spectra of cancer sites that are integral to the respective HBC syndromes. Targeted management must consider their biology, pathology, and molecular genetics, all in concert with their respective carcinogenic pathways, as they may differ significantly from one breast cancer syndrome to the next. A striking example of management differences pertains to BRCA1 and BRCA2 mutation‐positive breast cancers wherein those with BRCA1 mutations are frequently estrogen receptor (ER)‐negative in contrast to BRCA2 mutations which are more frequently ER‐positive; therein, significant differences exist with respect to anti‐estrogen therapy which will be more amenable to BRCA2 versus BRCA1 mutation carriers manifesting breast cancer. In turn, tumors that are negative for ER, PR, and Her2‐neu, often referred to as “triple negative” tumors, may also harbor a unique basal‐like gene expression profile and are characterized by poor prognosis wherein endocrine and/or Her2‐neu‐targeted therapies are not effective treatment options. A further confounder pertains to the lifetime risk for ovarian cancer, which differs strikingly between BRCA1 mutation carriers, who show a 40–60% lifetime risk, and their BRCA2 counterparts, who carry a lifetime risk of approximately 12–15% for ovarian cancer. It is clear that as we learn more about the biology and the molecular aspects of hereditary forms of breast cancer, it will be compelling for the clinician to integrate this knowledge with pharmacologic, radiologic, and surgical treatment options for these high‐risk patients.

This paper focuses on the importance of adaptation of evidence based clinical practice guidelines (CPG) in developing countries like Bosnia and Herzegovina in a culturally competent way. Evidence based CPG guidelines are not routinely used in Bosnia and Herzegovina. The first adapted, evidence-based guideline on the care of women requesting induced abortion was published in 2007 following a 2004 publication by the Royal College of Obstetricians and Gynecologists (RCOG) (Evidence-based Clinical Guideline Number 7, ‘The Care of Women Requesting Induced Abortion’). The first adapted clinical guideline initiated the development of a second one related to secondary prevention of cervical carcinoma. Appraisal of Guidelines for Research and Evaluation (AGREE) were used to assess the development of clinical practice guidelines with the purpose of assuring methodological quality. After receiving permission, electronic searches of medical databases were performed to identify research performed in international settings similar to ours and research that took place after the publication of the RCOG guideline. 226 articles were selected, yielding 68 recommendations related to clinical assessment questions. Using expert consensus and external reviews, recommendations were generated that provided the clinical guideline development group with an evidence base from which to make recommendations on the best possible clinical practice. Variation in values, needs, costs and resources were considered systematically in order to make a decision about which policies should be implemented locally. For the first time in B&H, the evidenced-based clinical guideline development process fostered a supportive environment for educating health care providers on evidence based methodology, and new evidence based guidelines can be initiated for potential health care providers.

Background: Germ-cell tumors (GCT) are a histologically and biologically diverse group of neoplasms which primarily occur in the gonads but also develop at different extragonadal sites in the midline of the body. The head and neck region including the upper respiratory tract is a very rare location for such tumors in both children and adults, which can cause diagnostic and therapeutic difficulties.

Li-Fraumeni syndrome (LFS) is a very rare autosomal dominant and highly penetrant cancer syndrome characterized by early-onset primary tumours, including soft tissue and bone sarcoma, breast cancer, leukemia, brain tumours and adrenocortical carcinoma. Here we report the first evidence-based case of LFS in Bosnia and Herzegovina and the whole Balkan region. A ten year-old girl developed multiple primary tumours (rhabdomyosarcoma) during a period of eight years, as well as fibroadenoma of the breast. Sequential analysis revealed a germ line mutation of TP53 in exon 8, a common mutation in patients with LFS, in both the patient and her mother.

This systematic review considers the most recent attitudes and news regarding the influence of the stroma on tumor initiation and progression. It is now widely accepted that tumor stroma plays an active role in carcinogenesis. Many different signaling molecules, ligands and signaling pathways recently have been discovered. This review considers the complexity of interactions between malignant cells and its stroma (cross-talk). The recent advances and better understanding of the tumor-stroma interactions will have important impact on the new and combined therapeutic approaches and modalities.

AIM To explore the potential prognostic value of cyclin D1 in invasive breast cancer and its correlation with basic histopathological parameters, hormonal status (estrogen [ER] and progesterone receptor [PR]), and bcl-2. METHODS Medical records of 48 patients, diagnosed in 1998, from the Central Database of the Institute of Oncology, Clinical Center University of Sarajevo, were analyzed. The mean follow-up was 61 months (range: 4-103 months). Routine histopathological evaluation was performed for 48 formalin-fixed and paraffin-embedded tissue samples. For immunohistochemical staining, we used monoclonal antibodies for ER, PR, bcl-2, and cyclin D1. RESULTS Cyclin D1 expression inversely correlated with tumor grade (P=0.010) and tumor size (P=0.023), whereas significant positive association was found with ER (P=0.001) and bcl-2 (P=0.001) expression. Patients with higher cyclin D1 expression had longer both overall survival (P=0.014) and relapse-free survival (P=0.037). Cox regression analysis for overall survival (OS) showed that lymph node status, ER expression, therapy, and cyclin D1 expression were independent prognostic factors. (P range from 0.003 to 0.04). CONCLUSION Expression of cyclin D1 is associated with better disease outcome in breast cancer.