Targeting HER2 expression in cancer: New drugs and new indications

Functional activation of human epidermal growth factor receptor 2 (HER2) has been shown to strongly promote carcinogenesis, leading to the investigation of HER2-directed agents in cancers with HER2 genomic alterations. This has been best documented in the context of HER2 gene amplification in breast and gastric/gastroesophageal junction carcinomas for which several HER2-directed agents are available and have become a part of standard treatment regimens. Somatic HER2 gene mutations have been recently described at low frequency in a variety of human cancers and have emerged as a novel predictive biomarker for HER2-directed therapies. Preclinical data also indicate that activating HER2 mutations are potent oncogenic drivers in a manner that is analogous to HER2 amplification. HER2 mutations may clinically confer sensitivity to HER2-directed agents as recently shown in a phase II clinical trial with antibody-drug conjugate against HER2 trastuzumab deruxtecan in patients with non-squamous non-small cell lung carcinoma

Effects of adding taxane to anthracycline-based neoadjuvant chemotherapy in locally advanced breast cancer

Aim To compare the effect of neoadjuvant chemotherapy based on taxane and/or anthracycline to the extent of an objective response in female patients with unresectable breast cancer with evaluation of the toxic profile of applied chemotherapy. Methods One hundred patients with histologically verified breast cancer, treated with neoadjuvant chemotherapy were divided into two groups: a study group A (50 patients), who had received 4 to 6 cycles of taxane-based chemotherapy, and control group B (50 patients), who had received 4 to 6 cycles of anthracyclines-based chemotherapy. Pathohistological response was evaluated after tumour excision and axillary resection at the end of chemotherapy and it was defined as pathologic complete (pCR), partial (pPR), or no response (pNR). Toxic effects were evaluated and quantified by the Common Terminology Criteria for Adverse Events v4.0. Results After neoadjuvant chemotherapy, 8% of patients in the group A achieved pCR, 54% achieved pPR, while 38% of patients had no tumour response to applied chemotherapy. In the group B pCR was achieved in 6%, pPR in 42% of patients, while 51% of patients were pNR to the administered chemotherapy. Significant reduction of tumour mass was achieved in the group of patients treated with taxanes: 20.00 (7.75-30.25) vs. 13.50 (6.00-25.00) mm (p=0.024). Toxicity of chemotherapy in group A and group B was within the limits of grade 2. Conclusion The addition of taxane to anthracycline-based neoadjuvant chemotherapy in patients with breast cancer resulted in a significant reduction in tumour mass compared to the group of patients treated with anthracyclines, but without increasing the overall side effects

The Oncology Association of Bosnia and Herzegovina's recommendations for fertility preservation in oncologic patients

Malignancy is one of the major public health problems in Bosnia and Herzegovina. Along with breakthroughs in specific oncological therapy, improving the quality of life of cancer patients and management of therapy-induced side effects need to be recognized as a priority in the comprehensive cancer patient care. Fertility loss after cancer treatment is a field requiring special attention due to its various consequences on patients themselves.  Although oncofertility is well-recognized area of oncology, low- to middle-income countries are facing issues with its implementation in everyday practice. Increased awareness about fertility preservation is of high priority for all specialists who participate in the medical care of cancer patients. The absence of a systemic solution and lack of expertise led to the founding of Fertility Preservation Working Group of the Oncology Association of Bosnia and Herzegovina. We have made recommendationsas an expert consensus with the ultimate goal of making the first step towards enhancement of oncofertility implementation in Bosnia and Herzegovina

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

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

The Bcl-2 protein: a prognostic indicator strongly related to ER and PR in breast cancer

Bcl-2, the protein product of the Bcl-2 gene, is a member of the Bcl-2 family of proteins that play a crucial role in a complex mechanism of apoptosis. It was recently proposed that bcl-2 could inhibit cancer progression. In this study, we evaluated the expression patterns of Bcl-2, estrogen receptors (ER), progesterone receptors (PR) in 71 primary invasive breast carcinomas and their association with other clinicopathological parameters. Samples from 71 patients with invasive breast cancer with follow-up ranging from 4-103 months (median 57 months) were included in the study. Forty-six patients (66%) obtained a complete response, while 5 (9%) were considered non-responders during the follow up period of 103 months. Eighteen (25%) patients died, 15 (21%) from primary disease and 3 (4%) from other disease. In unvaried analysis, tumor size (<2 cm), lymph node (<4 lymph nodes), hormonal status and Bcl-2 expression are correlated with longer overall (OS) and relapse-free survival (RFS). Patients with 4 or more positive axillary lymph nodes had significantly shorter OS (p=0.01) and RFS (p=0.009). Higher expression of Bcl-2 was associated with longer OS (p=0.02) and RFS (p=0.03), and this result were independent of axillary lymph nodes and tumor size in Cox multivariate analysis

Investigation of Ivs14+1G>A Polymorphism of Dpyd Gene in a Group of Bosnian Patients Treated with 5-Fluorouracil and Capecitabine

Adverse drug reactions still pose an important clinical problem. Dihydropyrimidine dehydrogenase (DPD) is an enzyme that regulates 5-FU quantities available for anabolic processes and hence affects its pharmacokinetics, toxicity and efficacy. There are several studies describing a hereditary (pharmacogenetic) disorder in which individuals with absent or significantly reduced DPD activity may even develop a life-threatening toxicity following exposure to 5-FU. The most common mutation is known as the DPYD*2A or as the splice-site mutation (IVS14 + 1G A) leading to creation of a dysfunctional protein. An objective behind the study was to ascertain existence of the IVS14+ 1G A mutation among the population of Bosnia and Herzegovina. Our research has undeniably attested to existence of one heterozygote for the DPYD gene mutation, i.e. one heterozygote for IVS14 + 1 G > A, DPYD*2A mutation

Differences in Outcomes Between Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Metastatic Breast Cancer Patients in Upper Middle-Income versus High-Income Countries: A Retrospective Study from 4 Oncology Centers

BACKGROUND Therapeutic options for human epidermal growth factor 2 (HER2)-positive metastatic breast cancer (mBC) are developing rapidly. This study aimed to determine the differences in the survival outcomes of patients with HER2-positive mBC in relation to access to anti-HER therapy at 3 oncology centers in upper-middle-income countries (UMICs) and 1 oncology center in a high-income country (HIC). MATERIAL AND METHODS We retrospectively identified 42 patients from Croatia (HIC), 71 patients from Serbia (UMIC), and 57 from Bosnia and Herzegovina (UMIC) diagnosed with HER2-positive mBC who were treated between January 2015 and December 2020. The pathohistological features of the tumors were obtained from the pathological findings, which were made according to standard procedures for each center. Patients were treated depending on the availability of therapy, which differed for centers in different countries. We evaluated disease-free survival, progression-free survival, and overall survival (OS) based on the availability of first- and second-line anti-HER2 therapy in UMICs vs HIC. RESULTS OS in first-line therapy was better in patients treated with dual HER2 blockade than in patients treated without dual HER2 blockade, P<0.001. OS in second-line therapy was significantly better in patients treated with trastuzumab emtansine than in patients treated with other reported regimens, P=0.004. CONCLUSIONS Results of our study showed superior survival among patients who were treated with dual first-line HER2 therapy as well as second-line trastuzumab emtansine therapy than in those patients in other centers where these drugs were not available. Raising awareness about this could help improve the situation