Pharmacological methods for ovarian function and fertility preservation in women with cancer: A literature review.

Oncofertility is an extremely significant topic that is increasingly being discussed owing to increased evidence indicating that fertility preservation does not affect the treatment outcomes of patients with cancer but significantly contributes to preserving life quality. The effect of chemotherapy can range from minimal effects to complete ovarian atrophy. Limited data are available on the effects of monoclonal antibodies and targeted therapies on the ovaries and fertility. Temporary ovarian suppression by administering a gonadotropin-releasing hormone agonist (GnRHa) during chemotherapy decreases the gonadotoxic effect of chemotherapy, thereby diminishing the chance of developing premature ovarian insufficiency (POI). At present, the concomitant administration of GnRH analogs during chemotherapy is the only accepted pharmacological method for preserving ovarian function. Notably, most randomized studies on the effectiveness of luteinizing hormone-releasing hormone agonists during chemotherapy in preventing POI have been conducted in women with breast cancer, with a considerably small number of studies on patients with hematological malignancies. Furthermore, most randomized controlled trials on breast cancer have revealed a decrease in treatment-induced POI risk, regardless of the hormone receptor status. In addition, studies on hematological malignancies have yielded negative results; nevertheless, the findings must be interpreted with caution owing to numerous limitations. Current guidelines from the American Society of Clinical Oncology and ESMO Clinical Practice Guidelines recommend sperm, oocyte, and embryo cryopreservation as a standard practice and only offering GnRHa to patients when proven fertility preservation methods are not feasible. In this manuscript, we present a comprehensive literature overview on the application of ovarian suppression with GnRHa during chemotherapy in patients with cancer by addressing preclinical and clinical data, as well as future perspectives in this field that upcoming research should focus on.

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.

Evaluation of Cyclin D1 expression by western blotting methods and immunohistochemistry in breast cancer patients.

PURPOSE: Considering that cyclin D1 had a prognostic and clinical value for breast cancer patients, adequate measurement of cyclin D1 is necessary. METHODS: In this investigation, we detect cyclin D1 expression in tumour and peritumoral tissue of breast cancer patients by Western blotting method and by immunohistochemistry. RESULTS: Cyclin D1 expression decreased significantly with each advanced clinical stage of disease and tumour size. Also, patients without lymph node involvement, with positive hormone receptors and Luminal A type of tumours had significantly increased the expression of cyclin D1. We show that cyclin D1 expression correlates with longer RFS in the entire group of patients, in the group of ER-positive and in the group of HER2-negative patients. Patients who were both ER and cyclin D1 positive had a better prognosis. CONCLUSION: Taken together, our results, showing correlation of cyclin D1 with clinical stage, tumour size and lymph nodes, suggest that cyclin D1 expression, detected by Western blotting, could be considered as an additional marker for the staging of breast cancer, as well as a marker for longer RFS and survival in ER-positive breast cancer patients.

Platinum - sensitive relapsed epithelial ovarian cancer: not all the patients benefit from reinduction with carboplatin and paclitaxel.

BACKGROUND: It is widely accepted that patients with ovarian cancer relapsing 6 to 12 months after completion of a platinum-based regimen are considered to be partially platinum-sensitive. The aim of this study was to evaluate and correlate the efficacy and toxicity of reinduction with paclitaxel-carboplatin in a platinum-sensitive epithelial ovarian cancer patient cohort with previous platinum-free interval (PFI). MATERIAL/METHODS: We studied retrospectively 39 patients with platinum-sensitive epithelial ovarian cancer, who received primary chemotherapy at the Institute for Oncology and Radiology of Serbia, between January 2002 and May 2008. All patients were treated with paclitaxel and carboplatin for metastatic disease. Subsequent to progression, patients were re-treated with the same chemotherapy in group A (PFI 6-12 months) or group B (PFI ≥12 months). RESULTS: The number of patients in group A was 14, and in group B it was 25. Response rate to reinduction in group A was 36% (partial response, 36%; stable disease, 0%; progressive disease, 64%) and in group B was 68% (complete response, 60%; partial response, 8%; stable disease, 4%; progressive disease, 28%; P=.05). The median response duration of the patients in group A arm was 20 months, whereas it was 17 months for those in group B (P=.721). There were no significant differences in the toxicity profile between the 2 groups. CONCLUSIONS: In terms of objective response rate this study supports the reinduction of carboplatin and paclitaxel in patients with a prior PFI of at least 12 months only. To define the best approach and the optimal treatment of patients with partially platinum-sensitive disease more precisely, future studies should apply treatment-free interval as a stratification criterion.