Medical Treatment of Breast Cancer Bone Metastasis: From Bisphosphonates to Targeted Drugs Breast cancer;bone metastasis;bisphosphonates;denosumab;targeted therapy; Breast cancer bone metastasis causing severe morbidity is commonly encountered in daily clinical practice. It causes pain, pathologic fractures, spinal cord and other nerve compression syndromes and life threatening hypercalcemia. Breast cancer metastasizes to bone through complicated steps in which numerous molecules play roles. Metastatic cells disrupt normal bone turnover and create a vicious cycle to which treatment efforts should be directed. Bisphosphonates have been used safely for more than two decades. As a group they delay time to first skeletal related event and reduce pain, but do not prevent development of bone metastasis in patients with no bone metastasis, and also do not prolong survival. The receptor activator for nuclear factor ${\kappa}B$ ligand inhibitor denosumab delays time to first skeletal related event and reduces the skeletal morbidity rate. Radionuclides are another treatment option for bone pain. New targeted therapies and radionuclides are still under investigation. In this review we will focus on mechanisms of bone metastasis and its medical treatment in breast cancer patients.

The aim of our study was to evaluate the incidence of KRAS/NRAS and BRAF mutations, analyze molecular patterns, and investigate associations with clinical parameters of these mutations in CRC KRAS/NRAS and BRAF mutations analyzed by next-generation sequencing. The detection rates of these mutations and patients’ demographics were recorded and the relationship between them was evaluated using the chi-square test. KRAS mutation was detected in 332 of 694 patients, while the mutation rates in KRAS exons 2/3 and 4 were 39.6%/3.2% and 5%, respectively. The most common mutation pattern was KRAS G12D. Five atypical variants were detected: V14I in KRAS exon 2, A18D, Q22K and T50I in exon 3, and T148P in exon 4. NRAS mutation was detected in 29 (4.5%) patients. One atypical variant L80W was detected in NRAS exon 3. BRAF mutation was seen in 37 (5.3%) patients, with BRAF^V600E (83.8%) being the most common mutation pattern. NRAS mutation was significantly more frequent in patients > 64 years of age, BRAF mutation in women, and NRAS/BRAF mutations in right colon tumors. Grouping BRAF mutations into BRAF^V600E and BRAF^non-V600E and their analysis according to specific tumor localizations showed that all four BRAF^non-V600E mutations originated in the rectum. In our study, KRAS exon 2 and other RAS mutation rates were higher than in the literature, while the BRAF v.600E mutation rate was similar. NRAS and BRAF mutations were significantly more frequent in the right colon. BRAF mutation was more common in women and in the right colon.

Objective: The Prognostic Nutritional Index (PNI), reflects the nutritional and immunological status of the patient and has been associated with outcomes in various cancers. In this study, the prognostic significance of PNI in metastatic hormone‐sensitive prostate cancer (mHSPC) and its potential role in guiding treatment decisions between abiraterone acetate and enzalutamide is investigated.Methods: Retrospective analysis was performed on 167 mHSPC patients treated between 2019 and 2024. PNI was calculated using the formula: 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (/mm³). Patients were stratified into high and low PNI groups according to a cutoff value of 49.98, determined via receiver operating characteristic (ROC) analysis. Survival outcomes, including overall survival (OS), radiographic progression‐free survival (rPFS), and PSA progression‐free survival (PSA‐PFS), were assessed. Treatment responses to abiraterone acetate and enzalutamide were compared within PNI strata.Results: Patients with PNI > 49.98 had significantly longer median OS than those with PNI ≤ 49.98 (36.6 months vs. 30.0 months, p < 0.01). Multivariate analysis identified high PNI, ECOG performance status 0–1, and absence of visceral metastasis as independent predictors of improved OS. Among patients with low PNI, those treated with enzalutamide had superior OS compared to those receiving abiraterone acetate (p = 0.004), while no significant OS difference was noted between treatments in the high PNI group (p = 0.55).Conclusion: PNI serves as a significant prognostic biomarker in mHSPC, correlating with overall survival and potentially influencing treatment efficacy between abiraterone acetate and enzalutamide. Integrating PNI into clinical practice may aid in tailoring individualized treatment options.

Prognostic factors and the standard treatment approach for gynaecological carcinosarcomas have not yet been clearly defined. Although carcinosarcomas are more aggressive than pure epithelial tumours, they are treated similarly. Serous/clear cell and endometrioid components may be predictive factors for the efficacy of adjuvant chemotherapy (CT) or radiotherapy (RT) or RT in patients with uterine and ovarian carcinosarcomas. Heterologous carcinosarcomas may benefit more from adjuvant CT. We aimed to define the prognostic and predictive factors associated with treatment options in ovarian (OCS) and uterine carcinosarcoma (UCS). Retrospective cross-sectional study. We retrospectively reviewed the medical records of patients with ovarian and uterine carcinosarcoma from 2000 to 2013, and 127 women were included in this study (24 ovarian and 103 uterine). Patients admitted to seventeen oncology centres in Turkey between 2000 and December 2013 with a histologically proven diagnosis of uterine carcinosarcoma with FIGO 2009 stage I-III and patients with sufficient data obtained from well-kept medical records were included in this study. Stage IV tumours were excluded. The patient records were retrospectively reviewed. Data from 104 patients were evaluated for this study. Age (≥70 years) was a poor prognostic factor for UCS (p=0.036). Pelvic±para aortic lymph node dissection did not affect overall survival (OS) (p=0.35). Macroscopic residual disease was related with OS (p<0.01). The median OS was significantly longer in stage I-II patients than stage III patients (p=0.03). Adjuvant treatment improved OS (p=0.013). Adjuvant radiotherapy tended to increase the median OS (p=0.075). However, this tendency was observed in UCS (p=0.08) rather than OCS (p=0.6).Adjuvant chemotherapy had no effect on OS (p=0.15).Adjuvant radiotherapy significantly prolonged the median OS in patients with endometrioid component (p=0.034). A serous/clear cell component was a negative prognostic factor (p=0.035). Patients with serous/clear cell histology for whom adjuvant chemotherapy was applied had significantly longer OS (p=0.019), and there was no beneficial effect of adjuvant radiotherapy (p=0.4). Adjuvant chemotherapy was effective in heterologous tumours (p=0.026). In multivariate analysis, the stage and chemotherapy were prognostic factors for all patients. Age was an independent prognostic factor for UCS. However, serous/clear cell histology and radiotherapy tended to be significant prognostic factors. The primary location, the histological type of sarcomatous and the epithelial component may be predictive factors for the efficacy of chemotherapy or radiotherapy in UCS and OCS.

Introduction: This study aimed to assess the role of the adjusted PNI-IMDC risk scoring system in stratifying the intermediate group of metastatic RCC patients who received TKIS in the first-line setting. Methods: A total of 185 patients were included. The adjusted PNI and IMDC model was used to divide the intermediate group into two groups: intermediate PNI-high and intermediate PNI-low groups. The statistical data were analyzed using Kaplan–Meier and Cox regression analysis. Results: The results showed that the adjusted PNI-IMDC risk score, classic IMDC, and PNI had similar prognostic values. Adjusted PNI-IMDC risk score might be used for a more homogeneous differentiation of the classic intermediate group. On the other hand, multivariate analysis revealed that the presence of nephrectomy, adjusted favorable/intermediate (PNI-high) group, ECOG performance score, and presence of bone metastasis were independent predictors of OS. Conclusions: Pre-treatment PNI, as a valuable and potential add-on biomarker to the adjusted PNI-IMDC classification model, can be helpful for establishing an improved prognostic model for intermediate group mRCC patients treated with first-line TKISs. Further validation studies are needed to clarify these findings.

Prostate carcinoma is androgen-dependent, and therefore the main target of treatment is lowering androgen levels. Medical or surgical castration, androgen receptor-blocking agents, androgen-synthesis inhibitors, chemotherapy, sipuleucel-T, and radium-223 are treatment options. Enzalutamide is a relatively new androgen-signaling inhibitor that has 5 to 8 times greater affinity for the androgen receptor (AR) than bicalutamide. Enzalutamide does not demonstrate agonistic activity on ARs. Enzalutamide induces apoptosis of prostate cancer cells. Enzalutamide is effective in metastatic castration-resistant prostate cancer in patients with progression after docetaxel treatment and in chemotherapy-naive patients. Enzalutamide is also superior to the commonly used AR blocking agent bicalutamide in chemotherapy-naive metastatic and non-metastatic castration-resistant prostate cancer patients. Its efficacy has been proven in hormonenaive patients, and several trials are ongoing. Enzalutamide has a favorable side effect profile and improves quality of life and pain scores. There are ongoing studies examining the efficacy and safety of enzalutamide on other several AR-expressing tumors.