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Background: To compare the clinicopathological characteristics of nonmetastatic breast cancer patients with and without BRCA variations and to investigate the impact of BRCA variations on prognosis., Methods: This retrospective single-center study involved an analysis of 938 patients with localized or locally advanced breast cancer who underwent BRCA variation testing. The patients were divided into three groups: 757 were without BRCA variation, 64 were with BRCA1 variation, and 117 were with BRCA2 variation., Results: In patients with BRCA1 variation, the Ki67, grade, and frequency of triple-negative breast cancer were significantly higher than in patients without BRCA variation and with BRCA2 variation. The 5-year disease-free survival in patients with BRCA1 variation was significantly worse than the other two groups (without BRCA, BRCA1, and BRCA2; 87.7%, 69.9%, and 95.3%, respectively, p = 0.049). Multivariate analysis detected no significant difference between groups. The pathological complete response rates with neoadjuvant therapy were significantly better in patients with BRCA variations than those without BRCA variations (49.2% vs. 29.6%, p = 0.024)., Conclusion: Patients with BRCA1 variation had more aggressive tumor characteristics, such as higher Ki67 and higher grade. Also, triple-negative breast cancer was more common. The presence of BRCA1 variation may worsen survival outcomes. Neoadjuvant treatment responses of patients with BRCA variations were significantly better, and neoadjuvant treatment may contribute to survival outcomes in nonmetastatic patients with BRCA variations., (© 2024 University College London (UCL) and John Wiley & Sons Ltd.)

Background: Currently, the combination of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors and endocrine therapy is a first-line treatment for hormone-receptor-positive and HER2-negative metastatic breast cancer. This study aimed to assess the impact of changes in Mean Corpuscular Volume (MCV) on predicting responses to treatment and survival in patients with hormone-receptor-positive, HER2-negative metastatic breast cancer receiving CDK4/6 inhibitors and endocrine therapy., Methods: Retrospectively, data on hemoglobin levels, MCV, B12, folate levels, and survival times were collected from 275 patients. Patients were categorized into two groups based on the degree of MCV change (delta MCV ≤ 10 vs. >10). Kaplan-Meier survival analysis was performed, with significance set at p < 0.05., Results: The average age of the patients was 56.1 ± 12.1 years. In total, 72.7% received CDK4/6 inhibitors as first-line treatment, while 27.3% received them as second-line treatment. Before CDK4/6 inhibitor use, the median MCV level was 87.7 fL (IQR: 83-91), which increased to 98 fL (IQR: 92-103) after treatment ( p < 0.001). ECOG performance score, CDK4/6 inhibitor treatment line, type of endocrine therapy, and MCV change were identified as independent predictors of progression-free survival in the Cox regression model. The median progression-free survival for the entire group was 28 months. Patients with MCV delta > 10 had a median progression-free survival of 33 months, compared to 23 months for those with MCV delta ≤ 10 ( p = 0.029). There was no significant difference in median overall survival times between the two groups ( p = 0.158)., Conclusion: This study highlights that patients with MCV delta > 10 had longer median progression-free survival compared to those with MCV delta ≤ 10.

Aims and Objectives: Although cyclin-dependent kinase 4/6 inhibitors (CDK 4/6i) are a vital part of the treatment of hormone receptor (HR)-positive/HER-2-negative metastatic breast cancer (BC), individuals have different sensitivities to CDK4/6i, indicating the need for biomarkers. The fasting triglyceride glucose (TyG) index is an easily accessible surrogate marker of insulin resistance (IR). Herein, we investigated the prognostic significance of the fasting triglyceride glucose (TyG) index in HR+/HER2- metastatic BC patients treated with CDK4/6i plus endocrine therapy (ET)., Methods: About 333 patients with HR+/HER2-metastatic BC treated with CDK4/6i plus ET were analyzed retrospectively. The TyG index was calculated within 3 months before the initiation of CDK4/6i plus ET. The median value of 8.43 was taken as the cutoff for the TyG index., Results: The median overall survival (OS) was 73.6 months (95% CI, 66.0-81.1) in the whole cohort. The progression-free survival (PFS) was significantly longer in the low-TyG subgroup than in the high-TyG subgroup (30.1 vs. 21.3 months, multivariate adjusted [HR] = 0.666, 95% CI, 0.450-0.987, P = .043). While the median OS was not reached in the low TyG subgroup, it was 69.0 months in the high TyG subgroup (multivariate-adjusted HR = 0.513, 95% CI, 0.281-0.936, P = .030). Although the ORR and DCR were numerically greater in the low-TyG subgroup, no significant differences were observed between the low-TyG subgroup and high-TyG subgroup (28.1% vs. 24.7%, P = .476; 83.2% vs. 80.1%, P = .463, respectively)., Conclusions: These data imply that the TyG index could be a predictive biomarker for the therapeutic efficacy of CDK4/6is. Extensive prospective studies are needed to confirm these findings., Competing Interests: Disclosure The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aim: Comparison of prognosis and survival in human epidermal growth factor receptor 2 (HER2)-low and HER2-negative patients with early stage or locally advanced, hormone receptor-positive breast cancer., Material and Methods: In a retrospective single center study, the patients with early stage or locally advanced stage, hormone receptor (HR)-positive [estrogen receptor (ER) ≥ 1% and/or progesterone receptor (PR) ≥ 1%] and HER2 negative or HER2 low invasive breast cancer diagnosis were included. A total of 444 patients were included in the study. Patients were divided into two groups: HER2 negative and HER2 low. There were 235 (53%) patients in the HER2 negative group and 209 (47%) patients in the HER2 low group., Results: The HER2 low group had significantly longer 5‑year disease-free survival (DFS) than the HER2 negative group. The patients with lower Ki67 (< 20%) also had a longer 5‑year DFS., Conclusion: Nonmetastatic HR+/HER2 low breast cancer patients had better DFS than HR+/HER2 negative ones. The Ki67 level and HER2 low status were independent prognostic factors. Randomized clinical trials are needed in early stage HER2 low breast cancer patients., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Objective: Hereditary cancer syndromes constitute 5-10% of all cancers. The development of next-generation sequencing technologies has made it possible to examine many hereditary cancer syndrome-causing genes in a single panel. This study's goal was to describe the prevalence and the variant spectrum using NGS in individuals who were thought to have a hereditary predisposition for cancer., Material and Method: Analysis was performed for 1254 who were thought to have a familial predisposition for cancer. We excluded 46 patients who were carrying BRCA1/2 variants in this study, for focusing on the rare gene mutations. Sequencing was performed using the Sophia Hereditary Cancer Solution v1.1 Panel and the Qiagen Large Hereditary Cancer Panel. The Illumina MiSeq system was used for the sequencing procedure. The software used for the data analyses was Sophia DDM and QIAGEN Clinical Insight (QCITM) Analyze. The resulting genomic changes were classified according to the current guidelines of ACMG/AMP., Results: Pathogenic/likely pathogenic variants were detected in 172 (13.7%) of 1254 patients. After excluding the 46 BRCA1/2-positive patients, among the remaining 126 patients; there were 60 (4.8%) breast cancer, 33 (2.6%) colorectal cancer, 9 (0.7%) ovarian cancer, 5 (0.4%) endometrium cancer, 5 (0.4%) stomach cancer, 3 (0.2%) prostate cancer patients. The most altered genes were MUTYH in 27 (2.1%) patients, MMR genes (MLH1, MSH6, MSH, MSH2, PMS2 and EPCAM) in 26 (2%) patients, and ATM in 25 (2%) patients. We also examined the genotype-phenotype correlation in rare variants. Additionally, we identified 11 novel variations., Conclusion: This study provided significant information regarding rare variants observed in the Turkish population because it was carried out with a large patient group. Personalized treatment options and genetic counseling for the patients are therefore made facilitated., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: Cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors are the new generation drugs that have been started to be used in our clinical practice recently. These drugs have been shown to have better progression-free survival compared to standard therapy in patients with hormone receptor-positive (HR) and human epidermal growth factor receptor 2 (HER-2)-negative breast cancer. The most common side effects of CDK 4-6 inhibitors are neutropenia, nausea, leukopenia, fatigue, and diarrhea. This case demonstrated vortex keratopathy in both eyes, a rare condition in patients with breast cancer treated with ribociclib., Case Report: A 68-year-old female patient was diagnosed with locally advanced HR (+)/HER2 (-) breast cancer in March 2015. In June 2021, bone metastases were detected. The patient was started on ribociclib and fulvestrant. After three cycles of ribociclib and fulvestrant treatment, she was admitted with the complaint of blurred vision in her left eye. Slit-lamp biomicroscopy examination revealed subepithelial haze with central subepithelial whorls in both corneas, more in the left eye, and also a mild punctate epithelial staining was observed with the application of fluorescein dye., Management and Outcome: Ribociclib treatment was immediately discontinued and no changes were observed in the cornea and vision levels during the one-month follow-up., Discussion: Routine and regular follow-up eye examinations in breast cancer patients treated with ribociclib may benefit patients in our daily clinical practice and may help us to detect side effects at an early stage and to manage them more effectively.