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Hikmat Abdel-Razeq,1,2 Baha Sharaf,1 Suhaib Khater,1 Huda Jafar Baidoun,2 Hira Bani Hani,1 Ayat Taqash,3 Osama El Khatib,1 Sarah Edaily,1 Mahmoud Abunasser,1 Faris Tamimi,1 Yosra Nabeel Al-Masri,1 Tamer Moh’d Waleed Al-Batsh,1 Anas Zayed,1 Tala Ghatasheh,1 Tala Radaideh1 1Department of Internal Medicine, Section of Hematology and Medical Oncology, King Hussein Cancer Center, Amman, Jordan; 2School of Medicine, the University of Jordan, Amman, Jordan; 3Office of Scientific Affairs and Research. King Hussein Cancer Center, Amman, JordanCorrespondence: Hikmat Abdel-Razeq, Department of Internal Medicine, Section of Hematology and Medical OncologyKing Hussein Cancer Center, 202 Queen Rania Al Abdullah Street, P.O. Box: 1269, Amman, 11941, Jordan, Tel: +962-6 5300460, Email habdelrazeq@khcc.joBackground: Cyclin-dependent kinase (CDK) 4/6 inhibitors have revolutionized the treatment landscape of hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2 −) metastatic breast cancer (MBC). Here, we present the real-world clinical outcomes and toxicity data of patients treated at a single cancer center.Methods: A retrospective analysis was conducted on patients with HR+/HER2− MBC treated with ribociclib plus endocrine therapy (ET). Outcomes measured included progression-free survival (PFS), overall survival (OS), and adverse events.Results: A total of 356 patients (median age 52, range 27– 91 years) were enrolled, all with metastatic disease; 204 (57.5%) had de novo metastasis, and 183 (51.4%) had visceral metastasis. Ribociclib was combined with aromatase inhibitors in 321 patients (90.2%) and with fulvestrant in 35 patients (9.8%). Dose reduction was needed in 101 patients (28.4%), primarily due to neutropenia (21.3%) and abnormal liver enzymes (5.9%). After a median follow-up of 36.3 months, median PFS was 27.3 months (95% CI: 21.3– 31.7). PFS was significantly better in patients receiving ribociclib as first-line therapy (32.1 months, 95% CI: 27.7– 42.1, p < 0.0001) and those with non-visceral metastasis (38.6 months, 95% CI: 29.8–NR, p < 0.0001). Similarly, OS was significantly better in first-line treatment (48.6 months, 95% CI: 39.1–NR) and non-visceral metastasis cases (NR, 95% CI: 40.6–NR, p < 0.0001). No significant differences in 3-year PFS and OS were found between patients with and without dose reductions.Conclusion: In real-world settings, and away from the stringency of controlled clinical trials, endocrine therapy in combination with ribociclib in patients with HR-positive/HER2-negative MBC is an effective and well-tolerated therapy with a manageable toxicity profile and a low drug discontinuation rate. Dose reduction due to toxicity did not worsen the outcome.Keywords: metastatic breast cancer, MBC, CDK4/6 inhibitors, ribociclib, aromatase inhibitors, fulvestrant

Background: Germline genetic testing (GGT) has significant implications in the management of patients with prostate cancer (PCa). Herein, we report on patterns and frequency of pathogenic/likely pathogenic germline variants (P/LPGVs) among newly diagnosed Arab patients with PCa., Methods: Patients meeting the National Comprehensive Cancer Network (NCCN) eligibility criteria for GGT were offered a 19-gene PCa panel or an expanded 84-gene multi-cancer panel., Results: During the study period, 231 patients were enrolled; 107 (46.3%) had metastatic disease at diagnosis. In total, 17 P/LPGVs were detected in 17 patients (7.4%). Among the 113 (48.9%) patients who underwent GGT with the 19-gene panel, eight (7.1%) had P/LPGVs, compared to nine (7.6%) of the 118 (51.1%) who did GGT through the expanded 84-gene panel (P = 0.88). Variant of uncertain significance (VUS) rate was higher (n = 73, 61.9%) among the group who underwent expanded 84-gene panel testing compared to those who underwent the 19-gene PCa panel (n = 35, 30.9%) (P = 0.001). P/LPGVs in DNA damage repair (DDR) genes, most frequently BRCA2 , CHEK2 and TP53 , were the most common P/LPGVs findings., Conclusion: This study is the first to characterize the germline genetic profile of an Arab population with PCa. All detected P/LPGVs were potentially actionable, with most variants able to be detected with a PCa-specific panel., Competing Interests: Edward D. Esplin and Sarah M. Nielsen are employees and shareholders of Invitae Corp. Brandie Heald are former employees and shareholders of Invitae Corp. Edward D. Esplin is an advisor and stockholder of Taproot Health and Exir Bio. All listed authors have no conflict of interest to declare., (Copyright 2024, Abu Hijlih et al.)

Purpose: Breast cancer that overexpresses the human epidermal growth factor receptor-2 (HER2) and both estrogen (ER) and progesterone (PR) receptors is recently recognized as a subtype (triple-positive) with distinctive behavior and response to treatment. In this study, we investigate the treatment outcomes and the beneficial effect of anti-HER2 treatment in relation to level of hormone-receptor (HR) expression., Methods: Consecutive breast cancer patients with triple-positive disease, diagnosed, treated and followed at our institution between 2006 and 2016 were enrolled. Disease-free survival (DFS) was studied in relation to the level of HR-positivity., Results: During the study period, a total of 312 were enrolled; median age (range) was 47 (20-83) years. Fifty (16.0%) of the enrolled patients received adjuvant chemotherapy without trastuzumab (cohort A). All remaining patients were treated with both chemotherapy and trastuzumab and were divided into two groups: Cohort B with both ER and PR scores ≥ 50% (n = 130, 41.7%) and Cohort C with ER and/or PR < 50% (n = 132, 42.3%). After a median follow-up of 47 months, 14 (28.0%), 30 (23.1%) and 20 (15.2%) patients in cohorts A, B, and C had an event in a form of local/system relapse or death while disease-free. The estimated 5-year DFS was 56.2%, 75.4%, and 80.8%, respectively, and at 7 year was 56.2%, 67.1%, and 78.0%, respectively (p < 0.001)., Conclusions: HER2-positive tumors are not homogeneous; stronger ER/PR co-expression may weaken the beneficial effect of anti-HER2 therapy. Such findings may have potential implication on modifying anti-HER2 treatment based on the strength of HR expression.