Very high frequencies of Familial Breast Cancer, low BRCA1/2 mutations and high Luminal molecular subtypes in Eastern Saudi Arabia necessitate the hunt for novel breast cancer hub genes

This study was carried out to find out incidence of familial breast cancer, frequencies of different histological and molecular subtypes of breast cancer, and proportion of breast cancer patient with BRCA1/2 mutations, to plan for its implementation in early cancer screening and personalized treatment in Eastern Saudi Arabia. The breast cancer incidence increased from 2009-2016 and peaked in 2012. Ductal carcinoma (80%) was the most common histological type and Luminal A/B the most common (74%) molecular types among all patients. The familial and non-familial breast cancer groups were compared based on their demographic and clinical characteristics. The mean age at diagnosis was 51.6±13.5 and 53.5±12.7 for familial and non-familial breast cancer patients respectively. A total of 10 (24.3%) of familial breast cancer patients were tested for BRCA gene mutations, and 5 (12.2%) were abnormal, making it 4.3% of total patients. In the familial group, significant correlation (p 0.04) was found between patients with age less than 50 and with more than one family member affected with breast or ovarian cancer. Significance was found between unilateral familial breast cancer and bone metastasis (p 0.004). In both familial and non-familial groups, significant correlation was found between unilateral breast cancer and liver metastasis (0.005 and 0.017 respectively). There was a significant association between unilateral non-familial breast cancer and luminal A molecular type (p 0.012). Analysis of TNM staging showed that (61%) of familial breast cancer patients were diagnosed at stage II. In conclusion, familial breast cancer incidence is increasingly high in Al-Ahsa region as compared to western populations which could be due to consanguineous marriage and social behaviors. It warrants further studies to explore familial breast cancer hub genes in Eastern Saudi Arabia and its implementation in early diagnosis and patient-tailored treatment of breast cancer. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Protocols ### Funding Statement This study did not receive any funding. This study was approved by King Abdullah International Medical Research Centre (KAIMRC) project # RA17.004.A. No funding was provided from KAIMRC for this study. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was carried out at King Abdulaziz Hospital and King Saud Bin Abdulaziz University of Health Sciences, Al-Ahsa, Saudi Arabia and study was approved by Scientific Committee and Institutional Review Board of King Abdullah Internatioanl Medical Research Centre (KAIMRC) that is the ethical review board for all participating centres. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present work are contained in the manuscript