<abstract xmlns="http://www.w3.org/1999/xhtml"><p>The most frequently identified genetic cause of breast cancer is the germline mutation of <italic>BRCA1</italic> and 2 genes. The carriers of these mutations are at high risk for breast and ovarian cancers and increased risk for pancreatic and prostate cancers. Personal and family history are routinely used to identify individuals at risk for carrying such mutations. Genetic counselling is required to guide them through genetic testing and risk management. Positive testing corresponds to a deleterious mutation, whereas negative testing is considered as uninformative; variants of unknown clinical significance are also classified as uninformative.</p><p>The most effective risk reduction strategy involves bilateral prophylactic mastectomy and bilateral salpingo-oophorectomy, eliminating 90% of breast and 97% of ovarian cancer risks, respectively. Before and until such surgery, surveillance with physical examination, mammography and magnetic resonance mammography, starting at 25–30 years of age, are recommended for the early diagnosis of breast cancer; semi-annual surveillance with physical examination, transvaginal ultrasound and serum CA-125 is recommended for women who have not had prophylactic surgery. Carriers diagnosed with breast cancer run a high risk for a new breast primary and this information should be used accordingly. PARP inhibitors is a new class of antineoplastic agents, already approved for advanced <italic>BRCA1/2</italic> mutant (germline or somatic) ovarian cancer.</p><p>Multigene panel testing may follow a negative <italic>BRCA</italic> genetic test, often identifying other genetic causes of cancer, expanding its role in oncology. Further adoption of PARP inhibitors, refinement in estimation of BRCA-associated cancer risks and wider population testing, through NGS technology, may become available in the near future.</p></abstract>

BRCA1/2 associated cancer susceptibility: a clinical overview

<abstract xmlns="http://www.w3.org/1999/xhtml"><p>Metabolic syndrome, a clustering of risk factors including obesity, has emerged as a global health plague. A lot of epidemiological and clinical evidence suggests that the metabolic syndrome is linked not only to cardiovascular diseases and diabetes mellitus type 2 but also to cancer development and progression. In this review the potential mechanisms tying the metabolic syndrome with cancer are presented. The role of insulin resistance and hyperinsulinemia, the activation of insulin-like growth factor-1 (IGF-1) pathway, and the induction of cytotoxic products are highlighted. Subsequent effects leading to oxidative stress, release of lipokines with signaling properties by adipocytes, development of a sustained systemic inflammation, production of inflammatory cytokines, and establishment of a tumorigenic environment are also discussed. The importance of the metabolic syndrome and obesity coupled with the deeper understanding of the underlying molecular mechanisms has trigger intensive clinical research with an aim to prevent the risk of cancer and improve outcomes. Moreover, the need for lifestyle changes with increased physical activity and improved dietary quality has been emerged as urgent health priority.</p></abstract>

Metabolic syndrome and Cancer: Do they share common molecular pathways?

<abstract xmlns="http://www.w3.org/1999/xhtml"><sec id="j_fco-2016-0007_s_333_w2aab3b8b8b1b7b1aab1c13b1Aa"><h3>Purpose</h3><p>Adjuvant trastuzumab is currently an internationally standard for the treatment of localised breast cancer that over express HER2 with the most adverse effect being cardiotoxicity. We conducted this study to evaluate the cardiac safety of trastuzumab in clinical practice.</p></sec><sec id="j_fco-2016-0007_s_334_w2aab3b8b8b1b7b1aab1c13b2Aa"><h3>Methods</h3><p>This study is a retrospective observational single institutional study conducted in the Oncology Center of King Abdulla Medical City (KAMC), Makkah, Saudi Arabia, from June 2011 to January 2014. We evaluated the incidence of cardio toxicity and associated risk factors during adjuvant trastuzumab treatment.</p></sec><sec id="j_fco-2016-0007_s_335_w2aab3b8b8b1b7b1aab1c13b3Aa"><h3>Results</h3><p>Of 57 patients, 20 patients (35%) exhibited cardiotoxicity. About 14% of patients had drop of left ventricular ejection fraction (LVEF) below 50%, whilst 10% and 15% drop of LVEF below their baseline levels were found in 30% and 5% of patients, respectively. About 98.3% of our patients have completed treatment, of whom 21% had a provisional interruption because of a fall in LVEF. A definitive trastuzumab discontinuation has been made in 1.75% of cases because of a nonregressive reduction in LVEF. Analysis of risk factors related to trastuzumab cardio toxicity found that patients older than 40 years were more likely to develop cardio toxicity compared to those younger than 40 years. This difference was statistically significant (p = 0.042).</p></sec><sec id="j_fco-2016-0007_s_336_w2aab3b8b8b1b7b1aab1c13b4Aa"><h3>Conclusion</h3><p>In our study, the cardiac safety seems comparable with the literature data. Trastuzumab-related cardiotoxicity is manifested by an asymptomatic decrease in the LVEF and less commonly by clinical heart failure. Most instances are transient, asymptomatic and reversible.</p></sec></abstract>

Clinical Oncology and Nuclear Medicine, Faculty of Medicine, Mansoura University, Egypt, Mansoura,

Cardiology, King Abdulla Medical City Makkah, Kingdom of

Medical Oncology, Oncology Center of King Abdulla Medical City (KAMC), Makkah, Kingdom of

Cardiotoxicity of the adjuvant trastuzumab in a Saudi population: clinical experience of a single institution

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Volume 7 (2016): Issue 2 (June 2016)

BRCA1/2 associated cancer susceptibility: a clinical overview

Metabolic syndrome and Cancer: Do they share common molecular pathways?

Cardiotoxicity of the adjuvant trastuzumab in a Saudi population: clinical experience of a single institution

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