Frequency and mutational spectrum of PIK3CA gene mutations in breast cancer patients: Largest and first report from Lebanon.

The PIK3CA pathway is one of the most frequently altered pathways in human cancers, especially in breast cancer with approximately 40% of HR+/HER2- advanced breast cancer cases exhibiting mutations in the PIK3CA gene. While the mutations can occur across the entire gene, the most common are observed in exon 9 corresponding to the helical domain, and in exon 20 encompassing the kinase domain. This study constitutes the first attempt at determining the frequency and mutational spectrum in Lebanese breast cancer patients. For this purpose, DNA samples from 280 breast cancer patients from across Lebanon were screened for PIK3CA mutations using the Therascreen® PIK3CA RGQ Real-time PCR assay. In line with previous reports, 38.57% of cases were positive for at least one PIK3CA mutation, among which approximately 59% were in exon 9 and 37% in exon 20. However, PIK3CA mutations are breast cancer are heterogeneous whereby 20% of known PIK3CA mutants might not be detected by compact PCR based assays. Thus, the adoption of comprehensive Next Generation Sequencing based panels to decipher the complete clinical, molecular and immunohistochemical profile of breast cancer tumor requires further investigation.

Prevalence of Her2-neu status and its clinicopathological association in newly diagnosed gastric cancer patients.

BACKGROUND: This study aimed to report the prevalence of HER2-neu in newly diagnosed early or metastatic gastric cancer (GC) patients, to determine the percentage of patients achieving various IHC scores correlating with the ISH results and to establish a database for GC patients in Lebanon. METHODS: This was a national, multicenter, descriptive and cross-sectional study in patients with histologically confirmed early or metastatic GC newly diagnosed. All eligible patients underwent the IHC and ISH tests in a central laboratory. Demographics, medical history and histopathology data were collected. RESULTS: One hundred fifty-seven patients were included (mean age at diagnosis: 63 ± 14.1 years) during a 3.5 year period. The prevalence of HER2-neu over expression was 21% (95% CI: 15.3-27.4) using ICH and ISH. Agreement between IHC and ISH results was significantly substantial (kappa = 0.681; p-value < 0.001). Over expressed HER2-neu status was significantly associated with high ECOG performance status only. CONCLUSIONS: The prevalence of HER2-neu over expression in newly diagnosed early or metastatic GC patients seemed to be high in Lebanon. The database generated allows to monitor trends in the epidemiology and management of GC.

Concomitant docetaxel plus gemcitabine versus sequential docetaxel followed by gemcitabine in anthracycline-pretreated metastatic or locally recurrent inoperable breast cancer patients: a prospective multicentre trial of the Central European Cooperative Oncology Group (CECOG).

Docetaxel (D) plus gemcitabine (G) is an active combination in anthracycline pre-treated breast cancer. Impact of sequential administration of these drugs is unclear. This trial aimed to compare concomitant DG with sequential D --> G. Patients were randomised to eight cycles of gemcitabine 1,000 mg/m2 on days 1 + 8 plus docetaxel 75 mg/m2 on day 8, or 4 cycles of docetaxel 100 mg/m2 on day 1, followed by four cycles of gemcitabine 1,250 mg/m2 on days 1 + 8, in a 21-day schedule. Time to progression (TTP) was defined as primary endpoint; secondary endpoints were overall response rate (ORR), response duration (RD), overall survival (OS) and toxicity. Due to poor recruitment, the trial was terminated after 100 of a pre-planned 430 patients. Patient characteristics were well balanced. No significant difference was observed in terms of TTP, ORR, RD and OS. Grade 3/4 adverse events encompassed leucopoenia (29 vs.68%, P < 0.001), neutropoenia (49 vs. 83%, P < 0.001) and febrile neutropoenia (4 vs. 9%, n.s.), all favouring D --> G. No difference in efficacy was observed between concomitant and sequential treatment. D --> G produced significantly more episodes of haematological toxicity due to the administration of docetaxel at 100 mg/m2 without GCSF support.