Prognostic impact of EGFR mutation in non-small-cell lung cancer patients with family history of lung cancer

Abstract

BackgroundA family history can be a valuable tool in the era of precision medicine. Although a few studies have described an association of family history of lung cancer with EGFR activating mutation, their impact on survival of lung cancer patients is unclear.MethodsThe study included consecutive 829 non-small-cell lung cancer patients who received analysis of EGFR mutation in a prospective lung cancer cohort. Family history of lung cancer was obtained by face-to-face interviews at the time of diagnosis. An association of EGFR activating mutation with a family history of lung cancer in first-degree relatives was evaluated with multivariate logistic regression analysis, and its association with survival was estimated with Cox’s proportional hazards model.ResultsSeventy five (9.0%) patients had family history of lung cancer. The EGFR mutation was commonly observed in patients with positive family history compared to those with no family history (46.7% v 31.3%, χ2 p = 0.007). The family history was significantly associated with the EGFR mutation (aOR and 95% CI: 2.01 and 1.18–3.60, p = 0.011). Patients with the positive family history survived longer compared to those without (MST, 17.9 v 13.0 months, log-rank p = 0.037). The presence of the EGFR mutation was associated with better survival in patients without the family history (aHR and 95% CI: 0.72 and 0.57–0.90, p = 0.005). However, this prognostic impact was not observed in patients with the positive family history (aHR and 95% CI: 1.01 and 0.50–2.36, p = 0.832).ConclusionsIn comparison to patients without the family history, EGFR activating mutation was common, and it did not affect prognosis in patients with positive family history.

Computer-Aided Nodule Assessment and Risk Yield (CANARY) may facilitate non-invasive prediction of EGFR mutation status in lung adenocarcinomas

“…Although we observed a trend towards less V-I-R-O among the small group (n = 6) of L858R EGFR mutant cases, the difference did not reach statistical significance and additional cases are needed to explore this association. EGFR has diverse mutations and as a whole is not clearly tied to outcome in adenocarcinoma of the lung 38 . We did not find a relationship between BCG and EGFR status as originally hypothesized – but rather the individual exemplars Y and G. BCG is tied to indolent histopathology and good prognosis in adenocarcinoma of the lung 23 , 25 , so the lack of a relationship between EGFR and BCG makes sense.…”

“…We did not find a relationship between BCG and EGFR status as originally hypothesized – but rather the individual exemplars Y and G. BCG is tied to indolent histopathology and good prognosis in adenocarcinoma of the lung 23 , 25 , so the lack of a relationship between EGFR and BCG makes sense. The histopathologic correlate of Y and G is not entirely clear–a mix of an exemplar associated with good prognosis (G) and associated with intermediate prognosis (Y) – however EGFR does not clearly impact prognosis either 38 . Perhaps this mix of exemplars suggests increased tumor heterogeneity in EGFR-mutated tumors – but this needs further determination.…”

Emerging role of EGFR and lung cancer treatments

“…It has been observed that about NSCLC, mutations in EGFR are common. 6 Frequent genetic polymorphisms and inactivation of tumor suppressor genes damage to chromosomes 3p, 5q, 13q, and 17p are predominantly regular in small cell lung carcinoma. [7][8][9][10]…”

<p>Safety, tolerability, and pharmacokinetics of simotinib, a novel specific EGFR tyrosine kinase inhibitor, in patients with advanced non-small cell lung cancer: results of a phase Ib trial</p>

“…In patients with NSCLC, the overall reported prevalence of EGFR -gene mutations is 33.1%, with higher prevalence in women, Asian populations (India, China, Japan and Taiwan), non-smokers and in those with adenocarcinoma 6. Also, their presence is associated with significantly longer survival of these patients as compared to EGFR wild type (13.3 vs 30.9 months, P <0.001) 4. The introduction of EGFR tyrosine kinase inhibitors (EGFR-TKIs) in the therapy of NSCLC has been an important step-forward with significant clinical benefit especially in those harboring EGFR mutations 7–11…”

“…Non-small cell lung cancer (NSCLC) represents up to 87.0% of the total lung cancer cases, is associated with 30–40% 1-year net survival rate, and many patients are diagnosed with advanced disease due to its insidious onset 2,3. Despite introduction of molecular-targeted therapies and histology-based cytotoxic chemotherapy, the survival of these patients is limited 4…”