Evaluation of the EGFR polymorphism R497K in two cohorts of neoadjuvantly treated breast cancer patients

Abstract

Pathological response of breast cancer to neoadjuvant chemotherapy (NAC) presents great variability, and new prognostic biomarkers are needed. Our aim was to evaluate the association of the epidermal growth factor receptor gene (EGFR) polymorphism R497K (rs2227983) with prognostic features and clinical outcomes of breast cancer, including the pathological response to NAC and the recurrence-free survival (RFS). Tumoral complete response (tCR) was defined by no remaining invasive cancer in the excised breast, whereas pathological complete response (pCR) was defined by no remaining invasive cancer both in the excised breast and lymph nodes. Two independent cohorts were analyzed: one from Brazil (INCA, n = 288) and one from The Netherlands (NKI-AVL, n = 255). In the INCA cohort, the variant (Lys-containing) genotypes were significantly associated with lower proportion of tCR (ORadj = 0.92; 95%CI = 0.85–0.99), whereas in the NKI-AVL cohort they were associated with tumor grade 3 (p = 0.035) and with triple-negative subtype (p = 0.032), but not with clinical outcomes. Such distinct prognostic associations may have arisen due to different neoadjuvant protocols (p < 0.001), or to lower age at diagnosis (p < 0.001) and higher proportion of tumor grade 3 (p = 0.018) at the NKI-AVL cohort. Moreover, NKI-AVL patients achieved better proportion of pCR (21.2% vs 8.3%, p < 0.001) and better RFS (HRadj = 0.48; 95% adjCI = 0.26–0.86) than patients from INCA. In conclusion, large scale studies comprehending different populations are needed to evaluate the impact of genome variants on breast cancer outcomes.

The Investigation of Associations between TP53 rs1042522, BBC3 rs2032809, CCND1 rs9344, EGFR rs2227983 Polymorphisms and Breast Cancer Phenotype and Prognosis

“…In the present study, we did not find significant associations between EGFR rs2227983 and clinicopathological features. In contrast, some studies showed that rs2227983 was statistically associated with differentiation degree (tumour grade) and lymph node involvement, which was not found in our study [19,34,35]. Interestingly, Sobral-Leite et al [34] reported that a poorly differentiated tumor was more common in patients with GA and AA genotypes.…”

“…In contrast, some studies showed that rs2227983 was statistically associated with differentiation degree (tumour grade) and lymph node involvement, which was not found in our study [19,34,35]. Interestingly, Sobral-Leite et al [34] reported that a poorly differentiated tumor was more common in patients with GA and AA genotypes. While, in the study by Kallel et al [19], a poorly differentiated tumor was more frequently diagnosed in patients who had GG genotype.…”

The association of epidermal growth factor variant with oral squamous cell carcinoma

“…In many independent studies using samples representing different malignancies such as lung, breast, renal, and prostate, the role of excessive EGF and EGFR activities in the carcinogenesis mechanism has been demonstrated. (Fujiwara, Eguchi, Sogawa, Ono, Murakami, Ibaragi, Asaumi, Calderwood, et al, 2018; Liu et al, 2015; Sobral‐Leite et al, 2017; Teixeira et al, 2014). In addition, increased signaling from EGF and EGFR has been shown in OSCC (Fujiwara, Eguchi, Sogawa, Ono, Murakami, Ibaragi, Asaumi, Okamoto, et al, 2018).…”

Association between the methylation status of PCDH17 and the efficacy of neoadjuvant chemotherapy in triple-negative breast cancer

“…Several molecular markers have been identified to predict responses to NAC, including p53 ( 12 ), cytokeratin ck5/6 ( 13 ), epidermal growth factor receptor ( 14 ), Ki67 ( 15 ), and methylation of Ras association domain family 1 isoform A ( RASSF1A ) and WNT inhibitory factor-1 ( WIF-1 ) ( 16 ) in serum. However, biomarkers that can accurately predict the response to NAC in clinical settings remain limited.…”