Survival and contralateral breast cancer in CHEK2 1100delC breast cancer patients: impact of adjuvant chemotherapy

Abstract

Background:We assessed the sensitivity to adjuvant chemotherapy in cell cycle checkpoint kinase 2 (CHEK2) vs non-CHEK2 breast cancer patients by comparing the contralateral breast cancer incidence and distant disease-free and breast cancer-specific survival between both groups, stratified for adjuvant chemotherapy.Methods:One Dutch hereditary non-BRCA1/2 breast cancer patient cohort (n=1220) and two Dutch cohorts unselected for family history (n=1014 and n=2488, respectively) were genotyped for CHEK2 1100delC. Hazard ratios for contralateral breast cancer, distant disease-free and breast cancer-specific death for mutation carriers vs noncarriers were calculated using the Cox proportional hazard method, stratified for adjuvant chemotherapy.Results:The CHEK2 mutation carriers (n=193) had an increased incidence of contralateral breast cancer (multivariate hazard ratio 3.97, 95% confidence interval 2.59–6.07). Distant disease-free and breast cancer-specific survival were similar in the first 6 years in mutation carriers compared with noncarriers, but diverted as of 6 years after breast cancer diagnosis (multivariate hazard ratios and 95% confidence intervals 2.65 (1.79–3.93) and 2.05 (1.41–2.99), respectively). No significant interaction between CHEK2 and adjuvant chemotherapy was observed.Conclusions:The CHEK2 1100delC-associated breast cancer is associated with a higher contralateral breast cancer rate as well as worse survival measures beyond 6 years after diagnosis. No differential sensitivity to adjuvant chemotherapy was observed in CHEK2 patients.

A Comparison between <b><i>CHEK2</i></b>*1100delC/I157T Mutation Carrier and Noncarrier Breast Cancer Patients: A Clinicopathological Analysis

“…An association between the CHEK2 *1100delC mutation and bilateral breast cancer was found in some studies [7,17,18]. The presence of this mutation was also associated with a 3.5-fold risk of a second breast cancer [12].…”

CHEK2 c.1100delC allele is rarely identified in Greek breast cancer cases

“…CHEK2 c.1100delC mutation carriers tend to develop contralateral breast cancer more frequently, when compared with non-carriers (32). It is not clear if this can be also attributed to radiation therapy used as a treatment method of the primary breast cancer.…”

Associations of pathogenic mutations responsible for breast cancer risk with histology and immunohistochemistry in Romanian population

“…Although this finding was interesting, due to the limited number of cases we cannot have a firm conclusion of this association, further studies being needed to clear up this question ( Table 2). This possible correlation can be argued by a Danish study from 2014, in which the authors claim an increased risk of contralateral breast cancer in patients CHEK2, but this risk was assessed only for 1100delC mutation which is the most common pathogenic variant of this gene [26].…”