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. 2014 Aug 26;111(5):1004-13.
doi: 10.1038/bjc.2014.306. Epub 2014 Jun 10.

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

M Kriege  1 , A Hollestelle  1 , A Jager  1 , P E A Huijts  2 , E M Berns  3 , A M Sieuwerts  3 , M E Meijer-van Gelder  3 , J M Collée  4 , P Devilee  2 , M J Hooning  1 , J W M Martens  1 , C Seynaeve  1
Affiliations

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

M Kriege et al. Br J Cancer. .

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.

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Figures

Figure 1
Figure 1
Contralateral breast cancer rate for CHEK2-positive (green line) and CHEK2-negative patients (blue line) in (A) all patients, (B) patients not treated with systemic therapy and (C) patients treated with systemic therapy. *Patients with synchronous contralateral breast cancer and patients from the non-BRCA1/2 cohort were excluded for this analysis regarding metachronous contralateral breast cancer. #In (B and C), stratified for adjuvant chemotherapy, one additional carrier and four noncarriers for whom treatment with adjuvant chemotherapy was unknown were excluded. The full colour version of this figure is available at British Journal of Cancer online.
Figure 2
Figure 2
Distant disease-free survival for CHEK2-positive (green line) and CHEK2-negative patients (blue line) in (A) all patients, (B) patients not treated with adjuvant chemotherapy and (C) patients treated with adjuvant chemotherapy, and breast cancer-specific survival for CHEK2-positive (green line) and CHEK2-negative patients (blue line) in (D) all patients, (E) patients not treated with adjuvant chemotherapy and (F) patients treated with adjuvant chemotherapy. *In (B, C, E and F) stratified for adjuvant chemotherapy, an additional 7 carriers and 54 noncarriers for whom treatment with adjuvant chemotherapy was unknown were excluded.
See this image and copyright information in PMC

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