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

Kriege M, Hollestelle A, Jager A, Huijts PE, Berns EM, Sieuwerts AM, Meijer-van Gelder ME, Collée JM, Devilee P, Hooning MJ, Martens JW, Seynaeve C - Br. J. Cancer (2014)

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

Affiliation: Family Cancer Clinic, Department of Medical Oncology, Erasmus MC Cancer Institute, Groene Hilledijk 301, 3075 EA Rotterdam, The Netherlands.

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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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.
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fig1: 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.

Mentions: The incidence of metachronous contralateral breast cancer was higher in CHEK2 1100delC mutation carriers than in noncarriers, with a 10-year risk of 28.9% vs 8.5%, respectively (Table 4 and Figure 1). In a multivariate analysis, the risk of contralateral breast cancer remained higher in mutation carriers compared with noncarriers (HR 3.97, 95% CI 2.59–6.07).


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

Kriege M, Hollestelle A, Jager A, Huijts PE, Berns EM, Sieuwerts AM, Meijer-van Gelder ME, Collée JM, Devilee P, Hooning MJ, Martens JW, Seynaeve C - Br. J. Cancer (2014)

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.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4150261&req=5

fig1: 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.
Mentions: The incidence of metachronous contralateral breast cancer was higher in CHEK2 1100delC mutation carriers than in noncarriers, with a 10-year risk of 28.9% vs 8.5%, respectively (Table 4 and Figure 1). In a multivariate analysis, the risk of contralateral breast cancer remained higher in mutation carriers compared with noncarriers (HR 3.97, 95% CI 2.59–6.07).

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

Affiliation: Family Cancer Clinic, Department of Medical Oncology, Erasmus MC Cancer Institute, Groene Hilledijk 301, 3075 EA Rotterdam, The Netherlands.

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.

Show MeSH
Related in: MedlinePlus