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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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Related in: MedlinePlus

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.
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fig2: 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.

Mentions: The data regarding distant disease-free survival are shown in Table 5 and Figure 2A–C and regarding breast cancer-specific survival in Table 5 and Figure 2D–F. The Kaplan–Meier curves showed a nonsignificant decreased distant disease-free (P=0.06) and breast cancer-specific survival (P=0.14) for CHEK2-associated patients compared with non-CHEK2 patients (Figure 2A and D).


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)

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

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

fig2: 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.
Mentions: The data regarding distant disease-free survival are shown in Table 5 and Figure 2A–C and regarding breast cancer-specific survival in Table 5 and Figure 2D–F. The Kaplan–Meier curves showed a nonsignificant decreased distant disease-free (P=0.06) and breast cancer-specific survival (P=0.14) for CHEK2-associated patients compared with non-CHEK2 patients (Figure 2A and D).

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