2
36 Breast Diseases: A Year Book ® Quarterly 36 Vol 19 No 1 2008 breast cancer event (adjusted hazard ratio, 0.96; 95% confidence interval, 0.80-1.14; P = .63), and 155 intervention group women (10.1%) vs 160 comparison group women (10.3%) died (adjusted hazard ratio, 0.91; 95% confidence inter- val, 0.72-1.15; P = .43). No significant in- teractions were observed between diet group and baseline demographics, char- acteristics of the original tumor, baseline dietary pattern, or breast cancer treatment. Conclusion.—Among survivors of early stage breast cancer, adoption of a diet that was very high in vegetables, fruit, and fiber and low in fat did not reduce ad- ditional breast cancer events or mortality during a 7.3-year follow-up period. Please see expert perspective by Chlebowski. Increased Risk of Breast Cancer Associated With CHEK2*1100delC Weischer M, Bojesen SE, Tybjærg-Hansen A, et al (Herlev Univ, Denmark; Copenhagen Univ; Bispebjerg Univ, Denmark; et al) J Clin Oncol 25:57-63, 2007 Purpose.CHEK2*1100delC het- erozygosity has been associated with in- creased risk of breast, prostate, and colo- rectal cancer in case-control studies. We tested the hypothesis that CHEK2* 1100delC heterozygosity in the general population increases the risk of cancer in general, and breast, prostate, and colorec- tal cancer in particular. Patients and Methods.—We per- formed a prospective study of 9,231 indi- viduals from the Danish general popula- tion, who were observed for 34 years, and we performed a case-control study in- cluding 1,101 cases of breast cancer and 4,665 controls. Results.—Of the general population, 0.5% were heterozygotes and 99.5% were noncarriers. In the prospective study, multifactorially adjusted hazard ra- tios by CHEK2*1100delC heterozygosi- ty versus noncarriers were 1.2 (95% CI, 0.7 to 2.1) for all cancers, 3.2 (95% CI, 1.0 to 9.9) for breast cancer, 2.3 (95% CI, 0.6 to 9.5) for prostate cancer, and 1.6 (95% CI, 0.4 to 6.5) for colorectal cancer. In the case-control study, age-matched odds ratio for breast cancer by CHEK2*1100delC heterozygosity versus noncarriers was 2.6 (95% CI, 1.3 to 5.4). The absolute 10-year risk of breast cancer in CHEK2*1100delC heterozygotes amounted to 24% in women older than 60 years undergoing hormone replacement therapy, with a body mass index of 25 kg/m 2 or higher. Conclusion. CHEK2*1100delC heterozygosity is associated with a three- fold risk of breast cancer in women in the general population. Please see expert perspective by Weischer, Bojesen, and Nordestgaard. Breast Cancer Survival and Tumor Characteristics in Premenopausal Women Carrying the CHEK2*1100delC Germline Mutation Schmidt MK, Tollenaar RAEM, de Kemp SR, et al (The Netherlands Cancer Inst, Amsterdam; Leiden Univ, The Netherlands) J Clin Oncol 25:64-69, 2007 Purpose.—Women carrying a CHEK2*1100delC germline mutation have an increased risk of developing breast cancer. This study aims to deter- mine the proportion of CHEK2*1100 delC carriers in a premenopausal breast cancer population, unselected for family history of breast cancer, and to investigate tumor characteristics and disease outcome with sufficient follow-up. Patients and Methods.—We identi- fied a retrospective cohort of 1,479 pa- tients, who received surgery for invasive breast cancer between 1970 and 1994. All patients were diagnosed before age 50. Paraffin-embedded tissue blocks were collected for DNA isolation (normal tis- sue), subsequent CHEK2*1100delC analysis, and tumor revision. Median follow-up was 10.1 years. Results.—We detected a CHEK2* 1100delC germline mutation in 54 pa- tients (3.7%). Tumor characteristics of CHEK2*1100delC carriers did not differ significantly from those of noncarriers. CHEK2*1100delC carriers had a two- fold increased risk (hazard ratio [HR], 2.1; 95% CI, 1.0 to 4.3; P = .049) of de- veloping a second breast cancer and they had worse recurrence-free survival (HR, 1.7; 95% CI, 1.2 to 2.4; P = .006) and worse breast cancer-specific survival (HR, 1.4; 95% CI, 1.0 to 2.1; P = .072)

Breast Cancer Survival and Tumor Characteristics in Premenopausal Women Carrying the CHEK2*1100delC Germline Mutation

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Page 1: Breast Cancer Survival and Tumor Characteristics in Premenopausal Women Carrying the CHEK2*1100delC Germline Mutation

36 Breast Diseases: A Year Book®

Quarterly36 Vol 19 No 1 2008

breast cancer event (adjusted hazard ratio,0.96; 95% confidence interval, 0.80-1.14;P = .63), and 155 intervention groupwomen (10.1%) vs 160 comparisongroup women (10.3%) died (adjustedhazard ratio, 0.91; 95% confidence inter-val, 0.72-1.15; P = .43). No significant in-

teractions were observed between dietgroup and baseline demographics, char-acteristics of the original tumor, baselinedietary pattern, or breast cancer treatment.

Conclusion.—Among survivors ofearly stage breast cancer, adoption of adiet that was very high in vegetables, fruit,

and fiber and low in fat did not reduce ad-ditional breast cancer events or mortalityduring a 7.3-year follow-up period.

Please see expert perspective byChlebowski.

Increased Risk of BreastCancer Associated WithCHEK2*1100delCWeischer M, Bojesen SE, Tybjærg-HansenA, et al (Herlev Univ, Denmark;Copenhagen Univ; Bispebjerg Univ,Denmark; et al)

J Clin Oncol 25:57-63, 2007

Purpose.—CHEK2*1100delC het-erozygosity has been associated with in-creased risk of breast, prostate, and colo-rectal cancer in case-control studies. We tested the hypothesis that CHEK2*1100delC heterozygosity in the generalpopulation increases the risk of cancer ingeneral, and breast, prostate, and colorec-tal cancer in particular.

Patients and Methods.—We per-formed a prospective study of 9,231 indi-viduals from the Danish general popula-tion, who were observed for 34 years, andwe performed a case-control study in-cluding 1,101 cases of breast cancer and4,665 controls.

Results.—Of the general population,0.5% were heterozygotes and 99.5%were noncarriers. In the prospectivestudy, multifactorially adjusted hazard ra-tios by CHEK2*1100delC heterozygosi-ty versus noncarriers were 1.2 (95% CI,0.7 to 2.1) for all cancers, 3.2 (95% CI,1.0 to 9.9) for breast cancer, 2.3 (95% CI, 0.6 to 9.5) for prostate cancer, and 1.6(95% CI, 0.4 to 6.5) for colorectal cancer.In the case-control study, age-matchedodds ratio for breast cancer by

CHEK2*1100delC heterozygosity versusnoncarriers was 2.6 (95% CI, 1.3 to 5.4).The absolute 10-year risk of breast cancerin CHEK2*1100delC heterozygotesamounted to 24% in women older than 60years undergoing hormone replacementtherapy, with a body mass index of 25kg/m2 or higher.

Conclusion.—CHEK2*1100delCheterozygosity is associated with a three-fold risk of breast cancer in women in thegeneral population.

Please see expert perspective byWeischer, Bojesen, and Nordestgaard.

Breast Cancer Survival andTumor Characteristics inPremenopausal WomenCarrying the CHEK2*1100delCGermline Mutation Schmidt MK, Tollenaar RAEM, de KempSR, et al (The Netherlands Cancer Inst,Amsterdam; Leiden Univ, The Netherlands)

J Clin Oncol 25:64-69, 2007

Purpose.—Women carrying aCHEK2*1100delC germline mutationhave an increased risk of developing

breast cancer. This study aims to deter-mine the proportion of CHEK2*1100 delCcarriers in a premenopausal breast cancerpopulation, unselected for family historyof breast cancer, and to investigate tumorcharacteristics and disease outcome withsufficient follow-up.

Patients and Methods.—We identi-fied a retrospective cohort of 1,479 pa-tients, who received surgery for invasivebreast cancer between 1970 and 1994. Allpatients were diagnosed before age 50.Paraffin-embedded tissue blocks werecollected for DNA isolation (normal tis-sue), subsequent CHEK2*1100delC

analysis, and tumor revision. Median follow-up was 10.1 years.

Results.—We detected a CHEK2*1100delC germline mutation in 54 pa-tients (3.7%). Tumor characteristics ofCHEK2*1100delC carriers did not differsignificantly from those of noncarriers.CHEK2*1100delC carriers had a two-fold increased risk (hazard ratio [HR],2.1; 95% CI, 1.0 to 4.3; P = .049) of de-veloping a second breast cancer and theyhad worse recurrence-free survival (HR,1.7; 95% CI, 1.2 to 2.4; P = .006) andworse breast cancer-specific survival(HR, 1.4; 95% CI, 1.0 to 2.1; P = .072)

Page 2: Breast Cancer Survival and Tumor Characteristics in Premenopausal Women Carrying the CHEK2*1100delC Germline Mutation

Breast Diseases: A Year Book®

Quarterly 37Vol 19 No 1 2008 37

compared with noncarriers. The poorerdisease outcome of CHEK2*1100delCcarriers could not be explained by the in-creased risk of second breast cancer.

Conclusion.—Our study, which isrepresentative for the premenopausal

breast cancer population, reveals approxi-mately 4% CHEK2*1100delC carriershave an increased risk of second breastcancer and a worse long-term recurrence-free survival rate. Their identification attime of diagnosis and prolonged intensive

follow-up should be considered to opti-mize clinical management.

Please see expert perspective byWeischer, Bojesen, and Nordestgaard.

Breast Cancer Mortality Trendsin the United States Accordingto Estrogen Receptor Status andAge at Diagnosis Jatoi I, Chen BE, Anderson WF, et al (Univof the Health Sciences, Bethesda, Md;NIH, Rockville, Md)

J Clin Oncol 25:1683-1690, 2007

Purpose.—Since 1990, overallbreast cancer mortality rates in the UnitedStates decreased 24%. This decline hasbeen attributed to mammography screen-ing and adjuvant systemic therapy.However, the efficacy of these modalitiesmay depend on estrogen receptor (ER)expression and age. We therefore exam-ined breast cancer mortality trends in the United States according to ER statusand age.

Methods.—Using the Surveillance,Epidemiology, and End Results (SEER)program (1990-2003), we calculatedtrends in incidence-based mortality(IBM), annual hazard rates for breast can-cer deaths after diagnosis, and relativehazard rates for women with ER-positiveand ER-negative tumors. Relative hazardrates were assessed with Cox proportion-

al hazards models, adjusted for stage andgrade, and stratified by age at diagnosis.

Results.—During the study period,IBM and annual hazard rates for breastcancer deaths decreased among womenwith ER-positive and ER-negative tu-mors, although declines were greater forthose with ER-positive tumors. Amongwomen younger than 70 years, relativehazard rates declined 38% for those withER-positive tumors versus 19% for thosewith ER-negative tumors. Among women70 years or older, relative hazard rates de-clined 14% for those with ER-positive tu-mors versus no significant decline forthose with ER-negative tumors.

Conclusion.—In the United States,breast cancer mortality rates have de-clined among women with ER-positiveand ER-negative tumors, with greater de-clines among younger women and thosewith ER-positive tumors. Although mor-tality in all groups remains unacceptablyhigh, additional emphasis should beplaced on improving outcomes of breastcancer patients older than 70 years andthose of all ages with ER-negative tumors.

Mortality rates for women withbreast cancer have been declining, like-

ly because of the increased use ofscreening mammography and improve-ments in treatment.1 However, it is un-clear whether all subsets of patientshave experienced similar declines inmortality rates. In this paper, the au-thors evaluated mortality trends by ageand ER status and showed that al-though patients with both ER-positiveand -negative tumors experienced a de-cline in mortality rates, the largest de-clines have been in women with ER-positive tumors. These improvementsare good news for most patients; how-ever, the authors also identified a subset of patients who had no improve-ment in survival: those with ER-negative tumors who were 70 years ofage or older at diagnosis.

The researchers were unable todetermine the cause of the changes inmortality rates, but the data suggestthat lower rates of mammography andadjuvant chemotherapy in older womenmay negatively affect survival. We re-cently evaluated the use of adjuvantchemotherapy in women 66 years ofage and older and found that only 16%of these women were treated with adju-vant chemotherapy, despite an increas-