CHEK2 Mutation Increases Mortality, Breast Cancer Recurrences

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Elsevier Global Medical News. 2009 Oct 21, S Boschert

SAN FRANCISCO (EGMN) - White women of European descent who have breast cancer and a CHEK2*1100delC mutation are 40% more likely to die of breast cancer or from any cause, and 170% more likely to develop a second breast cancer within 10 years, compared with those who don't have the mutation, an analysis of data on 11,873 patients found.

The increased mortality and recurrence risks in women with breast cancer and a heterozygous CHEK2*1100delC mutation don't appear until more than 5 years after breast cancer is diagnosed, which has clinical implications for follow-up schedules, Dr. Maren Weischer said at a breast cancer symposium sponsored by the American Society of Clinical Oncology.

At her institution, Herlev (Denmark) University Hospital, breast cancer patients conventionally have been followed for 5 years. They are declared disease free and released from further follow-up if cancer has not recurred in that time.
Because of the new findings, "for the last half-year we have been testing all the breast cancer patients for this CHEK2 mutation, and women who have that are offered lifelong follow-up instead of just the normal 5 years," she said. "I would recommend you all do the same."

The data came from centers in 10 countries participating in the Breast Cancer Association Consortium. The odds ratios for overall mortality, breast cancer-specific mortality, and development of a second breast cancer were adjusted for age at diagnosis, tumor size, lymph node status, hormone receptor positivity, and cancer morphology, stage, and grade, the investigators reported.

The findings build on previous studies that identified increased risk for the initial development of breast cancer in women with the mutation. In a meta-analysis of studies including approximately 26,000 white women with breast cancer and 27,000 controls, Dr. Weischer and her associates found that women with the mutation had a 2.7-fold increased risk for sporadic breast cancer, a 2.6-fold increased risk of early-onset breast cancer, and a 4.8-fold risk of hereditary breast cancer (J. Clin. Oncol. 2008;26:542-8).
Approximately 2% of whites of European descent have the CHEK2*1100delC mutation, she said. It is a germline mutation, meaning that it appears in all cells of the body when it is present. When a breast cancer patient is found to have this mutation, Dr. Weischer and her associates offer screening for the mutation to family members of the patient. The mutation does not appear to exist in women of Spanish, Italian, Middle Eastern, Jewish, Malaysian, Chinese, or South American descent.

There is no reason to believe that the increased risks that are seen in women with the mutation are due to the choice of drug treatments for breast cancer because patients with or without the mutation were not treated differently in the studies, she noted.

Homozygosity for the CHEK2*1100delC mutation appeared to confer even greater risk than did heterozygosity, but occurred in only three women in the study. In all, 274 were heterozygous for the mutation.

The investigators reported having no conflicts of interest related to this study.

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