Family History, Genes May Up Leukemia Risk in Breast Cancer Survivors

Survivors of breast cancer who went on to develop therapy-related leukemia were found to have personal and family histories that suggested that they may have an inherited risk for cancer; one in five were also found to have mutations in certain breast cancer susceptibility genes, according to the results of a study published in Cancer.

“The findings justify a long-term follow-up study of women with and without inherited breast cancer gene mutations who are treated with similar therapy for breast cancer. This would enable us to understand how these genes impact therapy-related leukemia risk and whether specific treatments come with higher risks based on a woman’s inherited genetics,” said Jane E. Churpek, MD, of the University of Chicago, in a prepared statement.

According to the study, therapy-related leukemia is a common late effect of the cytotoxic treatments undergone by many patients with cancer. Currently, breast cancer survivors account for a majority of cases of therapy-related leukemia.

In this study, Churpek and colleagues looked at germline DNA samples from 88 survivors of breast cancer with therapy-related leukemia to identify any common clinical or leukemia characteristics or inherited mutations.

Of the survivors studied, 22% were found to have an additional primary cancer diagnosis. All but seven survivors in the study had developed therapy-related myeloid neoplasm, with the remainder developing therapy-related acute lymphoblastic leukemia.

Of the 80% of survivors with a family history available, 57% of these women had at least one first- or second-degree relative with breast, ovarian, or pancreatic cancer.

DNA samples available from 47 patients showed that one in five (21%) women had a deleterious inherited mutation in one of the following genes: BRCA1 (3 patients; 6%), BRCA2 (2 patients; 4%), TP53 (3 patients; 6%), CHEK2 (1 patient; 2%), and PALB2 (1 patient; 2%).

“All of the breast cancer susceptibility genes with mutations identified in the current series function to sense or repair DNA damage and the majority are closely tied to leukemia risk,” the researchers noted.

In an accompanying editorial, Judith Karp, MD, and Antonio Wolff, MD, of the Johns Hopkins University School of Medicine, noted that it can be difficult to determine what constitutes therapy-related leukemia and what may be a second malignancy that is unrelated to a patient’s treatment.

“Existing familial cancer registries that are prospectively following breast cancer patients and their families are uniquely positioned to ascertain the true frequency of subsequent leukemias and their associations with the therapies received and the known germline genetic alterations,” they wrote. “A clearer understanding of these associations could inform clinical practice and potentially improve clinical outcomes.”