Breast cancer survivors with certain characteristics may have a higher risk of developing leukemia after chemotherapy or radiation therapy, according to a study published online in Cancer.
Certain cancer treatments that target tumor cells can also impact normal, healthy cells and may increase a patient's risk of developing leukemia at a later date. Therapy-related leukemia (TRL) is often fatal; currently, the majority of cases are breast cancer survivors.
TRL is thought to result directly from mutational events triggered by exposure to cytotoxic drugs, which are used in cancer treatment; but researchers do not know how this happens and what the risk factors are.
The fact that cancer survivors are now living longer after treatment makes efforts to understand and prevent this complication essential.
A team, led by Dr. Jane Churpek, of The University of Chicago, IL, examined the characteristics of 88 breast cancer survivors with therapy-related leukemia. The participants were aged 23-83 when breast cancer was first diagnosed, with an average age of 52 years.
Findings suggest underlying reasons for TRL
Information about previous cytotoxic exposure was available for 98% of the participants; 78% of the subjects had been treated with chemotherapy, and 79% with radiotherapy. Some participants received both forms of treatment.
Of the 88 participants studied, 22% had an additional cancer. Of the 70 participants with an available family history, 57% had a close relative with breast, ovarian or pancreatic cancer. Of the 47 subjects with available DNA data, 21% had an inherited mutation in a gene that has been associated with cancer, including BRCA1 and BRCA2.
Breast cancer survivors who develop TRL often have personal and family histories that suggest they could be prone to inherited cancer.
Dr. Churpek says:
"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."
She suggests that this knowledge could help doctors take a more individualized approach to the potential risks and benefits of initial treatments for breast cancer.
The researchers hope the findings will be a first step toward finding ways to prevent this serious and potentially life-threatening treatment-related complication.
In a linked editorial, Dr. Judith Karp and Dr. Antonio Wolff, of the Johns Hopkins University School of Medicine, Baltimore, MD, reiterate the authors' point that it can be difficult to determine what constitutes therapy-related leukemia and what may be a second malignancy that is unrelated to previous treatment.
They add that existing familial cancer registries could be useful to help ascertain the frequency of TRL and their associations with the therapies received and the known germline genetic alterations.
The editors comment that the growing body of information about the long-term effects of the various therapies will become increasingly important in cancer risk reduction and cancer prevention.