A new analysis, published early online Dec. 7, 2015, in CANCER, a peer-reviewed journal of the American Cancer Society, points to characteristics that may increase a breast cancer survivor’s risk of developing leukemia after undergoing chemotherapy and/or radiation.
The findings are an important first step toward finding ways to prevent this serious and potentially life-threatening, treatment-related complication. Breast cancer survivors now account for the majority of therapy-related leukemia cases.
The research team, led by Jane Churpek, MD, assistant professor of medicine at the University of Chicago, examined the characteristics of 88 breast cancer survivors with therapy-related leukemia. They found that breast cancer survivors who develop leukemia often have histories suggestive of inherited cancer susceptibility. One in five of the women in the study carried a mutation in a gene associated with an increased risk of breast 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 Churpek.
In an accompanying editorial, Judith Karp, MD, and Antonio Wolff, MD, of the Johns Hopkins University School of Medicine, note that the “data presented by Churpek et al expand on a growing body of knowledge for understanding an individual’s genetic risk, not only for breast cancer but also for second cancers such as leukemia, whether they are a direct result of cytotoxic therapy or an independent event.”
“These data will become increasingly critical to guide strategies for cancer risk reduction,” the authors add. This is important, because more and more patients are expected to survive after their breast cancer diagnosis.
Science Life: How would you summarize your findings for a lay audience?
Jane Churpek: We found that 1 in 5 women who developed therapy-related leukemia after treatment for breast cancer carried an inherited damaging change in one of the genes associated with increased risk of breast cancer.
What is therapy-related leukemia?
“Therapy-related” means the chemotherapy or radiation, or both, may have been involved in causing the leukemia. This is an uncommon but serious complication of cancer treatment. The factors that put women at risk for this complication are not well understood.
How did you design the study?
We designed this study to try to understand whether damaging, inherited changes in genes known to cause an increased risk of breast cancer are common in those who develop leukemia after getting chemotherapy and/or radiation for treatment of breast cancer.
We looked at the clinical histories of 88 such women. We found that most of them have relatives who also had cancer, suggesting they may be cancer-prone to begin with. Because we did not have a group of women who had similar breast cancer treatment and who did not get a therapy-related leukemia, we cannot definitively prove that more women with therapy-related leukemia than expected had these mutations. However, this study gives us reason to further study the role of these genes in therapy-related leukemia.
Why are your findings novel or important?
Our findings are novel because this was the first time a multi-gene breast cancer panel approach was used to look at many breast cancer risk genes at once in women with therapy-related leukemia after breast cancer. This work is important because it points to the need for bigger studies to examine the role of these genes as risk factors.
Understanding the connection between such risk factors and therapy-related leukemia is critical. Breast cancer survivors now make up the largest proportion of cancer survivors getting this often lethal complication and our current understanding of who is at most risk is limited.
How might your findings be put to use?
They suggest that genetic testing should be offered to all women with breast cancer who develop therapy-related leukemia. A significant proportion will have an inherited mutation that contributed to why they developed breast cancer. This knowledge can be used to guide cancer prevention in those who survive, and in their relatives.
They also 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.
How would this improve patient care?
This knowledge would help doctors have more individualized conversations about the potential risks versus benefits of initial treatment for breast cancer.
For example: consider a woman with an early stage estrogen-receptor-positive breast cancer who is estimated to have a low risk of the breast cancer coming back and for whom chemotherapy would decrease that small risk by only a few percent. With individualized estimates of her chances of developing a therapy-related leukemia (or other life-altering complication), she and her doctor could make more informed choices about whether or not to include chemotherapy and/or radiation in her treatment plan.