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Inherited mutations common in breast cancer survivors with therapy-related leukemia
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Breast cancer survivors who develop therapy-related leukemia often have personal and family histories that are suggestive of inherited cancer susceptibility, according to study results.
Further, one in five women with therapy-related leukemia carried an inherited gene mutation associated with increased risk for breast cancer.
“[These] 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,” Jane E. Churpek, MD, assistant professor of medicine and co-director of the comprehensive cancer risk and prevention program at University of Chicago, said in a press release. “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.”
Therapy-related leukemias can occur as a result of cytotoxic therapy for an initial cancer. Incidence is expected to increase as the number of cancer survivors rises, according to study background.
Churpek and colleagues identified and screened 88 patients who survived breast cancer and developed treatment-related leukemias. All study participants were evaluated for germline mutations with a comprehensive gene panel that covered all known inherited breast cancer susceptibility genes.
Twenty-two percent had an additional primary cancer, and of the 70 survivors with an available family history, 57% had a close relative with either breast, ovarian or pancreatic cancer.
From the cohort, 47 patients had available DNA samples and 21% were found to carry deleterious genetic mutations in BRCA1, BRCA2, TP53, CHEK2 and PALB2.
“These mutations … all [have] key roles in DNA repair and/or DNA damage-sensing pathways,” Churpek and colleagues wrote. “In addition, many of the well-annotated survivors of breast cancer with treatment-related leukemias in the current series had a personal history of additional malignancies and/or a family history of cancer in close relatives, suggesting a cancer prone population. The data from the current study support a role for inherited cancer susceptibility in treatment-related leukemias after breast cancer.”
It may be premature to advocate for population-based germline mutation screening, Judith Karp, MD and Antonio C. Wolff, MD, faculty members of the hematology/medical oncology fellowship program at The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, wrote in an accompanying editorial.
“It is certainly conceivable that germline mutation testing may, in the future, be used to help refine locoregional and systemic decision-making in patients with early-stage breast cancer,” Karp and Wolff wrote. “Improved characterization of the risk of treatment-related leukemias, both in terms of the selection of chemotherapy regimen and possibly even in deciding whether to administer adjuvant chemotherapy at all ― especially among patients with low-risk tumors, in whom the potential improvement in survival benefit may be small ― [may be warranted].” – by Anthony SanFilippo
Disclosure: The researchers report no relevant financial disclosures. Karp reports consultant/advisory roles for Cellerant Therapeutics and Tolero Pharmaceuticals. Wolff reports research funding from Genentech.
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