TY - JOUR
T1 - ATM Variants in Breast Cancer
T2 - Implications for Breast Radiation Therapy Treatment Recommendations
AU - McDuff, Susan G.R.
AU - Bellon, Jennifer R.
AU - Shannon, Kristen M.
AU - Gadd, Michele A.
AU - Dunn, Samantha
AU - Rosenstein, Barry S.
AU - Ho, Alice Y.
N1 - Funding Information:
Disclosures: A.Y.H. reports personal fees from Amgen, grants from Merck & Co., and grants from GSK, Inc. J.R.B. is an educational consultant for Varian; has received research funding from Prosigna; has received honorarium from Accuray, Leidos Pharmaceuticals, Oncoclinicas, and ASTRO (International Journal of Radiation Oncology, Biology, Physics editor); and has received royalties from Wolters Kluwer.
Funding Information:
The authors gratefully acknowledge the contributions of Lauren Bear, MS, LCGC, and Linda Rogers, MGC, LCGC, of the Massachusetts General Hospital Center for Cancer Risk Assessment for content and manuscript review. Disclosures: A.Y.H. reports personal fees from Amgen, grants from Merck & Co., and grants from GSK, Inc. J.R.B. is an educational consultant for Varian; has received research funding from Prosigna; has received honorarium from Accuray, Leidos Pharmaceuticals, Oncoclinicas, and ASTRO (International Journal of Radiation Oncology, Biology, Physics editor); and has received royalties from Wolters Kluwer.
Publisher Copyright:
© 2021 Elsevier Inc.
PY - 2021/8/1
Y1 - 2021/8/1
N2 - Purpose: Advances in germline genetic testing have led to a surge in identification of ataxia-telangiectasia mutated (ATM) variant carriers among breast cancer patients, raising numerous questions regarding use of breast radiation therapy (RT) in this population. Methods: A literature search using PubMed identified articles assessing association(s) between the germline ATM variant status and the risk of toxicity after breast RT. An expert panel of breast radiation oncologists, genetic counselors, and basic scientists convened to review the association between ATM variants and radiation-induced toxicity or secondary malignancy risk and to determine any impact on breast RT recommendations. Results: Carriers of pathogenic variants in ATM have a 2- to 4-fold increased risk for developing breast cancer. ATM variants do not consistently increase risks of toxicities after RT, except possibly among patients with the single nucleotide variant c5557G>A (rs1801516), in whom a small increased risk for the development of both acute and late radiation effects has been identified. In most breast cancer patients with ATM variants, the excess 5-year absolute risk of developing a secondary contralateral breast cancer (CBC) after radiation is extremely low. The exception is in women younger than 45 years old with deleterious rare ATM missense variants, who may be at higher risk for developing a radiation-induced CBC over time. Conclusions: Adjuvant radiation is safe for most breast cancer patients who harbor ATM variants. The possible exceptions are patients with the variant c5557G>A (rs1801516) and patients younger than 45 years old with certain rare deleterious ATM variants, who may be at higher risk for developing CBC. These latter patients should be counseled regarding this potential risk, and every effort should be made to minimize the contralateral breast dose. However, the inconsistency of published data limits precise recommendations, magnifying the need for further prospective studies and the development of a centralized database cataloging RT outcomes and genetic status.
AB - Purpose: Advances in germline genetic testing have led to a surge in identification of ataxia-telangiectasia mutated (ATM) variant carriers among breast cancer patients, raising numerous questions regarding use of breast radiation therapy (RT) in this population. Methods: A literature search using PubMed identified articles assessing association(s) between the germline ATM variant status and the risk of toxicity after breast RT. An expert panel of breast radiation oncologists, genetic counselors, and basic scientists convened to review the association between ATM variants and radiation-induced toxicity or secondary malignancy risk and to determine any impact on breast RT recommendations. Results: Carriers of pathogenic variants in ATM have a 2- to 4-fold increased risk for developing breast cancer. ATM variants do not consistently increase risks of toxicities after RT, except possibly among patients with the single nucleotide variant c5557G>A (rs1801516), in whom a small increased risk for the development of both acute and late radiation effects has been identified. In most breast cancer patients with ATM variants, the excess 5-year absolute risk of developing a secondary contralateral breast cancer (CBC) after radiation is extremely low. The exception is in women younger than 45 years old with deleterious rare ATM missense variants, who may be at higher risk for developing a radiation-induced CBC over time. Conclusions: Adjuvant radiation is safe for most breast cancer patients who harbor ATM variants. The possible exceptions are patients with the variant c5557G>A (rs1801516) and patients younger than 45 years old with certain rare deleterious ATM variants, who may be at higher risk for developing CBC. These latter patients should be counseled regarding this potential risk, and every effort should be made to minimize the contralateral breast dose. However, the inconsistency of published data limits precise recommendations, magnifying the need for further prospective studies and the development of a centralized database cataloging RT outcomes and genetic status.
UR - http://www.scopus.com/inward/record.url?scp=85109442277&partnerID=8YFLogxK
U2 - 10.1016/j.ijrobp.2021.01.045
DO - 10.1016/j.ijrobp.2021.01.045
M3 - Review article
C2 - 33545302
AN - SCOPUS:85109442277
SN - 0360-3016
VL - 110
SP - 1373
EP - 1382
JO - International Journal of Radiation Oncology Biology Physics
JF - International Journal of Radiation Oncology Biology Physics
IS - 5
ER -