ATM Variants in Breast Cancer: Implications for Breast Radiation Therapy Treatment Recommendations

Abstract

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

Evaluation of Hybrid VMAT Advantages and Robustness Considering Setup Errors Using Surface Guided Dose Accumulation for Internal Lymph Mammary Nodes Irradiation of Postmastectomy Radiotherapy

“…They found that younger patients were more likely to have a long-term risk of breast cancer (32). Macduff et al evaluated patients below 45 years who were carrying certain rare ATM variants, and they should be more aware of the risk of SCCP of CB cancer (33). This led us to analyze the secondary incidence of breast cancer using the T-VMAT technique, and the SCCP of CB was significantly higher than that in the other two techniques.…”

Whole Scalp Radiation Therapy for Recurrent Benign Cylindromas

“…In fact, radiotherapy via speculation has not been recommended as first line due to concern over loss of a tumor suppressor gene CLYD1, which could induce further malignancy [9]. However, in other disease sites such as breast cancer, loss of important tumor suppressor genes such as ATM in it of itself is not a contraindication to receiving radiotherapy and does not demonstrate increase in normal tissue side effects [10]. Furthermore, despite basal cell carcinoma demonstrating loss of several tumor suppressor genes, including CLYD, radiation is still routinely used to manage certain lesions without increase in side effects [11].…”

Hereditäre Karzinome in der Gynäkologie

“…Hinsichtlich einer pathogenen ATM-Mutation zeigen sich widersprüchliche Aussagen. Aktuell wird in der Literatur kontrovers diskutiert, ob eine Bestrahlung strahlenbedingte Schäden oder erneute Krebserkrankungen verursachen könnte [17,18]. Insbesondere bei jüngeren Patient*innen unter 45 Jahren geht man von einer signifikanten Risikoerhöhung aus.…”