Management of Pathogenic CHEK2 Variants

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • Management of pathogenic CHEK2 variants:
    • Should take into account the specific variant identified
  • Most of the risk data is based on frameshift variants:
    • Such as 1100delC:
      • With an estimated absolute lifetime breast cancer risk of 20% to 40%
  • The risks associated with other types of CHEK2 variants are not as well defined:
    • However, breast cancer risks associated with the specific missense variant Ile157Thr have been studied in more depth
  • Data from multiple studies, such as a large case-control study including 10,860 breast cancer patients from The CHEK2 Breast Cancer Case-Control Consortium:
    • Found a significantly increased risk of breast cancer with the 1100delC variant (OR 2.34; 95% CI 1.72-3.20; p=0.0000001)
  • Another similar study including 44,777 breast cancer patients:
    • Also demonstrated a significantly increased risk for breast cancer with the 1100delC variant (OR 2.26; 95% CI 1.90-2.69; p=2.3×10-20)
  • Unlike the 1100delC variant:
    • The Ile157Thr variant has been associated with a more modest elevation in risk for breast cancer
    • A meta-analysis of case-control studies, including 26,336 cases and 44,219 controls, demonstrated an association of the Ile157Thr variant with breast cancer (OR=1.58; 95% CI 1.42-1.75; p<0.000001)
  • Current National Comprehensive Cancer Network guidelines regarding frameshift CHEK2 variants:
    • Recommend beginning annual mammograms at 40 years old
    • Considering breast MRI starting at 30 to 35 years old
    • Evidence is inadequate to recommend risk reducing mastectomy (RRM)
    • On the other hand, supplementary breast cancer risk management for patients with the missense variant Ile157Thr is not suggested:
      • However, management should still be personalized based on family history, for instance:
        • Beginning breast imaging 5 to 10 years earlier than the youngest family member diagnosed with breast cancer
  • References:
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Published by Rodrigo Arrangoiz MS, MD, FACS, FSSO

My name is Rodrigo Arrangoiz I am a breast surgeon/ thyroid surgeon / parathyroid surgeon / head and neck surgeon / surgical oncologist that works at Center for Advanced Surgical Oncology in Miami, Florida. I was trained as a surgeon at Michigan State University from (2005 to 2010) where I was a chief resident in 2010. My surgical oncology and head and neck training was performed at the Fox Chase Cancer Center in Philadelphia from 2010 to 2012. At the same time I underwent a masters in science (Clinical research for health professionals) at the University of Drexel. Through the International Federation of Head and Neck Societies / Memorial Sloan Kettering Cancer Center I performed a two year head and neck surgery and oncology / endocrine fellowship that ended in 2016. Mi nombre es Rodrigo Arrangoiz, soy cirujano oncólogo / cirujano de tumores de cabeza y cuello / cirujano endocrino que trabaja Center for Advanced Surgical Oncology en Miami, Florida. Fui entrenado como cirujano en Michigan State University (2005 a 2010 ) donde fui jefe de residentes en 2010. Mi formación en oncología quirúrgica y e n tumores de cabeza y cuello se realizó en el Fox Chase Cancer Center en Filadelfia de 2010 a 2012. Al mismo tiempo, me sometí a una maestría en ciencias (investigación clínica para profesionales de la salud) en la Universidad de Drexel. A través de la Federación Internacional de Sociedades de Cabeza y Cuello / Memorial Sloan Kettering Cancer Center realicé una sub especialidad en cirugía de cabeza y cuello / cirugia endocrina de dos años que terminó en 2016.

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