PTEN Mutation and Breast Cancer

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • Phosphatase and Tensin Homolog (PTEN):
    • Is a tumor suppressor gene, and inherited mutations in this gene can be associated with Cowden’s syndrome
  • Cowden’s syndrome:
    • Is associated with increased risk of multiple types of cancer including:
      • Breast
      • Endometrial
      • Thyroid
      • Colorectal
      • Melanoma
  • PTEN mutations carriers:
    • Tend to develop cancers at younger ages than individuals with sporadic malignancies
    • Lifetime breast cancer risk with this syndrome is up to 85%:
      • As reported by Tan el al., although it is noted given the limitations in reported studies of women with Cowden’s syndrome, risk estimates are not stable
    • Hamartomas on the skin or mucous membranes are extremely common in this syndrome
    • Macrocephaly may also be seen
  • PTEN mutations are inherited in an autosomal dominant pattern with an estimated frequency of 1 in 200,000 people
  • Loss of PTEN gene expression at the somatic or germline level:
    • May affect response to HER2-directed therapies, and low levels of the protein in stromal cells have been associated with increased risk of recurrence related to radiation in pre-clinical models
  • The other genes with moderate risk of developing breast cancer with the following relative risks reported from a meta-analysis:
    • PALB2 RR 5.3
    • CDH1 RR 6.6
    • CHEK2 truncating mutations RR 3.0
    • ATM RR 2.8
  • References
    • Couch FJ, Shimelis H, Hu C, Hart SN, Polley EC, Na J, et al. Associations between cancer predisposition testing panel genes and breast cancer. JAMA Oncol.2017;3(9):1190-1196.
    • Gustafson S, Zbuk KM, Scacheri C, Eng C. Cowden syndrome. Semin Oncol.2007;34(5):428-434.
    • Ngeow J, Sesock K, Eng C. Breast cancer risk and clinical implications for germline PTEN mutation carriers. Breast Cancer Res Treat. 2017;165(1):1-8.
    • Tan MH, Mester JL, Ngeow J, Rybicki LA, Orloff MS, Eng C. Lifetime cancer risks in individuals with germline PTEN mutations. Clin Cancer Res. 2012;18(2):400-407.
    • Weiss A, Garber JE, King T. Breast cancer surgical risk reduction for patients with inherited mutations in moderate penetrance genes. JAMA Surg. 2018;153(12):1145-1146.
    • Kim C, Lee CK, Chon HJ, et al. PTEN loss and level of HER2 amplification is associated with trastuzumab resistance and prognosis in HER2-positive gastric cancer. Oncotarget. 2017;8(69):113494-113501.
    • Sizemore GM, Balakrishnan S, Thies KA, et al. Stromal PTEN determines mammary epithelial response to radiotherapy. Nat Commun. 2018;9(1):2783.
    • Easton DF, Pharoah PD, Antoniou AC, et al. Gene-panel sequencing and the prediction of breast-cancer risk. N Engl J Med. 2015;372(23):2243-2257.
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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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