Hereditary Breast Cancer

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • The list of cancer-associated genes continues to expand, and it is therefore increasingly important to obtain a thorough family history to assess any potential for hereditary cancer syndromes:
    • The BRCA1 and 2 genes account for the majority of hereditary breast cancer cases
  • The BRCA1 gene is located on chromosome 17q21:
    • It is part of the DNA repair pathway:
      • Functioning as a tumor suppressor gene
    • Presence of a deleterious BRCA1 mutation is associated with:
      • A lifetime breast cancer risk of:
        • 72% by age 80
      • A lifetime ovarian cancer risk of:
        • 44%
    • In addition, BRCA1 mutations have been associated with:
      • An increased risk of pancreatic cancer and melanoma
    • BRCA1 associated breast cancers:
      • Tend to occur at younger ages and are more likely to have aggressive phenotypes compared to non-BRCA-associated tumors
  • Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer syndrome:
    • Is caused by genetic mutations in the mismatch repair system:
      • With the most common associated gene mutations being MLH1, MSH2, MSH6, and PMS2
    • Lynch syndrome is the most common hereditary form of colorectal cancer, and is also associated with an increased risk of:
      • Endometrial, urogenital, pancreatic, biliary tract and ovarian cancers:
        • Women with Lynch syndrome have a 20% to 60% lifetime risk of endometrial cancer
  • Germline mutations in the PTEN gene:
    • Are associated with Cowden syndrome:
      • Characterized by the formation of multiple hamartomas as well as an increased risk of:
        • Breast, endometrial, non-medullary thyroid, and renal cell cancers
  • Hereditary diffuse gastric cancer syndrome:
    • Is associated with a mutation in the CDH1 gene
    • It leads to an increased risk of early onset gastric cancer and lobular breast cancer
  • PALB2 is a breast cancer susceptibility gene:
    • With an estimated breast cancer risk of 45%:
    • PALB2 mutations have also been reported to increase the risk of:
      • Ovarian cancer and possibly pancreatic and prostate cancer
  • BRIP1 mutations:
    • Have been shown to confirm a high-risk of ovarian cancer (OR 20.97), but no increase in breast cancer risk
  • References
    • Shulman LP. Hereditary breast and ovarian cancer (HBOC): clinical features and counseling for BRCA1 and BRCA2, Lynch syndrome, Cowden syndrome, and Li-Fraumeni syndrome. Obstet Gynecol Clin North Am. 2010;37(1):109-133, Table of Contents.
    • Kuchenbaecker KB, Hopper JL, Barnes DR, et al. Risks of Breast, Ovarian, and Contralateral Breast Cancer for BRCA1 and BRCA2 Mutation Carriers. Jama. 2017;317(23):2402-2416.
    • Mersch J, Jackson MA, Park M, et al. Cancers associated with BRCA1 and BRCA2 mutations other than breast and ovarian. Cancer. 2015;121(2):269-275.
    • Southey MC, Winship I, Nguyen-Dumont T. PALB2: research reaching to clinical outcomes for women with breast cancer. Hered Cancer Clin Pract. 2016;14:9.
    • Weber-Lassalle N, Hauke J, Ramser J, et al. BRIP1 loss-of-function mutations confer high risk for familial ovarian cancer, but not familial breast cancer. Breast Cancer Res. 2018;20(1):7.
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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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