Breast: Genetic Mutations

BRCA Genes

Definition

  • Tumor Suppressor Genes
    • Loss of Function Mutations Cause Increased Risk of Cancer
  • Higher Prevalence in Ashkenazi Jewish, Icelandic & French-Canadian Populations

Screening Indications

BRCA Genes 1

Breast & Ovarian Cancer

  • BRCA1 Breast Cancers Have Higher Risk for Being Hormone Receptor Negative
  • BRCA2 Significantly Increases Risk for Male Breast Cancer Mn
  BRCA1 BRCA2
Breast CA (Female) 55-70% 45-70%
Ovarian CA 40-45% 15-20%
Breast CA (Male) 1% 7-10%

Other Cancers

  • Pancreatic Cancer
    • BRCA1 – 2.26 Relative Risk & 1% Absolute Risk
    • BRCA2 – 3.51 Relative Risk & 4.9% Absolute Risk
  • Prostate Cancer
    • BRCA1 – 3-4 Relative Risk & 15-20% Absolute Risk
    • BRCA2 – 5-9 Relative Risk & 30-40% Absolute Risk
  • Other Gynecologic Cancers:
    • Fallopian Tube
    • Endometrial (Conflicting Date & Increased Risk is Uncertain)
  • Other Cancers:
    • Primary Peritoneal Carcinoma
    • Colorectal Cancer
    • Skin Cancer (Melanoma, etc.)
    • Stomach Cancer
    • Biliary Cancers

PALB2 (Partner and Localizer of BRCA2)

Basics

  • Encodes for an Interacting Protein Critical for BRCA2 Tumor Suppression Activity
  • Increases Risk of Breast Cancer
  • Also Increases Risk for Ovarian, Pancreas & Prostate Cancer

Relative Risk of Breast Cancer

  • Age < 40: 8-9x
  • Age 40-60: 6-8x
  • Age > 60: 5x

Genetic Syndromes

Genetic Syndromes

  • Li-Fraumeni Syndrome (TP53)
  • Peutz-Jeghers Syndrome (STK11)
  • Cowden/PTEN Hamartoma Syndrome (PTEN)
  • Hereditary Diffuse Gastric Cancer Syndrome (CDH1)
  • Lynch Syndrome (MSH1, MLH1, MSH6, PMS2 & EPCAM)
  • Ataxia Telangiectasia (ATM)
  • Muir-Torre Syndrome (MLH1 & MSH2)

Mnemonics

BRCA2 Increases Risk in Males

  • 2 Testicles: Type 2 Affects Men (Male Breast & Prostate Cancer)

References

  1. Tessssa 13. Wikimedia Commons. (License: CC BY-SA-4.0)