Patient Clinical Profile
Myriad myRisk® Panel Test Result:
Approximately five to ten percent of all cancers are hereditary.1 Over 10% of all breast cancers are now estimated to have a hereditary component.2 Many hereditary cancer syndromes have overlapping phenotypes, making it difficult for clinicians to determine which genetic test is more appropriate for their high risk patients.3 Though more is commonly known regarding the high-penetrant gene mutations like BRCA1 & BRCA2 related to Hereditary Breast and Ovarian Cancer syndrome, recent publications, including guidelines established by the National Comprehensive Cancer Networks® (NCCN), are bringing the significant impact of the more moderate-penetrant genes such as ATM, PALB2 & CHEK2, into the forefront of hereditary cancer risk assessment.9 The case study below study highlights how the discovery of a moderately-penetrant gene mutation broke the cycle of breast cancer in one family.
Mutations in the PALB2 gene are associated with the following:
- A significantly higher risk for breast cancer, up to 14% by age 50 & up to 58% by the age 704
- Twice the mortality risk for women with breast cancer + PALB2 mutation vs. those without PALB2 mutation5
- An increased risk for pancreatic cancer6,7
- An increased risk for male breast cancer8
Patient’s Family History
|Relative||Cancer||Age of Dx|
|Maternal Aunt||Breast||39 & 42|
- This patient’s maternal aunt was diagnosed with breast cancer at the age of 39 and had undergone BRCA1/2 testing with a negative test result back in October of 2011.
- The patient’s aunt received a second breast cancer diagnosis 3 years later and passed away at the age of 42.
- Her mother was recently diagnosed with breast cancer at the age of 45 and her doctor did not recommend further genetic testing due to sister’s negative test result.
PALB2 Cancer Risk Management Table
|CANCER TYPE||PROCEDURE||AGE & FREQUENCY|
||Starting 10 years younger than the earliest diagnosis in the family but not younger than 30y|
In this particular case…
This patient now knows her true risk for breast cancer and together with her health care provider team, can begin taking the appropriate steps to protect herself from developing not only breast, but pancreatic cancer as well. Due to the common clinical dilemma in the overlap of syndromes, her mother’s physician’s decision not to pursue any follow up-testing clearly missed an opportunity to properly diagnose her cancer risk. Panel testing, in this case, revealed a critical mutation in the family that not only changed this patient’s management, but her mother’s as well.
In addition to decreasing cost and the time involved for individual gene sequencing, a panel test approach helps assure the healthcare provider that a negative test result eliminates almost all of the likelihood of an inherited risk and help improve patient outcomes.
Utilize our Cancer Family History Tool to screen and identify patients at increased cancer risk.
- American Cancer Society. Family Cancer Syndromes. http://www.cancer.org/cancer/cancercauses/geneticsandcancer/heredity-and-cancer. Last accessed 1/11/17.
- Sharma L et. al Spectrum of Mutations Identified in a 25-gene Hereditary Cancer Panel for Patients with Breast Cancer. Presented at ESHG 2015.
- Saam J., et al. Overlap between Lynch Syndrome and Hereditary Breast and Ovarian Cancer Syndrome among Family Histories in Patients tested for Hereditary Cancer Syndromes. 3/2014.
- Antoniou AC, et al. Breast-cancer risk in families with mutations in PALB2. N Engl J Med. 2014 Aug 7;371(6):497-506. doi: 10.1056/NEJMoa1400382.https://www.ncbi.nlm.nih.gov/pubmed/25099575
- Cybulski et al. Lancet Oncology. Clinical outcomes in women with breast cancer and a PALB2 mutation: a prospective cohort analysis. V16, No. 6, p638-644, June 2015.
- Jones S, et al. Exomic sequencing identifies PALB2 as a pancreatic cancer susceptibility gene. Science. 2009 324:217.
- Slater EP, et al. PALB2 mutations in European familial pancreatic cancer families. Clin Genet. 2010 78:490-4.
- Casadei S, et al. Contribution of inherited mutations in the BRCA2-interacting protein PALB2 to familial breast cancer. Cancer Res. 2011 71:2222-9.
- Daly M et al. NCCN Clinical Practice Guidelines in Oncology®. Genetic/Familial High-Risk Assessment: Breast and Ovarian, Version 2.2017.
- Bevers TB, et al. NCCN Clinical Practice Guidelines in Oncology®: Breast Cancer Screening and Diagnosis. V 1.2015. July 15. Available at http://www.nccn.org.
- Canto MI, et al. International Cancer of the Pancreas Screening (CAPS) Consortium summit on the management of patients with increased risk for familial pancreatic cancer. Gut. 2013 62:339-47.