Patient Clinical Profile

  • Patient Age: 29
  • Gender: Female
  • Visit Type: Annual Wellness Exam
  • Visit notes: Patient has no personal history of cancer. She is seeing her ObGyn today for her routine annual exam. After reviewing this patient’s family history, her doctor noticed the mother’s additional cancer history which was recently added to her chart. The doctor was concerned about her significant breast cancer history that wasn’t explained by the single syndrome test already performed on her aunt, so she decided to order the Myriad myRisk® Hereditary Cancer test to rule out other hereditary causes of the breast cancer history.

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
Mother Breast 45
  • 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

Female Breast
  • Breast MRI with contrast in addition to mammography.9,10
  • Consider risk-reducing mastectomy based on family history.9
  • Consider additional risk-reduction strategies.9,10
Starting 10 years younger than the earliest diagnosis in the family but not younger than 30y
  • Consider available options for pancreatic cancer screening, including the possibility of endoscopic ultrasonography (EUS) and MRI/magnetic resonance cholangiopancreatography (MRCP). It is recommended that patients who are candidates for pancreatic cancer screening be managed by a multidisciplinary team with experience in the screening for pancreatic cancer, preferably within research protocols.11
Male Breast
  • Currently there are no specific medical management guidelines for breast cancer risk in mutation carriers. However, the increase in risk warrants consideration of options for male breast cancer screening, such as patient breast awareness education, clinical breast examinations, and mammography, particularly for men with gynecomastia. 9,10

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.

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  1. American Cancer Society. Family Cancer Syndromes. Last accessed 1/11/17.
  2. Sharma L et. al Spectrum of Mutations Identified in a 25-gene Hereditary Cancer Panel for Patients with Breast Cancer. Presented at ESHG 2015.
  3. 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.
  4. 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.
  5. 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.
  6. Jones S, et al. Exomic sequencing identifies PALB2 as a pancreatic cancer susceptibility gene. Science. 2009 324:217.
  7. Slater EP, et al. PALB2 mutations in European familial pancreatic cancer families. Clin Genet. 2010 78:490-4.
  8. Casadei S, et al. Contribution of inherited mutations in the BRCA2-interacting protein PALB2 to familial breast cancer. Cancer Res. 2011 71:2222-9.
  9. Daly M et al. NCCN Clinical Practice Guidelines in Oncology®. Genetic/Familial High-Risk Assessment: Breast and Ovarian, Version 2.2017.
  10. Bevers TB, et al. NCCN Clinical Practice Guidelines in Oncology®: Breast Cancer Screening and Diagnosis. V 1.2015. July 15. Available at
  11. 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.

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