Abstract
Objective
Our goal was to identify pathogenic variants (PV) associated with germline cancer
predisposition in an unselected cohort of older breast cancer survivors. Older patients
with cancer may also be at higher risk for clonal hematopoiesis (CH) due to their
age and chemotherapy exposure. Therefore, we also explored the prevalence of PVs suggestive
of CH.
Methods
We evaluated 44 older adults (65 years or older) diagnosed with breast cancer who
survived at least two years after diagnosis from a prospective study, compared to
healthy controls over the age of 65 (n = 36). DNA extracted from blood samples and a multi-gene panel test was used to evaluate
for common hereditary cancer predisposition and CH PVs. Fisher's exact test was used
to compare PV rates between groups.
Results
Eight PVs in ATM, BRCA2 (x2), PALB2, RAD51D, BRIP1, and MUTYH (x2) were identified in 7 of 44 individuals with breast cancer (15.9%, 95% CI: 7–30%),
whereas none were identified in healthy controls (p = .01). Results remained statistically significant after removal of MUTYH carriers (p = .045). PVs indicative of CH (ATM, NBN, and PPM1D [x2]) were identified in three of 27 individuals with breast cancer who received
chemotherapy and in one healthy control.
Conclusion
Moderate-risk and later disease onset high-risk hereditary cancer predisposition PVs
were statistically significantly enriched in our survivorship cohort compared to controls.
Because age- and chemotherapy-related CH are more frequent in this population, care
must be taken to differentiate potential CH PVs from germline cancer predisposition
PVs.
Keywords
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Article info
Publication history
Published online: September 28, 2019
Accepted:
September 4,
2019
Received in revised form:
August 20,
2019
Received:
April 26,
2019
Identification
Copyright
© 2019 Elsevier Ltd. All rights reserved.
