Carriers of CHEK2 Mutations Have a 2-Fold Increased Risk for Contralateral Breast Cancer, Says Expert

An expert from the Mayo Clinic discusses findings from a population-based study concerning germline genetic mutations as risk factors of contralateral breast cancer.

Patients with CHEK2 gene mutations have a 2-fold increased risk for developing contralateral breast cancer, according to Siddhartha Yadav, MD, MBBS, a medical oncologist and assistant professor of Medicine and Oncology at Mayo Clinic in Rochester, Minnesota.

During the 2022 San Antonio Breast Cancer Symposium (SABCS), CancerNetwork® spoke with Yadav about findings from the population-based prospective CARRIERS study assessing germline pathogenic variants and other factors as risks for developing contralateral breast cancer.

Based on data from the study, the 10-year cumulative incidence of contralateral breast cancer following first breast cancer diagnosis was 4.3% for those who did not have any genetic mutations and 8% for those with a CHEK2 mutation. Additionally, the 10-year cumulative incidence of contralateral breast cancer was 5.4% in those with a PALB2 mutation but 19.7% for those with estrogen receptor (ER)-negative breast cancer harboring a PALB2 mutation.

Yadav also spoke about other data points from the study that were related to the presence of BRCA1, BRCA2, and ATM mutations in contralateral breast cancer.


What we observed was that BRCA1 and BRCA2 were both associated with increased risk of contralateral breast cancer. Now, that's not surprising because that has been shown in multiple studies in the past. What's important to point out is that we did not know what the contralateral breast cancer risk in ATM, CHEK2, or PALB2 was. What our study demonstrates is that CHEK2 mutation carriers are at an approximately two-fold increased risk of contralateral breast cancer, whereas [for] ATM carriers, we did not observe that they were at an increased risk of contralateral breast cancer.

PALB2 was interesting because what we found was that PALB2 carriers were not at an increased risk of contralateral breast cancer in the overall study population or in the ER [estrogen receptor]-positive subset. But PALB2 carriers who were found to have ER-negative breast cancer were at an observed increased risk of contralateral breast cancer, roughly around a three-fold increased risk. Those were very interesting findings. Clarifying these ATM, CHEK2, and PALB2 [risks] was very important, and these are novel findings from our studies.


Yadav S, Boddicker NJ, Na J, et al. Population-based estimates of contralateral breast cancer risk among carriers of germline pathogenic variants in ATM, BRCA1, BRCA2, CHEK2, and PALB2. Presented at the 2022 San Antonio Breast Cancer Symposium; December 6-10, 2022; San Antonio, TX. Abstract GS4-04.

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