The first study on the mutational landscape of breast cancer diagnosed during pregnancy (BCP) using whole-genome sequencing found that BCP is associated with a higher number of putative driver mutations, including mutations in mucin genes. Researchers presented their findings on Thursday, December 7, during a poster session at the San Antonio Breast Cancer Symposium.

Pregnancy is already known to modulate breast cancer risk; BCP is a rare but potentially useful model to determine how pregnancy modulates breast cancer biology. Researchers in Belgium, Italy, and the United States used whole-genome sequencing (WGS) in a “unique series” of patients with BCP to better understand the effect of pregnancy on breast cancer biology.

WGS was performed for 35 BCP and 20 nonpregnant controls matched for age and stage with available clinic-pathologic data. DNA extracted from primary tumor and matched adjacent normal formalin fixed paraffin embedded (FFPE) tissue. The researchers assessed the tumor (60x coverage) and normal DNA (30x coverage) using WGS on the HiSeq X Ten (Illumina, San Diego, CA) platform. A Wilcoxon test for continuous variables and Fisher exact test for categorical variables were used to assess mutational profile differences between the two groups.

No differences existed in clinic-pathological features between the two groups. Of interest, a significantly higher number of mutations was found in the BCP group as compared to the control group when considering only mutations associated with a deleterious effect (median: 20 versus 12, p = 0.027). The researchers expected TP53 and PIK3CA to be the most frequently mutated genes both in BCP and control cases without any significant difference between the groups (34.3% versus 22.2%, p = 0.53 and 20.0% versus 16.7%, p = 1, respectively). Interestingly, a significant enrichment of nonsilent mutations was found in the mucin gene family in the BCP group: 45.7% of BCP versus 11.1% of control cases had at least one such mutation (p = 0.015). A similar significant result (45.7% versus 23.1%, p = 0.034) was found when comparing BCP with breast cancer control cases. When comparing the distribution of the 12 BC mutational signatures, a borderline significant enrichment with a signature depicting mismatch-repair deficiency (signature 20) was observed in the BCP patients (p = 0.059).

“These results could open new avenues for the development of targeted therapeutic approaches for patients diagnosed with breast cancer during pregnancy,” the researchers said.