Prognostic significance of germline BRCA mutations in
patients with HER2-POSITIVE breast cancer
by A. Viansone, B. Pellegrino, C. Omarini, M. Pistelli, D.
Boggiani, A. Sikokis, V. Uliana, D. Zanoni, C. Tommasi, B. Bortesi, F. Bonatti,
F. Piacentini, L. Cortesi, R. Camisa, P. Sgargi, M. Michiara, A. Musolino
The Breast: Published: July 31, 2022
Background
HER2-positive breast cancers are rare amongst BRCA mutation
carriers. No data exist regarding clinicopathological characteristics and
prognosis of this subgroup of patients.
Materials and methods
Using a retrospective matched cohort design, we collected
data from 700 women who were diagnosed with operable invasive breast cancer
from January 2006 to December 2016 and were screened for germline BRCA
mutations. Clinicopathological features and survival rates were analyzed by
BRCA and HER2 status.
Results
One hundred and fifteen HER2-positive/BRCA mutated cases
were evaluated in comparison to the three control groups: HER2-positive/BRCA
wild type (n = 129), HER2-negative/BRCA mutated (n = 222), HER2-negative/BRCA
wild type (n = 234). HER2-positive breast cancers were more likely to have high
histologic grade and high proliferation rate than HER2-negative neoplasms,
regardless of BRCA mutation status. An interaction between BRCA mutations and
HER2-positive status was found to correlate with worse survival after adjusting
for prognostic variables (HR = 3.4; 95% CI: 1.3–16.7).
Conclusions
Co-occurrence of BRCA mutations and HER2-positive status is
a poor prognostic factor in patients with early or locally advanced breast
cancer. This finding may be a proof of concept that a combined pharmacological
intervention directed to these targets could be synergistic.
