The study results confirmed that the triple-negative breast cancers emergence among young compared with elderly patients can be completely different entities.
Findings published in Cancer suggested that young patients with triple-negative breast cancer (TNBC) had an enhanced cell cycle, which may explain their poor short-term survival.
Additionally, homologous recombination deficiency and enriched pathogenic germline variants observed among this patient population indicated the need for genetic counseling and testing, as well as the possible use of DNA damage agents and poly (adenosine diphosphate ribose) polymerase (PARP) inhibitors.
Comparatively, molecular characteristics observed among elderly patients with TNBC, though pointing to less of a response from chemotherapy, provided a rationale for the routine detection of actionable somatic mutations.
“The results of the current study confirmed that TNBCs arising among young compared with elderly patients can be quite different entities,” the authors wrote.
Researchers used the study institution's largest, single-center, multiomics TNBC data set to analyze the clinical and genomic features of young (aged ≤39 years) and elderly (aged ≥65 years) patients. The study cohort included 50 patients, 354 patients, and 69 patients, respectively, grouped as young, intermediate, and elderly patients with TNBC.
Overall, young patients with TNBC were found to have worse short-term survival, upregulation of DNA repair, cell cycle and RNA metabolism gene sets, frequent pathogenic germline variants, and predominant homologous recombination deficiency-related mutational signatures. Moreover, several copy number alterations were also found to be enriched in young patients with TNBC.
In elderly patients with TNBC, almost half of the TNBC cases were of the luminal androgen receptor subtype. Notably, TNBC in elderly patients was identified as being correlated with severe fibrosis, a lower Ki-67 index, and somatic mutations in PIK3CA, KMT2D, ERBB2, ERBB3, and their corresponding pathways. Elderly patients with TNBC were also more likely to harbor targetable mutations.
“It is interesting to note that although we have observed a clear association between age at diagnosis and HRD mutational signature in patients with TNBC, CNA-derived HRD parameters demonstrated little difference between these age groups,” the authors wrote. “These ‘BRCAness’ parameters should be used with caution until more definitive evidence has been obtained.”
Importantly, the age-specific clinical and molecular features evaluated in this study were based on a retrospectively collected cohort, which is a possible limitation of the study. In addition, though the current study is the largest single-center, multiomic cohort of patients with TNBC presented to date, the cohort was not large enough achieve satisfying statistical power when investigating infrequent genomic events in specific age groups. Therefore, further research in a prospective cohort with a larger sample size and higher statistical power is warranted.
“Specifically, these potential strategies require clinical validation before they can be used for the clinical management of patients with TNBC,” the authors wrote. “Nevertheless, the results of the current study provide a clearer portrait of the heterogeneity of TNBC and help to refine precision medicine for its treatment.”
Ma D, Jiang Y, Xiao Y, et al. Integrated Molecular Profiling of Young and Elderly Patients With Triple-Negative Breast Cancer Indicates Different Biological Bases and Clinical Management Strategies. Cancer. doi:10.1002/cncr.32922.