E58: Staging for de novo Metastatic Breast Cancer: Can genomic data make it better?

A staging system was recently developed for de novo metastatic breast cancer (dnMBC) that stratifies patients into subgroups (IVA, IVB, IVC, IVD) based on 3-year overall survival (OS) and select disease characteristics, similar to those used for non-MBC. Here, we aim to evaluate the association of genomic data with prognosis in these subgroups.

Methods:

Patients with dnMBC who underwent commercially available genomic testing (324 genes analyzed) as a part of their routine clinical care at a single academic institution were identified. Stage groups were assigned based on published criteria, defined by T-category, grade, ER, PR, HER2, histology, organ system site of metastases (bone-only, brain-only, visceral), and number of organ systems involved. Unadjusted OS was estimated using the Kaplan-Meier method and log-rank tests were used to compare groups. Cox Proportional hazards models were used to estimate the association of genomic mutations with OS after adjustment for demographics, treatments, and stage.

Results:

For the overall cohort (N=92), the median age was 52 (IQR 43.5-61), and the median follow-up was 75.3 months (95% CI 64.4-142). The majority were non-Hispanic White (63%) or non-Hispanic Black (25%). Tumor subtypes included 52.2% HR+/HER2- (n=48), 19.6% HR-/HER2- (n=18), 13% HR+/HER2+ (n=12), and 6.5% HR-/HER2+ (n=6). At the time of diagnosis, the majority had distant metastases limited to one organ site (58.7%, n=54). Stage groups were assigned: 7.6% IVA (n=7), 43.5% IVB (n=40), 30.4% IVC (n=28), and 18.5% IVD (n=17). Most patients received chemotherapy (90.2%, n=83), but did not receive local surgery (88%, n=81). Although pathogenic mutations were identified in 143 genes across the entire cohort, the median number of genes with mutations per patient was 6 (IQR 3-9). The most common genes with mutations were TP53 (62%, n=57), PIK3CA (30.4%, n=28), ESR1 (25%, n=23), CCND1 (25%, n=23), MYC (21.7%, n=20), and FGFR1 (21.7%, n=20). After adjusting for stage group (IVA, IVB, IVC, IVD), age, race/ethnicity, treatments (chemotherapy, endocrine therapy, radiation therapy, and/or surgery), none of these most common mutations were individually associated with OS (all p >0.05; Table).

Conclusions: These findings suggest that the addition of mutation status for the most common mutated genes in patients with dnMBC may not improve the prognostic estimates beyond the already identified variables. However, larger cohorts and/or combinations of mutations may be worth further exploration.