TP53 Mutations and Outcomes in Breast Cancer: Reading beyond the Headlines

Abstract

TP53 is the most frequently mutated gene in breast cancer, but its role in survival is confounded by different studies concluding that TP53 mutations are associated with negative, neutral, or positive outcomes. Closer examination showed that many studies were limited by factors such as imprecise methods to detect TP53 mutations and small cohorts that combined patients treated with drugs having very different mechanisms of action. When only studies of patients receiving the same treatment(s) were compared, they tended to agree. These analyses reveal a role for TP53 in response to different treatments as complex as its different biological activities. We discuss studies that have assessed the role of TP53 mutations in breast cancer treatment and limitations in interpreting reported results.

Keywords: TP53; breast cancer; chemotherapy; hormone therapy; survival; tamoxifen; tumor suppressors.

Figure 1.. Breast Cancer Patient Survival after Stratification for TP53 Status and Treatment.

Median survival was determined for patients from the METABRIC database, stratified by TP53 mutation status and treatment exposure. Studies that analyzed patients under similar treatment conditions are listed in adjacent captions. (A) All patients (P <0.0001). (B) All chemotherapy-treated patients (P = ns). (C) All patients who did not receive chemotherapy (P <0.0001). (D) All patients treated with chemotherapy + HRT (P <0.05). (E) All patients treated with chemotherapy alone (P <0.05). (F) All patients treated with HRT only (P <0.0001). (G) All patients who did not receive chemotherapy or HRT (P = ns). Abbreviations: HRT, hormonal therapies; mut, mutant; ns, not significant; OS, overall survival; WT, wild type. (See [,–,–,–91].)