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Background  Previous studies on the role of  TP53  mutation in breast cancer treatment response and survival are contradictory and inconclusive, limited by the use of different endpoints to determine clinical significance and by small sample sizes that prohibit stratification by treatment.    Methods  We utilized large datasets to examine overall survival according to  TP53  mutation status in patients across multiple clinical features and treatments.    Results  Confirming other studies, we found that in all patients and in hormone therapy-treated patients,  TP53  wild-type status conferred superior 5-year overall survival, but survival curves crossed at 10 or more years. In contrast, further stratification within the large dataset revealed that in patients receiving chemotherapy and no hormone therapy, wild-type  TP53  status conferred remarkably poor overall survival. This previously unrecognized inferior survival is consistent with p53 inducing arrest/senescence instead of apoptosis. Addition of hormone therapy to chemotherapy improved survival notably in patients with  TP53  wild-type tumors, but not mutant, suggesting hormone therapy could eradicate arrested/senescent cells. Testing this, we found that estrogen receptor-positive,  TP53  wild-type breast cancer cells that were made senescent by doxorubicin treatment were sensitive to tamoxifen.    Conclusions  The poor survival of chemotherapy-treated patients with  TP53  wild-type tumors may be improved by strategies to eliminate senescent cells, including the addition of hormone therapy when appropriate.    Electronic supplementary material  The online version of this article (10.1186/s13058-018-1044-5) contains supplementary material, which is available to authorized users.

Breast cancer survival predicted by TP53 mutation status differs markedly depending on treatment