Worse survival for TP53 (p53)-mutated breast cancer patients receiving adjuvant CMF

Abstract

Background: TP53 has been described as a prognostic factor in many malignancies, including breast cancer. Whether it also might be a predictive factor with reference to chemo-and endocrine therapy is more controversial. Patients and methods: We investigated relapse-free (RFS), breast cancer-corrected (BCCS) and overall survival (OS) related to TP53 status in node-positive breast cancer patients that had received polychemotherapy [cyclophosphamide, methotrexate, 5-fluorouracil (CMF)] and/or endocrine therapy (tamoxifen). Sequence analyses of the whole TP53 coding region was performed in 376 patients operated on for primary breast cancer with axillary lymph node metastases between 1984 and 1989 (median follow-up time 84 months). Results: TP53 mutations were found in 105 patients (28%). We found 90 (82%) of the 110 mutations in the more frequently analysed exons 5 -8, while the other 20 (18%) were located in exons 3 -4 and 9 -10, respectively. Univariate analyses showed TP53 to be a significant prognostic factor with regard to RFS, BCCS and OS in patients who received adjuvant CMF. Conclusions: TP53 mutations might induce resistance to certain modalities of breast cancer therapy. Sequence-determined TP53 mutation was of negative prognostic value in the total patient population and in the CMF treated patients.

Targeting Chk1 in p53-deficient triple-negative breast cancer is therapeutically beneficial in human-in-mouse tumor models

“…TP53 mutation is one of the most common genetic abnormalities in breast cancer (40,41) and associates with more aggressive disease and a poor clinical outcome (40)(41)(42)(43). Although the overall frequency of TP53 mutation is 20%-30%, the incidence is much higher in certain breast cancer subtypes.…”

Significance of immunohistochemistry in breast cancer

“…Wild-type p53 is a tumour suppressor protein and plays an essential role in regulating genomic stability by controlling the cell cycle and inducing apoptosis when cell damage cannot be repaired [65][66][67] . In normal cells, p53 has a very short half-life due to ubiquitylation and proteasome degradation [68,69] . IHC can be used, as wild-type p53 protein is rapidly degraded, while TP53 mutations (18%-25% of primary breast carcinomas) are often associated with the production of a stable protein.…”

<i>TP53</i> Status and Response to Chemotherapy in Breast Cancer

“…Andersson et al [62] found that TP53 mutations (assessed by sequencing) might induce resistance to cyclophosphamide, methotrexate, 5-fluorouracil adjuvant treatment.…”