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

• 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Kirurgi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Surgery (hsv//eng)

Nyckelord

Adult

Aged

Aged

80 and over

Antineoplastic Combined Chemotherapy Protocols/*therapeutic use

Breast Neoplasms/drug therapy/*genetics/*mortality/pathology

Chemotherapy

Adjuvant

Cisplatin/therapeutic use

Cohort Studies

Female

Fluorouracil/therapeutic use

Gene Expression Regulation

Neoplastic

Genes

p53/*genetics

Genetic Markers/genetics

Humans

Methotrexate/therapeutic use

Middle Aged

Mutation

Neoplasm Staging

Neoplasms

Hormone-Dependent/drug therapy/*genetics/*mortality/pathology

Polymerase Chain Reaction

Probability

Prognosis

Retrospective Studies

Risk Assessment

Sensitivity and Specificity

Survival Analysis

Tamoxifen/therapeutic use

MEDICINE

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)