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.


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.
Andersson
J
J
Department of Oncology, Cancer Center Karolinska, Radiumhemmet, Karolinska Institute and University Hospital, Stockholm. jenny.andersson@cck.ki.se
Larsson
L
L
Klaar
S
S
Holmberg
L
L
Nilsson
J
J
Inganäs
M
M
Carlsson
G
G
Ohd
J
J
Rudenstam
C-M
CM
Gustavsson
B
B
Bergh
J
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000627:therapeutic use; D015331:Cohort Studies; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53 / Q000235:genetics*; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D016133:Polymerase Chain Reaction; D011336:Probability; D011379:Prognosis; D012189:Retrospective Studies; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D013629:Tamoxifen / Q000627:therapeutic use
D005819:Genetic Markers; D013629:Tamoxifen; D002945:Cisplatin; D005472:Fluorouracil; D008727:Methotrexate