Mutation and accumulation of p53 related to results of adjuvant therapy of postmenopausal breast cancer patients.
p53 protein accumulation and gene mutation have been implicated in resistance to cytotoxic treatment. This study was performed to further assess the predictive value of p53 in breast cancer. Postmenopausal patients were randomized to adjuvant chemotherapy with cyclophosphamide, metothrexate, or 5-fluorouracil (CMF) vs. postoperative radiotherapy. The patients were also randomized to adjuvant tamoxifen vs. no endocrine treatment. Immunohistochemistry (IHC) and single-strand conformation polymorphism (SSCP), followed by direct sequencing, was performed. The p53 altered group, regarded as positive for p53 gene mutation and/or p53 protein accumulation, tended to benefit more from CMF than from radiotherapy as compared with others regarding distant recurrences. In the group lacking p53 alteration there was a significantly decreased local recurrence rate in the radiotherapy group as compared with the CMF group (RR = 0.24, 95% CI = 0.083 0.62), whereas no benefit from radiotherapy was found for patients showing p53 alterations. Tamoxifen significantly decreased the rate of distant recurrence for estrogen receptor-positive patients with no apparent difference in relation to p53 alteration. It is suggested that p53 alteration indicates benefit from CMF compared with radiotherapy regarding distant recurrence-free survival and the best local control with radiotherapy is achieved in the absence of p53 alteration. Finally, altered p53 status is probably not a marker of resistance to tamoxifen.
Askmalm
Marie Stenmark
MS
Department of Biomedicine and Surgery, Division of Oncology, Faculty of Health, Sciences, Linköping University, Linköping, Sweden. marie.askmalm@lio.se
Carstensen
John
J
Nordenskjöld
Bo
B
Olsson
Birgit
B
Rutqvist
Lars Erik
LE
Skoog
Lambert
L
Stål
Olle
O
D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000628:therapy*; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000627:therapeutic use*; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D016158:Genes, p53; D006801:Humans; D008727:Methotrexate / Q000627:therapeutic use*; D009154:Mutation; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D017698:Postmenopause; D018714:Radiotherapy, Adjuvant; D013629:Tamoxifen; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D018931:Antineoplastic Agents, Hormonal; D016159:Tumor Suppressor Protein p53; D013629:Tamoxifen; D003520:Cyclophosphamide; D005472:Fluorouracil; D008727:Methotrexate