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Overexpression of p53 is correlated with poor outcome in premenopausal women with breast cancer treated with tamoxifen after chemotherapy

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Abstract

The aim of this study was to evaluate the difference in outcomes based on p53 overexpression of patients with breast cancer who received adjuvant therapy following local treatment for invasive ductal carcinoma, not otherwise specified. We analyzed data from 4,683 patients with cancer enrolled in two institutions between 1997 and 2006. We analyzed the correlation between p53 overexpression and relapse, response to adjuvant therapy, breast cancer-specific survival (BCSS), and relapse-free survival (RFS) in patients with primary breast cancer. Overexpression of p53 was noted in 1,091 patients (23.3%). A significant correlation existed between p53 overexpression and poor prognostic factors, an increased frequency of regional recurrence, visceral metastasis, and worse BCSS and RFS. Based upon subgroup analyses, combined age (<35, 35–50, and >50 years) and adjuvant therapy (hormone therapy only, chemotherapy only, and hormone therapy following chemotherapy), the greatest reduction of survival based on p53 overexpression was noted in patients 35–50 years of age who received hormone therapy following chemotherapy (P < 0.05). Multivariate analysis showed that p53 overexpression is an independent prognostic factor in patients treated with hormone therapy and chemotherapy (relative risk for BCSS, 2.003; 95% CI, 1.105–3.631; P = 0.022). The p53-overexpressing patients with breast cancer between 35 and 50 years of age who received tamoxifen following chemotherapy had the greatest adverse effect on outcome. Overexpression of p53 is significantly associated with tamoxifen resistance in premenopausal women with breast cancer.

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References

  1. Lynya IT, William EG, John WW, David B, Heidi W, Andra RF (2002) Hormone receptors and proliferation in breast carcinomas of equivalent histologic grades in pre- and postmenopausal women. Int J Cancer 98:118–127

    Article  Google Scholar 

  2. Talley L, Chhieng DC, Bell WC, Grizzle WE, Frost AR (2008) Immunohistochemical detection of EGFR, p185(erbB-2), Bcl-2 and p53 in breast carcinomas in pre-menopausal and post-menopausal women. Biotech Histochem 83:5–14. doi:10.1080/10520290701822436

    Article  CAS  PubMed  Google Scholar 

  3. Elledge RM, Allred DC (1994) The p53 tumor suppressor gene in breast cancer. Breast Cancer Res Treat 32:39–47

    Article  CAS  PubMed  Google Scholar 

  4. Talley LI, Grizzle WE, Waterbor JW, Brown D, Weiss H, Frost AR (2002) Hormone receptors and proliferation in breast carcinomas of equivalent histologic grades in pre- and postmenopausal women. Int J Cancer 98:118–12710. doi:1002/ijc.10171 pii

    Article  CAS  PubMed  Google Scholar 

  5. Network NCC NCCN Clinical Practice Guidelines in Oncology Breast Cancer

  6. Greene FL, Page DL, Fleming ID, Fritz AG, Balch CM, Haller DG, Morrow M (2002) AJCC cancer staging manual, 6th edn. pp 221–240

  7. Anelli A, Brentani RR, Gadelha AP, Amorim De Albuquerque A, Soares F (2003) Correlation of p53 status with outcome of neoadjuvant chemotherapy using paclitaxel and doxorubicin in stage IIIB breast cancer. Ann Oncol 14:428–432

    Article  CAS  PubMed  Google Scholar 

  8. Knoop AS, Bentzen SM, Nielsen MM, Rasmussen BB, Rose C (2001) Value of epidermal growth factor receptor, HER2, p53, and steroid receptors in predicting the efficacy of tamoxifen in high-risk postmenopausal breast cancer patients. J Clin Oncol 19:3376–3384

    CAS  PubMed  Google Scholar 

  9. Berry DA, Muss HB, Thor AD, Dressler L, Liu ET, Broadwater G, Budman DR, Henderson IC, Barcos M, Hayes D, Norton L (2000) HER-2/neu and p53 expression versus tamoxifen resistance in estrogen receptor-positive, node-positive breast cancer. J Clin Oncol 18:3471–3479

    CAS  PubMed  Google Scholar 

  10. Archer SG, Eliopoulos A, Spandidos D, Barnes D, Ellis IO, Blamey RW, Nicholson RI, Robertson JF (1995) Expression of ras p21, p53 and c-erbB-2 in advanced breast cancer and response to first line hormonal therapy. Br J Cancer 72:1259–1266

    CAS  PubMed  Google Scholar 

  11. Berns EM, Klijn JG, van Putten WL, de Witte HH, Look MP, Meijer-van Gelder ME, Willman K, Portengen H, Benraad TJ, Foekens JA (1998) p53 protein accumulation predicts poor response to tamoxifen therapy of patients with recurrent breast cancer. J Clin Oncol 16:121–127

    CAS  PubMed  Google Scholar 

  12. Leitzel K, Teramoto Y, Konrad K, Chinchilli VM, Volas G, Grossberg H, Harvey H, Demers L, Lipton A (1995) Elevated serum c-erbB-2 antigen levels and decreased response to hormone therapy of breast cancer. J Clin Oncol 13:1129–1135

    CAS  PubMed  Google Scholar 

  13. Elledge RM, Green S, Ciocca D, Pugh R, Allred DC, Clark GM, Hill J, Ravdin P, O’Sullivan J, Martino S, Osborne CK (1998) HER-2 expression and response to tamoxifen in estrogen receptor-positive breast cancer: a southwest oncology group study. Clin Cancer Res 4:7–12

    CAS  PubMed  Google Scholar 

  14. Carlomagno C, Perrone F, Gallo C, De Laurentiis M, Lauria R, Morabito A, Pettinato G, Panico L, D’Antonio A, Bianco AR, De Placido S (1996) c-erb B2 overexpression decreases the benefit of adjuvant tamoxifen in early-stage breast cancer without axillary lymph node metastases. J Clin Oncol 14:2702–2708

    CAS  PubMed  Google Scholar 

  15. Yamauchi H, Stearns V, Hayes DF (2001) When is a tumor marker ready for prime time? A case study of c-erbB-2 as a predictive factor in breast cancer. J Clin Oncol 19:2334–2356

    CAS  PubMed  Google Scholar 

  16. De Laurentiis M, Arpino G, Massarelli E, Ruggiero A, Carlomagno C, Ciardiello F, Tortora G, D’Agostino D, Caputo F, Cancello G, Montagna E, Malorni L, Zinno L, Lauria R, Bianco AR, De Placido S (2005) A meta-analysis on the interaction between HER-2 expression and response to endocrine treatment in advanced breast cancer. Clin Cancer Res 11:4741–4748. doi:10.1158/1078-0432.ccr-04-2569

    Article  PubMed  Google Scholar 

  17. Yamashita H, Nishio M, Toyama T, Sugiura H, Zhang Z, Kobayashi S, Iwase H (2004) Coexistence of HER2 over-expression and p53 protein accumulation is a strong prognostic molecular marker in breast cancer. Breast Cancer Res 6:R24–R30. doi:10.1186/bcr738 pii

    Article  CAS  PubMed  Google Scholar 

  18. Tovey S, Dunne B, Witton CJ, Forsyth A, Cooke TG, Bartlett JMS (2005) Can molecular markers predict when to implement treatment with aromatase inhibitors in invasive breast cancer? Clin Cancer Res 11:4835–4842. doi:10.1158/1078-0432.ccr-05-0196

    Article  CAS  PubMed  Google Scholar 

  19. Aas T, Borresen AL, Geisler S, Smith-Sorensen B, Johnsen H, Varhaug JE, Akslen LA, Lonning PE (1996) Specific P53 mutations are associated with de novo resistance to doxorubicin in breast cancer patients. Nat Med 2:811–814

    Article  CAS  PubMed  Google Scholar 

  20. Rahko E, Blanco G, Soini Y, Bloigu R, Jukkola A (2003) A mutant TP53 gene status is associated with a poor prognosis and anthracycline-resistance in breast cancer patients. Eur J Cancer 39:447–453

    Article  CAS  PubMed  Google Scholar 

  21. Bertheau P, Plassa F, Espi M, Turpin E, de Roquancourt A, Marty M, Lerebours F, Beuzard Y, Janin A, de Th H (2002) Effect of mutated TP53 on response of advanced breast cancers to high-dose chemotherapy. Lancet 360:852–854

    Article  CAS  PubMed  Google Scholar 

  22. Andersson J, Larsson L, Klaar S, Holmberg L, Nilsson J, Inganas M, Carlsson G, Ohd J, Rudenstam CM, Gustavsson B, Bergh J (2005) Worse survival for TP53 (p53)-mutated breast cancer patients receiving adjuvant CMF. Ann Oncol 16:743–748. doi:10.1093/annonc/mdi150

    Article  CAS  PubMed  Google Scholar 

  23. Bottini A, Berruti A, Bersiga A, Brizzi MP, Brunelli A, Gorzegno G, DiMarco B, Aguggini S, Bolsi G, Cirillo F, Filippini L, Betri E, Bertoli G, Alquati P, Dogliotti L (2000) p53 but not bcl-2 immunostaining is predictive of poor clinical complete response to primary chemotherapy in breast cancer patients. Clin Cancer Res 6:2751–2758

    CAS  PubMed  Google Scholar 

  24. Mottolese M, Benevolo M, Del Monte G, Buglioni S, Papaldo P, Nistico C, Di Filippo F, Vasselli S, Vici P, Botti C (2000) Role of P53 and BCL-2 in high-risk breast cancer patients treated with adjuvant anthracycline-based chemotherapy. J Cancer Res Clin Oncol 126:722–729

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Sei Hyun Ahn.

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Hee Sung Kim and Cha Kyong Yom made an equal contribution to this work.

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Kim, H.S., Yom, C.K., Kim, H.J. et al. Overexpression of p53 is correlated with poor outcome in premenopausal women with breast cancer treated with tamoxifen after chemotherapy. Breast Cancer Res Treat 121, 777–788 (2010). https://doi.org/10.1007/s10549-009-0560-5

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  • DOI: https://doi.org/10.1007/s10549-009-0560-5

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