Breast Cancer Research and Treatment

, Volume 102, Issue 1, pp 61–73 | Cite as

Local recurrence after mastectomy for breast cancer: analysis of clinicopathological, biological and prognostic characteristics

  • Guillermo Carreño
  • José M. del Casar
  • Ma Daniela Corte
  • Luis O. González
  • Miguel Bongera
  • Antonio M. Merino
  • Germán Juan
  • Raúl Obregón
  • Enrique Martínez
  • Francisco J. Vizoso
Clinical Trial

Abstract

Background

Despite the increasing use of breast-conserving therapy, modified radical mastectomy retains an important role in primary as well as in salvage treatment of breast cancer. Nevertheless, a significant number of patients will eventually develop a local recurrence (LR).

Aims

To identify the potential prognostic factors at the time of the first isolated LR, and to compare the expression of several parameters of the molecular biology of breast carcinomas by primary tumors and paired isolated LRs.

Methods

We analyzed the medical records from 1,087 women who underwent mastectomy for breast cancer, out of which 98 developed LRs as the first manifestation of tumor progression. We investigated the prognostic value of various classical prognostic factors, at the time of mastectomy as well as when the diagnosis of LR was made. In addition, by using tissue microarrays and immunohistochemical techniques, we analyzed the expression of estrogen (ER), progesterone (PR) and androgen receptors (AR), ki67, p53, c-erbB-2 and apolipoprotein D in primary tumors and paired isolated LRs from a subset of patients (n = 25).

Results

Patients who developed distant metastases as well as patients with local recurrent disease showed a significantly higher percentage of larger tumors, node-positive status and higher tumoral grade than patients without evidence of tumoral recurrence. Furthermore, patients with LR had a better outcome compared with those with distant metastases, although the former received less frequently adjuvant systemic therapy and/or radiotherapy. Tumor size, histological grade, ER and PR status, and a shorter disease-free interval (<12 months) were significantly associated with overall survival amongst mastectomized patients that developed isolated LR. There was a significant concordance between primary tumors and LRs regarding the expression of the following factors: ER, PR and p53. However, we were not able to demonstrate similar findings for AR, c-erbB-2 and ki67. In addition, ER, PR and p53 status in the LRs were significantly associated with a poorer overall survival.

Conclusions

Based on classical clinicopathological factors as well as on some new biological parameters we have been able to identify subgroups of mastectomized patients with LR differing in their prognosis. Thus, at the present time it would be possible to select group of patients candidates for further and individualized therapeutic strategies.

Keywords

Breast cancer Local recurrence p53 Estrogen receptors Tissue microarrays 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Halverson KJ, Perez CA, Kuske RR et al (1992) Survival following locoregional recurrence of breast cancer: univariate and multivariate analysis. Int J Radiat Oncol Biol Phys 23:285–291PubMedGoogle Scholar
  2. 2.
    Bedwinek J (1994) Natural history and management of isolated local-regional recurrence following mastectomy. Semin Radiat Oncol 4:260–269PubMedCrossRefGoogle Scholar
  3. 3.
    Kuske RR (1999) Adjuvant irradiation after mastectomy in women with one to three positive axillary nodes: then no; now yes. Semin Radiat Oncol 9:254–258PubMedCrossRefGoogle Scholar
  4. 4.
    Recht A, Gray R, Davidson NE et al (1999) Locoregional failure 10 years after mastectomy and adjuvant chemotherapy with or without tamoxifen without irradiation: experience of the Eastern Cooperative Oncology Group. J Clin Oncol 17:1689–1700PubMedGoogle Scholar
  5. 5.
    Fowble B, Gray R, Gilchrist K et al (1988) Identification of a subgroup of patients with breast cancer and histologically positive axillary nodes receiving adjuvant chemotherapy who may benefit from postoperative radiotherapy. J Clin Oncol 6:1107–1117PubMedGoogle Scholar
  6. 6.
    Pisansky TM, Ingle JN, Schaid DJ et al (1993) Patterns of tumor relapse following mastectomy and adjuvant systemic therapy in patients with axillary lymph node-positive breast cancer. Impact of clinical, histopathologic, and flow cytometric factors. Cancer 72:1247–1260PubMedCrossRefGoogle Scholar
  7. 7.
    Pineiro A, Salinas J, Illana J et al (2004) Locoregional recurrence and metastasis in the long-term follow-up of postmastectomy breast cancer patients with T1-T2 tumors and one to three positive lymph nodes. Rev Oncol 6:341– 346Google Scholar
  8. 8.
    Kamby C, Sengelov L (1999) Survival and pattern of failure following locoregional recurrence of breast cancer. Clin Oncol (R Coll Radiol) 11:156–163Google Scholar
  9. 9.
    Willner J, Kiricuta IC, Kolbl O (1997) Locoregional recurrence of breast cancer following mastectomy: always a fatal event? Results of univariate and multivariate analysis. Int J Radiat Oncol Biol Phys 37:853–863PubMedCrossRefGoogle Scholar
  10. 10.
    Lacour J, Le MG, Hill C et al (1987) Is it useful to remove internal mammary nodes in operable breast cancer? Eur J Surg Oncol 13:309–314PubMedGoogle Scholar
  11. 11.
    Kaae S, Johansen H (1962) Breast cancer; five year results: two random series of simple mastectomy with postoperative irradiation versus extended radical mastectomy. Am J Roentgenol Radium Ther Nucl Med 87:82–88PubMedGoogle Scholar
  12. 12.
    Lacour J, Le M, Caceres E et al (1983) Radical mastectomy versus radical mastectomy plus internal mammary dissection. Ten year results of an international cooperative trial in breast cancer. Cancer 51:1941–1943PubMedCrossRefGoogle Scholar
  13. 13.
    Alexander JW, Altemeier WA (1964) Susceptibility of injured tissues to hematogenous metastases: an experimental study. Ann Surg 159:933–944PubMedCrossRefGoogle Scholar
  14. 14.
    Fisher B, Fisher ER (1959) Experimental studies of factors influencing hepatic metastases. III. Effect of surgical trauma with special reference to liver injury. Ann Surg 150:731–744PubMedCrossRefGoogle Scholar
  15. 15.
    Murthy SM, Goldschmidt RA, Rao LN et al (1989) The influence of surgical trauma on experimental metastasis. Cancer 64:2035–2044PubMedCrossRefGoogle Scholar
  16. 16.
    Robinson KP, Hoppe E (1962) The development of blood-borne metastases. Effect of local trauma and ischemia. Arch Surg 85:720–724PubMedGoogle Scholar
  17. 17.
    Skipper D, Jeffrey MJ, Cooper AJ, Alexander P, Taylor I (1989) Enhanced growth of tumour cells in healing colonic anastomoses and laparotomy wounds. Int J Colorectal Dis 4:172–177PubMedCrossRefGoogle Scholar
  18. 18.
    Dao TL, Yogo H (1967) Enhancement of pulmonary metastases by x-irradiation in rats bearing mammary cancer. Cancer 20:2020–2025PubMedCrossRefGoogle Scholar
  19. 19.
    Fidler IJ, Zeidman I (1972) Enhancement of experimental metastasis by x-ray: a possible mechanism. J Med 3:172–177PubMedGoogle Scholar
  20. 20.
    Stefanik D, Goldberg R, Byrne P et al (1985) Local-regional failure in patients treated with adjuvant chemotherapy for breast cancer. J Clin Oncol 3:660–665PubMedGoogle Scholar
  21. 21.
    Sykes HF, Sim DA, Wong CJ, Cassady JR, Salmon SE (1989) Local-regional recurrence in breast cancer after mastectomy and adriamycin-based adjuvant chemotherapy: evaluation of the role of postoperative radiotherapy. Int J Radiat Oncol Biol Phys 16:641–647PubMedGoogle Scholar
  22. 22.
    Kamby C, Andersen J, Ejlertsen B et al (1991) Pattern of spread and progression in relation to the characteristics of the primary tumour in human breast cancer. Acta Oncol 30:301–308PubMedGoogle Scholar
  23. 23.
    Crowe JP Jr., Gordon NH, Antunez AR et al (1991) Local-regional breast cancer recurrence following mastectomy. Arch Surg 126:429–432PubMedGoogle Scholar
  24. 24.
    Berstock DA, Houghton J, Haybittle J, Baum M (1985) The role of radiotherapy following total mastectomy for patients with early breast cancer. World J Surg 9:667–670PubMedCrossRefGoogle Scholar
  25. 25.
    van Tienhoven G, Voogd AC, Peterse JL et al (1999) Prognosis after treatment for loco-regional recurrence after mastectomy or breast conserving therapy in two randomised trials (EORTC 10801 and DBCG-82TM). EORTC Breast Cancer Cooperative Group and the Danish Breast Cancer Cooperative Group. Eur J Cancer 35:32–38PubMedCrossRefGoogle Scholar
  26. 26.
    Dao TL, Nemoto T (1963) The clinical significance of skin recurrence after radical mastectomy in women with cancer of the Breast. Surg Gynecol Obstet 117:447–453PubMedGoogle Scholar
  27. 27.
    Donegan WL, Perez-Mesa CM, Watson FR (1966) A biostatistical study of locally recurrent breast carcinoma. Surg Gynecol Obstet 122:529–540PubMedGoogle Scholar
  28. 28.
    Spratt JS (1967) Locally recurrent cancer after radical mastectomy. Cancer 20:1051–1053PubMedCrossRefGoogle Scholar
  29. 29.
    Karabali-Dalamaga S, Souhami RL, O’Higgins NJ, Soumilas A, Clark CG (1978) Natural history and prognosis of recurrent breast cancer. Br Med J 2:730–733PubMedCrossRefGoogle Scholar
  30. 30.
    Bedwinek JM, Lee J, Fineberg B, Ocwieza M (1981) Prognostic indicators in patients with isolated local-regional recurrence of breast cancer. Cancer 47:2232–2235PubMedCrossRefGoogle Scholar
  31. 31.
    Borner M, Bacchi M, Goldhirsch A et al (1994) First isolated locoregional recurrence following mastectomy for breast cancer: results of a phase III multicenter study comparing systemic treatment with observation after excision and radiation. Swiss Group for Clinical Cancer Research. J Clin Oncol 12:2071–2077PubMedGoogle Scholar
  32. 32.
    Schuck A, Konemann S, Matthees B et al (2002) Radiotherapy in the treatment of locoregional relapses of breast cancer. Br J Radiol 75:663–669PubMedGoogle Scholar
  33. 33.
    Rimm DL, Camp RL, Charette LA et al (2001) Tissue microarray: a new technology for amplification of tissue resources. Cancer J 7:24–31PubMedGoogle Scholar
  34. 34.
    Allred DC, Harvey JM, Berardo M, Clark GM (1998) Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Mod Pathol 11:155–168PubMedGoogle Scholar
  35. 35.
    Greco M, Cascinelli N, Galluzzo D et al (1992) Locally recurrent breast cancer after ‘radical’ surgery. Eur J Surg Oncol 18:209–214PubMedGoogle Scholar
  36. 36.
    Aberizk WJ, Silver B, Henderson IC, Cady B, Harris JR (1986) The use of radiotherapy for treatment of isolated locoregional recurrence of breast carcinoma after mastectomy. Cancer 58:1214–1218PubMedCrossRefGoogle Scholar
  37. 37.
    Auchincloss H Jr. (1958) The nature of local recurrence following radical mastectomy. Cancer 11:611–619PubMedCrossRefGoogle Scholar
  38. 38.
    Scanlon EF (1985) Local recurrence in the pectoralis muscles following modified radical mastectomy for carcinoma. J Surg Oncol 30:149–151PubMedCrossRefGoogle Scholar
  39. 39.
    Toonkel LM, Fix I, Jacobson LH, Wallach CB (1983) The significance of local recurrence of carcinoma of the breast. Int J Radiat Oncol Biol Phys 9:33–39PubMedGoogle Scholar
  40. 40.
    Crile G Jr. (1972) Low incidence and morbidity of local recurrence after conservative operations for cancer of the breast. Ann Surg 175:249–253PubMedCrossRefGoogle Scholar
  41. 41.
    Baral E, Ogenstad S, Wallgren A (1985) The effect of adjuvant radiotherapy on the time of occurrence and prognosis of local recurrence in primary operable breast cancer. Cancer 56:2779–2782PubMedCrossRefGoogle Scholar
  42. 42.
    Fisher B, Redmond C, Fisher ER (1980) The contribution of recent NSABP clinical trials of primary breast cancer therapy to an understanding of tumor biology–an overview of findings. Cancer 46:1009–1025PubMedCrossRefGoogle Scholar
  43. 43.
    Gilliland MD, Barton RM, Copeland EM 3rd (1983) The implications of local recurrence of breast cancer as the first site of therapeutic failure. Ann Surg 197:284–287PubMedCrossRefGoogle Scholar
  44. 44.
    Papaioannou AN (1985) Hypothesis: increasingly intensive locoregional treatment of breast cancer may promote recurrence. J Surg Oncol 30:33–41PubMedCrossRefGoogle Scholar
  45. 45.
    Valagussa P, Bonadonna G, Veronesi U (1978) Patterns of relapse and survival following radical mastectomy. Analysis of 716 consecutive patients. Cancer 41:1170–1178PubMedCrossRefGoogle Scholar
  46. 46.
    Andry G, Suciu S, Vico P et al (1989) Locoregional recurrences after 649 modified radical mastectomies: incidence and significance. Eur J Surg Oncol 15:476–485PubMedGoogle Scholar
  47. 47.
    Schwaibold F, Fowble BL, Solin LJ, Schultz DJ, Goodman RL (1991) The results of radiation therapy for isolated local regional recurrence after mastectomy. Int J Radiat Oncol Biol Phys 21:299–310PubMedGoogle Scholar
  48. 48.
    Hsi RA, Antell A, Schultz DJ, Solin LJ (1998) Radiation therapy for chest wall recurrence of breast cancer after mastectomy in a favorable subgroup of patients. Int J Radiat Oncol Biol Phys 42:495–499PubMedCrossRefGoogle Scholar
  49. 49.
    Borner MM, Bacchi M, Castiglione M (1996) Possible deleterious effect of tamoxifen in premenopausal women with locoregional recurrence of breast cancer. Eur J Cancer 32A:2173–2176PubMedCrossRefGoogle Scholar
  50. 50.
    Janni W, Shabani N, Dimpfl T et al (2001) Matched pair analysis of survival after chest-wall recurrence compared to mammary recurrence: a long-term follow up. J Cancer Res Clin Oncol 127:455–462PubMedCrossRefGoogle Scholar
  51. 51.
    Duffy SW, Tabar L, Fagerberg G et al (1991) Breast screening, prognostic factors and survival–results from the Swedish two county study. Br J Cancer 64:1133–1138PubMedGoogle Scholar
  52. 52.
    Tabar L, Fagerberg G, Day NE, Duffy SW, Kitchin RM (1992) Breast cancer treatment and natural history: new insights from results of screening. Lancet 339:412–414PubMedCrossRefGoogle Scholar
  53. 53.
    Tabar L, Fagerberg G, Duffy SW et al (1992) Update of the Swedish two-county program of mammographic screening for breast cancer. Radiol Clin North Am 30:187–210PubMedGoogle Scholar
  54. 54.
    Bloom HJ, Richardson WW (1957) Histological grading and prognosis in breast cancer; a study of 1409 cases of which 359 have been followed for 15 years. Br J Cancer 11:359–377PubMedGoogle Scholar
  55. 55.
    Millis RR, Barnes DM, Lampejo OT, Egan MK, Smith P (1998) Tumour grade does not change between primary and recurrent mammary carcinoma. Eur J Cancer 34:548–553PubMedCrossRefGoogle Scholar
  56. 56.
    Cserni G (2002) Tumour histological grade may progress between primary and recurrent invasive mammary carcinoma. J Clin Pathol 55:293–297PubMedCrossRefGoogle Scholar
  57. 57.
    Diez-Itza I, Vizoso F, Merino AM et al (1994) Expression and prognostic significance of apolipoprotein D in breast cancer. Am J Pathol 144:310–320PubMedGoogle Scholar
  58. 58.
    Haffty BG, Hauser A, Choi DH et al (2004) Molecular markers for prognosis after isolated postmastectomy chest wall recurrence. Cancer 100:252–263PubMedCrossRefGoogle Scholar
  59. 59.
    Allred DC, Clark GM, Elledge R et al (1993) Association of p53 protein expression with tumor cell proliferation rate and clinical outcome in node-negative breast cancer. J Natl Cancer Inst 85:200–206PubMedCrossRefGoogle Scholar
  60. 60.
    Elledge RM, Fuqua SA, Clark GM, Pujol P, Allred DC (1993) William L. McGuire Memorial Symposium. The role and prognostic significance of p53 gene alterations in breast cancer. Breast Cancer Res Treat 27:95–102PubMedCrossRefGoogle Scholar
  61. 61.
    Kovach JS, Hartmann A, Blaszyk H et al (1996) Mutation detection by highly sensitive methods indicates that p53 gene mutations in breast cancer can have important prognostic value. Proc Natl Acad Sci USA 93:1093–1096PubMedCrossRefGoogle Scholar
  62. 62.
    Schmoor C, Sauerbrei W, Bastert G, Schumacher M (2000) Role of isolated locoregional recurrence of breast cancer: results of four prospective studies. J Clin Oncol 18:1696–1708PubMedGoogle Scholar
  63. 63.
    Zellars RC, Hilsenbeck SG, Clark GM et al (2000) Prognostic value of p53 for local failure in mastectomy-treated breast cancer patients. J Clin Oncol 18:1906–1913PubMedGoogle Scholar
  64. 64.
    Haylock BJ, Coppin CM, Jackson J, Basco VE, Wilson KS (2000) Locoregional first recurrence after mastectomy: prospective cohort studies with and without immediate chemotherapy. Int J Radiat Oncol Biol Phys 46:355–362PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2006

Authors and Affiliations

  • Guillermo Carreño
    • 1
  • José M. del Casar
    • 2
    • 3
  • Ma Daniela Corte
    • 2
    • 4
  • Luis O. González
    • 4
  • Miguel Bongera
    • 2
    • 3
  • Antonio M. Merino
    • 4
    • 5
  • Germán Juan
    • 6
  • Raúl Obregón
    • 1
  • Enrique Martínez
    • 4
    • 7
  • Francisco J. Vizoso
    • 2
    • 3
    • 4
  1. 1.Servicio de Cirugía GeneralHospital de CabueñesGijón, AsturiasSpain
  2. 2.Unidad de InvestigaciónHospital de JoveGijónSpain
  3. 3.Servicio de Cirugía GeneralHospital de JoveGijónSpain
  4. 4.Instituto Universitario de Oncología del Principado de AsturiasOviedoSpain
  5. 5.Servicio de Anatomía PatológicaHospital de CabueñesGijónSpain
  6. 6.Servicio de RadioterapiaHospital de JoveGijónSpain
  7. 7.Departamento de Cirugía y Especialidades Médico-QuirúrgicasUniversidad de OviedoOviedoSpain

Personalised recommendations