Abstract
The most important subgroup of breast cancer patients for whom reliable prognostic indicators are needed is women without axillary lymph node metastases. We evaluated the clinical significance of occult micrometastases in axillary lymph nodes in 148 consecutive “node‐negative” breast cancer patients. The median age of the patients at surgery was 52 years and the median follow‐up period after surgery was 98.5 months. Occult micrometastases were detected in 21 of 148 patients (14.2%) by means of immunohistochemical analysis using AE1/3 antibody and a single unstained section after routine histopathological examination. Log‐rank tests indicated that the 7–year disease‐free survival (DFS) and overall survival (OS) rates by Kaplan‐Meier methods were significantly better in patients without occult micrometastases than in patients with occult micrometastases [DFS, 93% versus 71% (P=0.0009); OS, 96% versus 76% (P=0.0001)]. According to Cox's multivariate analysis, the presence of occult micrometastases had the most significant effect on DFS (P=0.0053) and OS (P=0.0035). These findings suggest that the presence of occult micrometastases is an independent and significant predictor of clinical outcome, and that their immunohistochemical detection after routine histopathological examination is useful for selecting the “node‐negative” breast cancer patient subgroup at high risk for relapse and death.
Keywords: Immunohistochemistry, Breast cancer, Micrometastases
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REFERENCES
- 1. ) Fisher , B. , Bauer , M. , Wickerham , L. , Redmond , C. K. and Fisher , E. R.Relation of number of positive axillary nodes to the prognosis of patients with primary breast cancer: an NSABP update . Cancer , 52 , 1551 – 1557 ( 1983. ). [DOI] [PubMed] [Google Scholar]
- 2. ) Rosen , P. P. , Saigo , P. E. , Braun , D. W. , Weathers , E. and Depalo , A.Predictors of recurrence in stage I (T1N0M0) breast carcinoma . Ann. Surg. , 193 , 15 ( 1981. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3. ) Cote , R. J. , Peterson , H. F. , Chaiwun , B. , Gelber , R. D. , Goldhirsch , A. , Castiglione‐Gertsch , M. , Gusterson , B. and Neville , A. M.(International Breast Cancer Study Group). Role of immunohistochemical detection of lymph node metastases in management of breast cancer . Lancet , 354 , 896 – 900 ( 1999. ). [DOI] [PubMed] [Google Scholar]
- 4. ) Hainsworth , P. J. , Tjandra , J. J. , Stillwell , R. G. , Machet , D. , Henderson , M. A. , Rennie , G. C. , Mckenzie , I. F. C. and Bennett , R. C.Detection and significance of occult metastases in node‐negative breast cancer . Br. J. Surg. , 80 , 459 – 463 ( 1993. ). [DOI] [PubMed] [Google Scholar]
- 5. ) Nasser , I. A. , Lee , A. K. C. , Bosari , S. , Saganich , R. , Heatley , G. and Silverman , M. L.Occult axillary lymph node metastases in “node‐negative” breast carcinoma . Hum. Pathol. , 24 , 950 – 957 ( 1993. ). [DOI] [PubMed] [Google Scholar]
- 6. ) de Mascarel , L , Bonichon , F. , Coindre , J. M. and Trojani , M.Prognostic significance of breast cancer axillary lymph node micrometastases assessed by two special techniques: reevaluation with longer follow‐up . Br. J. Cancer , 66 , 523 – 527 ( 1992. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7. ) McGuire , W. L. , De La Garza , M. and Chammnes , G. C.Evaluation of estrogen receptor assays in human breast cancer tissue . Cancer Res. , 37 , 637 – 639 ( 1977. ). [PubMed] [Google Scholar]
- 8. ) Elston , C. W. and Ellis , I. O.Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long‐term follow‐up . Histopathology , 19 , 403 – 410 ( 1991. ). [DOI] [PubMed] [Google Scholar]
- 9. ) Umekita , Y. , Sagara , Y. and Yoshida , H.Estrogen receptor mutations and changes in estrogen receptor and progesterone receptor protein expression in metastatic or recurrent breast cancer . Jpn. J. Cancer Res. , 89 , 27 – 32 ( 1998. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10. ) Kaplan , E. L. and Meier , P.Nonparametric estimation from incomplete observations . J. Am. Stat. Assoc. , 53 , 457 – 481 ( 1958. ). [Google Scholar]
- 11. ) Cox , D. R.Regression models and life‐tables . J. R. Stat. Soc. , 34 , 187 – 220 ( 1972. ). [Google Scholar]
- 12. ) Trojani , M. , de Mascarel , I. , Bonichon , F. , Coindre , J. M. and Delsol , G.Micrometastases to axillary lymph nodes from carcinoma of breast: detection by immunohistochemistry and prognostic significance . Br. J. Cancer , 55 , 303 – 306 ( 1987. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13. ) Doglioni , C. , Dell'Orto , P. , Zanetti , G. , Iuzzolino , P. , Coggi , G. and Viale , G.Cytokeratin‐immunoreactive cells of human lymph nodes and spleen in normal and pathological conditions: an immunohistochemical study . Virchows Arch. Pathol. Anat. , 416 , 479 – 490 ( 1990. ). [DOI] [PubMed] [Google Scholar]
- 14. ) Saimura , M. , Fukutomi , T. , Tsuda , H. , Sato , H. , Miyamoto , K. , Akashi‐Tanaka , S. and Nanasawa , T.Prognosis of a series of 763 consecutive node‐negative invasive breast cancer patients without adjuvant therapy: analysis of clinicopathological prognostic factor . J. Surg. Oncol. , 71 , 101 – 105 ( 1999. ). [DOI] [PubMed] [Google Scholar]
- 15. ) Masuda , N. , Tamaki , Y. , Sakita , L , Ooka , M. , Ohnishi , T. , Kadota , M. , Aritake , N. , Okubo , K. and Monden , M.Clinical significance of micrometastases in axillary lymph nodes assessed by reverse transcription‐polymerase chain reaction in breast cancer patients . Clin. Cancer Res. , 6 , 4176 – 4185 ( 2000. ). [PubMed] [Google Scholar]