Oncology| Volume 158, ISSUE 2, P494-500, August 2015

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Occult metastases in node-negative breast cancer: A Surveillance, Epidemiology, and End Results−based analysis


      The role of immunohistochemistry (IHC) for detecting occult lymph node disease in patients initially found to be node-negative by routine pathology is controversial. In this study, we evaluated trends associated with overall survival in node-negative breast cancer patients staged by IHC.


      The Surveillance, Epidemiology, and End Results database was queried for all patients with invasive breast adenocarcinoma and negative lymph nodes on routine pathology between 2004 and 2011 who underwent IHC to evaluate for occult nodal disease. Overall survival stratified by N-stage was compared with Kaplan-Meier analysis. Multivariate analysis was performed using a Cox proportional hazards model.


      Overall, 93,070 patients were identified, including 4,657 patients with isolated tumor cells (<0.2 mm diameter or <200 cells) and 6,720 patients with micrometastases (0.2–2 mm diameter). Kaplan-Meier curves demonstrated a difference in overall survival across all groups (P < .0001). On multivariate analysis, micrometastases remained an independent predictor for survival compared with IHC-negative patients (hazard ratio 1.40, 95% confidence interval 1.28–1.53), whereas isolated tumor cells were not a significant predictor (hazard ratio 1.05, 95% confidence interval 0.92–1.20).


      Patients with occult micrometastases in axillary lymph nodes found via IHC demonstrated a significant overall survival difference, but isolated tumor cells have no prognostic significance.
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      1. Breast Cancer Facts and Figures 2013-2014. American Cancer Society, Inc, Atlanta, GA2013
        • Fisher B.
        • Bauer M.
        • Wickerham D.L.
        • Redmond C.K.
        • Fisher E.R.
        • Cruz A.B.
        • et al.
        Relation of number of positive axillary nodes to the prognosis of patients with primary breast cancer. An NSABP update.
        Cancer. 1983; 52: 1551-1557
        • Saphir O.
        • Amromin G.D.
        Obscure axillary lymph-node metastasis in carcinoma of the breast.
        Cancer. 1948; 1: 238-241
        • Cserni G.
        Surgical pathological staging of breast cancer by sentinel lymph node biopsy with special emphasis on the histological work-up of axillary sentinel lymph nodes.
        Breast Cancer. 2004; 11 (discussion 64–66): 242-249
        • Liberman L.
        Pathologic analysis of sentinel lymph nodes in breast carcinoma.
        Cancer. 2000; 88: 971-977
        • Tan L.K.
        • Giri D.
        • Hummer A.J.
        • Panageas K.S.
        • Brogi E.
        • Norton L.
        • et al.
        Occult axillary node metastases in breast cancer are prognostically significant: results in 368 node-negative patients with 20-year follow-up.
        J Clin Oncol. 2008; 26: 1803-1809
        • Querzoli P.
        • Pedriali M.
        • Rinaldi R.
        • Lombardi A.R.
        • Biganzoli E.
        • Boracchi P.
        • et al.
        Axillary lymph node nanometastases are prognostic factors for disease-free survival and metastatic relapse in breast cancer patients.
        Clin Cancer Res. 2006; 12: 6696-6701
        • Chen S.L.
        • Hoehne F.M.
        • Giuliano A.E.
        The prognostic significance of micrometastases in breast cancer: a SEER population-based analysis.
        Ann Surg Oncol. 2007; 14: 3378-3384
        • Millis R.R.
        • Springall R.
        • Lee A.H.
        • Ryder K.
        • Rytina E.R.
        • Fentiman I.S.
        Occult axillary lymph node metastases are of no prognostic significance in breast cancer.
        Br J Cancer. 2002; 86: 396-401
        • Nasser I.A.
        • Lee A.K.
        • Bosari S.
        • Saganich R.
        • Heatley G.
        • Silverman M.L.
        Occult axillary lymph node metastases in “node-negative” breast carcinoma.
        Human Pathol. 1993; 24: 950-957
        • Reed W.
        • Bohler P.J.
        • Sandstad B.
        • Nesland J.M.
        Occult metastases in axillary lymph nodes as a predictor of survival in node-negative breast carcinoma with long-term follow-up.
        Breast J. 2004; 10: 174-180
        • de Boer M.
        • van Dijck J.A.
        • Bult P.
        • Borm G.F.
        • Tjan-Heijnen V.C.
        Breast cancer prognosis and occult lymph node metastases, isolated tumor cells, and micrometastases.
        J Natl Cancer Inst. 2010; 102: 410-425
        • de Boer M.
        • van Deurzen C.H.
        • van Dijck J.A.
        • Borm G.F.
        • van Diest P.J.
        • Adang E.M.
        • et al.
        Micrometastases or isolated tumor cells and the outcome of breast cancer.
        N Engl J Med. 2009; 361: 653-663
        • Hansen N.M.
        • Grube B.
        • Ye X.
        • Turner R.R.
        • Brenner R.J.
        • Sim M.S.
        • et al.
        Impact of micrometastases in the sentinel node of patients with invasive breast cancer.
        J Clin Oncol. 2009; 27: 4679-4684
        • van der Heiden-van der Loo M.
        • Schaapveld M.
        • Ho V.K.
        • Siesling S.
        • Rutgers E.J.
        • Peeters P.H.
        Outcomes of a population-based series of early breast cancer patients with micrometastases and isolated tumour cells in axillary lymph nodes.
        Ann Oncol. 2013; 24: 2794-2801
        • Singletary S.E.
        • Connolly J.L.
        Breast cancer staging: working with the sixth edition of the AJCC Cancer Staging Manual.
        CA Cancer J Clin. 2006; 56 (quiz 50–51): 37-47
        • Weaver D.L.
        • Ashikaga T.
        • Krag D.N.
        • Skelly J.M.
        • Anderson S.J.
        • Harlow S.P.
        • et al.
        Effect of occult metastases on survival in node-negative breast cancer.
        N Engl J Med. 2011; 364: 412-421
        • Giuliano A.E.
        • Hawes D.
        • Ballman K.V.
        • Whitworth P.W.
        • Blumencranz P.W.
        • Reintgen D.S.
        • et al.
        Association of occult metastases in sentinel lymph nodes and bone marrow with survival among women with early-stage invasive breast cancer.
        JAMA. 2011; 306: 385-393
        • Gradisher W.J.
        • Anderson B.O.
        NCCN Clinical Practice Guidelines in Oncology: Breast Cancer.
        National Comprehensive Cancer Network, 2014 (Available from:) (Accessed January 2, 2015)
        • Howlader N.
        • Chen V.W.
        • Ries L.A.
        • Loch M.M.
        • Lee R.
        • DeSantis C.
        • et al.
        Overview of breast cancer collaborative stage data items-their definitions, quality, usage, and clinical implications: a review of SEER data for 2004-2010.
        Cancer. 2014; 120: 3771-3780
        • Moore K.H.
        • Thaler H.T.
        • Tan L.K.
        • Borgen P.I.
        • Cody 3rd, H.S.
        Immunohistochemically detected tumor cells in the sentinel lymph nodes of patients with breast carcinoma: biologic metastasis or procedural artifact?.
        Cancer. 2004; 100: 929-934
        • Dowlatshahi K.
        • Fan M.
        • Snider H.C.
        • Habib F.A.
        Lymph node micrometastases from breast carcinoma: reviewing the dilemma.
        Cancer. 1997; 80: 1188-1197
        • Pepels M.J.
        • de Boer M.
        • Bult P.
        • van Dijck J.A.
        • van Deurzen C.H.
        • Menke-Pluymers M.B.
        • et al.
        Regional recurrence in breast cancer patients with sentinel node micrometastases and isolated tumor cells.
        Ann Surg. 2012; 255: 116-121
        • Degnim A.C.
        • Zakaria S.
        • Boughey J.C.
        • Sookhan N.
        • Reynolds C.
        • Donohue J.H.
        • et al.
        Axillary recurrence in breast cancer patients with isolated tumor cells in the sentinel lymph node [AJCC N0(i+)].
        Ann Surg Oncol. 2010; 17: 2685-2689
        • Karam I.
        • Lesperance M.F.
        • Berrang T.
        • Speers C.
        • Tyldesley S.
        • Truong P.T.
        pN0(i+) breast cancer: treatment patterns, locoregional recurrence, and survival outcomes.
        Int J Radiat Oncol Biol Phys. 2013; 87: 731-737