Prognostic value of isolated tumour cells in sentinel lymph
nodes in early-stage breast cancer: a prospective study
Jenni S. Liikanen
, Marjut H. Leidenius
, Heikki Joensuu
, Jaana H. Vironen
and Tuomo J. Meretoja
BACKGROUND: The prognostic signiﬁcance of isolated tumour cells (ITCs) in the sentinel nodes (SNs) is controversial in early breast
cancer, and some centres have abandoned immunohistochemistry to detect ITCs.
METHODS: Patients with unilateral pT1N0 breast cancer, operated between February 2001 and August 2005 at a university hospital
were included in this prospective, population-based cohort study. Survival of 936 patients with or without isolated tumour cells
(ITC) in their SNs were compared with the log-rank test and Cox regression analysis.
RESULTS: Eight hundred sixty one (92.0%) patients were ITC-negative (pN0i−) and 75 (8.0%) ITC-positive (pN0i+). Patients with ITC-
positive cancer received more frequently adjuvant systemic therapies than those with ITC-negative cancer. The median follow-up
time was 9.5 years. Ten-year distant disease-free survival was 95.3% in the pN0i− group and 88.8% in the pN0i+ group (P = 0.013).
ITCs were an independent prognostic factor in a Cox regression model (HR = 2.34, 95% CI 1.09–5.04; P = 0.029), together with
tumour Ki-67 proliferation index and diameter. ITCs were associated with unfavourable overall survival (P = 0.005) and breast
cancer-speciﬁc survival (P = 0.001).
CONCLUSIONS: We conclude that presence of ITCs in the SNs is an adverse prognostic factor in early small node-negative breast
cancer, and may be considered in the decision-making for adjuvant therapy.
British Journal of Cancer (2018) 118:1529–1535; https://doi.org/10.1038/s41416-018-0052-7
The regional lymph node status has long been known to be an
important prognostic factor in early breast cancer.
axillary ultrasound and a subsequent sentinel node biopsy (SNB)
are currently the standard of care in the staging of clinically node-
negative breast cancer. After harvesting, the sentinel nodes (SNs)
are evaluated with immunohistochemical (IHC) staining of several
tissue sections, which allows reasonably accurate assessment of
both isolated tumour cells (ITCs) and micrometastases, whereas
routine haematoxylin and eosin (H&E) staining often fails to detect
In 2002, the American Joint Committee on Cancer (AJCC) TNM-
classiﬁcation (the 6th edition) deﬁned and distinguished ITCs
(pN0i+) from micrometastases (pN1mi).
Since the deﬁnition of
the ITCs their clinical importance has been debated, some arguing
ITCs to have true metastatic potential and prognostic importance,
while others consider them as artefacts from benign transporta-
tion after tumour manipulation, or otherwise of little importance
In the beginning of the SN era, even the
detection of small tumour deposits (including ITCs) in the lymph
nodes led to axillary lymph node dissection (ALND), but data from
clinical trials and other evidence now indicates that ALND does
not improve survival of patients with limited SN involvement.
Consequently, several guidelines now recommend to stop looking
for ITCs, and many centres have abandoned IHC analysis of the
Although it is evident that patients with only ITCs in their SNs
do not beneﬁt from an ALND, the long-term prognostic
signiﬁcance of ITCs and their impact on the decision-making
regarding the need of adjuvant therapy is unclear.
the clinical signiﬁcance of ITCs, we aimed to investigate in the
present study the long-term prognostic importance of ITCs in a
large population-based cohort of patients with early node-
negative breast cancer.
PATIENTS AND METHODS
A total of 1865 patients who had not been treated with
neoadjuvant systemic therapy underwent breast surgery for
unilateral, invasive pT1 (the largest tumour diameter ≤ 2 cm)
breast cancer at the Breast Surgery Unit of the Comprehensive
Cancer Center of Helsinki University Hospital, Finland, between
February 2001 and August 2005, and were considered for this
prospective cohort study. Since the Breast Surgery Unit of the
Helsinki University Hospital is the only dedicated breast unit in a
deﬁned geographical region encompassing the Helsinki metro-
politan area, serving a population of approximately 1.5 million,
Received: 30 October 2017 Revised: 1 February 2018 Accepted: 14 February 2018
Published online: 24 April 2018
Comprehensive Cancer Center, Breast Surgery Unit, Helsinki University Hospital and University of Helsinki, P.O. Box 263, FIN-00029 HUS Helsinki, Finland;
Cancer Center, Helsinki University Hospital and University of Helsinki, P.O. Box 180, FIN-00029 HUS Helsinki, Finland and
Abdominal Center, Helsinki University Hospital and
University of Helsinki, P.O. Box 340, FIN-00029 HUS Helsinki, Finland
Correspondence: Jenni S. Liikanen (jenni.liikanen@helsinki.ﬁ)
© Cancer Research UK 2018