Breast Cancer Research and Treatment (2018) 171:359–369
Long-term breast cancer survival in relation to the metastatic tumor
burden in axillary lymph nodes
· L. Bergkvist
· J. Frisell
· J. de Boniface
Received: 23 April 2018 / Accepted: 3 May 2018 / Published online: 30 May 2018
© Springer Science+Business Media, LLC, part of Springer Nature 2018
Purpose The clinical signiﬁcance of lymph node micrometastases and isolated tumor cells (ITCs) in breast cancer is still
controversial. After a median follow-up of 52 months, a report from the Swedish Multicenter Cohort Study presented a
worse cancer-speciﬁc and event-free survival for patients with micrometastases than node-negative individuals, but could
not demonstrate a signiﬁcant diﬀerence in overall survival (OS). Due to the tendency of breast cancer to relapse after more
than 5–10 years, we now report the long-term survival of the cohort.
Methods Between September 2000 and January 2004, 3355 breast cancer patients were included in a prospective cohort.
Sentinel lymph node biopsy was always performed. Patients were classiﬁed in four groups according to their overall nodal
stage: node negative (N0, 2372), ITCs (113), micrometastases (123), and macrometastases (747). Kaplan–Meier survival
estimates and Cox proportional hazard regression models were applied.
Results Median follow-up was 156 months. Ten-year cancer-speciﬁc survival and OS were signiﬁcantly lower in case of
micrometastases than in N0 (84.7 vs. 93.5%, p = 0.001, and 75.5 vs. 84.2%, p = 0.046, respectively). In case of macrome-
tastases, corresponding survival rates were 82.8 and 74.3%. Only for those aged less than 50 years, cancer-speciﬁc survival
and OS were signiﬁcantly worse in case of ITCs than N0. Patients with micrometastases received less often chemotherapy
than those with macrometastases (24.4 vs. 53.9%).
Conclusions Lymph node micrometastases in breast cancer have a prognostic signiﬁcance. This study demonstrates a similar
survival for patients with micrometastases and those with macrometastases, possibly due to systemic undertreatment.
Keywords Breast cancer · Sentinel node biopsy · Lymph node status · Micrometastases · Isolated tumor cells · Prognosis
Lymph node stage has traditionally been regarded as the
most important prognostic factor for breast cancer patients
. Since the introduction of sentinel lymph node (SLN)
biopsy, there is a targeted assessment of lymph nodes, where
the most important nodes (the SLNs) undergo a more thor-
ough histopathologic examination. This has conveyed a
considerable stage migration with an increased detection
of isolated tumor cells (ITCs) and micrometastases in the
SLN [2, 3].
The clinical signiﬁcance of micrometastases is still some-
what controversial, and there is a debate whether the pres-
ence of SLN micrometastases should have an impact on the
recommendation on adjuvant treatment [4–8]. Previous stud-
ies are heterogeneous, from both pre- and post-SLN eras,
and are often retrospective or include few patients [9–13].
There are some more recent reports that dispute the clinical
Presented in part at the 22nd Annual Meeting of the Swedish
Surgeon’s Society, August 21–25, 2017 Jonkoping, Sweden.
Electronic supplementary material The online version of this
article (https ://doi.org/10.1007/s1054 9-018-4820-0) contains
supplementary material, which is available to authorized users.
* Yvette Andersson
Department of Surgery, Västmanland County Hospital,
72189 Västerås, Sweden
Center for Clinical Research, Västmanland County Hospital,
Uppsala University, Västerås, Sweden
Department of Breast and Endocrine Surgery, Karolinska
University Hospital, Stockholm, Sweden
Department of Molecular Medicine and Surgery, Karolinska
Institutet, Stockholm, Sweden
Department of Surgery, Capio St Göran’s Hospital,