Breast Cancer Research and Treatment (2018) 168:269–275
Validation of the 8th AJCC prognostic staging system for breast cancer
in a population‑based setting
Received: 4 August 2017 / Accepted: 11 November 2017 / Published online: 15 November 2017
© Springer Science+Business Media, LLC, part of Springer Nature 2017
Objectives To validate the newly proposed American Joint Committee on Cancer (AJCC) prognostic staging system for
Methods Surveillance, epidemiology, and end results (SEER) database (2010–2014) was accessed. Cumulative incidence
function was conducted (through assessment of sub-distribution hazard) according to both anatomical and prognostic stages.
Likewise, Cox cause-speciﬁc hazard ratio with pairwise hazard ratio comparisons were also assessed for both anatomical and
prognostic stages. Survival analyses according to both anatomical and prognostic staging systems were conducted through
Kaplan–Meier analysis/log-rank testing.
Results A total of 209,304 patients with non-metastatic breast cancer and upfront surgical treatment were included. Accord-
ing to anatomical stages, pairwise Cox hazard ratio comparisons between diﬀerent stages were signiﬁcant (P < 0.0001)
except between stage IIIB and stage IIIC, while according to prognostic stages, all pairwise hazard ratio comparisons between
diﬀerent stages were signiﬁcant (P < 0.05). Sub-distribution hazard ratio (using breast cancer death as the primary failure
endpoint and using other causes of death as competing causes of death) adjusted for age, race, and surgery was as follows:
for the anatomical groups, it was 1.671 (95% CI 1.627–1.716; P < 0.0001) indicating increasing risk of death from breast
cancer with increasing stage; however, for the prognostic groups it was 1.790 (95% CI 1.744–1.838; P < 0.0001) indicating
increasing risk of death from breast cancer with increasing stage. C-statistic was assessed using breast cancer death as the
dependent variable; and the ﬁndings for the two staging systems were as follows: anatomical staging: 0.767 (SE 0.004; 95%
CI 0.759–0.776); prognostic staging: 0.814 (SE 0.004; 95% CI 0.807–0.822).
Conclusions The current analysis showed an improvement in the discriminatory value for the prognostic staging system
compared to the anatomical staging system and endorsed its routine use in clinical practice.
Keywords Breast cancer · Staging · Prognosis · SEER
More than 1.5 million patients were estimated to be aﬀected
with breast cancer in 2012 (according to globocan) . This
made breast cancer the second most common cancer in the
world as well as the most common cancer among women.
Moreover, breast cancer is the ﬁfth leading cause of cancer
mortality in the world and the leading cause of cancer mor-
tality among women in the developing countries .
Approaches for the management of non-metastatic
breast cancer have evolved in recent years focusing on a
number of domains, namely disease domain (biology and
extent of disease) and patient domain (performance status
and co-morbidity) . The most commonly used breast
cancer staging system (Tumor/Node/Metastasis (TNM)/
American Joint Committee on Cancer (AJCC) system)
provided an excellent account on anatomical extent of the
disease. However until recently, it provided little or no
account on the biology of the disease [4, 5]. More recently,
the 8th edition of the AJCC staging system was released
and it incorporated dual staging system; anatomical stag-
ing system which is identical to the 7th AJCC staging
system and prognostic staging system which incorporated
multiple relevant biomarkers (ER: estrogen receptor; PR:
* Omar Abdel-Rahman
Clinical Oncology Department, Faculty of Medicine, Ain
Shams University, Lotfy Elsayed Street, Cairo 11566, Egypt