Identifying clinically relevant prognostic subgroups of postmenopausal women with node-positive hormone receptor-positive early-stage breast cancer treated with endocrine therapy: a combined analysis of ABCSG-8 and ATAC using the PAM50 risk of recurrence score and intrinsic subtype.
BACKGROUND
In the adjuvant treatment of hormone receptor-positive (HR+) breast cancer, variables like tumour size, grade and nodal status have great impact on therapy decisions. As most node-positive patients with HR+ breast cancer currently receive adjuvant chemotherapy improved methods for characterization of individuals' metastasis risk are needed to reduce overtreatment.


METHODS
Tissue specimens from node-positive patients of the ABCSG-8 and ATAC trials who received adjuvant tamoxifen and/or anastrozole were included in this study. Analysing RNA from paraffin blocks using the PAM50 test, the primary objective was to evaluate the prognostic information of the risk of recurrence (ROR) score added to combined clinical standard variables in patients with one positive node (1N+) and in patients with two or three positive nodes (2-3N+), using log-likelihood ratio tests.


RESULTS
At a median follow-up of 9.6 years, distant metastases occurred in 97 (18%) of 543 node-positive patients. In a multivariate analysis, the PAM50-derived ROR score provided reliable prognostic information in addition to and beyond established clinical factors for 1N+ (P < 0.0001) and 2-3N+ patients (P = 0.0002). Ten-year distant recurrence risk was significantly increased in the high-risk compared with the low-risk group derived from ROR score for 1N+ [25.5%, 95% confidence interval (CI) 17.5% to 36.1%versus 6.6%, 95% CI 3.3% to 12.8%] and compared with the combined low/intermediate risk group for 2-3N+ patients (33.7%, 95% CI 25.5% to 43.8% versus 12.5%, 95% CI 6.6% to 22.8%). Additionally, the luminal A intrinsic subtype (IS) exhibited significantly lower risk of distant recurrence compared with the luminal B subtype in 1N+ and 2-3N+ patients.


CONCLUSIONS
PAM50 ROR score and IS can identify node-positive patient subgroups with limited risk of metastasis after endocrine therapy, for whom adjuvant chemotherapy can be spared. The PAM50 test is a valuable tool in determining treatment of node-positive early-stage breast cancer patients.
Department of Surgery and Comprehensive Cancer Centre, Medical University of Vienna, Vienna, Austria michael.gnant@meduniwien.ac.at.
M
M
Gnant
Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, UK.
I
I
Sestak
Department of Medicine I, Medical University of Vienna, Vienna, Austria.
M
M
Filipits
Academic Department of Biochemistry, Royal Marsden Hospital and Breakthrough Breast Cancer Centre, London, UK.
M
M
Dowsett
Department of Internal Medicine, Medical University Graz, Graz, Austria.
M
M
Balic
Institute of Cancer Research, Royal Marsden Hospital and Breakthrough Breast Cancer Research Centre, London, UK.
E
E
Lopez-Knowles
Department of Internal Medicine III, Paracelsus Medical University Salzburg, Salzburg.
R
R
Greil
Department of Surgery and Comprehensive Cancer Centre, Medical University of Vienna, Vienna, Austria.
P
P
Dubsky
Department of Internal Medicine, Medical University Graz, Graz, Austria.
H
H
Stoeger
Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria.
M
M
Rudas
Department of Surgery and Comprehensive Cancer Centre, Medical University of Vienna, Vienna, Austria.
R
R
Jakesz
NanoString Technologies, Seattle, USA.
S
S
Ferree
NanoString Technologies, Seattle, USA.
J W
JW
Cowens
Department of Pathology, University of British Columbia, Vancouver, Canada.
T
T
Nielsen
Independent Statistical Consultant New York, New York, USA.
C
C
Schaper
Department of Statistics, Austrian Breast and Colorectal Cancer Study Group, Vienna, Austria.
C
C
Fesl
Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, UK.
J
J
Cuzick
D000077384:Anastrozole; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000145:classification / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology*; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D009570:Nitriles / Q000627:therapeutic use*; D017698:Postmenopause; D011379:Prognosis; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D018570:Risk Assessment; D013629:Tamoxifen / Q000627:therapeutic use*; D014230:Triazoles / Q000627:therapeutic use*
D018931:Antineoplastic Agents, Hormonal; D009570:Nitriles; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D014230:Triazoles; D013629:Tamoxifen; D000077384:Anastrozole
early-stage breast cancer (EBC); intrinsic subtype (IS); multigenomic testing; node-positive patients; prognostic subtypes; risk of recurrence (ROR)