TY - JOUR
T1 - Predicted sensitivity to endocrine therapy for stage II-III hormone receptor-positive and HER2-negative (HR+/HER2−) breast cancer before chemo-endocrine therapy
AU - Du, L.
AU - Yau, C.
AU - Brown-Swigart, L.
AU - Gould, R.
AU - Krings, G.
AU - Hirst, G. L.
AU - Bedrosian, I.
AU - Layman, R. M.
AU - Carter, J. M.
AU - Klein, M.
AU - Venters, S.
AU - Shad, S.
AU - van der Noordaa, M.
AU - Chien, A. J.
AU - Haddad, T.
AU - Isaacs, C.
AU - Pusztai, L.
AU - Albain, K.
AU - Nanda, R.
AU - Tripathy, D.
AU - Liu, M. C.
AU - Boughey, J.
AU - Schwab, R.
AU - Hylton, N.
AU - DeMichele, A.
AU - Perlmutter, J.
AU - Yee, D.
AU - Berry, D.
AU - van't Veer, L.
AU - Valero, V.
AU - Esserman, L. J.
AU - Symmans, W. F.
N1 - Publisher Copyright:
© 2021 European Society for Medical Oncology
PY - 2021/5
Y1 - 2021/5
N2 - BACKGROUND: We proposed that a test for sensitivity to the adjuvant endocrine therapy component of treatment for patients with stage II-III breast cancer (SET2,3) should measure transcription related to estrogen and progesterone receptors (SET
ER/PR index) adjusted for a baseline prognostic index (BPI) combining clinical tumor and nodal stage with molecular subtype by RNA4 (ESR1, PGR, ERBB2, and AURKA).
PATIENTS AND METHODS: Patients with clinically high-risk, hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative (HR+/HER2-) breast cancer received neoadjuvant taxane-anthracycline chemotherapy, surgery with measurement of residual cancer burden (RCB), and then adjuvant endocrine therapy. SET2,3 was measured from pre-treatment tumor biopsies, evaluated first in an MD Anderson Cancer Center (MDACC) cohort (n = 307, 11 years' follow-up, U133A microarrays), cut point was determined, and then independent, blinded evaluation was carried out in the I-SPY2 trial (n = 268, high-risk MammaPrint result, 3.8 years' follow-up, Agilent-44K microarrays, NCI Clinical Trials ID: NCT01042379). Primary outcome measure was distant relapse-free survival. Multivariate Cox regression models tested prognostic independence of SET2,3 relative to RCB and other molecular prognostic signatures, and whether other prognostic signatures could substitute for SET
ER/PR or RNA4 components of SET2,3.
RESULTS: SET2,3 added independent prognostic information to RCB in the MDACC cohort: SET2,3 [hazard ratio (HR) 0.23, P = 0.004] and RCB (HR 1.77, P < 0.001); and the I-SPY2 trial: SET2,3 (HR 0.27, P = 0.031) and RCB (HR 1.68, P = 0.008). SET2,3 provided similar prognostic information irrespective of whether RCB-II or RCB-III after chemotherapy, and in both luminal subtypes. Conversely, RCB was most strongly prognostic in cancers with low SET2,3 status (MDACC P < 0.001, I-SPY2 P < 0.001). Other molecular signatures were not independently prognostic; they could effectively substitute for RNA4 subtype within the BPI component of SET2,3, but they could not effectively substitute for SET
ER/PR index.
CONCLUSIONS: SET2,3 added independent prognostic information to chemotherapy response (RCB) and baseline prognostic score or subtype. Approximately 40% of patients with clinically high-risk HR+/HER2- disease had high SET2,3 and could be considered for clinical trials of neoadjuvant endocrine-based treatment.
AB - BACKGROUND: We proposed that a test for sensitivity to the adjuvant endocrine therapy component of treatment for patients with stage II-III breast cancer (SET2,3) should measure transcription related to estrogen and progesterone receptors (SET
ER/PR index) adjusted for a baseline prognostic index (BPI) combining clinical tumor and nodal stage with molecular subtype by RNA4 (ESR1, PGR, ERBB2, and AURKA).
PATIENTS AND METHODS: Patients with clinically high-risk, hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative (HR+/HER2-) breast cancer received neoadjuvant taxane-anthracycline chemotherapy, surgery with measurement of residual cancer burden (RCB), and then adjuvant endocrine therapy. SET2,3 was measured from pre-treatment tumor biopsies, evaluated first in an MD Anderson Cancer Center (MDACC) cohort (n = 307, 11 years' follow-up, U133A microarrays), cut point was determined, and then independent, blinded evaluation was carried out in the I-SPY2 trial (n = 268, high-risk MammaPrint result, 3.8 years' follow-up, Agilent-44K microarrays, NCI Clinical Trials ID: NCT01042379). Primary outcome measure was distant relapse-free survival. Multivariate Cox regression models tested prognostic independence of SET2,3 relative to RCB and other molecular prognostic signatures, and whether other prognostic signatures could substitute for SET
ER/PR or RNA4 components of SET2,3.
RESULTS: SET2,3 added independent prognostic information to RCB in the MDACC cohort: SET2,3 [hazard ratio (HR) 0.23, P = 0.004] and RCB (HR 1.77, P < 0.001); and the I-SPY2 trial: SET2,3 (HR 0.27, P = 0.031) and RCB (HR 1.68, P = 0.008). SET2,3 provided similar prognostic information irrespective of whether RCB-II or RCB-III after chemotherapy, and in both luminal subtypes. Conversely, RCB was most strongly prognostic in cancers with low SET2,3 status (MDACC P < 0.001, I-SPY2 P < 0.001). Other molecular signatures were not independently prognostic; they could effectively substitute for RNA4 subtype within the BPI component of SET2,3, but they could not effectively substitute for SET
ER/PR index.
CONCLUSIONS: SET2,3 added independent prognostic information to chemotherapy response (RCB) and baseline prognostic score or subtype. Approximately 40% of patients with clinically high-risk HR+/HER2- disease had high SET2,3 and could be considered for clinical trials of neoadjuvant endocrine-based treatment.
KW - chemo-endocrine
KW - hormonal
KW - prediction
KW - prognosis
KW - response
KW - treatments
KW - Receptors, Progesterone/genetics
KW - Prognosis
KW - Humans
KW - Neoplasm Recurrence, Local
KW - Receptor, ErbB-2/genetics
KW - Biomarkers, Tumor/genetics
KW - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
KW - Female
KW - Neoadjuvant Therapy
KW - Hormones/therapeutic use
KW - Breast Neoplasms/drug therapy
UR - http://www.scopus.com/inward/record.url?scp=85102757482&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85102757482&partnerID=8YFLogxK
U2 - 10.1016/j.annonc.2021.02.011
DO - 10.1016/j.annonc.2021.02.011
M3 - Article
C2 - 33617937
AN - SCOPUS:85102757482
SN - 0923-7534
VL - 32
SP - 642
EP - 651
JO - Annals of Oncology
JF - Annals of Oncology
IS - 5
ER -