Title
Predictive value and clinical utility of centrally assessed ER, PgR, and Ki-67 to select adjuvant endocrine therapy for premenopausal women with hormone receptor-positive, HER2-negative early breast cancer: TEXT and SOFT trials
Date Issued
01 November 2015
Access level
open access
Resource Type
journal article
Author(s)
Regan M.M.
Pagani O.
Francis P.A.
Fleming G.F.
Walley B.A.
Kammler R.
Dell’Orto P.
Russo L.
Szőke J.
Villani L.
Pizzolitto S.
Öhlschlegel C.
Sessa F.
Peg Cámara V.
Rodríguez Peralto J.L.
MacGrogan G.
Colleoni M.
Goldhirsch A.
Price K.N.
Coates A.S.
Gelber R.D.
Viale G.
Publisher(s)
Springer New York LLC
Abstract
The SOFT and TEXT randomized phase III trials investigated adjuvant endocrine therapies for premenopausal women with hormone receptor-positive (HR+) early breast cancer. We investigated the prognostic and predictive value of centrally assessed levels of estrogen receptor (ER), progesterone receptor (PgR), and Ki-67 expression in women with HER2-negative disease. Of 5707 women enrolled, 4115 with HER2-negative (HR+/HER2−) disease had ER, PgR, and Ki-67 centrally assessed by immunohistochemistry. Breast cancer-free interval (BCFI) was defined from randomization to first invasive local, regional, or distant recurrence or contralateral breast cancer. The prognostic and predictive values of ER, PgR and Ki-67 expression levels were assessed using Cox modeling and STEPP methodology. In this HR+/HER2- population, the median ER, PgR, and Ki-67 expressions were 95, 90, and 18 % immunostained cells. As most patients had strongly ER-positive tumors, the predictive value of ER levels could not be investigated. Lower PgR and higher Ki-67 expression were associated with reduced BCFI. There was no consistent evidence of heterogeneity of the relative treatment effects according to PgR or Ki-67 expression levels, though there was a greater 5-year absolute benefit of exemestane + ovarian function suppression (OFS) versus tamoxifen with or without OFS at lower levels of PgR and higher levels of Ki-67. Women with poor prognostic features of low PgR and/or high Ki-67 have greater absolute benefit from exemestane + OFS versus tamoxifen + OFS or tamoxifen alone, but individually PgR and Ki-67 are of limited predictive value for selecting adjuvant endocrine therapy for premenopausal women with HR+/HER2− early breast cancer.
Start page
275
End page
286
Volume
154
Issue
2
Language
English
OCDE Knowledge area
Oncología
Obstetricia, Ginecología
Patología
Subjects
Scopus EID
2-s2.0-84947611492
PubMed ID
Source
Breast Cancer Research and Treatment
ISSN of the container
01676806
Sponsor(s)
We thank many pathologists who submitted tumor blocks and slides, and the patients, physicians, nurses and data managers who participated in the TEXT and SOFT clinical trials. We thank Stefania Andrighetto and Elvira Bianca Benini of the IBCSG Central Pathology Office and Wilbur Helfer of the IBCSG Coordinating Center. TEXT and SOFT received financial support for trial conduct from Pfizer, the International Breast Cancer Study Group, and the US National Cancer Institute. Pfizer and Ipsen provided drug supply. Support for the coordinating group, IBCSG: Frontier Science and Technology Research Foundation, Swiss Group for Clinical Cancer Research (SAKK), Cancer Research Switzerland/Oncosuisse, the Foundation for Clinical Cancer Research of Eastern Switzerland (OSKK), US National Cancer Institute (NCI) (US NIH CA75362), Susan G. Komen for the Cure Promise Grant (KG080081), Breast Cancer Research Foundation. Grant support of cooperative groups: Australia and New Zealand Breast Cancer Trials Group (NHMRC 351161 and 510788); SWOG (US NIH CA32102); Alliance/CALGB (US NIH U10-CA180821); ECOG-ACRIN (US NIH CA21115 and CA16116); NSABP/NRG (US NIH U10-CA-12027, U10-CA-69651, U10-CA-37377, U10-CA-69974); NCIC-CTG (US NIH CA077202 and CCSRI 015469 and 021039); ICR-CTSU on behalf of the National Cancer Research Institute (NCRI) Breast Clinical Studies Group United Kingdom (NCRI-BCSG—ICR-CTSU Partnership) was supported by CRUK, CRUKE/03/022, CRUKE/03/023, A15955, NIHR RM/ICR Biomedical Research Centre, and by NIHR Cambridge Biomedical Research Centre.
Sources of information:
Directorio de Producción Científica
Scopus