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.
| Original language | English |
|---|---|
| Pages (from-to) | 275-286 |
| Number of pages | 12 |
| Journal | Breast Cancer Research and Treatment |
| Volume | 154 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Nov 1 2015 |
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Keywords
- Estrogen receptor
- Exemestane
- Ki-67
- Ovarian function suppression
- Progesterone receptor
- Tamoxifen
ASJC Scopus subject areas
- Oncology
- Cancer Research
Cite this
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. / Regan, Meredith M.; Pagani, Olivia; Francis, Prudence A.; Fleming, Gini F.; Walley, Barbara A.; Kammler, Roswitha; Dell’Orto, Patrizia; Russo, Leila; Szőke, János; Doimi, Franco; Villani, Laura; Pizzolitto, Stefano; Öhlschlegel, Christian; Sessa, Fausto; Peg Cámara, Vicente; Rodríguez Peralto, José Luis; MacGrogan, Gaëtan; Colleoni, Marco; Goldhirsch, Aron; Price, Karen N.; Coates, Alan S.; Gelber, Richard D.; Viale, Giuseppe.
In: Breast Cancer Research and Treatment, Vol. 154, No. 2, 01.11.2015, p. 275-286.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - 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
T2 - TEXT and SOFT trials
AU - Regan, Meredith M.
AU - Pagani, Olivia
AU - Francis, Prudence A.
AU - Fleming, Gini F.
AU - Walley, Barbara A.
AU - Kammler, Roswitha
AU - Dell’Orto, Patrizia
AU - Russo, Leila
AU - Szőke, János
AU - Doimi, Franco
AU - Villani, Laura
AU - Pizzolitto, Stefano
AU - Öhlschlegel, Christian
AU - Sessa, Fausto
AU - Peg Cámara, Vicente
AU - Rodríguez Peralto, José Luis
AU - MacGrogan, Gaëtan
AU - Colleoni, Marco
AU - Goldhirsch, Aron
AU - Price, Karen N.
AU - Coates, Alan S.
AU - Gelber, Richard D.
AU - Viale, Giuseppe
PY - 2015/11/1
Y1 - 2015/11/1
N2 - 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.
AB - 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.
KW - Estrogen receptor
KW - Exemestane
KW - Ki-67
KW - Ovarian function suppression
KW - Progesterone receptor
KW - Tamoxifen
UR - http://www.scopus.com/inward/record.url?scp=84947611492&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84947611492&partnerID=8YFLogxK
U2 - 10.1007/s10549-015-3612-z
DO - 10.1007/s10549-015-3612-z
M3 - Article
VL - 154
SP - 275
EP - 286
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
SN - 0167-6806
IS - 2
ER -