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. 2015 Nov;154(2):275-86.
doi: 10.1007/s10549-015-3612-z. Epub 2015 Oct 22.

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

Meredith M Regan  1 , Olivia Pagani  2 , Prudence A Francis  3   4 , Gini F Fleming  5 , Barbara A Walley  6 , Roswitha Kammler  7 , Patrizia Dell'Orto  8 , Leila Russo  9 , János Szőke  10 , Franco Doimi  11 , Laura Villani  12 , Stefano Pizzolitto  13 , Christian Öhlschlegel  14 , Fausto Sessa  15 , Vicente Peg Cámara  16 , José Luis Rodríguez Peralto  17 , Gaëtan MacGrogan  18   19 , Marco Colleoni  20 , Aron Goldhirsch  21 , Karen N Price  22 , Alan S Coates  23 , Richard D Gelber  24   25   26 , Giuseppe Viale  27 ; SOFT and TEXT Investigators and International Breast Cancer Study Group
Affiliations

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

Meredith M Regan et al. Breast Cancer Res Treat. 2015 Nov.

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.

Keywords: Estrogen receptor; Exemestane; Ki-67; Ovarian function suppression; Progesterone receptor; Tamoxifen.

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Conflict of interest statement

Conflicts of Interest: Dr. Francis reports uncompensated presentation of results of SOFT and TEXT for Pfizer at an international meeting.

The remaining authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Kaplan-Meier estimates of breast cancer-free interval (BCFI) and STEPPs of 5-year BCFI in the overall HR+/HER2- population, according to: (A) level of estrogen receptor (ER) expression; (B) level of progesterone receptor (PgR) expression; (C) level of Ki-67 expression Abbreviations: HR+=hormone receptor positive; SE=standard error; STEPP=subpopulation treatment effect pattern plot
Fig. 2
Fig. 2
Kaplan-Meier estimates of breast cancer-free interval (BCFI) in the overall HR+/HER2- population, according to luminal A/B-like status (Status is defined by the 2013 St. Gallen Consensus: in HR+/HER2-negative disease, Luminal A-like is PgR≥20% and Ki-67<20%; B-like is either PgR<20% or Ki-67≥20%) Abbreviations: HR+=hormone receptor positive; SE=standard error
Fig. 3
Fig. 3
STEPP of 5-year breast cancer-free interval (BCFI) in the HR+/HER2- population, according to level of progesterone receptor (PgR) expression, for each of the four cohorts defined by trial and chemotherapy use: (A) SOFT no chemotherapy; (B) TEXT no chemotherapy; (C) TEXT chemotherapy; (D) SOFT prior chemotherapy Abbreviations: HR+=hormone receptor positive; STEPP=subpopulation treatment effect pattern plot
Fig. 4
Fig. 4
STEPP of 5-year breast cancer-free interval (BCFI) in the HR+/HER2- population, according to level of Ki-67 expression, for each of the four cohorts defined by trial and chemotherapy use: (A) SOFT no chemotherapy; (B) TEXT no chemotherapy; (C) TEXT chemotherapy; (D) SOFT prior chemotherapy. P-values are from permutation tests of Ki-67-by- treatment interaction Abbreviations: HR+=hormone receptor positive; OFS=ovarian function suppression; STEPP=subpopulation treatment effect pattern plot
Fig. 5
Fig. 5
Kaplan-Meier estimates of breast cancer-free interval (BCFI) in the HR+/HER2- population according to luminal A/B-like status and treatment assignment, separately by cohort (Status is defined using the 2013 St. Gallen Consensus: in HR+/HER2-negative disease, Luminal A-like is PgR≥20% and Ki-67<20%; B-like is either PgR<20% or Ki-67≥20%.)
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References

    1. Regan MM, Pagani O, Fleming GF, Walley BA, Price KN, Rabaglio M, Maibach R, Ruepp B, Coates AS, Goldhirsch A, Colleoni M, Gelber RD, Francis PA. Adjuvant treatment of premenopausal women with endocrine-responsive early breast cancer: design of the TEXT and SOFT trials. Breast. 2013;22(6):1094–1100. doi: 10.1016/j.breast.2013.08.009. - DOI - PMC - PubMed
    1. Pagani O, Regan MM, Walley BA, Fleming GF, Colleoni M, Lang I, Gomez HL, Tondini C, Burstein HJ, Perez EA, Ciruelos E, Stearns V, Bonnefoi HR, Martino S, Geyer CE, Jr, Pinotti G, Puglisi F, Crivellari D, Ruhstaller T, Winer EP, Rabaglio-Poretti M, Maibach R, Ruepp B, Giobbie-Hurder A, Price KN, Bernhard J, Luo W, Ribi K, Viale G, Coates AS, Gelber RD, Goldhirsch A, Francis PA. Adjuvant exemestane with ovarian suppression in premenopausal breast cancer. N Engl J Med. 2014;371(2):107–118. doi: 10.1056/NEJMoa1404037. - DOI - PMC - PubMed
    1. Francis PA, Regan MM, Fleming GF, Lang I, Ciruelos E, Bellet M, Bonnefoi HR, Climent MA, Da Prada GA, Burstein HJ, Martino S, Davidson NE, Geyer CE, Jr, Walley BA, Coleman R, Kerbrat P, Buchholz S, Ingle JN, Winer EP, Rabaglio-Poretti M, Maibach R, Ruepp B, Giobbie-Hurder A, Price KN, Colleoni M, Viale G, Coates AS, Goldhirsch A, Gelber RD. Adjuvant ovarian suppression in premenopausal breast cancer. N Engl J Med. 2015;372(5):436–446. doi: 10.1056/NEJMoa1412379. - DOI - PMC - PubMed
    1. Viale G, Giobbie-Hurder A, Regan MM, Coates AS, Mastropasqua MG, Dell'Orto P, Maiorano E, MacGrogan G, Braye SG, Ohlschlegel C, Neven P, Orosz Z, Olszewski WP, Knox F, Thurlimann B, Price KN, Castiglione-Gertsch M, Gelber RD, Gusterson BA, Goldhirsch A. Prognostic and predictive value of centrally reviewed Ki-67 labeling index in postmenopausal women with endocrine-responsive breast cancer: results from Breast International Group Trial 1-98 comparing adjuvant tamoxifen with letrozole. J Clin Oncol. 2008;26(34):5569–5575. doi: 10.1200/jco.2008.17.0829. - DOI - PMC - PubMed
    1. Viale G, Regan MM, Maiorano E, Mastropasqua MG, Dell'Orto P, Rasmussen BB, Raffoul J, Neven P, Orosz Z, Braye S, Ohlschlegel C, Thurlimann B, Gelber RD, Castiglione-Gertsch M, Price KN, Goldhirsch A, Gusterson BA, Coates AS. Prognostic and predictive value of centrally reviewed expression of estrogen and progesterone receptors in a randomized trial comparing letrozole and tamoxifen adjuvant therapy for postmenopausal early breast cancer: BIG 1-98. J Clin Oncol. 2007;25(25):3846–3852. doi: 10.1200/jco.2007.11.9453. - DOI - PubMed

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