Breast Cancer Research and Treatment Journal

Effect of Adjuvant Endocrine Therapy on Hormonal Levels in Premenopausal Women with Breast Cancer –

The ProBONE II study

--Supplementary Material—

Authors / Peyman Hadji,1 Annette Kauka,1 May Ziller,1 Katrin Birkholz,2* Monika Baier,3 Mathias Muth,2 Peter Kann4
Title / Effect of Adjuvant Endocrine Therapy on Hormonal Levels in Premenopausal Women with Breast Cancer – The ProBONE II study
Affiliations / 1Department of Endocrinology, Reproductive Medicine and Osteoporosis, Philipps-University of Marburg, 35033 Marburg, Germany;
2*BU Oncology, Novartis Pharma GmbH, Roonstraße 25, D-90429 Nuernberg, Germany;
3Clinical & Regulatory Affairs/Biometrics Department, Novartis Pharma GmbH, Roonstraße 25, D-90429 Nuernberg, Germany;
4Department of Endocrinology and Diabetes, Philipps - University of Marburg, 35033 Marburg, Germany
*Katrin Birkholz was an employee of Novartis Pharma GmbH at the time of study conduct and during manuscript development until November 28, 2013
Corresponding Author / Prof. Dr. P. Hadji
Head of the Department of Endocrinology
Department of Endocrinology, Reproductive Medicine and Osteoporosis, Philipps-University of Marburg,
Baldingerstrasse
35033 Marburg, Germany
Phone: +49-6421-586-6486
Fax: +49-6421-586-7070
E-mail:

Supplementary Table 1. Sub analysis of patients treated with GnRH analogs plus tamoxifen. Change in serum biomarkers from baseline to end of study is reported

Serum hormones / Treatment groups / n / LS-Mean / p value
Estradiol / Placebo / 18 / -91.669 / 0.2332
ZOL / 16 / -21.353
Inhibin A / Placebo / 17 / -22.157 / 0.4875
ZOL / 16 / -14.385
Inhibin B / Placebo / 17 / -24.324 / 0.3041
ZOL / 16 / -41.778
AMH / Placebo / 17 / -0.419 / 0.3536
ZOL / 16 / -0.671
SHBG / Placebo / 18 / 14.168 / 0.8637
ZOL / 16 / 12.254
Testosterone / Placebo / 18 / 0.039 / 0.6725
ZOL / 16 / 0.025
FSH / Placebo / 18 / -11.120 / 0.1509
ZOL / 16 / -4.253
PTH / Placebo / 17 / 7.830 / 0.3026
ZOL / 16 / 3.787
Vitamin D / Placebo / 18 / 12.679 / 0.1861
ZOL / 16 / 9.049

AMH anti-muellerian hormone, FSH follicle-stimulating hormone,

PTH parathyroid hormone, SHBG sex hormone-binding globulin

Supplementary Table 2. Serum hormone levels (Median ± interquartile range) at baseline and end of study reported in all patients

Serum hormones / Time points / Treatment groups / n / Median / Interquartile range
AMH (ng/ml) / Baseline / Placebo / 35 / 0.36 / 0.69
ZOL / 34 / 0.50 / 0.91
Total / 69 / 0.40 / 0.82
Month 24 / Placebo / 35 / 0.08 / 0.00
ZOL / 34 / 0.08 / 0.00
Total / 69 / 0.08 / 0.00
Estradiol (pg/ml) / Baseline / Placebo / 36 / 36.90 / 52.85
ZOL / 34 / 21.25 / 38.20
Total / 70 / 24.45 / 49.40
Month 24 / Placebo / 35 / 10.00 / 0.00
ZOL / 34 / 10.00 / 0.00
Total / 69 / 10.00 / 0.00
FSH (mIU/ml) / Baseline / Placebo / 36 / 5.13 / 7.10
ZOL / 34 / 5.65 / 5.01
Total / 70 / 5.40 / 5.40
Month 24 / Placebo / 35 / 2.50 / 2.60
ZOL / 34 / 2.60 / 8.10
Total / 69 / 2.50 / 3.50
Inhibin A (pg/ml) / Baseline / Placebo / 35 / 14.68 / 19.96
ZOL / 34 / 13.10 / 10.00
Total / 69 / 13.80 / 17.47
Month 24 / Placebo / 35 / 5.00 / 0.66
ZOL / 34 / 5.00 / 1.10
Total / 69 / 5.00 / 0.98
Inhibin B (pg/ml) / Baseline / Placebo / 35 / 11.30 / 36.58
ZOL / 34 / 22.69 / 80.31
Total / 69 / 14.66 / 60.94
Month 24 / Placebo / 35 / 2.60 / 0.00
ZOL / 34 / 2.60 / 0.60
Total / 69 / 2.60 / 0.00
PTH (pg/ml) / Baseline / Placebo / 35 / 28.80 / 17.90
ZOL / 34 / 29.10 / 15.00
Total / 69 / 29.10 / 16.00
Month 24 / Placebo / 35 / 35.10 / 14.90
ZOL / 34 / 35.65 / 14.70
Total / 69 / 35.60 / 16.50
SHBG (nmol/l) / Baseline / Placebo / 36 / 92.05 / 52.70
ZOL / 34 / 69.20 / 54.60
Total / 70 / 82.00 / 60.10
Month 24 / Placebo / 35 / 109.60 / 60.50
ZOL / 34 / 96.00 / 58.80
Total / 69 / 104.40 / 52.40
Testosterone (ng/ml) / Baseline / Placebo / 36 / 0.27 / 0.15
ZOL / 34 / 0.27 / 0.19
Total / 70 / 0.27 / 0.16
Month 24 / Placebo / 35 / 0.29 / 0.23
ZOL / 34 / 0.28 / 0.15
Total / 69 / 0.28 / 0.18
Vitamin D (ng/ml) / Baseline / Placebo / 36 / 21.80 / 21.05
ZOL / 34 / 23.45 / 13.60
Total / 70 / 22.40 / 17.30
Month 24 / Placebo / 35 / 34.20 / 16.90
ZOL / 34 / 32.10 / 15.60
Total / 69 / 33.30 / 15.70

AMH anti-muellerian hormone, FSH follicle-stimulating hormone,

PTH parathyroid hormone, SHBG sex hormone-binding globulin

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