Impact of endocrine therapy on serum cortisol levels in breast cancer patients and its possible link to bone health

Background: Aromatase inhibitors (AI) are standard of care as adjuvant treatment for postmenopausal patients with hormone receptor positive (HR⁺) breast cancer (BC). High risk HR+ premenopausal patients are recommended to receive AI in combination with GNRH analoga for adjuvant treatment. Both endocrine treatment options significantly improve disease outcome but negatively impact on bone health thereby increasing bone fractures. This could be due to lowering of estradiol serum levels but also to the increase of estradiol precursors because of aromatase inhibition. In the present trial we investigated the change of serum hormone levels on bone parameters in pre- and postmenopausal BC patients treated with AI.

Methods: In this prospective single center study, pre- and postmenopausal patients with HR+ BC were included. A complete hormone status including measurement of estradiol (E), FSH, LH, cortisol, DHEA, P1NP (amino-terminal pro-peptide of pro-collagen type1) and crosslaps (C-terminal telopeptide) was performed before AI therapy initiation. Follow-ups were performed at 3,6,9 and 12 months. Bone mineral density was investigated at baseline and 1 year thereafter.

Results: 17 premenopausal and 88 postmenopausal patients could be included. BMI as well as cortisol, P1NP and crosslaps values were similar between groups at baseline. After 3 months, premenopausal women showed lower levels of estradiol (34.80 ± 59.73 vs. 9.93 ± 5.98 p = 0.135), FSH (46.20 ± 38.69 vs. 26.79 ± 28.35 p = 0.055), LH (26.37 ± 20.27 vs. 8.21 ± 12.31 p = 0.006) and higher levels of P1NP (80.00 ± 51.73 vs. 83.87 ± 58.83 p = 0.513) and crosslaps (0.47 ± 0.43 vs. 0.62 ± 0.33 p = 0.064). After 12 months higher levels of cortisol (10.01 ± 3.47 vs. 15.05 ± 5.48 p = 0.053), P1NP (74.66 ± 49.65 vs. 79.77 ± 45.89 p = 0.076) and crosslaps (0.43 ± 0.42 vs. 0.53 ± 0.30 p = 0.214) were found. Three months after baseline, postmenopausal women showed lower estradiol (17.85 ± 20.54 vs. 11.78 ± 27.21 p = 0.0038), higher FSH (66.86 ± 24.88 vs. 72.69 ± 25.48 p < 0.001), cortisol (10.38 ± 3.76 vs. 11.68 ± 3.72 p = 0.006) and crosslaps (0.45 ± 0.46 vs. 0.48 ± 0.37 p = 0.177) levels. One year after therapy initiation, postmenopausal women showed statistically significant higher levels of cortisol (n = 32 9.24 ± 2.60 vs. 12.24 ± 4.27 p < 0.001), higher crosslaps (n = 32 0.52 ± 0.64 vs. 0.90 ± 1.7 p = 0.187) as well as P1NP (n = 31: 104.22 ± 193.81 vs. 99.96 ± 162.71 p = 0.552) values.

Conclusion: AI therapy leads to important changes not only in estradiol but several other hormone levels in pre- as well as in postmenopausal women. The increase in cortisol serum levels in pre- and postmenopausal patients may additionally impact on bone health. This observation should be investigated in a larger trial with longer follow up.

Publication History

Article published online:
02 June 2020