Abstract P4-10-17: Changes of bone turnover markers during perioperative anthracycline- and/or taxane-based chemotherapy in pre- and postmenopausal patients with primary breast cancer

Abstract Background: Loss of bone mineral density (BMD) is among the well known sequelae of pharmacological therapy of patients (pts) with primary breast cancer (PBC). Cancer therapy induced bone loss (CTIBL) progresses more rapidly as compared to normal age-related changes of BMD and is best known to be associated with aromatase inhibitors in postmenopausal pts. Chemotherapy (Ctx) may also lead to a deterioration of BMD but in contast to endocrine Tx, this phenomenon is by far less elucidated and, at least in younger pts, mostly interpreted as a secondary effect following Ctx induced ovarian failure. Previous investigations focused on the classical CMF scheme, whereas conclusive data regarding direct effects of more recent Ctx protocols on the bone metabolism of PBC pts are still lacking. This translational project was initiated to gain detailed insights into the influence of anthracycline (A)- and/or taxane (T)-based Ctx on bone turnover of both pre- and postmenopausal PBC pts in the clinical routine. Methods: Data of 109 pts (premenopausal: 49; postmenopausal: 60) with non-metastatic Ctx-naïve PBC exposed to neoadjuvant or adjuvant Ctx were analyzed. 84 pts (75%) had estrogen receptor-positive (ER+) disease, HER2- overexpression was found in 18 pts (17%). 16 pts (15%) received A-based Ctx, 34 pts (31%) received T-based Ctx, and 59 pts (54%) received A/T-based Ctx. Trastuzumab was given to 17 pts (16%) with HER2-positive disease. Serum bone markers including the C-telopeptide of type I collagen (ICTP) indicating osteoclast activity, the N-propeptide of type I collagen (P1NP) measuring osteoblast activity, and alkaline phosphatase (AP) were determined at baseline and prior to each subsequent Ctx cycle (C) up to C6. Changes of ICTP, P1NP, and AP over time were analyzed by repeated-measure ANOVA. Results: 600 Ctx cycles were analyzed. Baseline levels of ICTP (p = 0.0027), P1NP (p = 0.0063), and AP (p = 0.0007) were significantly higher in post- versus premenopausal pts. AP levels remained largely unchanged during Ctx. Trends showing an increase of ICTP from baseline until C6 in premenopausal pts and a decrease in postmenopausal pts did not reach statistical significance. In contrast, P1NP significantly declined in postmenopausal pts from baseline to C6 (p = 0.0152). In premenopausal pts, P1NP declined from baseline to C3 and thereafter increased to C6. These changes were highly significant (p = 0.0024). Conclusions: Our study represents one of the first systematic evaluations of bone turnover in pts exposed to modern A- and/or T-based Ctx for PBC in the clinical routine. Postmenopausal pts presented with higher baseline levels of all three markers which may be attributable to an enhanced bone turnover related to the loss of ovarian function prior to the initiation of Ctx. In postmenopausal pts, Ctx was associated with a sustained suppression of osteoblast activity whereas osteoblast suppression recovered until the end of Ctx in premenopausal pts. Whether these effects will translate into an increased risk of CTIBL remains a matter of further investigations which should clearly focus on the individual menopausal status. Citation Format: Kurbacher CM, Rauschenbach N, Kurbacher AT, Sperling S, Herz S, Monreal K, Kurbacher JA. Changes of bone turnover markers during perioperative anthracycline- and/or taxane-based chemotherapy in pre- and postmenopausal patients with primary breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-10-17.