Background Whereas one-quarter of premenopausal women might have osteopenia, dual-energy Xray absorptiometry (DXA) are omitted to those with early-stage breast cancer (eBC). To this, rapid advances of deep learning (DL) have enabled to evaluate their risk of osteoporosis (RO) by utilizing perioperative chest radiography. Although osteoporosis fundamentally provide fertile premetastatic niches, the association of osteoporosis with bone metastasis (BM) remains unknown. This study aimed to clarify the association in women after eBC surgery, and to perform the stratified analysis by menopause status.

Methods This multicenter retrospective cohort study enrolled 785 women who had surgery for stage 2-3 estrogen receptor-positive breast cancer from 2007 to 2019, excluding cases with adjuvant use of bone-modifying agent (BMA). Perioperative chest radiography was input to DL producing RO score (0-1). They were classified by the score into 359 women with low-risk of osteoporosis (LRO) and 426 with high-risk (HRO). 5-year BM-free survival (BMFS) was compared by cox-hazard proportional models.

Findings The multivariate analyses for the enrolled women (median [interquartile range] age, 56 [46-66] years) identified RO as a poor prognostic factor (hazard ratio [HR] 4.23, 95% confidence interval [CI]; 1.71-10.13, p<0.01). The stratification analyses by menopausal status revealed that the number of the premenopause was 325, discovering HRO (23.1% [75/325]) in the premenopause was associated with low BMFS (HR2.53, 95% CI; 1.37-4.67, p<0.01) whereas no association was observed in the others (p=0.71). The conduction rate of DXA was lower in premenopause (31/325 vs 317/461, p<0.01).

Interpretation RO is an independent prognostic factor for BM in the enrolled women with eBC. This study discovered the association of RO with BM specifically in premenopausal women with eBC, whose bone health have been poorly checked. An expanded indication of adjuvant use of BMA is suggested to the premenopausal women with the risk.

Funding No funding was received for this research.

The authors have declared no competing interest.

This study did not receive any funding

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The study was approved by the local ethics committees of Hokkaido University Hospital (022-0118) and NHO Hokkaido Cancer Center. As all participant agreed on the use of data, informed consents were obtained. Clinical trial number was not applicable to this study. The study was conducted in accordance with the principles of human ethics set forth by the Declaration of Helsinki.

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All data produced in the present study are available upon reasonable request to the corresponding authors