SHBG as a breast cancer risk biomarker in premenopausal women? Results from an individual patient's pooled analysis and a meta-analysis
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ID: 328389
2026
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Abstract
BACKGROUND: Low levels of sex hormone-binding globulin (SHBG) have been associated with increased breast cancer (BC) risk, particularly in postmenopausal women. Whether this association extends to premenopausal women remains uncertain. We therefore performed an individual-patient pooled analysis and a meta-analysis to evaluate SHBG's role as a biomarker across menopausal status. METHODS: The pooled analysis included women at increased BC risk enrolled in two low-dose tamoxifen trials. The meta-analysis included 11 independent published studies assessing the association of SHBG with BC risk in healthy premenopausal women. RESULTS: Among premenopausal women in the pooled high-risk cohort, SHBG levels above the lowest tertile were associated with a 40% lower hazard of subsequent breast cancer events (HR = 0.60; 95% CI, 0.38-0.96; p = 0.03). In the meta-analysis, comprising 35,167 premenopausal women and 2,302 BC events, the summary estimate in premenopausal women showed a non-significant 8% risk reduction (SOR=0.92; 95% CI, 0.78-1.09). On the other hand, among the seven studies reporting stratified data by menopausal status, postmenopausal women experienced a significant 28% risk reduction (SOR=0.77; 95% CI, 0.69-0.87), with no statistically significant heterogeneity by menopausal status (P = 0.28). CONCLUSIONS: In a selected high-risk population, higher baseline SHBG was associated with fewer subsequent BC events. However, the meta-analysis did not provide statistically significant evidence of an inverse association with breast cancer occurrence in premenopausal women. These findings suggest that SHBG may be a biomarker of subsequent breast events in high-risk settings but do not confirm its role as a risk biomarker in the general premenopausal population.
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| Authors | Davide Serrano, Roberta Rizzo, Harriet Johansson, Debora Macis, Valentina Aristarco, Aliana Guerrieri‐Gonzaga, Matteo Lazzeroni, Gaetano Aurilio, Alessio Carbone, Sofia Ramalho, Bernardo Bonanni, Andrea DeCensi, Sara Gandini |
| Journal | JNCI Journal of the National Cancer Institute |
| Year | 2026 |
| DOI |
10.1093/jnci/djag318
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| URL | |
| Keywords | Keywords not found |
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