Risk Factors and Prognostic Implications in Synchronous Breast-Thyroid Dual Primary Cancers: A Matched Case-Control Study

Tao Li,* Bin Lu,* Yantao Zhang, Peng Zhang, Jun Qi, Yong Sun* Department of Thyroid and Breast Surgery, People’s Hospital Affiliated To Shandong First Medical University, Jinan, Shandong, 271199, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yong Sun, Email [email protected]: To characterize the distinct clinicopathological patterns and identify independent risk factors in synchronous breast-thyroid dual primary malignancies (DBTMs), a rare yet clinically significant entity.Methods: In this retrospective case-control study (2019.03– 2021.12), 58 DBTM patients were compared with 89 age-matched solitary breast cancer controls. Comprehensive clinicopathological parameters including hormone receptor status and molecular profiles were analyzed. Multivariable logistic regression identified prognostic determinants with 2-year follow-up for recurrence/metastasis and survival outcomes.Results: Statistically significant differences were observed in age, BMI, menopausal status, ER, PR, and HER-2 status between the study and control groups (P < 0.05). During the 2-year follow-up, the study group had 12 cases of recurrence or metastasis and 5 deaths, while the control group had 9 cases of recurrence or metastasis and 2 deaths (P < 0.05). Univariate analysis indicated that age, breast cancer stage, and ER status were associated with overall survival in patients with synchronous primary breast and thyroid cancer. Additionally, age, breast cancer stage, ER status, menopausal status, and a family history of breast cancer were significantly associated with recurrence or metastasis (P < 0.05). Multivariate logistic regression analysis identified age, ER positivity, and a family history of breast cancer as independent risk factors for synchronous primary breast and thyroid cancer (P < 0.05).Conclusion: This first matched case-control analysis reveals that synchronous DBTMs represent a unique clinical subgroup with aggressive biological behavior. The identified triad of young age, ER positivity, and familial predisposition provides a risk stratification framework for dual-cancer screening and targeted surveillance strategies.Keywords: synchronous dual primary cancers, breast-thyroid malignancies, risk stratification, hormone receptor paradox, familial predisposition