To analyze whether there is a threshold effect between thyroid hormone sensitivity indexes and breast cancer, and to analyze the subgroup analysis and interaction test of age.

2 892 adults from NHANES were collected between 2007 and 2012, including 83 breast cancer patients. Central thyroid hormone sensitivity indices were calculated, including Thyroid Feedback Quantile Index for T4(TFQI_FT4) and T3(TFQI_FT3), Thyroid Stimulating Hormone T4 Resistance Index(TT4RI), Thyroid Stimulating Hormone T3 Resistance Index(TT3RI), and TSH Index(TSHI), as well as peripheral thyroid hormone sensitivity index FT3/FT4. The association between breast cancer and the thyroid system was investigated using a multivariable logistic regression model. Smooth curve fitting and stratified analysis were used too, and subgroup analysis and interaction tests were performed based on age.

Model3 showed that Thyroid Stimulating Hormone (TSH) (OR=1.33, 95%CI:1.08-1.63), TFQI_FT4(OR=2.61, 95%CI:1.25-5.45), TFQI_FT3(OR=3.15, 95%CI:1.18-8.44), TT4RI(OR=1.03, 95%CI:1.01-1.05), TT3RI(OR=1.10, 95%CI:1.03-1.18), and TSHI(OR=1.68, 95%CI:1.14-2.50) were significantly positively associated with the risk of breast cancer. A linear relationship with breast cancer was observed when TFQI_FT3≥0.7, TSHI≥2.4, and TT4RI<50(P<0.05). TFQI_FT4 showed a threshold effect(likelihood ratio test=0.040) when TFQI_FT4<0.25. The relationship between TFQI_FT4 and breast cancer was not significant(OR=1.07, 95%CI:0.36-3.15), but when TFQI_FT4≥0.25, it was significantly associated with an increased risk of breast cancer(OR=12.79, 95%CI:2.50-65.40). Subgroup analysis further revealed that in women over 55 years old, increased central thyroid hormone sensitivity indices were associated with breast cancer risk(P<0.05).

Increased central thyroid hormone sensitivity indices are significantly associated with the risk of breast cancer, which may be a potential indicator for breast cancer detection in the future.