Menopausal hormone therapy: assessing associations with breast and colorectal cancers by familial risk

Abstract

Menopausal users of hormone replacement therapy (HRT) are at increased breast cancer risk and decreased colorectal cancer (CRC) risk compared with individuals who have never used HRT, but these opposing associations may differ by familial risk of breast cancer and CRC. We harmonized data from 3 cohorts and generated separate breast cancer and CRC familial risk scores based on cancer family history. We defined moderate or strong family history as a risk score of 0.4 or higher, where 0.4 was equivalent to a 50-year-old woman with 1 parent diagnosed with either breast cancer or CRC at 55 years of age. Of 24 486 women assessed, 1243 and 405 were diagnosed with incident breast cancer and CRC, respectively. For breast cancer, menopausal HRT ever use versus never use hazard ratios were 1.27 (95% CI = 1.11 to 1.45) for a breast cancer familial risk score below 0.4 and 1.01 (95% CI = 0.82 to 1.25) for a breast cancer familial risk score of 0.4 or higher (Pdifference = .08). For CRC, menopausal HRT hazard ratios were 0.63 (95% CI = 0.50 to 0.78) for a CRC familial risk score below 0.4 and 1.21 (95% CI = 0.73 to 2.00) for a CRC familial risk score of 0.4 or higher (Pdifference = .03). Associations with menopausal HRT use that apply to the general population may not hold for women at moderate or strong familial risk of these cancers.

Figure 1.

Hazard ratios (solid lines) and 95% confidence intervals (dashed lines) of breast and colorectal cancer risk in relation to ever vs never use of menopausal HRT by their cancer-specific familial risk score. A familial risk score of 0 denotes the population average. Analyses were stratified by study and adjusted for body mass index (continuous), parity (0, 1, 2, 3, ≥4 live births), education level (high school or less, some college or university, bachelor’s degree or higher), smoking status (never, former, current), oral contraceptive use (never, ever), and country of residence (Australia, Canada, United States). HRT = hormone replacement therapy.

Figure 2.

Hazard ratios (dots) and 95% confidence intervals (lines) of breast cancer and CRC risk in relation to subgroups of menopausal HRT use, by groups’ cancer-specific familial risk score. Minimal family history was defined as having a familial risk score greater than 0 and less than 0.4; moderate to strong family history was defined as having a familial risk score of 0.4 or higher. Analyses were stratified by study and adjusted for body mass index (continuous), parity (0, 1, 2, 3, ≥4 live births), education level (high school or less, some college or university, bachelor’s degree or higher), smoking status (never, former, current), oral contraceptive use (never, ever), and country of residence (Australia, Canada, United States). CRC = colorectal cancer; HRT = hormone replacement therapy.