A Randomized Controlled Trial Evaluating Low-Dose Tamoxifen for Breast Cancer Prevention and Mammographic Density Reduction

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In the adjuvant setting, tamoxifen prevents breast cancer in high-risk women and reduces cancer recurrence yet is associated with side effects. To optimize increased uptake and retain therapeutic effect, the optimal dose has not yet been determined. Using mammographic density as a marker for response to treatment, researchers at the Karolinska Institute in Sweden evaluated whether the efficacy of low-dose tamoxifen is noninferior to the standard dose and if lower doses are associated with fewer symptoms.

A mammography screening program focused on women ranging from 40 to 74 years of age invited participation from healthy pre- and postmenopausal women.

Women (N = 2314) were screened for eligibility. Excluded from the study were patients who had low mammographic density, high blood pressure, a previous history of cardiovascular disease, uncontrolled diabetes, and any history of previous cancer. Patients who were pregnant or used hormonal therapy were also excluded.

Between 2016 and 2019, eligible women (N = 1440) entered a double-blind, placebo-controlled, randomized dose-determination trial. These participants were assigned to different treatment groups for 6 months and received either placebo or oral tamoxifen, based on a dose of 1, 2.5, 5, 10, or 20 mg. Radiographic assessment of dense fibroglandular tissue was conducted using a fully automated tool. A self-reported questionnaire was used to assess symptoms, including signs of joint pain, as well as gynecologic, sexual, and vasomotor concerns. Patients were evaluated for the presence of fewer severe symptoms and reduced mammographic density. Menopausal status was used for post-hoc analysis. A detailed evaluation was conducted on both the per-protocol and intent-to-treat populations.

The study included both postmenopausal (N = 873) and premenopausal (N = 566) women. Participants who were premenopausal demonstrated noninferior reduction in mammographic density following treatment with 2.5, 5, and 10 mg of tamoxifen; this was compared with the 20-mg group that showed a 9.7% decrease. Stratified by menopausal status and tamoxifen dose, the researchers highlighted the relative number of women who experienced a more significant reduction in side effects when receiving the lower dose.

The investigators illustrated the prevalence ratios of severe vasomotor symptoms stratified by menopausal status and tamoxifen dose, noting that at 6 months there was a 50% reduction in severe vasomotor symptoms (hot flashes, cold sweats, and night sweats) in the 2.5-mg cohort compared with the standard 20-mg tamoxifen dose cohort. In patients who were postmenopausal, no density reduction was seen.

Within the group of premenopausal women, fewer side effects were reported and there was a noninferior decrease in breast density at the lower 2.5-mg dose of tamoxifen compared with the standard 20-mg dose. The investigators concluded that in premenopausal women, a low dose of tamoxifen could be used preventively, and this could increase the sensitivity of mammography studies.

Source:

Hall P, Eriksson M, Czene K, et al. Low dose tamoxifen for breast cancer prevention and mammographic density reduction: a randomized controlled trial. Presented at 2020 San Antonio Breast Cancer Symposium, December 8-11, 2020. PS8-41.

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