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A Randomized Phase IIb Study of Low-dose Tamoxifen in Chest-irradiated Cancer Survivors at Risk for Breast Cancer
Low-dose tamoxifen reduces breast cancer risk, but remains untested in chest-irradiated cancer survivors-a population with breast cancer risk comparable with mutation carriers. We hypothesized that low-dose tamoxifen would be safe and efficacious in reducing radiation-related breast cancer risk. We...
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Published in: | Clinical cancer research 2021-02, Vol.27 (4), p.967-974 |
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Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
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Online Access: | Get full text |
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Summary: | Low-dose tamoxifen reduces breast cancer risk, but remains untested in chest-irradiated cancer survivors-a population with breast cancer risk comparable with
mutation carriers. We hypothesized that low-dose tamoxifen would be safe and efficacious in reducing radiation-related breast cancer risk.
We conducted an investigator-initiated, randomized, phase IIb, double-blinded, placebo-controlled trial (FDA IND107367) between 2010 and 2016 at 15 U.S. sites. Eligibility included ≥12 Gy of chest radiation by age 40 years and age at enrollment ≥25 years. Patients were randomized 1:1 to low-dose tamoxifen (5 mg/day) or identical placebo tablets for 2 years. The primary endpoint was mammographic dense area at baseline, 1 and 2 years. IGF-1 plays a role in breast carcinogenesis; circulating IGF-1 and IGF-BP3 levels at baseline, 1 and 2 years served as secondary endpoints.
Seventy-two participants (low-dose tamoxifen:
= 34, placebo:
= 38) enrolled at a median age of 43.8 years (35-49) were evaluable. They had received chest radiation at a median dose of 30.3 Gy. Compared with the placebo arm, the low-dose tamoxifen arm participants had significantly lower mammographic dense area (
= 0.02) and IGF1 levels (
< 0.0001), and higher IGFBP-3 levels (
= 0.02). There was no difference in toxicity biomarkers (serum bone-specific alkaline phosphatase, lipids, and antithrombin III; urine N-telopeptide cross-links) between the treatment arms. We did not identify any grade 3-4 adverse events related to low-dose tamoxifen.
In this randomized trial in chest-irradiated cancer survivors, we find that low-dose tamoxifen is effective in reducing established biomarkers of breast cancer risk and could serve as a risk-reduction strategy. |
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ISSN: | 1078-0432 1557-3265 |
DOI: | 10.1158/1078-0432.CCR-20-3609 |