Publication Date:
2019-11-13
Description:
Background: Lymphoma patients exposed to chest RT during adolescence/young adulthood are at increased risk for BC; the cumulative incidence exceeds 20% by age 45 and the BC risk is comparable to that in women with BRCA1 mutations. These findings present an urgent yet unmet need to reduce the risk of BC in RT-exposed lymphoma survivors. The risk of BC is 50% lower in chest RT-exposed survivors who also receive ovarian radiation, suggesting a critical role of endogenous estrogens in RT-related breast carcinogenesis, making tamoxifen (a selective estrogen receptor modulator) an attractive risk-reducing option. Tamoxifen administered at 20 mg/d is effective in BC prevention in other high risk populations, but severe adverse events (SAE: venous thromboembolism, endometrial cancer) have limited its broad use. Previous biomarker trials in the general population have shown that LDTam (5mg/d) is not inferior to tamoxifen at 20 mg/d in reducing BC risk, and is associated with a safer AE profile. Mammographic breast density (MBD) is an established biomarker of BC risk; high MBD is associated with a 4-fold higher risk of BC. We hypothesized that LDTam would be effective in reducing BC risk (using MBD as a primary endpoint) in chest RT-exposed lymphoma survivors. We used an investigator-initiated, multi-institutional, randomized phase IIb, double blind, placebo controlled trial (FDA IND 107367) to test this hypothesis. Methods: Female patients from 13 sites were ≥25y at enrollment, with a history of exposure to chest RT at ≥12 Gy by age 40 for their primary cancer, and were off therapy for ≥6 mo. Subjects with a prior history of BC/DCIS, B/L mastectomy, or baseline MBD
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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