London Regional Cancer Centre, London, ON, Canada
John Gordon Lenehan , Wendy A. Teft , Richard B. Kim
Background: Male breast cancer is rare and accounts for less than 1% of breast cancer diagnoses. The majority of male breast cancers are hormone-receptor positive and tamoxifen is the standard adjuvant hormone treatment. Tamoxifen is metabolized primarily by CYP2D6 and CYP3A4 in the liver to the active metabolite endoxifen, increasingly recognized as a clinically relevant biomarker of therapeutic benefit. Plasma levels of endoxifen above a threshold of 15 nM appear to confer maximal anti-hormonal benefit and potentially improved outcomes. Methods: We have carried out a prospective assessment of endoxifen levels in men with breast cancer followed in a personalized tamoxifen clinic. Eleven men with breast cancer were assessed and compared with age and genotype matched female patients, with both groups initially treated at the usual tamoxifen dose of 20 mg/day. Results: Mean baseline endoxifen levels in male CYP2D6 extensive metabolizers (EM) were significantly lower than female EMs (30.88 ± 5.9 nM versus 53.92 ± 8.9 nM; p = 0.005), although all patients were in the therapeutic range. Baseline endoxifen levels in male intermediate metabolizers (IM) were not significantly different from matched females (17.68 ± 11.9 nM versus 25.74 ± 10.6 nM; p = 0.20), but were more likely to be sub-therapeutic (4/7 (57%) versus 5/19 (26%)). Male IMs remained more likely to be sub-therapeutic when all follow-up samples were considered (3/7 (43%) versus 1/19 (5%)). For those with plasma endoxifen levels below the threshold of 15 nM, increasing the tamoxifen dose to 30 or 40 mg/day resulted in attainment of therapeutic endoxifen levels in both groups. Conclusions: Our results suggest that endoxifen levels in men are more likely to be low, and they may benefit from CYP2D6 genotyping and plasma endoxifen level monitoring.
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Abstract Disclosures
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