The mechanisms of variable response to tamoxifen have been the subject of much scrutiny in the published literature. Early studies attempting to link a clinical response to tamoxifen therapy with plasma tamoxifen concentrations reported no statistically significant differences in outcomes between women who received 20 mg of tamoxifen daily and those who received 40 mg of tamoxifen daily, even though women in the 40 mg tamoxifen group had higher plasma tamoxifen concentrations than those in the 20 mg tamoxifen group. These results have been reported as evidence that plasma tamoxifen concentration is not a predictor of clinical outcome. Because there is evidence that tamoxifen is converted to anti-estrogenic metabolites, one hypothesis is that altered patterns of metabolism of tamoxifen might contribute to inter-individual variability in effects (Jin et al, 2005). Plasma concentrations of the active tamoxifen metabolite endoxifen are associated with the cytochrome P450 (CYP) 2D6 genotype.
Like aspirin and indometacin , ibuprofen is a nonselective COX inhibitor, in that it inhibits two isoforms of cyclooxygenase, COX-1 and COX-2. The analgesic , antipyretic , and anti-inflammatory activity of NSAIDs appears to operate mainly through inhibition of COX-2, which decreases the synthesis of prostaglandins involved in mediating inflammation, pain, fever, and swelling. Antipyretic effects may be due to action on the hypothalamus, resulting in an increased peripheral blood flow, vasodilation, and subsequent heat dissipation. Inhibition of COX-1 instead would be responsible for unwanted effects on the gastrointestinal tract.  However, the role of the individual COX isoforms in the analgesic, anti-inflammatory, and gastric damage effects of NSAIDs is uncertain and different compounds cause different degrees of analgesia and gastric damage.