title: Association of tamoxifen (TAM) and TAM metabolite concentrations with self-reported side effects of TAM in women with breast cancer.
abstract: The positive effects of tamoxifen (TAM) on breast cancer recurrence and survival as well as on overall mortality have led to its use as the predominant adjuvant therapy among women with breast cancer. However, the association of TAM intake with undesirable side effects has been reported in numerous studies. This analysis was carried out to assess whether the concentrations of TAM or TAM metabolites, N -desmethyltamoxifen ( N -DMT) and 4-hydroxytamoxifen (4-OHT), were associated with self-reported side effects of TAM. Participants were 99 breast cancer patients who had been taking TAM for at least 30 days. Each participant completed a questionnaire that was used to ascertain whether she experienced certain specific symptoms while taking TAM. In addition, each woman provided a blood sample that was used to measure plasma concentrations of TAM, N -DMT, and 4-OHT by high performance liquid chromatography. Results of the analysis showed that women who experienced at least one TAM-related side effect had significantly higher levels of TAM than women not experiencing any TAM-related side effects. Furthermore, women who reported experiencing visual problems had significantly higher levels of both TAM and N -DMT compared to those women who reported experiencing no visual problems. The levels of 4-OHT were negatively associated with the occurrence of vaginal discharge. The results of this study suggest that the self-reported occurrence of certain symptoms during TAM treatment is related to TAM metabolism. Future studies should assess subgroups of women with specific TAM and TAM metabolite profiles to determine whether alternate, equally effective therapies would decrease their risk of experiencing certain undesirable side effects.
authors.affiliation: Department of Epidemiology and Preventive Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Gallicchio
authors.forename: Gwyn
authors.initials: G
authors.lastname: Lord
authors.forename: Katherine
authors.initials: K
authors.lastname: Tkaczuk
authors.forename: Malcolm
authors.initials: M
authors.lastname: Danton
authors.forename: Lynn M
authors.initials: LM
authors.lastname: Lewis
authors.forename: Chang K
authors.initials: CK
authors.lastname: Lim
authors.forename: Jodi A
authors.initials: JA
authors.lastname: Flaws
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects* / Q000097:blood / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy*; D005260:Female; D019584:Hot Flashes / Q000139:chemically induced; D006801:Humans; D001523:Mental Disorders / Q000139:chemically induced; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009422:Nervous System Diseases / Q000139:chemically induced; D011795:Surveys and Questionnaires; D013629:Tamoxifen / Q000009:adverse effects* / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism; D014623:Vaginal Diseases / Q000139:chemically induced
chemical_list: D018931:Antineoplastic Agents, Hormonal; D013629:Tamoxifen; C016601:afimoxifene; C028787:N-desmethyltamoxifen