Aging may be associated with concentrations of tamoxifen and its metabolites in breast cancer patients.
BACKGROUND
Although tamoxifen (TAM) is the predominant adjuvant therapy for estrogen receptor positive (ER(+)) breast tumors, 50% of breast cancer patients do not respond positively to this therapy, or they experience adverse side effects. This variability in TAM responsiveness may be due to differences in TAM metabolism that stem from differences in race, age, and body mass index (BMI). Thus, the purpose of this study was to test the hypothesis that race, age, and BMI are associated with the metabolism of TAM to two primary metabolites, N-desmethyltamoxifen (N-DMT) and 4-hydroxytamoxifen (4-OHT).


METHODS
The study design was cross-sectional, and data were analyzed using independent sample t tests and multiple linear regression models. Breast cancer patients (n = 99) taking TAM for at least 30 days were recruited from a local hospital clinic. Each participant provided informed consent, completed a questionnaire, and donated a blood sample. The questionnaire was used to ascertain race, age, and BMI. The blood samples were used to measure plasma concentrations of TAM, N-DMT, and 4-OHT.


RESULTS
Plasma concentrations of TAM, N-DMT, and 4-OHT differed among individual patients. Age, but not race and BMI, was positively associated with plasma concentrations of TAM and N-DMT, even after adjustment for potential confounders (p = 0.02 for TAM and p = 0.03 for N-DMT).


CONCLUSIONS
This study suggests that aging may alter the metabolism of TAM. As increased levels of TAM and TAM metabolites may provide a possible explanation for why older women taking TAM are at increased risk for adverse side effects, future studies should determine whether age-related differences in the concentrations of TAM and TAM metabolites are associated with differences in TAM toxicity or responsiveness.
Sheth
Hetal R
HR
Department of Epidemiology and Preventive Medicine, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
Lord
Gwyn
G
Tkaczuk
Katherine
K
Danton
Malcolm
M
Lewis
Lynn M
LM
Langenberg
Patricia
P
Lim
Chang K
CK
Flaws
Jodi Anne
JA
D000328:Adult; D000368:Aged; D000375:Aging; D018931:Antineoplastic Agents, Hormonal / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy; D003430:Cross-Sectional Studies; D005006:Ethnicity; D005260:Female; D006801:Humans; D006915:Hydroxytestosterones / Q000097:blood; D008396:Maryland; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000097:blood* / Q000188:drug therapy; D011795:Surveys and Questionnaires; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use
D018931:Antineoplastic Agents, Hormonal; D006915:Hydroxytestosterones; D013629:Tamoxifen; C032278:4,17 beta-dihydroxy-4-androstene-3-one; C028787:N-desmethyltamoxifen