ABSTRACT
BACKGROUND: Young women treated with chest radiation therapy (RT) for Hodgkin lymphoma (HL) experience a strongly increased risk of breast cancer (BC). It is unknown whether endogenous and exogenous gonadal hormones affect RT-associated BC risk. METHODS: We conducted a nested case-control study among female 5-year HL survivors treated before age 41. Hormone exposure and HL treatment data were collected through medical records and questionnaires for 174 BC case patients and 466 control patients. Radiation dose to breast tumor location was estimated based on RT charts, simulation films, and mammography reports. RESULTS: We observed a linear radiation dose-response curve with an adjusted excess odds ratio (EOR) of 6.1%/Gy (95% confidence interval [CI]: 2.1%-15.4%). Women with menopause <30 years (caused by high-dose procarbazine or pelvic RT) had a lower BC risk (OR, 0.13; 95% CI, 0.03-0.51) than did women with menopause ≥50 years. BC risk increased by 6.4% per additional year of post-RT intact ovarian function (P<.001). Among women with early menopause (<45 years), hormone replacement therapy (HRT) use for ≥2 years did not increase BC risk (OR, 0.86; 95% CI, 0.32-2.32), whereas this risk was nonsignificantly increased among women without early menopause (OR, 3.69; 95% CI, 0.97-14.0; P for interaction: .06). Stratification by duration of post-RT intact ovarian function or HRT use did not statistically significantly modify the radiation dose-response curve. CONCLUSIONS: BC risk in female HL survivors increases linearly with radiation dose. HRT does not appear to increase BC risk for HL survivors with therapy-induced early menopause. There are no indications that endogenous and exogenous gonadal hormones affect the radiation dose-response relationship.
Subject(s)
Breast Neoplasms/etiology , Breast/radiation effects , Gonadal Steroid Hormones , Hodgkin Disease/radiotherapy , Neoplasms, Radiation-Induced/etiology , Adult , Antineoplastic Agents/adverse effects , Antineoplastic Agents, Alkylating/adverse effects , Antineoplastic Agents, Alkylating/therapeutic use , Breast/drug effects , Carcinoma, Intraductal, Noninfiltrating/etiology , Case-Control Studies , Confidence Intervals , Dose-Response Relationship, Radiation , Female , Gonadal Steroid Hormones/pharmacology , Gonadal Steroid Hormones/physiology , Hodgkin Disease/drug therapy , Hormone Replacement Therapy/adverse effects , Humans , Menopause, Premature , Middle Aged , Netherlands , Ovary/physiology , Procarbazine/adverse effects , Radiotherapy Dosage , Risk Factors , Survivors , Time Factors , Young AdultABSTRACT
OBJECTIVES: Three studies have reported a seasonal variation in lithium serum levels, with higher levels during summer. Our objective was to investigate the impact of actual environmental temperature on lithium serum levels. METHODS: A retrospective study was conducted using available records of lithium serum levels for the period between January 1995 and July 2004, obtained from three large teaching hospitals in The Netherlands. Lithium serum levels were linked to season and average daily temperature data obtained from the Royal Netherlands Meteorological Institute. An analysis was performed on all lithium serum levels not accounting for the intra-individual dependency of lithium serum levels. The association between season, temperature and both absolute lithium serum level and the frequency of potentially toxic serum levels was investigated. A mixed model analysis, accounting for intra-individual dependency of lithium serum levels, was performed. RESULTS: A total of 41,102 lithium serum levels (3,054 patients) were included. A significant difference in mean lithium serum levels across seasons (p < 0.001) and temperature categories (p = 0.001) was found, peaking in summer [0.761 mmol/L, +/- standard error of the mean (SEM) 0.002] and at temperatures of 15-20 degrees C [0.762 mmol/L (+/- SEM 0.005)], and at a minimum in winter [0.748 mmol/L (+/- SEM 0.002)] and at <0 degrees C [0.741 mmol/L (+/- SEM 0.005)]. The relative frequency of potentially toxic serum levels significantly differed between seasons (p = 0.023, highest in winter), but not between temperature categories (p = 0.481). A significant positive association for intra-individual lithium serum level and season (p < 0.001) and temperature (p < 0.001) was established. CONCLUSIONS: Season and environmental temperature have a statistically significant but therapeutically irrelevant effect on lithium serum levels.
