Background:We previously reported evidence of a dose–response relationship between ionising-radiation exposure from paediatric computed tomography (CT) scans and the risk of leukaemia and brain tumours in a large UK cohort. Underlying unreported conditions could have introduced bias into these findings.Methods:We collected and reviewed additional clinical information from radiology information systems (RIS) databases, underlying cause of death and pathology reports. We conducted sensitivity analyses excluding participants with cancer-predisposing conditions or previous unreported cancers and compared the dose–response analyses with our original results.Results:We obtained information from the RIS and death certificates for about 40% of the cohort (n∼180 000) and found cancer-predisposing conditions in 4 out of 74 leukaemia/myelodysplastic syndrome (MDS) cases and 13 out of 135 brain tumour cases. As these conditions were unrelated to CT exposure, exclusion of these participants did not alter the dose–response relationships. We found evidence of previous unreported cancers in 2 leukaemia/MDS cases, 7 brain tumour cases and 232 in non-cases. These previous cancers were related to increased number of CTs. Exclusion of these cancers reduced the excess relative risk per mGy by 15% from 0.036 to 0.033 for leukaemia/MDS (P-trend=0.02) and by 30% from 0.023 to 0.016 (P-trend<0.0001) for brain tumours. When we included pathology reports we had additional clinical information for 90% of the cases. Additional exclusions from these reports further reduced the risk estimates, but this sensitivity analysis may have underestimated risks as reports were only available for cases.Conclusions:Although there was evidence of some bias in our original risk estimates, re-analysis of the cohort with additional clinical data still showed an increased cancer risk after low-dose radiation exposure from CT scans in young patients.

Importance Within ten years after breast cancer diagnosis, 5% of patients develop contralateral primary breast cancer (CBC). Randomized trials have found that tamoxifen and aromatase inhibitors (AIs) reduce CBC risk. However, little is known about the magnitude and duration of protective effects within the context of “real world” clinical management settings, where varying durations and gaps in treatment are common. Objective To determine the influence of adjuvant tamoxifen and AIs on CBC risk within the general community setting. Design Retrospective cohort study of CBC risk among breast cancer patients diagnosed with a first primary unilateral invasive breast cancer at Kaiser Permanente Northwest or Colorado from 1990–2008 and followed through 2011. Setting General community health care plan. Participants 7,541 breast cancer patients, ages 24–85 years, diagnosed with invasive breast cancer, and survived for ≥one year. Exposures Adjuvant tamoxifen and AIs assessed using prescription records. Main Outcome Measure Incident contralateral breast cancer. Results Over a median(range) of 6.3(1.0–20.9) years, 248 women developed CBC. CBC risk decreased significantly with increasing tamoxifen duration. In current users, the relative risk (RR) per year of use was 0.76 (95%CI:0.64–0.89), with a 66% reduction for 4 years of use (RR=0.34, 95%CI:0.29–0.40). Risk reductions were slightly smaller for past users, but still significant 5+ years after stopping (RR/year use=0.85, 95%CI:0.71–0.995). AI use without tamoxifen was also associated with reduced CBC risk (RR=0.48, 95%CI:0.22–0.97). Risk reductions were most apparent among women whose primary and CBCs were ER-positive. Conclusions and Relevance We found that tamoxifen reduced CBC risk during treatment and after cessation, with risk progressively decreasing as tamoxifen duration increased. Tamoxifen use for 4+ years was estimated to result in the prevention of three CBCs per 100 women by 10 years following an ER-positive first breast cancer, an absolute risk reduction which is consistent with findings from clinical trials. If adjuvant endocrine therapy is indicated for breast cancer treatment, our findings, in concert with trial data, suggest that women should be encouraged to complete the full course.

PurposeUV radiation exposure is the primary risk factor for basal cell carcinoma (BCC), the most common human malignancy. Although the photosensitizing properties of estrogens have been recognized for decades, few studies have examined the relationship between reproductive factors or exogenous estrogen use and BCC.MethodsUsing data from the US Radiologic Technologists Study, a large, nationwide, prospective cohort, we assessed the relationship between reproductive factors, exogenous estrogen use, and first primary BCC while accounting for sun exposure, personal sun sensitivity, and lifestyle factors for geographically dispersed women exposed to a wide range of ambient UV radiation.ResultsElevated risk of BCC was associated with late age at natural menopause (hazard ratio [HR] for ≥ 55 years v 50 to 54 years, 1.50; 95% CI, 1.04 to 2.17) and any use of menopausal hormone therapy (MHT; HR, 1.16; 95% CI, 1.03 to 1.30; P for trend for duration = .001). BCC risk was most increased among women reporting natural menopause who used MHT for 10 or more years versus women who never used MHT (HR, 1.97; 95% CI, 1.35 to 2.87). Risk of BCC was not associated with age at menarche, parity, age at first birth, infertility, use of diethylstilbestrol by participant's mother, age at hysterectomy, or use of oral contraceptives.ConclusionThese analyses confirm a previous finding of increased risk of BCC associated with MHT. Novel findings of increased BCC risk associated with MHT in women experiencing natural menopause and for late age at natural menopause warrant further investigation. Users of MHT may constitute an additional high-risk group in need of more frequent skin cancer screening.