Impact of use of hormone replacement therapy on false positive recall in the NHS breast screening programme: results from the Million Women Study.
From June 1996 to March 1998, 87 967 postmenopausal women aged 50-64 invited to routine breast cancer screening at 10 NHS breast screening programme centres joined the million women study, by completing a self administered questionnaire before screening, and were followed up through records from screening centres for their screening outcome. Overall, a diagnosis of breast cancer was made in 399 (0.5%) and 2629 (3.0%) had false positive recall (recall to assessment with no diagnosis of breast cancer during that screening episode). Among women with false positive recall, 398 (15.1%) had a negative biopsy (fine needle aspiration cytology, wide bore needle biopsy, or open surgical biopsy, with no diagnosis of breast cancer). We used conditional logistic regression, stratified by the factors listed in the figure, to calculate the relative risk of false positive recall. False positive recall was significantly increased in current users of hormone replacement therapy (relative risk 1.64, 95% confidence interval 1.50 to 1.80, P < 0.0001) and past users (1.21, 1.06 to 1.38, P = 0.004), compared with never users. The relative risk of false positive recall decreased significantly with increasing time since last use of hormone replacement therapy ( 2 (df = 1) for trend = 14.0, P < 0.0001), and was still significantly raised among women ceasing use within the past five years (figure). We found no significant variation in the relative risk of false positive recall between current users of oestrogen only (1.62, 1.43 to 1.83) and combined oestrogen and progestogen (1.80, 1.62 to 2.00) ( 2 (df = 1) for heterogeneity = 2.3, P = 0.1), nor were there significant differences in risk according to the dose or hormonal constituents of these types of hormone replacement therapy. Current, but not past, users of hormone replacement therapy had a significantly increased risk of having a negative biopsy compared with never users (relative risk 1.42, 1.14 to 1.78, and 0.94, 0.69 to 1.30, respectively ( 2 (df = 1) for heterogeneity = 6.5, P = 0.01)). When these relative risks and the prevalences of use of hormone replacement therapy in the million women study are applied to recall rates in the NHS breast screening programme, use of hormone replacement therapy during the study period is estimated to have been responsible for around 20% of the cases of false positive recall in the NHS breast screening programme, amounting to an excess of 14 000 cases per year.