Effect of second timed appointments for non-attenders of breast cancer screening in England: a randomised controlled trial.

BACKGROUND: In England, participation in breast cancer screening has been decreasing in the past 10 years, approaching the national minimum standard of 70%. Interventions aimed at improving participation need to be investigated and put into practice to stop this downward trend. We assessed the effect on participation of sending invitations for breast screening with a timed appointment to women who did not attend their first offered appointment within the NHS Breast Screening Programme (NHSBSP). METHODS: In this open, randomised controlled trial, women in six centres in the NHSBSP in England who were invited for routine breast cancer screening were randomly assigned (1:1) to receive an invitation to a second appointment with fixed date and time (intervention) or an invitation letter with a telephone number to call to book their new screening appointment (control) in the event of non-attendance at the first offered appointment. Randomisation was by SX number, a sequential unique identifier of each woman within the NHSBSP, and at the beginning of the study a coin toss decided whether women with odd or even SX numbers would be allocated to the intervention group. Women aged 50-70 years who did not attend their first offered appointment were eligible for the analysis. The primary endpoint was participation (ie, attendance at breast cancer screening) within 90 days of the date of the first offered appointment; we used Poisson regression to compare the proportion of women who participated in screening in the study groups. All analyses were by intention to treat. This trial is registered with Barts Health, number 009304QM. FINDINGS: We obtained 33 146 records of women invited for breast cancer screening at the six centres between June 2, 2014, and Sept 30, 2015, who did not attend their first offered appointment. 26 054 women were eligible for this analysis (12 807 in the intervention group and 13 247 in the control group). Participation within 90 days of the first offered appointment was significantly higher in the intervention group (2861 [22%] of 12 807) than in the control group (1632 [12%] of 13 247); relative risk of participation 1·81 (95% CI 1·70-1·93; p<0·0001). INTERPRETATION: These findings show that a policy of second appointments with fixed date and time for non-attenders of breast screening is effective in improving participation. This strategy can be easily implemented by the screening sites and, if combined with simple interventions, could further increase participation and ensure an upward shift in the participation trend nationally. Whether the policy should vary by time since last attended screen will have to be considered. FUNDING: National Health Service Cancer Screening Programmes and Department of Health Policy Research Programme.

Neoadjuvant chemotherapy with or without zoledronic acid in early breast cancer--a randomized biomarker pilot study.

PURPOSE: To investigate the short-term biologic effects of neoadjuvant chemotherapy +/- zoledronic acid (ZOL) in invasive breast cancer. EXPERIMENTAL DESIGN: Forty patients were randomized to receive a single 4 mg infusion of ZOL 24 hours after the first cycle of FE100C chemotherapy, or chemotherapy alone. Randomization was stratified for tumor stage, ER, HER2, and menopausal status. All patients had repeat breast core biopsy at day 5 (D5) ± day 21 (D21). Effects on apoptotic index, proliferation (Ki67), growth index, surrogate serum markers of angiogenesis (VEGF), and serum reproductive hormones within the TGFß family (activin-A, TGFß1, inhibin-A, and follistatin) were evaluated and compared. RESULTS: Baseline clinicopathologic characteristics were well balanced. Cell growth index (increased apoptosis and reduced proliferation) fell at D5 in both groups but recovered more rapidly with chemotherapy + ZOL compared with chemotherapy alone by D21 (P = 0.006). At D5, a greater reduction in serum VEGF occurred with chemotherapy + ZOL compared with chemotherapy: median percentage change -23.8% [interquartile range (IQR): -32.9 to -15.8] versus -8.4% (IQR: -27.3 to +8.9; P = 0.02), but these effects were lost by D21. Postmenopausal women showed a decrease in follistatin levels from baseline in the chemotherapy + ZOL group at D5 and D21, compared with chemotherapy alone (P(interaction) = 0.051). CONCLUSIONS: In this pilot study, short-term changes in biomarkers suggest potentially relevant interactions between tumor biology, chemotherapy, modification of the bone microenvironment, and the endocrine status of the host. Larger studies with more frequent dosing of zoledronic acid are needed to assess these complex interactions more thoroughly.

Ten-Year Follow-Up of a Patient with Metastatic Ewing's Sarcoma of the Pelvis.

PATIENT: We report a 32-year-old women with a pelvic Ewing's sarcoma, who developed skeletal metastases within 20 months of diagnosis but following treatment remains disease-free at 10 years. DISCUSSION: Ewing's sarcoma is a highly malignant tumour of bone. Presentation of a pelvic tumour over the age of 30 years is extremely rare and associated with a poor prognosis. Early recurrence is also associated with an extremely grave prognosis. In our patient there was little or no response to salvage chemotherapy, but, against the odds, remission was induced with pamidronate and palliative radiotherapy to some but not all sites of disease.This remission has been maintained without additional therapy for a further 5 years.