20-Year Risks of Breast-Cancer Recurrence after Stopping Endocrine Therapy at 5 Years

The administration of endocrine therapy for 5 years substantially reduces recurrence rates during and after treatment in women with early-stage, estrogen-receptor (ER)-positive breast cancer. Extending such therapy beyond 5 years offers further protection but has additional side effects. Obtaining data on the absolute risk of subsequent distant recurrence if therapy stops at 5 years could help determine whether to extend treatment

Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials

Background Neoadjuvant chemotherapy (NACT) for early breast cancer can make breast-conserving surgery more feasible and might be more likely to eradicate micrometastatic disease than might the same chemotherapy given after surgery. We investigated the long-term benefits and risks of NACT and the influence of tumour characteristics on outcome with a collaborative meta-analysis of individual patient data from relevant randomised trials. Methods We obtained information about prerandomisation tumour characteristics, clinical tumour response, surgery, recurrence, and mortality for 4756 women in ten randomised trials in early breast cancer that began before 2005 and compared NACT with the same chemotherapy given postoperatively. Primary outcomes were tumour response, extent of local therapy, local and distant recurrence, breast cancer death, and overall mortality. Analyses by intention-to-treat used standard regression (for response and frequency of breast-conserving therapy) and log-rank methods (for recurrence and mortality). Findings Patients entered the trials from 1983 to 2002 and median follow-up was 9 years (IQR 5–14), with the last follow-up in 2013. Most chemotherapy was anthracycline based (3838 [81%] of 4756 women). More than two thirds (1349 [69%] of 1947) of women allocated NACT had a complete or partial clinical response. Patients allocated NACT had an increased frequency of breast-conserving therapy (1504 [65%] of 2320 treated with NACT vs 1135 [49%] of 2318 treated with adjuvant chemotherapy). NACT was associated with more frequent local recurrence than was adjuvant chemotherapy: the 15 year local recurrence was 21·4% for NACT versus 15·9% for adjuvant chemotherapy (5·5% increase [95% CI 2·4–8·6]; rate ratio 1·37 [95% CI 1·17–1·61]; p=0·0001). No significant difference between NACT and adjuvant chemotherapy was noted for distant recurrence (15 year risk 38·2% for NACT vs 38·0% for adjuvant chemotherapy; rate ratio 1·02 [95% CI 0·92–1·14]; p=0·66), breast cancer mortality (34·4% vs 33·7%; 1·06 [0·95–1·18]; p=0·31), or death from any cause (40·9% vs 41·2%; 1·04 [0·94–1·15]; p=0·45). Interpretation Tumours downsized by NACT might have higher local recurrence after breast-conserving therapy than might tumours of the same dimensions in women who have not received NACT. Strategies to mitigate the increased local recurrence after breast-conserving therapy in tumours downsized by NACT should be considered—eg, careful tumour localisation, detailed pathological assessment, and appropriate radiotherapy

The influence of clinicopathological features on the predictive accuracy of conventional breast imaging in determining the extent of screen-detected high-grade pure ductal carcinoma in situ

INTRODUCTION: The extent of calcified ductal carcinoma in situ (DCIS) detected by screening mammography is a determinant for treatment with breast conserving surgery (BCS). However, DCIS may be uncalcified and almost a quarter of patients with DCIS treated initially by BCS either require a second operation or are found to have unexpected invasive disease following surgery. Identification of these cases might guide selective implementation of additional diagnostic procedures.METHODS: A retrospective review of patients with a preoperative diagnosis of pure high-grade DCIS at the Southampton and Salisbury Breast Screening Unit over a ten-year period was carried out. Mammograms were reviewed independently by a consultant radiologist and additional factors including the Breast Imaging Reporting and Data System (BI-RADS®) breast density score, DCIS extent and disease location within the breast recorded.RESULTS: Unexpected invasive disease was found in 35 of 144 patients (24%). Within our unit the re-excision rate for all screen-detected DCIS is currently 23% but for patients included in this study with high-grade DCIS the re-excision rate was 39% (34/87). The extent of DCIS (p=0.008) and lack of expression of the oestrogen receptor (ER) predicted the requirement for re-excision in both univariate (p=0.004) and multivariate analysis (p=0.005).CONCLUSIONS: High-grade DCIS may be focally uncalcified, leading to underestimation of disease extent, which might be related to ER status. Invasive foci associated with high-grade DCIS are often mammographically occult. Exploration of additional biomarkers and targeted use of further diagnostic techniques may improve the preoperative staging of DCIS