Background: The standard of care for most early breast cancer patients is breast conserving surgery (BCS), adjuvant radiotherapy (RT) and systemic therapy. Several trials have confirmed that RT reduces local recurrence, but there are few reports of trials with longterm follow up assessing the impact of omission of RT on overall survival. The Scottish Conservation trial of BCS & systemic therapy appropriate to ER status ± postoperative whole breast RT (Forrest et al. Lancet 1996;348:708–13) showed ipsilateral breast tumour recurrence (IBTR) of 24.5% in the no RT arm and 5.8% in the RT arm but no difference in overall survival at 6 years after randomisation. We report the long-term impact within this study of postoperative loco-regional RT or its omission on IBTR, overall survival, regional recurrence, metastases and breast cancer deaths. Methods: 585 patients aged ≤70 years with early breast cancer ≤4cm (T0, T1a, T2a, N0, N1a, N1b, M0) underwent local excision with a 1 cm margin, axillary node sampling or axillary node clearance. Adjuvant systemic therapy of tamoxifen or CMF was given dependent on ER status. Patients were stratified by menopausal and ER status (≥20,<20, unknown) then randomised to RT (291) versus noRT (294). Clinical outcomes were compared by Log-Rank test. Point estimates for actuarial rates at 10, 20 and 30 years are given in the table. Hazard ratios (HR) are reported with no RT as the reference. Failures of the proportional hazards (PH) assumption are reported if significant. Results: The two arms were well balanced for age, menopausal status, adjuvant systemic therapy, type of axillary surgery, laterality, tumour size, grade, histological type, nodal status and ER status. IBTR was significantly lower in the RT arm: HR = 0.39 (95%CI 0.27–0.55), although there was evidence of a failure of the PH assumption (p < 0.0001). The Log Rank test was similarly statistically significant (p < 0.0001). Exploration of the hazard rate suggests that there are differences in the first 10 years after treatment, but beyond that the risk is similar in both arms. There was no difference in overall survival, HR = 1.08 (95% CI 0.89, 1.30), p = 0.43, with survival rates similar to 30 years (table 1).Tabled 1Rate (95% CI)10 years20 years30 yearsRTNo RTRTNo RTRTNo RTLR8.8% (5.3, 12.2%)31% (25.5, 36.5%)15.2% (10.2, 20.2%)37.6% (31.6, 43.7%)27.8% (19.0, 36.5%)42.7% (35.8, 49.6%)OS72.5% (67.3, 77.6%)70.8% (65.5, 76.0%)48.6% (42.7, 54.4%)48.4% (42.5, 54.2%)23.7% (18.3, 29.0%)27.5% (22.0, 32.9%) Open table in a new tab Conclusions: Adjuvant loco-regional RT with systemic therapy appropriate to ER status reduces the risk of IBTR in the first 10 years of follow up but has no impact thereafter on IBTR nor on overall survival up to 30 years. No conflict of interest.

The aim was to determine long‐term overall, breast cancer‐specific and metastasis‐free survival as well as axillary relapse rate from a pooled analysis of two randomized trials in women with operable breast cancer. These trials compared axillary node sampling (ANS), combined with axillary radiotherapy (AXRT) if the sampled nodes were involved, with axillary node clearance (ANC).

Background: We investigated the impact of follow-up duration to determine whether two immunohistochemical prognostic panels, IHC4 and Mammostrat, provide information on the risk of early or late distant recurrence using the Edinburgh Breast Conservation Series and the Tamoxifen vs Exemestane Adjuvant Multinational (TEAM) trial. Methods: The multivariable fractional polynomial time (MFPT) algorithm was used to determine which variables had possible non-proportional effects. The performance of the scores was assessed at various lengths of follow-up and Cox regression modelling was performed over the intervals of 0–5 years and >5 years. Results: We observed a strong time dependence of both the IHC4 and Mammostrat scores, with their effects decreasing over time. In the first 5 years of follow-up only, the addition of both scores to clinical factors provided statistically significant information ( P <0.05), with increases in R 2 between 5 and 6% and increases in D-statistic between 0.16 and 0.21. Conclusions: Our analyses confirm that the IHC4 and Mammostrat scores are strong prognostic factors for time to distant recurrence but this is restricted to the first 5 years after diagnosis. This provides evidence for their combined use to predict early recurrence events in order to select those patients who may/will benefit from adjuvant chemotherapy.

Background: We investigated the impact of follow-up duration to determine whether two immunohistochemical prognostic panels, IHC4 and Mammostrat, provide information on the risk of early or late distant recurrence using the Edinburgh Breast Conservation Series and the Tamoxifen vs Exemestane Adjuvant Multinational (TEAM) trial. Methods: The multivariable fractional polynomial time (MFPT) algorithm was used to determine which variables had possible non-proportional effects. The performance of the scores was assessed at various lengths of follow-up and Cox regression modelling was performed over the intervals of 0–5 years and 4 5 years. Results: We observed a strong time dependence of both the IHC4 and Mammostrat scores, with their effects decreasing over time. In the first 5 years of follow-up only, the addition of both scores to clinical factors provided statistically significant information ( P o 0.05), with increases in R 2 between 5 and 6% and increases in D-statistic between 0.16 and 0.21. Conclusions: Our analyses confirm that the IHC4 and Mammostrat scores are strong prognostic factors for time to distant recurrence but this is restricted to the first 5 years after diagnosis. This provides evidence for their combined use to predict early recurrence events in order to select those patients who may/will benefit from adjuvant chemotherapy. Prediction of residual risk following adjuvant endocrine treatment in early breast cancer has become a critical component in the selection of treatment options. In addition, recent data on the impact of up to 10 years of adjuvant endocrine therapy in early breast cancer suggest that some women may benefit from extended treatment with tamoxifen(Goss et al , 2003; Davies et al , 2013; Gray et al , 2013). At present, patients and their clinicians may be presented with three time-related choices related to the treatment of luminal breast cancers: (1) whether it is beneficial to treat patients with adjuvant chemotherapy and therefore delay endocrine therapy; (2) whether to follow a switch strategy for endocrine therapy; and (3) whether to extend endocrine therapy after 5 years for a total of 10 years. Multiple diagnostic algorithms have been developed to provide information on residual risk for patients facing these choices; however, there is limited information on how time impacts the risk assessments provided by these diagnostic tools.

Background: Following primary breast cancer treatment, the early detection of ipsilateral breast tumour recurrence (IBTR) or ipsilateral secondary cancer in the treated breast and detection of new primary cancers in the contralateral breast is beneficial for survival. Surveillance mammography is used to detect these cancers, but the optimal frequency of surveillance and the length of follow-up are unclear. Objectives: To identify feasible management strategies for surveillance and follow-up of women after treatment for primary breast cancer in a UK setting, and to determine the effectiveness and cost-effectiveness of differing regimens. Methods: A survey of UK breast surgeons and radiologists to identify current surveillance mammography regimens and inform feasible alternatives; two discrete systematic reviews of evidence published from 1990 to mid 2009 to determine (i) the clinical effectiveness and cost-effectiveness of differing surveillance mammography regimens for patient health outcomes and (ii) the test performance of surveillance mammography in the detection of IBTR and metachronous contralateral breast cancer (MCBC); statistical analysis of individual patient data (West Midlands Cancer Intelligence Unit Breast Cancer Registry and Edinburgh data sets); and economic modelling using the systematic reviews results, existing data sets, and focused searches for specific data analysis to determine the effectiveness and cost–utility of differing surveillance regimens. Results: The majority of survey respondents initiate surveillance mammography 12 months after breast-conserving surgery (BCS) (87%) or mastectomy (79%). Annual surveillance mammography was most commonly reported for women after BCS or after mastectomy (72% and 53%, respectively). Most (74%) discharge women from surveillance mammography, most frequently 10 years after surgery. The majority (82%) discharge from clinical follow-up, most frequently at 5 years. Combining initiation, frequency and duration of surveillance mammography resulted in 54 differing surveillance regimens for women after BCS and 56 for women following mastectomy. The eight studies included in the clinical effectiveness systematic review suggest surveillance mammography offers a survival benefit compared with a surveillance regimen that does not include surveillance mammography. Nine studies were included in the test performance systematic review. For routine IBTR detection, surveillance mammography sensitivity ranged from 64% to 67% and specificity ranged from 85% to 97%. For magnetic resonance imaging (MRI), sensitivity ranged from 86% to 100% and specificity was 93%. For non-routine IBTR detection, sensitivity and specificity for surveillance mammography ranged from 50% to 83% and from 57% to 75%, respectively, and for MRI from 93% to 100% and from 88% to 96%, respectively. For routine MCBC detection, one study reported sensitivity of 67% and specificity of 50% for both surveillance mammography and MRI, although this was a highly select population. Data set analysis showed that IBTR has an adverse effect on survival. Furthermore, women experiencing a second tumour measuring > 20 mm in diameter were at a significantly greater risk of death than those with no recurrence or those whose tumour was < 10 mm in diameter. In the base-case analysis, the strategy with the highest net benefit, and most likely to be considered cost-effective, was surveillance mammography alone, provided every 12 months at a societal willingness to pay for a quality-adjusted life-year of either £20,000 or £30,000. The incremental cost-effectiveness ratio for surveillance mammography alone every 12 months compared with no surveillance was £4727. Limitations: Few studies met the review inclusion criteria and none of the studies was a randomised controlled trial. The limited and variable nature of the data available precluded any quantitative analysis. There was no useable evidence contained in the Breast Cancer Registry database to assess the effectiveness of surveillance mammography directly. The results of the economic model should be considered exploratory and interpreted with caution given the paucity of data available to inform the economic model. Conclusions: Surveillance is likely to improve survival and patients should gain maximum benefit through optimal use of resources, with those women with a greater likelihood of developing IBTR or MCBC being offered more comprehensive and more frequent surveillance. Further evidence is required to make a robust and informed judgement on the effectiveness of surveillance mammography and follow-up. The utility of national data sets could be improved and there is a need for high-quality, direct head-to-head studies comparing the diagnostic accuracy of tests used in the surveillance population. Funding: The National Institute for Health Research Health Technology Assessment programme.

Introduction: Sentinel node biopsy (SNB) has become routine for axillary staging in patients with invasive breast cancer. Despite reducing the number of patients who undergo axillary node clearance (ANC), a number of patients still undergo both SNB and delayed ANC. Preoperative axillary ultrasonography (AUS) and fine needle aspiration (FNA) of suspicious nodes can be used to identify patients with axillary metastases who can proceed directly to ANC. The aim of this study was to assess the use of AUS FNA as a means of routine preoperative staging of the axilla in patients with invasive breast cancer in our unit.

OBJECTIVES:To assess whether omission of post-operative radiotherapy (RT) in women with 'low-risk' axillary node-negative breast cancer [tumour size of less than 5 cm (T0-2) although the eligibility criteria further reduce the eligible size to a maximum of 3 cm] treated by breast-conserving surgery and endocrine therapy improves quality of life and is more cost-effective. DESIGN:A randomised controlled clinical trial, using a method of minimisation balanced by centre, grade of cancer, age, lymphovascular invasion and preoperative endocrine therapy was performed. SETTING:Breast cancer clinics in cancer centres in the UK. PARTICIPANTS:Patients aged ≥ 65 years were eligible provided that their breast cancers were considered to be at low risk of local recurrence, they were suitable for breast conservation surgery, they were receiving endocrine therapy and they were willing and able to give informed consent. INTERVENTIONS:The standard treatment of post-operative whole breast irradiation or the omission of RT. MAIN OUTCOME MEASURES:Quality of life was the primary outcome measure, together with anxiety and depression and cost-effectiveness. Secondary outcome measures were recurrence rates and survival, and treatment-related morbidity. The principal method of data collection was by questionnaire, completed at home with a research nurse on four occasions over 15 months, then by postal questionnaire at 3 and 5 years after surgery. RESULTS:The hypothesised improvement in overall quality of life with the omission of RT was not seen in the summary domains of the European Organisation for Research in the Treatment of Cancer (EORTC) scales. Some differences were apparent within subscales of the EORTC questionnaires, and insights into the impact of treatment were also provided by the qualitative data obtained by open-ended questions added by the trial team. Differences were most apparent shortly after the time of completion of RT. RT was then associated with increased breast symptoms and with greater (self-reported) fatigue, but with lower levels of insomnia and endocrine side effects. These statistically significant differences in breast symptoms persisted for up to 5 years after RT [mean difference, RT was 5.27 units greater than no RT, 95% confidence interval (CI) of 1.46 to 9.07], with similar, though non-significant, trends in insomnia. No significant difference was found in the overall quality of life measure, with the no RT group having 0.36 units greater quality of life than the RT group (95% CI -5.09 to 5.81). CONCLUSIONS:Breast RT is tolerated well by most older breast cancer patients without impairing their overall health-related quality of life (HRQoL). Although HRQoL should always be taken into account when determining treatment, our results show that the addition of RT does not impair overall quality of life. Further economic modelling on the longer-term costs and consequences of omitting RT is required. TRIAL REGISTRATION:Current Controlled Trials ISRCTN14817328. FUNDING:This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol 15, No. 12. See the HTA programme website for further project information.