National randomised controlled trial is needed
BMJ 2008; 336 doi: https://doi.org/10.1136/bmj.39500.469664.1F (Published 28 February 2008) Cite this as: BMJ 2008;336:461
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Follow-up after breast cancer
We were dismayed at Donnelly and colleagues’ letter in the BMJ this week(1). They accuse us of writing a non-evidence based review of the topic of follow up in breast cancer. It is true that there are no prospective data to recommend any particular method of follow up, but in the absence of such data the only available evidence comes from retrospective audits of pattern of relapse and method of detection of such relapse. It may be that Donnelly and colleagues are unaware of our work in this area, in which we have not only reviewed the topic of follow up in breast cancer extensively, but also published new data pertaining to recurrence pattern and method of detection in thousands of patients both in the UK and abroad(2-6). Our conclusions based on that large body of evidence is that the value of routine clinical examination is limited. Patient self examination detects more than twice the number of relapses. We have demonstrated that the detection rate of annual mammographic examination in breast cancer patients is at least equivalent to that of 3 yearly screening mammography in the general population during the same period.
At no stage in our editorial did we suggest that follow up should be delegated to the general practitioner, as is implied by Donnelly and colleagues. Specifically, we stated that ‘Discharging patients from breast units to breast screening programmes after two years is unlikely to meet their specific needs”. Follow-up care and the health professionals involved will vary in different settings’. Donnelly and colleagues also take our comments regarding notes review out of context. We suggest this only as a method of identifying patients who may be suitable for switching or extending hormonal therapy. We advocate the use of quality of life questionnaires and open access to breast care nurses and to the clinic for symptoms and for detection of psychological problems, both in our leader and in the previous publications on which these recommendations are based. We support fully studies of follow up methods, with some of these alternatives having been trialled by us with some success. We specifically state that patients needs vary and that a flexible approach should be adopted. We stand by our affirmation that in relation to detecting treatable local and regional disease, regular and frequent clinical examination is not cost effective.
Donnelly and colleagues suggest a trial is needed of hospital based follow up vs alternative follow up. The cancer plan suggests risk stratified follow up and Donnely suggests using the Nottingham Prognostic Index (NPI) to stratify patients in their proposed trial. It is not at all clear what the end points of such a trial will be, but if the aim is to detect and treat local recurrence then stratifying risk on the NPI makes no sense because the risk of local recurrence after breast conserving surgery which is the most common treatment for breast cancer is not related to tumour size or node status, 2 of the 3 factors used in the NPI. Likewise disease status at presentation does not predict for treatable contralateral cancer(2). Any trial would also require huge numbers of patients and prolonged follow up when one considers the current low rate of local relapse. Many have accepted that frequent clinical examination is unnecessary, a fact conceded by Donnelly and colleagues when they highlight the ‘innovative’ new strategies for follow up (not based on clinical examination) which ‘could meet our needs’. There is a need to better define the most effective way of detecting psychological problems and providing support for these problems. In addition, more work needs to be done to better define the optimal frequency and duration of mammographic examination. Some work in this area has been funded and one of us is a grant holder on this study which will report later this year(7). The funding bodies will decide whether the trial proposed by Donnelly takes place but whether the study proposed will provide a better evidence base on which to determine the optimal programme of follow up is not at all clear.
1. Donnelly PK, Hiller L, Dunn JA. Follow up after breast cancer: National randomised controlled trial is needed. BMJ 2008;336:461-462 (1 March).
2. Montgomery DA, Krupa K, Jack W, Kerr G, Kunkler I, Thomas J, Dixon JM. Changing Pattern of Recurrence Detection in Breast Cancer: The Edinburgh Experience. Br J Cancer 2007; 96(12): 1802-7
3. Montgomery DA, Krupa K, Cooke TG. Alternative Methods of Follow Up in Breast Cancer: A Systematic Review of the Literature. Br J Cancer 2007; 96(11): 1625-32
4. Montgomery DA, Krupa K, Cooke TG. Follow up in Breast Cancer: Does routine clinical examination improve outcome? A systematic review of the literature. Br J Cancer 2007; 97(12): 1632-41.
5. Montgomery DA, Krupa K, Cooke TG. Locoregional relapse after breast cancer: Most relapses occur late and are not clinically detected. Breast 2008 in press.
6. Montgomery DA, Krupa K, Wilson C, Cooke TG. Patients’ expectations for follow up in breast cancer – A preliminary, questionnaire based study. Breast 2008 in press
7. Gilbert, FJ, Dixon JM, Vale LD et al. The clinical cost-effectiveness of different surveillance mammography regimes after the treatment of primary breast cancer. Funded by HTA, NHS R & D. December 2007.
Competing interests: None declared
Competing interests: No competing interests
Need for the iBreast trial – risk adjusted breast cancer follow-up trial
Whilst we appreciate that Dixon’s reviews on breast cancer follow-up are evidence-based, we are concerned that neither his recommendations for discharge 2 years post-treatment (1) nor the current NICE guidelines for discharge before 3 years (2) are based on randomised evidence; a concern previously shared by others (3).
Dixon’s response (4) illustrates the abundance of retrospective audits and reviews but the paucity of prospective data in the area of breast cancer follow-up, Randomised Controlled Trials (RCTs) being the essential requirement for defining evidence-based guidelines. There have in fact been several RCTs from both the UK and overseas, most recently in 2006 Grunfeld’s group reported a Canadian multi-centre study (5) which demonstrated the equivalence of benefit to patients from annual mammography coupled with protocol-driven clinical review by the General Practitioner rather than the specialist, commencing one year after diagnosis. These and other studies were reviewed by the members of the NCRI Breast and Primary Care Development Groups who agreed that whilst a large UK RCT was essential, the level of clinical assessment conducted in the privately-funded Canadian system was not achievable within the NHS where a more imaginative flexible cost-effective approach was necessary. General practice in the UK is however uniquely placed to provide both the necessary emotional support for patients with social deprivation (6) and to handle treatment compliance with hormone blocking therapy, bone health and possibly trial follow-up. Our proposed iBreast study has therefore emerged with broad-based support as a vehicle for including General Practice as one of several alternatives satisfying consumers’ need for choice in follow-up requirements. The consumer representatives of the NCRI Breast Clinical Studies Group having been integral to the development of our proposed trial as have the ongoing clinical collaborators involved in small pilot RCTs assessing alternative follow-up models to hospital consultant, the results of which fed through into the design of iBreast.
Whilst Dixon’s editorial relates predominantly to the well documented annual risk of recurrence following breast conservation, any proposed model of follow-up should perhaps take account of broader follow-up outcomes that include the growing number of patients treated by mastectomy and their access to reconstructive or symmetrising surgery. Furthermore whilst there is limited evidence that treatment of surveillance-detected recurrent disease improves long-term survival, there is abundant evidence that effective primary locoregional control combined with long-term adjuvant therapy can both prevent recurrence and improve survival (7). A focus for follow-up is therefore addressing patient concerns regarding treatment and ensuring long-term compliance (8).
If follow-up is to be risk adjusted, as recommended by the cancer reform strategy, the Nottingham Prognostic Index (NPI) is well evidenced to patients and staff as a predictor of survival from breast cancer (9); a view endorsed in the 2006 HTA report which concludes that, with respect to adjuvant therapy, no other prognostic model has emerged as clearly superior to NPI (10). Whilst tumour grade may be an important predictor of local relapse, tumour size and lymph node stage are important predictors of the extent of surgery, radiotherapy and chemotherapy given and resultant treatment-related morbidity, which is a key factor in prolonging hospital based follow-up.
Our iBreast study draws on results from the NCRI sponsored survey (11) which was acknowledged by BASO as reflecting mainstream opinion, and which favoured NPI in risk-adjusted follow-up which ranged from <1 year to > 11 years around a median of 5 years. The trial will therefore test the limits of acceptability by contrasting discharge at 1 versus 3 years for low risk (NPI < 3.4, approx 35% of caseload), 3 versus 5 years for moderate risk (NPI > 3.4 < 5.4, 49% of caseload) and 5 versus 10 years follow-up for high risk (NPI > 5.4, 16% of caseload). The study will be the first UK multi-centre trial of this type and therefore aims to have appropriate resource and be accessible to the large number of new and existing patients with prolonged follow-up which will include patient choice of model of care after the initial randomisation period. The study is powered on outcome variables to include not only long-term disease-free survival but patient satisfaction, compliance and re-referral extending beyond 10 years. This issue will assume increasing importance given the emerging evidence from San Antonio that patients can benefit from Hormone Blocking Therapy given for more than 5 years after diagnosis and when many have already been lost to specialist review (12).
We look forward to the results of Fiona Gilbert’s audit of surveillance mammography which will, in addition to exploring cost efficiency provide some large-scale data on surveillance protocol default which is a more common hazard in elderly patients (13). A large multi- centre prospective study is however essential as imaging alone does not satisfy follow-up needs, particularly in an era where there is no satisfactory benchmark for mammography after oncoplastic or aesthetic surgery.
References
1/Dixon JM and Montgomery DA. Follow-up after breast cancer. BMJ 2008;336:107-108
2/National Institute for Clinical Excellence. Follow-up after treatment for early breast cancer. In Guidance on Cancer Services. Improving Outcomes in Breast Cancer. Manual Update. London, UK: National Institute for Clinical Excellence 2002; 58-64.
3/Hays SD, Chaturvedi S, Hutcheon AW, Sarkar TK. Guidelines, guidelines and more guidelines: and we still do not know how to follow up patients with breast cancer. World J Surg Oncol 2005, 3:54
4/Dixon JM and Montgomery DA. Follow-up after breast cancer. BMJ 2008 (3rd March)
5/Grunfeld E, Levine MN, Julian J, et al. Randomised trial of long term follow up for early breast cancer: a comparison of family physician versus specialist care. J Clin Oncol 2006, 24(6): 848-855.
6/Macleod U, Ross S, Twelves C, George WE, Gillis C, Watt GC. Primary and Secondary Care Management of women with early breast cancer from affluent and deprived areas: retrospective review of hospital and general practice records. BMJ 2000, 320 (724): 1442-5.
7/Hayes DF. Follow up patients with early breast cancer. NEJM 2007, 356(21): 2505-2513.
8/Kahn KL, Schneider EC, Malin JL. Patient centered experiences in breast cancer: predicting long term adherence to tamoxifen use. Med Care 2007, 45 (5): 431-9.
9/Blamey RW, Ellis IO, Pinder SE, et al. Survival of invasive breast cancer according to the Nottingham Prognostic Index in cases diagnosed 1990-1999. Eur J Cancer 2007, 43(10):1548-55.
10/Williams C, Bronskill S, Attman D, Briggs A, Campbell H, Clarke M et al. Cost effectiveness of using prognostic information to select women with breast cancer for adjuvant systemic therapy. Health Technology Assess 2006 10(34): 133.
11/Donnelly P, Hiller L, Bathers S, Bowen S, Coleman R. Questioning specialists’ attitudes to breast cancer follow-up in primary care. Ann Oncol 2007; 18: 1467-1476.
12/Goss FE et al. A randomised trial of Letrozole in postmenopausal women after 5 years of Tamoxifen Therapy for Early-Stage breast cancer. NEJM 2003,349:1793-1802.
13/Field TS, Doubeni C, Fox MP et al. Under-utilisation of surveillance mammography among older breast cancer survivors. J Gen Intern Med 2008, 23(2): 158-63.
Competing interests: None declared
Competing interests: No competing interests