Recommendations for research
The 2014 and 2009 guideline committees made the following recommendations for research.
What is the role of arm and shoulder specific exercises compared with and/or used as an adjunct to established lymphoedema treatments (such as compression garments and complex decongestive therapy)?
Well-designed randomised controlled trials should consider differing arm and shoulder-specific aerobic and/or resistive exercises that focus on strength and flexibility to improve local lymph flow, for example, swimming, weight lifting, tai chi and yoga. The studies should have a follow-up period that is sufficient to capture long-term outcomes including changes to current lymphoedema or any new-onset lymphoedema in other parts of the limb. Outcomes for this research should include quality-of-life measures. 
Clinical trials are needed to investigate the most effective endocrine therapy for postmenopausal women with ER-positive tumours who progress on treatment with an aromatase inhibitor.
Randomised clinical trials should evaluate the clinical and cost effectiveness of different sequences of chemotherapy for advanced breast cancer.
Most patients with advanced breast cancer who receive chemotherapy will be given at least two different regimens and many will receive three. The available evidence to support decisions about the most clinically and cost effective sequence in which to use these drugs is extremely limited. There is also very little good-quality evidence about the relative clinical and cost effectiveness of currently recommended treatments, either in combination or in sequence. Following on from the recommendations in this guideline, it would be important to establish clinical trials to investigate this problem in a more systematic fashion than hitherto. 
The use of continued trastuzumab in patients with progressive metastatic disease should be investigated as part of a randomised controlled trial. Trial design should incorporate collection of data required for prospective cost-effectiveness analysis.
There is currently no high-quality published evidence about whether continuing trastuzumab is effective in prolonging survival in patients with HER2-positive advanced breast cancer who develop progressive disease (outside the central nervous system) during or after first-line treatment with trastuzumab and cytotoxic chemotherapy. Any studies should be carefully planned to permit a high quality cost-effectiveness analysis. 
Randomised controlled trials are needed to assess whether patients who have had adjuvant trastuzumab should be offered further biological response modifiers. Trial design should incorporate collection of data required for prospective cost-effectiveness analysis.
As more patients with HER2-positive advanced breast cancer have trastuzumab as part of their initial adjuvant treatment following a diagnosis of early breast cancer, an increasing number of patients with advanced breast cancer will have had previous exposure to this agent. There is no evidence currently about whether trastuzumab or other biological therapies are effective in this situation. 
The relevant research organisations should be encouraged to address the topic of uncontrolled local disease and devise appropriate research studies. This might include development of a national register.
The problem of how best to manage uncontrolled local disease is very poorly addressed by the current evidence. Although it is probably quite an uncommon condition, it is likely that across the country there are enough patients to generate evidence from well-coordinated national studies. A national register should be considered as part of this because of the current uncertainties about the frequency of the problem.