Patients with advanced breast cancer have incurable disease, either because the breast tumour is too extensive for radical therapy or more commonly because of metastatic spread. Most will have a history of previously treated primary breast cancer, but around 5% will have metastases at the time of the initial diagnosis. It is difficult to obtain an accurate picture of the prevalence of advanced breast cancer, but it is estimated that 35% of primary breast cancers will go on to develop metastases within 10 years.1
There have been considerable advances in the management of metastatic breast cancer in the past few years, particularly with regard to systemic treatments (i.e. chemotherapy, and endocrine and biological therapies) resulting in longer remissions and enhanced quality of life. It is now often regarded as a chronic illness with patients surviving many years while receiving several lines of therapy. The total burden on healthcare services is considerable. Conservative estimates put the direct cost of lifetime treatment of all patients in the UK presenting with stage IV breast cancer within a given year at approximately £26 million.2 Although, there is a need to rationalise the use of resources to the best effect, it is important to make sure that all patients have access to the best possible care.
The NICE guideline Advanced breast cancer: diagnosis and treatment3,4 was written for everyone involved in caring for patients with advanced breast cancer, and although most of the listed recommendations concentrate on management within the hospital sector, there are important implications for primary care. This article briefly discusses the development and content of the guideline and how it impacts on general practice.
Remit of the guideline
The guideline is not intended to be a textbook covering every aspect of the diagnosis and treatment of advanced breast cancer, but focuses on those areas of clinical practice that are controversial or in which there is practice variation, and interventions that are likely to have the most impact on patient care. An overview of the content of the guideline is shown in Box 1. Throughout the document there is an emphasis on appropriate information and support, as well as the need for seamless integration of services in primary and secondary care. There is recognition that GPs have an important role in contributing to the former and enabling the latter.
The NICE guideline is based on the best evidence available or, where evidence is lacking, on the consensus of the Guideline Development Group (GDG). Unfortunately, despite a plethora of research papers on all aspects of breast-cancer care, in many areas the evidence is sparse and one of the remits of the GDG was to provide recommendations for further research.
|Box 1: Focus of the recommendations in the NICE guideline on advanced breast cancer3,4|
Diagnosis and assessment
Providing information and support for decision making
Systemic disease-modifying therapy
Community based treatment and supportive care
|CT=computed tomography; MRI=magnetic resonance imaging; PET=positron emission tomography; ER=oestrogen receptor; PR=progesterone receptor; HER-2=human epidermal growth factor receptor-2; MDT=multidisciplinary team|
Diagnosis and assessment
General practitioners are likely to be the first healthcare professionals to see patients with symptoms from advanced disease and this diagnosis should always be considered in a person with a history of treated breast cancer, even if it was many years previously. In many patients, initial investigation will therefore be undertaken in primary care, whether it is a chest X-ray for dyspnoea or a plain radiograph for bone pain.4 In cases where there is no clinical doubt regarding the diagnosis, or if the patient requires further assessment, it is usual to refer to a member of the breast-cancer multidisciplinary team (MDT): either the treating surgeon or oncologist.
The NICE guideline provides advice for MDTs about what further investigations are appropriate. For example: proximal limb bones should be assessed for the risk of pathological fracture in patients with bone metastases elsewhere, using bone scintigraphy and/or plain radiography; and re-biopsy is not necessary to assess oestrogen receptor (ER) or human epidermal growth factor receptor-2 (HER-2) status where this is already known from primary tumour tissue.3,4
Providing information and support for decision making
Increasing treatment options have resulted in more complex decisions for both healthcare professionals and patients who require adequate and appropriate information in order to be involved in decision making. This is not a one-off process and requires input from various professionals at different times—the GP should be part of this.
It is important to establish the information needs of the individual patient and to provide this in an understandable and appropriate way, with the opportunity to discuss issues and ask questions. Needless to say, it is vital that there is good communication between primary and secondary care to enable a consistent and seamless approach. In this respect, decision aids, such as tape recordings of consultations, question prompt sheets, face-to-face counselling, and interactive computer programmes have been shown to be effective.5,6
Systemic disease-modifying therapy
There have been considerable advances in the use of systemic therapy in the past few years, with more effective drugs and combinations becoming available. Treatment decisions are complex with a trade-off between quality of life, risks of toxicity, and the probabilities of benefit. Although the patient usually makes these decisions after consultation with the surgeon or oncologist, it is important for GPs to understand the rationale behind such choices and to help support patients through treatment.
Endocrine therapy is the first-line treatment for the majority of patients with ER-positive advanced breast cancer; however, chemotherapy should be used when disease is imminently life-threatening or early relief of symptoms is required because of significant visceral organ involvement, provided that patients understand and are prepared to accept the toxicity.7 Aromatase inhibitors (anastrozole, letrozole, and exemestane) are recommended as treatment options for post-menopausal women,8 and tamoxifen and ovarian suppression are used in pre-menopausal women. Tamoxifen should be offered as first-line treatment for men with ER-positive disease.3,4
Sequential use of single-agent chemotherapy is recommended in the majority of cases, but combinations of drugs can be considered where the greater probability of response is important and if the patient understands and is likely to tolerate the additional toxicity.9,10 The evidence does not allow strict guidance regarding which specific drugs to use, but a complex cost-effective analysis was undertaken by NICE to look at the sequencing of single agent and combination regimens commonly used in UK practice after failure of anthracyclines.4 This resulted in a recommendation to offer single-agent chemotherapy in the following sequence:3,4
- first-line docetaxel
- second-line vinorelbine or capecitabine
- third-line capecitabine or vinorelbine (whichever was not used as second-line treatment).
Perhaps the most controversial recommendation as far as oncologists are concerned is the one relating to discontinuation of trastuzumab following disease progression outside the central nervous system.3,4 Although limited recent evidence suggests benefit from continued use,11 the GDG was unable to recommend this therapy without more robust evidence of cost effectiveness.
Community based treatment and supportive care
The NICE guideline section on community based treatment and supportive care has great relevance to general practice. Primary care is the first point of contact for patients and most of their long illness will be spent at home. As more chemotherapy and other systemic therapies are given near or at home by outreach teams, the greater is the need for community healthcare professionals to be involved with the development of protocols, care pathways, and enhanced clinical skills.
Integration of oncology, supportive, and palliative care services is also required, with patients being given a choice of where and how these are provided. Specific recommendations in this area are limited to ensuring that the organisation and provision of supportive care services comply with previous NICE guidance.12,13 In particular, patients’ needs for physical, psychological, social, spiritual, and financial support should be assessed and discussed at key points, such as at diagnosis, start and end of therapy, relapse, and when death is approaching. Mechanisms should also be developed to promote continuity of care, including the possible nomination of a ‘key worker’ for individual patients. The latter might, for example, be a clinical nurse specialist in advanced breast cancer.13
Clearly, many clinical scenarios could be considered regarding complications as a result of breast cancer, but five specific conditions were singled out for discussion. These are discussed below.
Lymphoedema is often a result of treatment of primary breast cancer (surgery and/or radiotherapy), but can occur because the disease damages lymph nodes and vessels.4 It is important to establish the cause as sometimes this can be treated (for example, axillary thrombosis or extensive axillary disease). Early identification and management of lymphoedema is important, so patients should be referred back to the breast-cancer team or directly to the lymphoedema service for complex decongestive therapy, information, and support.3,4
Cancer-related fatigue is a symptom of advanced cancer that often goes unrecognised.4 Again, it is important to exclude treatable factors, such as anaemia and depression, but in many cases there is no single identifiable cause, and aetiology is likely to be multifactorial. Information about cancer-related fatigue and psychosocial support should be made available to patients.3,4 There is good evidence that exercise programmes are beneficial for this condition.14
Uncontrolled local disease with ulceration involving the chest wall or axilla can be extremely unpleasant for patients to live with; it is a visible reminder of their illness and can lead to social isolation.4 It is a difficult condition to either eradicate or provide palliative care for, but a number of measures, such as control of infection, wound management, analgesia, and psychological support, can help. The NICE guideline recommends that a breast-cancer MDT should assess all patients presenting with symptoms, and that wound-care and palliative-care teams should be involved in management strategies.3,4 In most parts of the country such facilities will probably need to be developed. Meanwhile, GPs are best advised to refer patients to a member of the breast-cancer MDT in the first instance.
Bone metastases commonly occur in patients with breast cancer and can cause significant morbidity because of pain, pathological fracture, hypercalcaemia, and spinal cord compression. Bisphosphonates have been proven to reduce these complications15 and should be offered to all patients, usually by the oncology team, either as regular intravenous therapy (zoledronate, ibandronate, or pamidronate) or tablets (clodronate or ibandronate). Radiotherapy is extremely beneficial for localised bone pain and evidence shows that single fractions are as effective as longer courses of treatment.16 Early referral to a clinical oncologist for treatment is advisable. Patients at risk of long-bone fracture should be referred to an orthopaedic surgeon to consider prophylactic fixation.3,4
Brain metastases can have profound physical and psychological effects, but treatment can often alleviate symptoms and provide a reasonable period of remission. Initial therapy usually involves the use of steroids and selected patients will go on to receive palliative radiotherapy to the whole brain for what are usually multiple metastases. In a limited number of cases, surgery can be offered prior to radiotherapy if there is a single or limited number of lesions and the patient has a good performance status. The role of the GP here is to consider the diagnosis and refer the patient back to the breast-cancer MDT at an early stage. Active rehabilitation with physiotherapy will optimise recovery and function following treatment.3,4
As the NICE guideline largely reflects good practice there are no major obstacles to its implementation. However, some areas of the country may not have access to services, which should be uniformly available, and a few innovative recommendations would require some investment, including provision of:
- lymphoedema services
- exercise programmes
- key workers, such as clinical nurse specialists
- specialist MDTs for uncontrolled local disease.
In addition, more time would be required for clinicians to satisfy patients’ information needs and to enhance communication between primary and secondary care.
NICE implementation tools
NICE has developed the following tools to support implementation of its guideline on Advanced breast cancer—diagnosis and treatment. They are now available to download from the NICE website: www.nice.org.uk
Slide set The slides are aimed at supporting organisations to raise awareness of the guideline and resulting implementation issues at a local level, and can be edited to cater for local audiences. This information does not supersede or replace the guidance itself.
Advanced breast cancer is an incurable, often chronic, condition that profoundly affects patients’ lives. However, advances in treatment and supportive care can prolong and enhance the quality of life for the majority. The NICE guideline is designed to help ensure that all patients receive the best possible care, based on good evidence where possible, to reduce unacceptable variation in practice, and to make the best use of healthcare resources. This can only be achieved by:
- optimum use of available therapies
- appropriate information and support throughout the patient-treatment pathway
- seamless integration of primary and secondary care.
- The needs of patients with advanced breast cancer demand cooperative commissioning of services spanning primary care and secondary care
- Local services and pathways should be agreed between groups of local primary and secondary care clinicians
- Many of the treatments and interventions are suitable for community delivery and thus could be negotiated at costs below full tariff price (particularly specialist nurse services)
- However these services should remain linked to and supervised by the multidisciplinary team through the pre-agreed clinical protocols and pathways
- PBC consortia should be including end-of-life care services in their plans for future commissioning under the ‘Transforming community services program’a
- Secondary Breast Cancer Taskforce. Stand up and be counted: The need for the collection of data on incidence of secondary breast cancer and survival. London: Breast Cancer Care, 2007.
- Remák E, Brazil L. Cost of managing women presenting with stage IV breast cancer in the United Kingdom. Br J Cancer 2004; 91 (1): 77–83.
- National Institute for Health and Care Excellence. Advanced breast cancer: diagnosis and treatment. Clinical Guideline 81. London: NICE, 2009. Available at: www.nice.org.uk/guidance/CG81/NiceGuidance/pdf/English
- National Collaborating Centre for Cancer. Advanced breast cancer: diagnosis and treatment. London: NCCC, 2009. Available at: www.nice.org.uk/guidance/CG81/Guidance/pdf/English
- Whelan T, O’Brien M, Villasis-Keever M et al. Impact of cancer-related decision aids. Evidence report/Technology assessment Number 46. AHRQ Publication No. 02-E004. Rockville, MD: Agency for Healthcare Research and Quality, 2002.
- O’Connor A, Stacey D, Entwistle V et al. Decision aids for people facing health treatment or screening decisions. Cochrane Database Syst Rev 2003; (2): CD001431.
- Wilcken N, Hornbuckle J, Ghersi D. Chemotherapy alone versus endocrine therapy alone for metastatic breast cancer. Cochrane Database Syst Rev 2003; (2): CD002747.
- Gibson L, Dawson C, Lawrence D, Bliss J. Aromatase inhibitors for treatment of advanced breast cancer in postmenopausal women. Cochrane Database Syst Rev 2007; (1): CD003370.
- Chlebowski R, Smalley R, Weiner J et al. Combination versus sequential single agent chemotherapy in advanced breast cancer: associations with metastatic sites and long-term survival. The Western Cancer Study Group and The Southeastern Cancer Study Group. Br J Cancer 1989; 59 (2): 227–230.
- Sledge G, Neuberg D, Bernardo P et al. Phase III trial of doxorubicin, paclitaxel, and the combination of doxorubicin and paclitaxel as front-line chemotherapy for metastatic breast cancer: an intergroup trial (E1193). J Clin Oncol 2003; 21 (4): 588–592.
- Von Minckwitz G, Zielinski C, Maarteense E et al. Capecitabine vs capecitabine + trastuzumab in patients with HER2-positive metastatic breast cancer progressing during trastuzumab treatment. The TBP phase III study (GBG 26/BIG 3-05). J Clin Oncol 2008; 26 (May 20): Abstract 1025.
- National Institute for Clinical Excellence. Improving outcomes in breast cancer: manual update. NICE cancer service guidance. London: NICE, 2002. Available at: www.nice.org.uk/guidance/CSGBC/Guidance/pdf/English
- National Institute for Clinical Excellence. Improving supportive and palliative care for adults with cancer: the manual. NICE cancer service guidance. London, NICE: 2004. Available at: www.nice.org.uk/guidance/CSGSP/Guidance/pdf/English
- Cramp F, Daniel J. Exercise for the management of cancer-related fatigue in adults. Cochrane Database Syst Rev 2008; (2): CD006145.
- Pavlakis N, Schmidt R, Stockler M. Bisphosphonates for breast cancer. Cochrane Database Syst Rev 2005; (3): CD003474.
- Sze W, Shelley M, Held I, Mason M. Palliation of metastatic bone pain: single fraction versus multifraction radiotherapy—a systematic review of the randomised trials. Cochrane Database Syst Rev 2004; (2): CD004721.G