Dr Adrian Harnett discusses the NICE guideline on the diagnosis and treatment of early and locally advanced breast cancer, and outlines the role of primary care

Early breast cancer is defined as being confined to the breast, with possible involvement of the axillary nodes, and a tumour size of up to 5 cm in diameter. It includes invasive and non-invasive (ductal carcinoma in situ [DCIS]) disease. Locally advanced cancer involves a tumour larger than 5 cm where there is no evidence of distant metastatic disease, and includes inflammatory breast cancer.1 These two groups of cancers are treated radically as opposed to advanced breast cancer, which is treated palliatively.

Early and locally advanced breast cancer: diagnosis and treatment is the first guideline on breast cancer produced by NICE; it was developed on behalf of NICE by the National Collaborating Centre for Cancer (NCC-C).1,2 It is the largest NCC-C guideline, with the evidence review extending to over 2000 pages.3 However, it is only part of the breast cancer story as there is a separate guideline for advanced disease,4 which was published at the same time.

Remit of the guideline

The NICE guideline was produced to provide recommendations on best practice, and to address the issues of practice variation across the country and the patchy availability of certain treatments and procedures. It covers five groups of patients:1,2

  1. Women with newly diagnosed invasive carcinoma where the primary tumour is less than 5 cm in maximum diameter and there is no sign of spread beyond the breast and axillary lymph nodes—this includes stage 1 or 2 disease.
  2. Women with invasive carcinoma where the primary tumours are larger than 5 cm in diameter, and includes inflammatory carcinomas (stage 3 disease).
  3. Men with newly diagnosed breast cancer as above (stage 1, 2, and 3).
  4. Women with DCIS.
  5. Women with Paget’s disease.

Throughout the care process, there should be particular emphasis on communication and giving appropriate information and support to the patient, and their family and/or carers. The recommendations on clinical management include:

  • diagnostic investigation
  • staging
  • pathological assessment, including receptor analysis
  • surgical management and breast reconstruction
  • neo-adjuvant therapy (primary medical therapy)
  • radiotherapy
  • post-operative rehabilitation
  • prevention of lymphoedema
  • adjuvant systemic therapy with hormone therapy, chemotherapy, and biological agents
  • management of menopausal symptoms
  • follow up.

Health economics evidence and modelling were incorporated for the following priorities:1

  • Breast magnetic resonance imaging (MRI)
  • Preoperative staging of the axilla
  • Sentinel lymph node biopsy (SLNB)
  • Taxane chemotherapy
  • Trastuzumab
  • Measuring bone mineral density (BMD)
  • Radiotherapy after breast conservation
  • Complications of local treatment (lymphoedema)
  • Follow-up imaging.

The guideline on early and locally advanced cancer is available in a variety of versions: the main clinical guideline, including an evidence review and search strategies on an accompanying CD-ROM;1 the NICE guideline;2 a quick reference guide;5 and Understanding NICE guidance for patients, relatives, and carers.6

Diagnosis and treatment

The patient pathway from symptomatic presentation (most frequently a breast lump), or detection from screening, through to treatment and follow up is shown in Figure 1.

Figure 1: Patient pathway for diagnosis and treatment

FNAC=fine needle aspiration cytology; MDT=multidisciplinary team
*Following the publication of the Cancer Reform Strategy (Department of Health, 2007), by December 2009 all patients presenting with breast problems referred by their GP to a specialist should be seen within 2 weeks, in England
†Include repeat core biopsy/open biopsy/magnetic resonance imaging, etc
‡Not all patients will require staging: Scottish Intercollegiate Guidelines Network. Management of breast cancer in women: A national clinical guideline. SIGN 84. Edinburgh: SIGN, 2005. ISBN: 1 899893 34 2
§For elderly or unfit patients, surgery may not be appropriate. For locally advanced but non-metastatic, primary systemic therapy precedes
therapeutic surgery in order to reduce size of tumour
|Could include breast conservation (wide local excision), mastectomy, and axillary staging (sentinel lymph node biopsy, sampling, or clearance)
Reproduced from Early and locally advanced breast cancer: diagnosis and treatment. NICE clinical guideline no. 80 with permission from the National Collaborating Centre for Cancer and Velindre Hospital NHS Trust.

Key priorities for implementation

The guideline contains over 80 recommendations and highlights the key priorities for implementation:

  • Preoperative assessment of the breast
  • Staging of the axilla
  • Surgery to the axilla
  • Breast reconstruction
  • Adjuvant therapy planning
  • Aromatase inhibitors
  • Assessment of bone loss
  • Primary systemic therapy
  • Follow-up imaging
  • Clinical follow up.

Several of these priorities will involve GPs and primary healthcare teams and are discussed below.

The role of GPs and primary healthcare teams

Preoperative assessment and breast reconstruction
Clinicians and the healthcare team will need to discuss with the patient, decisions about the most appropriate management. The decision to carry out breast conservation or mastectomy largely depends on the extent of locoregional disease. Although the routine use of MRI of the breast is not recommended, it may be used if there is doubt about the extent of the disease and if the breast is very dense on mammography.1,2 General practitioners and other professionals in the primary care healthcare team may be an important source of support and advice, especially for patients advised to have a mastectomy, and those who are considering immediate breast reconstruction.

Aromatase inhibitors
The aromatase inhibitors (AIs) (anastrozole, exemestane, or letrozole) have replaced tamoxifen as the commonest adjuvant hormonal therapy for hormone-receptor-positive breast cancer in post-menopausal women. However, it has made management more complicated as AIs can be used in different circumstances:

  • An AI can be used as initial adjuvant treatment (initial or primary treatment)
  • Exemestane or anastrozole can be offered instead of tamoxifen after 2–3 years of therapy of tamoxifen (switching hormone therapy)
  • Letrozole can be used for 2–3 years as an extended therapy, after a patient has been treated with tamoxifen for 5 years (extended hormonal therapy).

Tamoxifen is recommended in pre-menopausal patients with hormone-receptor-positive breast cancer and in post-menopausal patients if an AI is not tolerated or contraindicated.

Patients should have an individual treatment programme planned for them.1,2 General practitioners can help to ensure this programme is carried out, and give advice to the patient if side-effects occur (these are quite different for AIs and tamoxifen). Different follow up investigations may be necessary, particularly with respect to bone health (see below).

Assessment of bone loss

The consequence of improving survival has focused attention on the late morbidity of cancer treatment. Systemic treatment with chemotherapy or tamoxifen may cause premature menopause and can have adverse effects on bone health. Moreover, in post-menopausal women who already have increased bone loss, AIs accelerate this process further.1 Patients with early invasive breast cancer should, therefore, have a baseline dual energy X-ray absorptiometry scan to assess BMD if they:1,2

  • are starting adjuvant AI treatment
  • have treatment-induced menopause
  • are starting ovarian ablation/suppression therapy.

Women who are receiving AIs should be assessed for their risk of bone loss using algorithms from Guidance for the management of breast cancer treatment-induced bone loss: a consensus position statement from a UK expert group.7 Management recommendations for a post-menopausal woman requiring adjuvant AI therapy are shown in Figure 2. This may include providing lifestyle advice, calcium and vitamin D supplementation, or treating with bisphosphonates.
Again, GPs and the primary care healthcare team are important in coordinating this care, treatment, and follow up. The GP will be able to offer treatment and management advice on osteopenia and osteoporosis.

Figure 2: Post-menopausal adjuvant treatment with aromatase inhibitors7

BMD=bone mineral density; DXA=dual energy x-ray absorptiometry
*Previous low-trauma fracture after 50 years of age, parental history of hip fracture, alcohol intake of ?4 units/day, diseases associated with
secondary osteoporosis, prior corticosteroids for >6 months, low body mass index (<22)
†Erythrocyte sedimentation rate, full blood count, bone and liver function (calcium, phosphate, alkaline phosphatase, albumin, aspartate
aminotransferase/glutamyl transferase), serum creatinine, endomysial antibodies, serum thyroid-stimulating hormone
‡Alendronate 70 mg per week, risedronate 35 mg per week, ibandronate (150 mg po monthly or 3 mg iv 3-monthly), zoledronic acid 4 mg iv
6-monthly
§To be given as ?1 g of calcium and ?800 IU of vitamin D
|Biochemical markers such as serum C-terminal telopeptide of type I collagen or urinary N–telopeptide of type I collagen
Reproduced from Cancer treatment reviews, 34 (1), Reid D, Doughty J, Eastelic R et al. Guidance for the management of breast cancer treatment-induced bone loss: A consensus position statement from a UK expert group, S3–S18 (2008). With permission from Elsevier.

Follow-up imaging

After the diagnosis and treatment of invasive carcinoma or DCIS, annual mammography should be performed for 5 years on patients eligible for screening. On reaching the screening age or after 5 years of annual mammography, it is recommended that the National Health Service Breast Screening Programme (NHSBSP)/Breast Test Wales Screening Programme (BTWSP) stratify the frequency of screening in line with patient-risk category.1,2 General practitioners may need to provide reassurance or support to patients who are undergoing the screening process.

Clinical follow up

Each patient should have an agreed written care plan recorded by a named healthcare professional. A copy should be sent to the GP and a personal copy given to the patient. This plan is often coordinated by the GP, and should include:1,2

  • dates for review of any adjuvant therapy
  • designated named healthcare professionals
  • details of surveillance mammography
  • signs and symptoms to look for and seek advice on
  • contact details for immediate referral to specialist care
  • contact details for support services.

It is likely that the majority of patients, especially those with low-risk disease and thus an excellent prognosis, are going to want follow up outside the hospital setting. In this situation it is therefore important that communication between primary and secondary care is very good, and that the service is seamless.

In particular, patients should know how and who to contact; and there should be robust and efficient pathways for immediate referral back to the breast unit when required.

Implementation

There are several challenges in the implementation of the NICE guideline. These include:

  • the provision of ultrasound equipment; time and training for preoperative staging of the axilla (although there is a cost benefit as a result of the reduction in second operations)
  • the requirement of a nuclear medicine department to provide isotopes for sentinel lymph node detection in preference to blue dye
  • the training and availability of all types of breast reconstruction—this could have considerable cost implications
  • guidance from NHSBSP/BTWSP regarding stratifying screening frequency in line with patient-risk category
  • setting up and coordination of locally written individual care plans.

Research recommendations

The guideline development group identified a number of key areas for research, including:1,2

  1. Optimum treatment of the axilla—with the aim of reducing morbidity by more limited surgery with techniques such as SLNB and avoiding radiotherapy.
  2. Trastuzumab—what is the ideal duration of treatment? Is there a role combined with hormone therapy, and when should it be used in a neo-adjuvant regimen?
  3. Radiotherapy—what is the ideal fractionation regimen, and can partial breast irradiation be given in low-risk patients?
  4. Cognitive behavioural therapy—depression is common among many patients and yet psychological services and support is often poor. What is the effectiveness of cognitive behavioural therapy compared with other psychological interventions for patients with breast cancer?
  5. Follow-up mammography—what is the optimum frequency and length of surveillance of follow-up mammography in patients treated for invasive and in situ disease?

Summary

The NICE guideline on early and locally advanced breast cancer ensures not only the routine use of newer technologies and treatments throughout the country, but stresses the importance of reducing the late side-effects of treatment, monitoring health, and improving quality of life for patients. This includes closer cooperation between primary care and breast units, the use of shared care plans, and encouraging patient choice.

Acknowledgements

This work was carried out by the guideline development group, under the chairmanship of Mr Jim Smallwood for the NCC-C, Cardiff, on behalf of NICE. The input, work, and support of staff of the NCC-C were crucial to the completion of this guideline. The views expressed above are those of the author and not necessarily those of the NCC-C or NICE.

NICE implementation tools

NICE has developed the following tools to support implementation of its guideline on Breast cancer (early and locally advanced): diagnosis and treatment. They are now available to download from the NICE website: www.nice.org.uk

Costing tools

National cost reports and local cost templates for the guideline have been produced:

  • costing reports are estimates of the national cost impact arising from implementation based on assumptions about current practice, and predictions of how it might change following implementation of the guideline.

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.

Audit support

This has been developed to support the implementation of the NICE guideline on early and locally advanced breast cancer. The aim is to help NHS organisations with a baseline assessment and to assist with the audit process, thereby helping to ensure that practice is in line with the NICE recommendations. The audit support is based on the key recommendations of the guidance and includes criteria and data collection tools.

 

  • There is an important role for primary care in the management of bone health in women receiving aromatase inhibitors
  • Follow up of some cases of breast cancer could be conducted in primary care as directed by patient choice
  • This could help save on out-patient follow-up costs, but needs to be underpinned by a care plan to ensure safe and consistent care
  • A community specialist nurse could be considered in this role as breast cancer is a common presenting problem
  • Tariff prices: breast surgery outpatient = £138 (new), £72 (follow up)a
  1. National Collaborating Centre for Cancer. Early and locally advanced breast cancer: diagnosis and treatment. Cardiff: NCCC, 2009. Available at: www.nice.org.uk/guidance/CG80/Guidance/pdf/English
  2. National Institute for Health and Care Excellence. Early and locally advanced breast cancer: diagnosis and treatment. Clinical Guideline 80. London: NICE, 2009. Available at: www.nice.org.uk/guidance/CG80/NiceGuidance/pdf/English
  3. National Institute for Health and Care Excellence. Breast cancer (early and locally advanced): diagnosis and treatment. Evidence review. London: NICE, 2009. Available at: www.nice.org.uk/guidance/index.jsp?action=download&o=44049
  4. 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
  5. National Institute for Health and Care Excellence. Early and locally advanced breast cancer. Quick reference guide. Clinical Guideline 80. London: NICE, 2009. Available at: www.nice.org.uk/guidance/CG80/QuickRefGuide/pdf/English
  6. National Institute for Health and Care Excellence. Understanding NICE guidance: Early and locally advanced breast cancer. London: NICE, 2009. Available at: www.nice.org.uk/guidance/CG80/PublicInfo/pdf/English
  7. Reid D, Doughty J, Eastell R et al. Guidance for the management of breast cancer treatment-induced bone loss: A consensus position statement from a UK Expert Group. Cancer Treat Rev 2008; 34 (1): S3–S18.G