Professor Malcolm Reed (left) and Mr James Harvey discuss the management and treatment of breast cancer and the increasing role of primary care in the follow up of patients


Breast cancer is the most common cancer in UK women. On average over 46,000 women are diagnosed each year1 meaning that approximately 1 in 9 women will develop breast cancer in their lifetime. The incidence of breast cancer is increasing because of a combination of factors, including an ageing population and improved breast screening. However, more importantly, individuals with breast cancer also have a higher survival rate than in previous years.2 Primary care physicians play a significant role in the care of individuals with breast cancer, including referral for diagnosis and subsequent contact for physical problems associated with the disease, its treatment, and social and psychological support. This article introduces the key changes in the clinical management of patients with breast cancer and highlights how some of these alterations may affect primary care services.

Who should be referred?

NICE published Clinical Guideline (CG) 80 on Early and locally advanced breast cancer: diagnosis and treatment in 2009 and is currently in the process of updating its guideline on referral for suspected cancer (CG 27).3,4 This update is expected to result in minor changes to the urgent referral criteria for breast cancer, with an increased emphasis on the likelihood of malignant disease when presented with a breast lump.3

The Cancer Reform Strategy Working Group recently released an excellent and thorough guideline on the appropriate investigation of breast disease.5 This is a very relevant document for both primary and secondary care physicians. It not only outlines how to approach referral and investigation of suspected cancers, but also provides guidance on the investigation of benign breast disease including gynaecomastia.5 This guideline supports the use of mammography in women once they reach the age of 40 years, compared with previous use from 35 years onwards.6 This recommendation was based on a lack of evidence in the benefit of mammography in a younger age group. The guideline also moves away from recommending radiological screening for all women referred to secondary care. For instance, women with breast pain with no focal clinical signs (localised tenderness, nodularity, swelling) do not require imaging or further assessment. These patients will receive verbal and written advice about management of their symptoms.5

Changes to the NHS Breast Screening Programme

The updated Cancer Reform Strategy, published in January 2011, outlines plans to run an extension of the randomisation project for breast screening age, over two 3-year screening rounds. This study is currently taking place in all screening centres in England to ascertain the benefit of an extra screening for women aged 47–49 years or 71–73 years. Full roll-out to women in these age groups is expected to be completed after 2016.7,8

Other changes to breast cancer screening include the NICE recommendations on:3

  • offering annual mammography to all patients with early breast cancer, including ductal carcinoma in-situ (DCIS), until they enter the NHS Breast Screening Programme
  • providing annual mammography for 5 years for patients diagnosed with early breast cancer who are already eligible for screening.

Treatment

Optimal treatment for early and locally advanced breast cancer continues to evolve, but surgery remains the cornerstone of therapy in gaining local control.9

Ductal carcinoma in-situ
<<<<<<< .mine Surgery—DCIS on its own is non-invasive and can be cured by adequate treatment of the breast. Patients should be offered a choice between breast-conserving surgery (BCS) or mastectomy if the lesion is small. If the latter procedure is mandated by the extent of the disease, breast reconstruction should be discussed.9 Lymph node staging is performed during the surgical treatment of a DCIS of ?5 cm due to the approximately 10% risk of metastases from an area of (occult) invasive disease.

Radiotherapy—this is given locally to the chest wall after wide local excision or mastectomy in women who are at higher risk of locally recurrent disease (e.g narrow excision margins, higher grade disease).3,9

======= Surgery—DCIS on its own is non-invasive and can be cured by adequate treatment of the breast. Patients should be offered a choice between breast-conserving surgery (BCS) or mastectomy if the lesion is small. If the latter procedure is mandated by the extent of the disease, breast reconstruction should be discussed.9 Lymph node staging is performed during the surgical treatment of a DCIS of ?5 cm due to the approximately 10% risk of metastases from an area of (occult) invasive disease.

Radiotherapy—this is given locally to the chest wall after wide local excision or mastectomy in women who are at higher risk of locally recurrent disease
(e.g narrow excision margins, higher grade disease).3,9

Early invasive carcinoma
Surgery—unless mastectomy is mandated due to tumour size, multifocality, or previous radiotherapy, a choice should be offered between BCS (plus radiotherapy) or mastectomy.9 Breast-conserving surgery plus radiotherapy gives equivalent cancer survival when compared to mastectomy. However, it does carry a higher risk of locally recurrent disease, which in the majority of patients will still be curable. Breast reconstruction should be discussed with all patients offered mastectomy. All patients known to have lymph node metastases will have an axillary clearance during the surgical procedure and those thought to be node negative will have a staging procedure performed (sentinel node biopsy or sampling).3,9

Radiotherapy—this is given to patients having BCS and also to patients following mastectomy who are at higher risk of locally recurrent disease.3,9

Endocrine treatment—given to patients whose tumours express significant oestrogen-receptor staining on histological analysis.3,9

Chemotherapy—for patients who are at higher risk of microscopic systemic disease (e.g. lymph node involvement, high grade, or larger cancer).10

Trastuzumab—given to patients expressing human epidermal growth factor receptor 2. It is given in combination with chemotherapy and treatment takes approximately 12 months to complete. Trastuzumab can cause significant cardiac impairment.11

Locally advanced breast cancer
Neoadjuvant chemotherapy or endocrine treatment—up front chemotherapy (3 months) or endocrine therapy (up to 9 months to take effect) is given to patients with large tumours that are not operable at the time of diagnosis. The aim is to downstage the tumour so that it becomes operable. Patients with larger tumours who are suitable for mastectomy may also be offered neoadjuvant chemotherapy or endocrine therapy to shrink tumours so that BCS can be performed.

Radiotherapy, chemotherapy, and endocrine treatment—given as for early invasive cancer. However, radiotherapy may also be given to the supraclavicular fossae for women with large tumours or extensive nodal involvement.3 Radiation therapy may occasionally be given as neo-adjuvant treatment to downstage a large breast cancer so that it is operable.


Aromatase inhibitor therapy

The NICE guideline recommends that post-menopausal women with oestrogen receptor-positive early breast cancer who are not considered to be at low risk should be offered an aromatase inhibitor (anastrozole or letrozole) as adjuvant therapy.3 Tamoxifen should now only be offered to post-menopausal women if an aromatase inhibitor is contraindicated or not tolerated. The choice of inhibitor will depend on the local cancer network guidance. There is insufficient current evidence to support the use of aromatase inhibitors in patients with DCIS.12

Bone health

The use of aromatase inhibitors has a profound effect on bone health in post-menopausal women, causing a significant risk of osteoporosis and fractures.13 It is not only post-menopausal women who are at risk during treatment for breast cancer; pre-menopausal women who are undergoing ovarian suppression either directly or as a result of chemotherapy have accelerated bone loss. Other risk factors such as smoking, fractures, and family history also need to be assessed in women.

The NICE recommendations state that patients with early invasive breast cancer should have a baseline dual energy X-ray absorptiometry (DEXA) scan to assess bone mineral density if they:3

  • are beginning adjuvant treatment with an aromatase inhibitor
  • have treatment-induced menopause
  • are starting ovarian ablation/suppression therapy.
<<<<<<< .mine

Patients receiving tamoxifen alone do not require a DEXA scan. The recommendations for the management of bone loss in women who are receiving adjuvant treatments associated with ovarian suppression/failure with or without concomitant aromatase inhibitor use are summarised concisely in Figure 1.14 All patients starting an aromatase inhibitor should have an initial consultation with their primary care physician at 3 months to assess their fracture risk. A DEXA scan is generally performed/requested by secondary care services and the results of this should be incorporated into the patient's assessment (see Figure 1).14 The choice of bisphosphonate for treating osteoporosis will be selected by their primary care physician based upon local protocols and funding arrangements.

=======

Patients receiving tamoxifen alone do not require a DEXA scan. The recommendations for the management of bone loss in women who are receiving adjuvant treatments associated with ovarian suppression/failure with or without concomitant aromatase inhibitor use are summarised concisely in Figure 1.14 All patients starting an aromatase inhibitor should have an initial consultation with their primary care physician at 3 months to assess their fracture risk. A DEXA scan is generally performed/requested by secondary care services and the results of this should be incorporated into the patient's assessment (see Figure 1, p.13).14 The choice of bisphosphonate for treating osteoporosis will be selected by their primary care physician based upon local protocols and funding arrangements.

Figure 1: Adjuvant treatment associated with ovarian suppression/failure with or without concomitant aromatase inhibitor use in women who experience premature menopause14

graph

*ESR, FBC, 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 + ?800 IU of vitamin D

§ Biochemical markers such as serum C-terminal telopeptide of type collagen or urinary N-telopeptide of type I collagen

BMD=bone mineral density; DEXA=dual energy x-ray absorptiometry; AI=aromatase inhibitor; ESR= erythrocyte sedimentation rate; FBC=full blood count

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.


Menopausal symptoms

Menopausal symptoms are extremely common in women undergoing adjuvant treatment for breast cancer. Approximately 25% of women are pre-menopausal at the time of diagnosis and many of them will undergo chemotherapy, which may induce menopause in up to 90% of women over the age of 40 years.15 Menopausal symptoms are also very common in women taking endocrine treatments (tamoxifen and aromatase inhibitors). Hormone replacement therapy (HRT) should not be prescribed to women with a history of breast cancer3 because of the risk of tumour growth. Topical HRT preparations are absorbed systemically and should therefore be used with caution and only in exceptional circumstances, and may be offered to women who are severely symptomatic and who have been fully informed of the potential risk.3,16,17

Hot flushes

The selective serotonin reuptake inhibitor (SSRI) antidepressants, paroxetine* and fluoxetine,* may be offered to women with breast cancer for troublesome menopausal symptoms, particularly hot flushes, but not to individuals taking tamoxifen.3 This group of antidepressants may interfere with the metabolism of tamoxifen and potentially reduce its effectiveness. Clonidine, venlafaxine,* and gabapentin* should only be offered to treat hot flushes in women with breast cancer after they have been fully informed of the significant side-effects.3

Soy (isoflavone), red clover, black cohosh, vitamin E, and magnetic devices are not recommended for the treatment of menopausal symptoms in women with breast cancer due to a lack of evidence of their effectiveness.3

*These drugs are not licensed for this use; informed consent should be obtained and documented.

Variation in care

Availability of breast reconstruction
The NICE guideline recommends that breast reconstruction should be discussed with all patients who are being advised to have a mastectomy.3 Breast reconstruction should be offered unless co-morbidities or adjuvant therapy prevents this option.3 Importantly, all reconstructive options should be discussed with the patient, irrespective of whether they are available locally.3 The National Mastectomy and Reconstructive Audit demonstrates that the availability of breast reconstruction is increasing nationally, but that wide variation exists between regions in the availability of services.18

It is important for primary care physicians to be aware of the range of reconstructive options available in their local region. If services are limited locally, it may be necessary to refer patients who are keen on pursuing or discussing this option to a centre with appropriate expertise. A good starting point for patients interested in breast reconstruction is the new publication by the British Association of Plastic, Reconstructive and Aesthetic Surgeons: Your guide to breast reconstruction.19

Treatment of the elderly and vulnerable groups
<<<<<<< .mine The high prevalence of breast cancer with increasing age (81% of cases occur in women aged over 50 years20) means that large numbers of elderly patients are treated for early stage and locally advanced breast cancer. Elderly patients, especially those with concurrent systemic health issues have historically been spared surgical intervention and given primary endocrine treatment such as tamoxifen or an aromatase inhibitor. Primary endocrine treatment was used to try and avoid the potential morbidity of surgery in an elderly population with associated systemic health problems. Although this therapy still has a role in some patients, it is recognised that outcomes are improved if the patient receives conventional treatment, usually starting with breast surgery.

A delicate balance must be struck as elderly people are at risk of both under-treatment and over-treatment.21,22 Elderly patients have improved survival if they are fit enough to undergo conventional treatment,22 and on this basis, NICE recommends that patients with early breast cancer 'irrespective of age' should be treated with appropriate systemic treatment including surgery.3 Primary care practitioners should refer elderly patients with breast symptoms and cancers in the same way as any other patient. Older patients should be promptly referred for assessment and if a diagnosis of cancer is subsequently made, standard treatment should be recommended unless there is a clear contraindication.

======= 20) means that large numbers of elderly patients are treated for early stage and locally advanced breast cancer. Elderly patients, especially those with concurrent systemic health issues have historically been spared surgical intervention and given primary endocrine treatment such as tamoxifen or an aromatase inhibitor. Primary endocrine treatment was used to try and avoid the potential morbidity of surgery in an elderly population with associated systemic health problems. Although this therapy still has a role in some patients, it is recognised that outcomes are improved if the patient receives conventional treatment, usually starting with breast surgery.

A delicate balance must be struck as elderly people are at risk of both under-treatment and over-treatment.21,22 Elderly patients have improved survival if they are fit enough to undergo conventional treatment,22 and on this basis, NICE recommends that patients with early breast cancer 'irrespective of age' should be treated with appropriate systemic treatment including surgery.3 Primary care practitioners should refer elderly patients with breast symptoms and cancers in the same way as any other patient. Older patients should be promptly referred for assessment and if a diagnosis of cancer is subsequently made, standard treatment should be recommended unless there is a clear contraindication.

Women from lower socio-economic groups who may present to primary care with more locally advanced disease are also a vulnerable group. The provision of educational material in primary care, which stresses the importance of breast examination and screening, may help these women to present at an earlier stage.


Follow up in primary care

As one of its cornerstones, the new White Paper on Equality and excellence—liberating the NHS23 sets out that patients should be put at the heart of the decision-making process. Breast cancer care is at the forefront of patient-led decision making and there is a large amount of data on Patient Reported Outcome Measures (PROMs).18 In the majority of cancer networks, cancer follow up has been in the domain of secondary care. There is no substantive evidence that this benefits survival and it carries a significant cost implication. NICE now suggests that patients should exercise choice after completion of adjuvant treatment (including chemotherapy, and/or radiotherapy where indicated) for early breast cancer (i.e. patients should be asked where they would like follow up to be performed).3

The NICE guidance on improving outcomes in breast cancer specifies that hospital-based follow up (after treatment of early breast cancer) should be limited to a maximum of 3 years.24 A total of 40% of cancer networks failed to implement this and several other recommendations,25 and despite having guidelines to that effect, did not expect them to be followed (i.e. women are still being followed up for a period longer than 3 years).

Giving patients an unbiased choice on where to receive follow up is a difficult discussion, which depends on the patient's prior experiences of primary and secondary care practitioners and the expertise available in primary care. Local networks may commission a limited number of secondary care follow-up appointments, with the shortfall being made up in primary care. For many patients, follow up in primary care has many advantages including:

  • improved accessibility
  • shorter waiting times
  • easier travel links
  • continuity of care
  • preference for being seen by a primary care practitioner with whom they have had a relationship for many years.

Primary care practitioners are in a privileged position for many patients and may be better able to give the patient and their support group more psychological support. Follow up of patients with cancer is demanding and up-to-date knowledge is required to be able to answer queries and offer reassurance. If follow up is increasingly performed in primary care, practitioners will have to think about how they will provide this service and, importantly, how they will continue to be updated on an evolving subject. This may include having a dedicated cancer lead practitioner in each practice and having closer links with breast cancer secondary care services for education and/or experience.

Support in the community

Community health services provide invaluable support for patients and carers affected by breast cancer. This includes contacts for physical problems associated with the disease and its treatment, plus social and psychological support. Primary care data is not recorded or compiled in a way that allows analysis of the workload within primary care, but survey estimates are available. The 2007 Royal College of General Practitioners' Annual prevalence report revealed that an average practice of 10,000 patients has approximately 23 registered patients who consult their GP regarding breast cancer annually.26 Clinical follow up in the community should begin with an agreed written care plan from secondary care, which should be recorded by a named healthcare professional (or professionals), a copy sent to the primary care practitioner, and a personal copy given to the patient. This plan should include:

  • dates for review of any adjuvant therapy
  • details of surveillance mammography
  • signs and symptoms to look for and seek advice on
  • contact details for immediate referral to specialist care (usually a key worker such as a breast care nurse)
  • contact details for support services (e.g. support for patients with lymphoedema).

Increased follow up in primary care has many advantages for patients with breast cancer (as described previously). Primary care healthcare facilities need to consider their arrangements for dealing with an increase in demand for this service and for a potential increase in the level of care they are required to provide for these patients.


Conclusion

Patients diagnosed with breast cancer are being offered increasing choice about where to receive treatment, what surgery they wish to undergo, and the option of breast reconstruction. Primary care groups should be aware of the services offered in their region and also the quality of those services. Increasingly, follow up of patients with breast cancer will occur in primary care. Primary care practitioners should ensure that they have the skills and knowledge within their care group to provide follow-up support for these patients.

Key priorities for primary care
  • Breast screening is currently being trialled in 47–49 and 71–73 year-old women in England
  • Breast reconstruction should be discussed with all women who are offered mastectomy
  • Primary care practitioners must be aware of the quality (safety, effectiveness, and experience) of the reconstructive services available in their region to enable appropriate referral for a woman facing mastectomy
  • Elderly patients should receive conventional treatment for breast cancer irrespective of age
  • Patients should be offered a choice of where they wish to have their follow up: in primary or secondary care
  • Primary care practitioners will have increased responsibility for cancer follow up
  • Women receiving aromatase inhibitors or who have treatment-induced early menopause should undergo a DEXA bone scan
  • Hormone replacement therapy should not be offered to women with a history of breast cancer
  • Lower socio-economic groups are at risk of presenting with advanced breast cancer—focused education and examination is required in these patients
  • There should be increased interaction between primary and secondary care services.

DEXA=dual energy X-ray absorptiometry

  • Increasing numbers of women are developing breast cancer and surviving longer with it
  • NICE recommends that hospital-based follow up should continue for only 3 years (without recurrence)
  • GP commissioners will need to agree local follow-up protocols for breast cancer care with local specialists and cancer networks. This will need to define the role of GPs, clinical nurse specialists, and consultants, and where new or follow-up tariff is payable
  • There will be increased demands:
    • on prescribing budgets
    • for funding bone health protection for people receiving aromatase inhibitors
    • for dual energy X-ray absorptiometry scans
  • Tariff charges: breast surgery= £147 (new), £77 (follow up).a

awww.dh.gov.uk/paymentbyresults/

  1. Cancer Research UK. Breast cancer—A to Z. Available at: info.cancerresearchuk.org/utilities/atozindex/atoz-breast-cancer (accessed 15 April 2011).
  2. Office for National Statistics. Breast cancer: incidence rates rise, mortality rates fall. Available at www.statistics.gov.uk/CCI/nugget.asp?ID=575
  3. 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 nhs_accreditation
  4. National Institute for Health and Care Excellence, Centre for Clinical Practice. Review of clinical guideline (CG27)—referral guidelines for suspected cancer. NICE, 2011. Available at: www.nice.org.uk/guidance/CG27/ReviewDecision/pdf/English
  5. Willett A, Michell M, Lee M. Best practice diagnostic guidelines for patients presenting with breast symptoms. Breakthrough Breast Cancer, 2010. Available at: www.rcrbreastgroup.com/Documents/BBCDiagnosticGuidelines.pdf
  6. Royal College of Radiologists. Making the best use of clinical radiology services. Referral guidelines. 6th Edition. London: RCR, 2007.
  7. Department of Health. Improving outcomes: a strategy for cancer. January 2011. London: DH, 2011. Available at: www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyAndGuidance/DH_123371
  8. NHS Breast Cancer Screening Programme. Future developments in breast screening. Available at: www.cancerscreening.nhs.uk/breastscreen/future-developments.html (accessed 14 April 2011).
  9. Association of Breast Surgery at Baso 2009. Surgical guidelines for the management of breast cancer. Eur J Surg Oncol 2009; 35 (Suppl 1): 1–22.
  10. Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 2005; 365 (9472): 1687–1717.
  11. Suter T, Procter M, van Veldhuisen D et al. Trastuzumab-associated cardiac adverse events in the Herceptin Adjuvant Trial. J Clin Oncol 2007; 25 (25): 3859–3865.
  12. Petrelli F, Barni S. Tamoxifen added to radiotherapy and surgery for the treatment of ductal carcinoma in situ of the breast: a meta-analysis of 2 randomized trials. Radiother Oncol 2011 (Epub ahead of print).
  13. Arimidex, Tamoxifen, Alone or in Combination (ATAC) Trialists' Group, Forbes J, Cuzick J, Buzdar A et al. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 100-month analysis of the ATAC trial. Lancet Oncol 2008; 9 (1): 45–53.
  14. 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.
  15. Bines J, Oleske D, Cobleigh M. Ovarian function in premenopausal women treated with adjuvant chemotherapy for breast cancer. J Clin Oncol 1996; 14 (5): 1718?1729.
  16. Martin P, Yen S, Burnier A, Hermann H. Systemic absorption and sustained effects of vaginal estrogen creams. JAMA 1979; 242 (24): 2699–2700.
  17. Biglia N, Peano E, Sgandurra P et al. Low-dose vaginal estrogens or vaginal moisturizer in breast cancer survivors with urogenital atrophy: a preliminary study. Gynecol Endocrinol 2010; 26 (6): 404–412.
  18. NHS Information Centre. National mastectomy and breast reconstruction audit 2011. NHS Information Centre, 2011. Available at: www.ic.nhs.uk/services/national-clinical-audit-support-programme-ncasp/audit-reports/mastectomy-and-breast-reconstruction
  19. British Association of Plastic Reconstructive and Aesthetic Surgeons. Your guide to breast reconstruction. BAPRAS, 2010. Available at: www.bapras.org.uk (accessed 12th April 2011).
  20. Cancer Research UK. CancerStats. Breast cancer—UK. May 2009. Available at: publications.cancerresearchuk.org/epages/crukstore.sf/en_GB/?ObjectPath=/Shops/crukstore/Products/CSBREA09
  21. Traa M, Meijs C, de Jongh M et al. Elderly women with breast cancer often die due to other causes regardless of primary endocrine therapy or primary surgical therapy. Breast 2011; Feb 14 [Epub:ahead of print]. www.ncbi.nlm.nih.gov/pubmed/21324698
  22. Bouchardy C, Rapiti E, Fioretta G et al. Undertreatment strongly decreases prognosis of breast cancer in elderly women. J Clin Oncol 2003; 21 (19): 3580–3587.
  23. Department of Health. Equity and excellence: liberating the NHS. London: DH, 2010. Available at: www.dh.gov.uk/en/Healthcare/LiberatingtheNHS/index.htm
  24. National Institute for Clinical Excellence. Improving outcomes in breast cancer. London: NICE, 2002. Available at: www.nice.org.uk/guidance/CSGBC
  25. National Collaborating Centre for Cancer . Early and locally advanced breast cancer: diagnosis and treatment. London: NCCC, 2009. Available at: www.nice.org.uk/guidance/CG80/Guidance/pdf/English nhs_accreditation
  26. Birmingham Research Unit. Weekly returns service annual prevalence report 2007. Royal College of General Practitioners, 2007. Available at: www.rcgp.org.uk/clinical_and_research/rsc/annual_prevalence.aspx G