It has long been recognised that family history is a risk factor for breast cancer.1 In the past decade some of the genes underlying familial breast cancer have been identified, and cancer genetic services have developed to provide counselling and genetic testing for individuals with a family history of breast and other familial cancers.
NICE has recently published clinical guidelines for the care of women with a family history of breast cancer, to promote consistent advice and equitable access to mammography and genetic services across England and Wales.
A GP with an average list has approximately one consultation per month about family history of breast cancer.2 Patients and GPs tend to overestimate the risk of breast cancer associated with a family history.3,4 Between a quarter and a third of referrals for women with a family history of breast cancer are for women whose risk is not significantly raised. In a practice list of 2000 one would expect 103 women with a family history of breast cancer, of whom 94 would not be at significantly increased risk.5
The dilemma therefore for primary care lies in determining who has a significant family history and who can be reassured about their risk.
Clinical Guidelines and Evidence Review for the Classification and Care of Women at Risk of Familial Breast Cancer was developed using standard NICE guideline development methods by a multidisciplinary group which included cancer geneticists, oncologists, a genetics nurse, patient representatives, a psycho-oncologist and a GP.
Literature search strategies were informed by a detailed patient pathway to identify key points of intervention. The scope of the guideline meant that it was not feasible to conduct systematic reviews of all the areas it would cover. However, a systematic approach to identification and a narrative synthesis of the evidence was conducted.
The evidence reviewed to inform recommendations included few randomised trials. This partly reflects the stage of development of research into familial breast cancer but also the fact that many of the recommendations are based on a wider range of research methods than those employed in the assessment of a new drug, including genetic, epidemiological and qualitative studies.
Thus, the majority of the guideline's recommendations are graded C and D (see Table 1, below, for evidence grading scheme). Several recommendations are grade D since they reflect perceived best clinical practice for which there is little evidence to inform decisions, for example taking a family history.
|Table 1: Classification of evidence and grading of recommendations|
|Reproduced from NICE Clinical Guideline 14. Clinical Guidelines and Evidence Review for the Classification and Care of Women at Risk of Familial Breast Cancer by kind permission of NICE|
An interesting methodological issue is the grading of the 2001 paper by the Collaborative Group on Hormonal Factors in Breast Cancer 6 as level III evidence when it is a form of metaanalysis of primary data from all epidemiological studies examining breast cancer risk factors.
The system of care for women with a family history of breast cancer is based around the risk assessment criteria in the guideline (Figure 1, below).These were developed on the basis of the Collaborative reanalysis 6 and the Claus model, a specific breast cancer risk model.7 The criteria aim to categorise women into three levels of risk which determine their management.
|Figure 1: Algorithm for the primary care management of women at risk of familial breast cancer|
|Reproduced from NICE Clinical Guideline 14. Clinical Guidelines and Evidence Review for The Classification and Care of Women at Risk of Familial Breast Cancer by kind permission of NICE|
The cut-off points were developed by consensus and are based on the following:
- Women at or near the population risk of breast cancer (i.e. 10-year risk of less than 3% between 40 and 50 years and lifetime risk of less than 17%) are cared for in primary care.
- Women at moderate risk of breast cancer (i.e. 10-year risk of 3-8% between 40 and 50 years or lifetime risk of 17-29%) are cared for in secondary care (breast unit).
- Women at high risk of breast cancer (i.e. 10-year risk greater than 8% between 40 and 50 years or lifetime risk of 30% or greater or at least a 20% risk of carrying a faulty gene for breast cancer) are managed in tertiary care (regional genetics clinic).
A woman whose 10-year breast cancer risk at age 40 years is 3% has the same level of risk as a woman in the general population at age 50 years, when women are eligible to enter the NHS Breast Screening Programme. This is the basis for determining the moderate risk cut-off.
The high risk cut-off is based partly on breast cancer risk but also on risk of carrying a mutation in a gene predisposing to breast cancer, reflecting a pragmatic approach to deciding who should be offered genetic testing.
In primary care any woman with breast symptoms or concerns about breast cancer risk should have a family history of first and second degree relatives taken, considering maternal and paternal history separately (grade D).
The guideline also recommends taking a family history before prescribing oral contraceptives to women over 35 years or hormone replacement to account for the combined familial and oestrogen-related breast cancer risks (grade D).
The family history of breast cancer does not meet established criteria for a screening tool and so health professionals should not actively identify women at increased risk (grade D).
Women can be managed in primary care if the family history shows only one first or second degree relative diagnosed with breast cancer after the age of 40 years, provided none of the following are present (grade D):
- Bilateral or male breast cancer
- Ovarian cancer
- Sarcoma at age less than 45 years
- Childhood adrenocortical carcinoma
- Two or more affected relatives on the paternal side
- Complicated patterns of multiple cancers at a young age
- Jewish ancestry (1-2% of Jews carry specific mutations in BRCA1 or BRCA2).8
Women aged 40-49 years meeting moderate risk criteria should be offered referral to the breast unit for annual mammography (grade D). There is evidence from a number of studies that mammography is effective in detecting breast cancers in women with a family history of breast cancer.9 However, there is no evidence that breast screening reduces mortality from breast cancer in this group of women.
Thus women should be provided with written information about the benefits and potential risks of mammography, for example reduced sensitivity and chances of false positives (grade D).
The small proportion of women who meet high risk criteria should be referred from the breast unit to the regional genetics clinic for genetic counselling (grade C). A recent metaanalysis of genetic counselling for familial cancer demonstrated improvements in knowledge and risk perception without any negative emotional effects.10
Women at high risk should have access to genetic testing which should usually start by testing an affected individual in the family to identify a mutation in the relevant gene, such as BRCA1, BRCA2 or TP53 (grade D).
Genetic testing can have psychological benefits, especially for those identified as non-carriers, and can inform women's decisions about the management of their risk (level III).11
Women at high risk should be counselled about risk reducing surgery such as bilateral mastectomy and oophorectomy (grade D). Bilateral mastectomy reduces the risk of breast cancer by 90% 12 and bilateral oophorectomy by 50-75% in women at high and moderate risk 13 (level III).
Although a meta-analysis of trials of tamoxifen demonstrated a 38% reduction in breast cancer incidence in women at moderate and high risk (level 1a),14 tamoxifen is not licensed in this country for breast cancer prophylaxis and so the guideline makes no recommendation about its use.
The guideline recommends that women at all levels of care should have access to consistent written information about breast cancer risks (grade D). Thus women in primary care should be informed about breast awareness and given lifestyle advice which should cover HRT, oral contraceptives, alcohol, breastfeeding, and family size and timing 15, 16 (all grade III evidence), and told to return if details of their family history change.
This is the first NICE guideline to attempt to integrate advances in genetic medicine into primary care. Successful national implementation will require adequate funding for mammography in women at moderate risk and the establishment of familial breast cancer services in secondary care with a designated contact for primary care to discuss more complex cases.
On the basis of randomised controlled studies in primary care the guideline also recommends access to educational materials 17 (level 1b) and computer decision support 18 (level III) to implement this relatively complex guideline in primary care and support the important role that GPs play in advising women about their risk of breast cancer.
NICE Clinical Guideline 14. Clinical Guidelines and Evidence Review for The Classification and Care of Women at Risk of Familial Breast Cancer can be downloaded from the NICE website: www.nice.org.uk
- Emery J, Lucassen A, Murphy M. Common hereditary cancers and implications for primary care. Lancet 2001; 358: 56-63.
- Hyland F, Kinmonth AL, Marteau TM et al. Raising concerns about family history of breast cancer in primary care consultations: prospective, population based study. Women's Concerns Study Group. Br Med J 2001; 322: 27-8.
- Rose PW,Watson E, Yudkin P et al. Referral of patients with a family history of breast/ovarian cancer GPs' knowledge and expectations. Fam Pract 2001; 18: 487-90.
- Watson M, Lloyd S, Davidson J et al.The impact of genetic counselling on risk perception and mental health in women with a family history of breast cancer. Br J Cancer 1999; 79: 868-74.
- Report of the Consensus Meeting on the Management of Women with a Family History of Breast Cancer. Wellcome Trust. 12 January 1998. http://www.phgu.org.uk/info_database/public_documents/breastcaconsen.html
- Collaborative Group on Hormonal Factors in Breast Cancer. Familial breast cancer: collaborative reanalysis of individual data from 52 epidemiological studies including 58,209 women with breast cancer and 101,986 women without the disease. Lancet 2001; 358: 1389-99.
- Claus EB, Schildkraut JM, Thompson WD, Risch NJ. The genetic attributable risk of breast and ovarian cancer. Cancer 1996; 77: 2318-24.
- Fodor FH,Weston A,Bleiweiss IJ et al.Frequency and carrier risk associated with common BRCA1 and BRCA2 mutations in Ashkenazi Jewish breast cancer patients. Am J Hum Genet 1998; 63:45-51.
- Myles J,Duffy S, Nixon R et al. Initial results of a study into the effectiveness of breast cancer screening in a population identified to be at high risk. Rev Epidemiol Sante Publique 2001;49: 471-5.
- Braithwaite D,Emery J,Walter F,Prevost AT,Sutton S.Psychological impact of genetic counseling for familial cancer: a systematic review and metaanalysis. J Natl Cancer Inst 2004; 96: 122-33.
- Lerman C, Narod S, Schulman K et al. BRCA1 testing in families with hereditary breast-ovarian cancer.A prospective study of patient decision making and outcomes. JAMA 1996; 275: 1885-92.
- Hartmann LC,Schaid DJ,Woods JE et al. Efficacy of bilateral prophylactic mastectomy in women with a family history of breast cancer. N Engl J Med 1999; 340: 77-84.
- Rebbeck TR, Lynch HT, Neuhausen SL et al. Prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations. N Engl J Med 2002;346:1616-22.
- Cuzick J, Powles T,Veronesi U et al. Overview of the main outcomes in breast-cancer prevention trials. Lancet 2003; 361: 296-300.
- Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and hormone replacement therapy: collaborative reanalysis of data from 51 epidemiological studies of 52,705 women with breast cancer and 108,411 women without breast cancer. Lancet 1997; 350: 1047-59 [published erratum appears in Lancet 1997; 350: 1484].
- Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and breastfeeding: collaborative reanalysis of individual data from 47 epidemiological studies in 30 countries, including 50302 women with breast cancer and 96973 women without the disease. Lancet 2002; 360: 187-95.
- Watson E, Clements A, Lucassen A et al. Education improves general practitioner (GP) management of familial breast/ovarian cancer: findings from a cluster randomised controlled trial. J Med Genet 2002;39: 779-81.
- Emery J,Walton R, Murphy M et al. Computer support for interpreting family histories of breast and ovarian cancer in primary care: comparative study with simulated cases. Br Med J 2000; 321: 28-32.