Breast cancer - managing FH

Source:
Clinical Knowledge Summaries
Publication date:
01 December 2018

Abstract

Breast cancer - managing FH Last revised in December 2018 Summary Back to topBreast cancer - managing FH: Summary A family history of breast cancer is a strong risk factor for developing the disease. The risk increases with the number of relatives affected and the age at diagnosis of the relative (the younger the age of diagnosis the greater the risk), and is modified by other breast cancer risk factors, including age at menopause, parity, oral contraception, hormone replacement therapy (HRT), and breastfeeding. People without a personal history of breast cancer can be managed in primary care if they have only one first-degree relative (mother, father, daughter, son, sister, or brother) or second-degree relative (grandparents, grandchildren, aunt, uncle, niece, nephew, half-sister, or half-brother) diagnosed with breast cancer when over 40 years of age, provided that none of the following are present in the family history:Bilateral breast cancer.Male breast cancer.Ovarian cancer.Jewish ancestry.Sarcoma in a relative younger than 45 years of age.Glioma or childhood adrenal cortical carcinomas.Complicated patterns of multiple cancers at a young age.Two or more relatives with breast cancer on the father's side of the family.Secondary care referral is indicated for people without a personal history of breast cancer who have any of the following:One first-degree female relative diagnosed with breast cancer under the age of 40 years.One first-degree male relative diagnosed with breast cancer at any age.One first-degree relative with bilateral breast cancer where the first primary was diagnosed under the age of 50 years.Two first-degree relatives, or one first-degree and one second-degree relative, diagnosed with breast cancer at any age.One first-degree or second-degree relative diagnosed with breast cancer at any age and one first-degree or second-degree relative diagnosed with ovarian cancer at any age (one of these should be a first-degree relative).Three first-degree or second-degree relatives diagnosed with breast cancer at any age.Specialist advice should be sought if:Any of the following are present in the family history in addition to breast cancers in relatives not fulfilling the above criteria:  bilateral breast cancer, male breast cancer, ovarian cancer, Jewish ancestry, sarcoma in a relative younger than 45 years of age, glioma or childhood adrenal cortical carcinomas, complicated patterns of multiple cancers at a young age, and two or more relatives with breast cancer on the father's side of the family.There is uncertainty about whether or not to refer.The person is not sufficiently reassured by the information provided.If a faulty gene (for example BRCA1 or BRCA2) has been identified in the family, direct referral to a specialist genetics service should be offered.Appropriate information and support should be provided to the person, including:Information on breast cancer risk, breast awareness, and the NHS Breast Screening Programme.Lifestyle advice regarding breast cancer risk, including advice on alcohol, weight, physical exercise, and smoking cessation (where appropriate). Advice on hormonal contraception and HRT. Have I got the right topic? Back to topHave I got the right topic? From age 16 years onwards.This CKS topic is based on the National Institute for Health and Care Excellence (NICE) guideline Familial breast cancer: classification, care and managing breast cancer and related risks in people with a family history of breast cancer [NICE, 2017].This CKS topic covers the primary care management of women and men who are concerned that their family history indicates an increased risk of breast cancer.This CKS topic does not cover secondary care or tertiary care management of women or men with concerns about breast cancer.There are separate CKS topics on Breast cancer - recognition and referral, Breast screening, Gynaecological cancers - recognition and referral, and Menopause.The target audience for this CKS topic is healthcare professionals working within the NHS in the UK, and providing first contact or primary healthcare. How up-to-date is this topic? Back to topHow up-to-date is this topic? Back to top Changes Changes December 2018 — reviewed. A literature search was conducted in December 2018 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of this topic. No major changes to clinical recommendations have been made. Back to top Previous changes Previous changes December 2013 — reviewed. A literature search was conducted in August 2013 to identify evidence-based guidelines, UK policy, systematic reviews, and key RCTs published since the last revision of this topic. Recommendations on who to refer have been changed to reflect the most recent guidance from the National Institute for Health and Care Excellence (2013).June 2012 — minor update. Recommendation and basis reworded in the Advice on hormonal contraception node to clarify that women with a family history of breast cancer can use any combined hormonal contraceptive (CHC), not just combined oral contraceptives (COC). Also, in women who are known carriers of a gene mutation, all CHCs (not just COCs) should be avoided.September 2011 — minor update. Information added about the roll out of the NHS breast screening programme across England to include women aged 47 to 49 years and women aged 71 to 73 years. Issued November 2011.November 2009 — correction to age range in Advice on risk reduction. Issued in November 2009.July to November 2009 — converted from CKS guidance to CKS topic structure. The evidence base has been reviewed in detail, and recommendations are more clearly justified and transparently linked to the supporting evidence. There are no major changes to the recommendations.September 2008 — minor correction to the Changes section. Issued in September 2008.May 2007 — updated. The new advice on magnetic resonance imaging (MRI) for breast cancer screening from the recent update of the NICE guideline on Familial breast cancer has been included. Issued in May 2007.October 2005 — minor technical update. Issued in November 2005.August 2004 — written. Validated in November 2004 and issued in February 2005. Back to top Update Update Back to top New evidence New evidence Evidence-based guidelinesNo new evidence-based guidelines since 1 December 2018.HTAs (Health Technology Assessments)No new HTAs since 1 December 2018.Economic appraisalsNo new economic appraisals relevant to England since 1 December 2018.Systematic reviews and meta-analysesNo new systematic reviews since 1 December 2018.Primary evidenceNo new randomized controlled trials published in the major journals since 1 December 2018. Back to top New policies New policies No new national policies or guidelines since 1 December 2018. Back to top New safety alerts New safety alerts No new safety alerts since 1 December 2018. Back to top Changes in product availability Changes in product availability No changes in product availability since 1 December 2018. Goals and outcome measures Back to topGoals and outcome measures Back to top Goals Goals To support primary healthcare professionals to:Make an assessment of a person's risk of developing breast cancer.Refer appropriately to secondary care or other specialist service.Provide appropriate information and advice to the person. Back to top Outcome measures Outcome measures No outcome measures were found during the review of this topic. Back to top Audit criteria Audit criteria No audit criteria were found during the review of this topic. Back to top QOF indicators QOF indicators No QOF indicators were found during the review of this topic. Back to top QIPP - Options for local implementation QIPP - Options for local implementation No QIPP indicators were found during the review of this topic. Back to top NICE quality standards NICE quality standards No NICE quality standards were found during the review of this topic. Background information Back to topBackground information Back to top Definition What is it? Familial breast cancer occurs in women with more family members with breast or related cancers than would have been expected by chance alone. It may be that members of such a family carry genes that cause or, more likely, contribute to the development of breast cancer [National Collaborating Centre for Cancer, 2013].A family history of breast cancer is a strong risk factor for developing the disease [Emery et al, 2001; National Collaborating Centre for Cancer, 2013; Cancer Research UK, 2018a].The risk increases with the number of relatives affected and the age at diagnosis of the relative (the younger the age of diagnosis the greater the risk), and is modified by other breast cancer risk factors, including age at menopause, parity, oral contraception, hormone replacement therapy, and breastfeeding.A person's risk can be calculated based on their family history by the use of specialist computer programmes in secondary care, or in specialist genetic clinics [Collaborative Group on Hormonal Factors in Breast Cancer, 2001; National Collaborating Centre for Cancer, 2013].It is important to note that [National Collaborating Centre for Cancer, 2013]:Most women will never develop breast cancer and most of those who do will not have familial breast cancer. Given the high prevalence of breast cancer, many people have a relative with the disease, but this may be due to chance rather than to genetic or shared lifestyle factors.Most women with a family history of breast cancer are not at a substantially increased risk of breast cancer. Back to top Prevalence How common is it? Breast cancer is the most common cancer in the UK, accounting for 15% of all new cancer cases [Cancer Research UK, 2018b].It is the most common cancer in women in the UK, accounting for nearly 1 in 3 (31%) of all new female cancer cases.In 2015, there were 55,122 cases diagnosed in the UK (54,751 in females and 371 in males).In the UK, the lifetime risk of developing breast cancer is about 15% (1 in 7) for women born after 1960 [Cancer Research UK, 2018b], and less than 0.1% for men [National Collaborating Centre for Cancer, 2013]. However [National Collaborating Centre for Cancer, 2013]:People with a family history of breast, ovarian, or a related cancer might have a higher lifetime risk than the general population. The lifetime risk of breast cancer in women with a gene mutation is substantially increased compared to the general population.The incidence of breast cancer is strongly related to age, with the highest incidence rates being in older people. In the UK [Cancer Research UK, 2018b]:In 2013–2015, on average each year 25% of new cases were in people aged 75 years and older.Age-specific incidence rates rise steadily from around age 30–34 years and more steeply from around age 70–74 years. The highest rates are in women aged 85–89 years and in men aged over 90 years.Incidence rates are significantly lower in men than women in a number of (mainly older) age groups. The gap is widest at age 45–49 years, when the age-specific incidence rate is 423 times lower in males than females.Between 6–19% of women with breast cancer will have a family history of the disease [National Collaborating Centre for Cancer, 2013]. Inherited mutations in specific genes, including BRCA1and BRCA2, account for about 5% of all breast cancer cases [National Collaborating Centre for Cancer, 2013]. Back to top Genetic risk factors What is known about the genetic risk factors? A hereditary cancer syndrome is a genetic predisposition to certain types of cancer.It is caused by a germline mutations, inherited from either parent, resulting in a significantly elevated risk of cancer compared with that of the general population that does not have a mutation in a cancer susceptibility gene [ACOG, 2015; Paluch-Shimon, 2016].Onset at an early age, a high incidence of bilateral disease, and an association with other malignancies (such as ovarian cancer) usually characterize hereditary breast cancer [Hill et al, 1997; ACOG, 2015].Most inherited cases (more than 90%) of breast (and ovarian) cancer are associated with mutations in two genes: BRCA1 and BRCA2 [Paluch-Shimon, 2016].The estimated lifetime risk of breast cancer in people with a BRCA1 or BRCA2 mutation varies, depending on the population studies. In general:In women with BRCA1 mutation, the estimated lifetime risk of breast cancer is 65–85% [National Collaborating Centre for Cancer, 2013; Gabai-Kapara, 2014; RCOG, 2015; Paluch-Shimon, 2016]. The estimated lifetime risk of ovarian cancer in these women is 40–63% [National Collaborating Centre for Cancer, 2013; RCOG, 2015].In women with BRCA2 mutation, the estimated lifetime risk of breast cancer is 40–85% [National Collaborating Centre for Cancer, 2013; Gabai-Kapara, 2014; RCOG, 2015; Paluch-Shimon, 2016]. The estimated lifetime risk of ovarian cancer in these women is 10–27% [National Collaborating Centre for Cancer, 2013; RCOG, 2015].In men with a BRCA1 or BRCA2 mutation, there is an estimated lifetime risk of breast cancer of 1.2% to less than 8%, respectively, and a doubling of prostate cancer risk [Paluch-Shimon, 2016].Over 2000 different BRCA1/2 gene mutations have been identified, and in some populations, founder mutations (that is, the initial mutation in a family or population) are the most prevalent ones [Paluch-Shimon, 2016].For example, the Ashkenazi Jewish community has three founder mutations, two in BRCA1 and one in BRCA2, which account for most of inherited cancer risk due to BRCA1 and BRCA2 [National Collaborating Centre for Cancer, 2013; Gabai-Kapara, 2014; Paluch-Shimon, 2016]. In this population, 2.5% of people carry one of these three mutations, which account for 11% of breast cancer and 40% of ovarian cancer cases [Gabai-Kapara, 2014]. Founder mutations have also been described in Northern, Western, and Eastern Europe [Paluch-Shimon, 2016].Other gene mutations identified include:TP53 mutation on chromosome 17 — most women with this mutation develop breast cancer by 50 years of age. TP53 is also associated with sarcomas of childhood, leukaemias, adrenocortical carcinomas, and brain tumours (Li–Fraumeni syndrome) [Hill et al, 1997; Emery et al, 2001; National Collaborating Centre for Cancer, 2013].PTEN gene (Cowden's syndrome) — this predisposes to breast, thyroid, and uterine cancers, and hamartomatous lesions of the skin [Emery et al, 2001].ATM, CHEK2, BRIP1, and PALB2 genes — these confer moderate risk of breast cancer [Ahmed et al, 2009; National Collaborating Centre for Cancer, 2013].It is important to emphazise that [National Collaborating Centre for Cancer, 2013]:Some people may carry the abnormal gene without developing cancer themselves.Most women who have a family history of breast cancer do not have a specific identifiable gene mutation. Some of these family histories will be due to lower-penetrance genes not yet discovered. Management Back to topManagement Scenario: Breast cancer - managing FH: covers the primary care management of women and men who are concerned that their family history indicates an increased risk of breast cancer. Back to top Scenario: Breast cancer - managing FH Scenario: Breast cancer - managing family history From age 16 years onwards. Back to top Taking the family history When and how should I take a family history? Take a family history of breast cancer when:A person has concerns about their family history of breast cancer.A person has breast symptoms.It is clinically relevant, for example:In women over 35 years of age using an oral contraceptive pill.In women being considered for long-term hormone replacement therapy (HRT).Document a family tree including the person and their first-degree relatives (mother, father, daughter, son, sister, and brother) and second-degree relatives (grandparents, grandchildren, aunt, uncle, niece, nephew, half-sister, and half-brother).Ask about:All cancer diagnoses (including breast cancer).People in whom a faulty gene (such as BRCA1, BRCA2, or TP53) has been identified.Age at diagnosis.Presence of bilateral disease.Male breast cancer.Multiple cases in the family (particularly on one side).Jewish ancestry.Other related early onset tumours, such as ovarian, pancreatic, and prostate cancer, sarcoma, glioma, and adrenal carcinoma. Back to top Basis for recommendation Basis for recommendation These recommendations are based on the National Institute for Health and Care Excellence (NICE) guideline Familial breast cancer: classification, care and managing breast cancer and related risks in people with a family history of breast cancer [NICE, 2017]. NICE commissioned the National Collaborating Centre for Cancer to produce the evidence review and develop the full NICE clinical guidelines [National Collaborating Centre for Cancer, 2013]. When to take a family history for breast cancerNICE recommends that if a person has breast symptoms or has concerns about relatives with breast cancer, a first- and second-degree family history should be taken in primary care. A family history allows a classification of risk to be made that will direct further management decisions [NICE, 2017].NICE found [National Collaborating Centre for Cancer, 2013]:Four observational studies that assessed the accuracy of the family history provided by women (735 women with breast cancer and 251 women without breast cancer) and concluded that family histories were generally reliable.A review of five case studies that showed the importance of verifying the history.One longitudinal, qualitative study of 46 women attending a UK genetics clinic for familial breast/ovarian cancer which found that poor communication between family members may impede the collection of family history.Criteria used to determine risk of breast cancerNICE reviewed the evidence for risk factors for breast cancer, including evidence from epidemiological studies, and concluded that [National Collaborating Centre for Cancer, 2013]:The risk of breast cancer in women with an affected first-degree relative is approximately twice the risk in other women.The risk of breast cancer increases with the number of affected relatives, and increases as the age of those affected decreases. Only a minority of this increase in risk is due to the presence of gene mutations, such as BRCA1, BRCA2, or TP53.The presence of other malignancies (such as ovarian, prostate, pancreatic cancer) or male breast cancer in a family in addition to female breast cancer increases the likelihood of having a BRCA1/2 mutation.The presence of early-onset sarcoma and childhood cancers, such as adrenal carcinoma, increases the likelihood of having a TP53 mutation. Back to top Who to refer How do I assess a woman's risk of breast cancer and need for referral? People without a personal history of breast cancer can be managed in primary care if they have only one first-degree relative (mother, father, daughter, son, sister, or brother) or second-degree relative (grandparents, grandchildren, aunt, uncle, niece, nephew, half-sister, or half-brother) diagnosed with breast cancer when over 40 years of age, provided that none of the following are present in the family history:Bilateral breast cancer.Male breast cancer.Ovarian cancer.Jewish ancestry.Sarcoma in a relative younger than 45 years of age.Glioma or childhood adrenal cortical carcinomas.Complicated patterns of multiple cancers at a young age.Two or more relatives with breast cancer on the father's side of the family.Offer referral to secondary care to people without a personal history of breast cancer who have any of the following:One first-degree female relative diagnosed with breast cancer under the age of 40 years.One first-degree male relative diagnosed with breast cancer at any age.One first-degree relative with bilateral breast cancer where the first primary was diagnosed under the age of 50 years.Two first-degree relatives, or one first-degree and one second-degree relative, diagnosed with breast cancer at any age.One first-degree or second-degree relative diagnosed with breast cancer at any age and one first-degree or second-degree relative diagnosed with ovarian cancer at any age (one of these should be a first-degree relative).Three first-degree or second-degree relatives diagnosed with breast cancer at any age.Seek specialist advice from secondary care or a specialist genetics service if:Any of the following are present in the family history in addition to breast cancers in relatives not fulfilling the above criteria:Bilateral breast cancer.Male breast cancer.Ovarian cancer.Jewish ancestry.Sarcoma in a relative younger than 45 years of age.Glioma or childhood adrenal cortical carcinomas.Complicated patterns of multiple cancers at a young age.Two or more relatives with breast cancer on the father's side of the family.There is uncertainty about whether or not to refer.The person is not sufficiently reassured by the information provided.Refer directly to a specialist genetics service if a high-risk predisposing gene mutation (such as BRCA1, BRCA2, or TP53) has been identified.Give appropriate information and support. Back to top Basis for recommendation Basis for recommendation These recommendations are based largely on the National Institute for Health and Care Excellence (NICE) guideline Familial breast cancer: classification, care and managing breast cancer and related risks in people with a family history of breast cancer [NICE, 2017]. NICE commissioned the National Collaborating Centre for Cancer to produce the evidence review and develop the full NICE clinical guidelines [National Collaborating Centre for Cancer, 2013]. NICE reviewed the evidence for risk factors for breast cancer, including evidence from epidemiological studies, and concluded that:Women with an affected first-degree relative have approximately twice the risk of breast cancer compared with other women.The risk of breast cancer increases with the number of affected relatives, and increases as the age of those affected decreases. Only a minority of this increase in risk is due to the presence of gene mutations, such as BRCA1, BRCA2, or TP53.The presence of other malignancies (such as ovarian, prostate, pancreatic cancer) or male breast cancer in a family in addition to female breast cancer increases the likelihood of having a BRCA1 or BRCA2 mutation.The presence of early-onset sarcoma and childhood cancers, such as adrenal carcinoma, increases the likelihood of having a TP53 mutation.The Ashkenazi Jewish community has three founder mutations, two in BRCA1 and one in BRCA2, which account for most of the inherited cancer risk due to BRCA1 and BRCA2 [National Collaborating Centre for Cancer, 2013; Gabai-Kapara, 2014; Paluch-Shimon, 2016]. In this population, 2.5% of people carry one of these three mutations, which account for 11% of breast cancer and 40% of ovarian cancer cases [Gabai-Kapara, 2014]. Back to top Information and support What information and support should I provide? For all people:Provide information on breast cancer risk, including information on family history and genetic risk factors.The leaflet Family history, genes and breast cancer published by Breast Cancer Care (www.breastcancercare.org.uk) explains how family history can affect breast cancer risk. It includes information on how risk is assessed, the options for managing risk, and genetic testing.Explain the principles of breast awareness.This is a process whereby the person becomes familiar with their own breasts by looking and feeling and reporting promptly any changes, such as discomfort or pain; lumps, thickening, or bumpy areas; nipple changes or discharge; or changes in the appearance of the breast, such as in the shape or the presence of dimpling of the skin.The leaflet Be breast aware published by Public Health England (PHE, www.gov.uk) can be used by healthcare professionals to explain to women how to be aware of changes in their breasts. Give lifestyle advice regarding breast cancer risk.Advise on reduction of alcohol intake, maintenance of a healthy weight, increasing physical exercise, and smoking cessation (where appropriate).Advise women that the following may reduce the risk of breast cancer: having a first child at a younger age, having a large family, and breastfeeding.Give women appropriate information on oral contraceptives and hormone replacement therapy.Provide details for sources of support and information, including local and national support groups. The National Hereditary Breast Cancer Helpline (01629 813000, available 8am–10pm) provides help and information to those concerned about their family history of breast cancer.Cancer Research UK provides cancer information to the public, including leaflets on prevention, diagnosis, and understanding cancer and information on breast cancer and general support organizations.CancerNetUK provides information and links to various cancer support groups throughout the UK as well as other European and English speaking countries. Provide other useful advice and information, for example:Advise that they can bring a family member/ friend with them to appointments.Provide details of any trials or studies that may be appropriate.For people who are being referred to secondary care or a specialist genetic clinic, also provide information on:The risk assessment exercise that will take place. Advise the person on how to obtain a comprehensive family history if required.Potential outcomes, depending on the outcome of the risk assessment (including referral back to primary care, management within secondary care, or referral to a specialist genetics service) and what may happen at each level.For people who are not being referred, also advise that they should come for review with their GP if:There is a change in family history (as their risk of breast cancer may have altered).Breast symptoms develop.Encourage attendance at the local NHS Breast Screening Programme for women 50 years of age and older.The NHS Breast Screening Programme is a rolling scheme which invites women aged 50–70 years in England, Northern Ireland, Scotland, and Wales who are registered with a GP for a routine mammogram every three years.  Women at increased risk of breast cancer (for example those with a strong family history) may be eligible for breast screening before 50 years of age.For further information, see the CKS topic on Breast screening. Back to top Basis for recommendation Basis for recommendation Explaining the principles of breast awarenessEvidence from a Cochrane systemtic review (search date: October 2007) did not suggest a beneficial effect of breast screening by either self-examination or clinical examination, but suggested increased harms in terms of increased numbers of benign lesions identified and an increased number of biopsies performed [Kosters and Gotsche, 2003]. However, there is a consensus among cancer geneticists supporting its use to help early detection in women who are at increased risk because of a family history of breast cancer.Measures to reduce the risk of breast cancerThese recommendations are based largely on the National Institute for Health and Care Excellence (NICE) guideline Familial breast cancer: classification, care and managing breast cancer and related risks in people with a family history of breast cancer  [NICE, 2017]. NICE commissioned the National Collaborating Centre for Cancer to produce the evidence review and develop the full NICE clinical guidelines [National Collaborating Centre for Cancer, 2013]. AlcoholNICE examined five meta-analyses, one systematic review, and one cohort study and concluded that there is no good evidence to suggest that the risk from drinking alcohol is any different for women with a family history of breast cancer compared with women as a whole. Women who drink a moderate amount of alcohol have a slightly higher risk of breast cancer than those who abstain.A subsequent case-controlled study investigated women with BRCA1 or BRCA2 mutations who had a history of breast cancer (cases [n = 195 and 128, respectively]) or did not have a history of breast cancer (controls [n = 302 and 179, respectively]) [McGuire et al, 2006]. No positive association was found between alcohol intake and the risk of breast cancer in women with either BRCA1 or BRCA2 mutations.WeightNICE found evidence that a high body mass index is associated with a clinically significant increase in postmenopausal breast cancer risk in the general population.Physical activityNICE reviewed the evidence and concluded that moderate physical exercise is associated with a decreased risk of breast cancer in the general population.Smoking cessationNICE found conflicting evidence for an association between smoking and breast cancer but advises that women should be advised not to smoke, in line with current health advice.Menstrual/reproductive factorsAfter reviewing the available limited evidence, NICE concluded that the risk of breast cancer is:Increased by a late menopause (55 years of age or older), older age at first birth, and early menarche.Decreased by pregnancy, with increasing numbers of pregnancies conferring greater risk reduction.However, in women who carry mutations in BRCA1 or BRCA2:An analysis of data from a cohort study of 1601 women (1187 with a BRCA1 mutation and 414 women with a BRCA2 mutation) found no association between the age of either the menarche or the menopause on breast cancer risk [Chang-Claude et al, 2007].There is conflicting evidence about whether younger age at first birth alters the risk of breast cancer, but there is evidence that increased parity offers protection [Andrieu et al, 2006; Antoniou et al, 2006; Kotsopoulos et al, 2007].BreastfeedingAfter reviewing the available evidence (one meta-analysis, one systematic review, and a collaborative group re-analysis of individual data from 47 epidemiological studies), NICE concluded that breastfeeding confers a small protective effect on the risk of breast cancer.According to Cancer Research UK [Cancer Research UK, 2018a]:Alcohol drinking causes 8% of breast cancer cases in the UK.Overweight and obesity cause 8% of breast cancer cases in the UK.Breast cancer risk is 13–25% lower in the most active (including recreational and household activity) women compared with the least active women. Breast cancer risk decreases by 5% for every 2 hours per week increment in recreational activity (moderate and vigorous). Light-intensity activity may be insufficient to reduce breast cancer risk.Breast cancer risk is 7–13% higher in current smokers, and 6–9% higher in former smokers, compared with people who have never smoked; however, confounding by alcohol is possible. Breast cancer risk among BRCA1 mutation carriers is not associated with smoking, but breast cancer risk among BRCA2 mutation carriers is higher in people who smoke.Post-menopausal hormones cause 2% of breast cancer cases in the UK.Not breastfeeding causes 5% of breast cancer cases in the UK.Oral contraceptives cause fewer than 1% of breast cancer cases in the UK.Breast screeningFor detailed information and evidence behind the NHS Breast Screening Programme, see the CKS topic on Breast screening. Back to top Advice on hormonal contraception Which hormonal contraception can be considered? For women with a family history of breast cancer, the following may, therefore, be used without restriction (UKMEC category 1):The copper-bearing intrauterine device (Cu-IUD). For more information, see the CKS topic on Contraception - IUS/IUD.The levonorgestrel-releasing intrauterine system (LNG-IUS, for example, Mirena®). For more information, see the CKS topic on Contraception - IUS/IUD.Etonogestrel-only implant (Nexplanon®). For more information, see the CKS topic on Contraception - progestogen-only methods.Depot medroxyprogesterone acetate (Depo-Provera®, SAYANA PRESS®). For more information, see the CKS topic on Contraception - progestogen-only methods.Progestogen-only pill (POP). For more information, see the CKS topic on Contraception - progestogen-only methods.Combined hormonal contraceptives (CHC). For more information, see the CKS topic on Contraception - combined hormonal methods.Inform women aged over 35 years with a family history of breast cancer that there is an increased risk of breast cancer associated with taking the oral contraceptive pill, given that their absolute risk increases with age. Advice to women up to age 35 years with a family history of breast cancer should be in keeping with general health advice on the use of the oral contraceptive pill. For more information, see the section on Combined oral contraceptives in the CKS topic on Contraception - combined hormonal methods.For women who are known carriers of a gene mutation associated with breast cancer (such as BRCA1 or BRCA2):The Cu-IUD may be used without restriction (UKMEC category 1).The following methods may be generally used (UKMEC category 2):POP.Depot medroxyprogesterone acetate (Depot-Provera®, SAYANA PRESS®).Etonogestrel-only implant (Nexplanon®).LNG-IUS.If the CHC is being considered (UKMEC category 3), discuss with (or refer the woman to) a specialist genetics service, as views are conflicting on whether or not the protective effects of CHC against ovarian cancer outweigh the increased risk of breast cancer.   Back to top Basis for recommendation Basis for recommendation These recommendations are based largely on the Faculty of Sexual and Reproductive Healthcare (FSRH) UK Medical Eligibility Criteria (UKMEC) for contraceptive use [FSRH, 2016] and the National Institute for Health and Care Excellence (NICE) guideline Familial breast cancer: classification, care and managing breast cancer and related risks in people with a family history of breast cancer [NICE, 2017]. NICE commissioned the National Collaborating Centre for Cancer to produce the evidence review and develop the full NICE clinical guidelines [National Collaborating Centre for Cancer, 2013]. Women with a family history of breast cancer who are not known to be carriers of a gene mutationThe UKMEC for contraceptive use states that a family history of breast cancer is not a contraindication to any form of hormonal contraception or intrauterine device (UKMEC category 1: a condition for which there is no restriction for the use of the contraceptive method) [FSRH, 2016].NICE found consistent evidence from three meta-analyses of case-control and cohort studies, plus one large case-controlled study (4575 women with breast cancer and 4682 women without breast cancer) that the effect of oral contraception on breast cancer risk is similar in women with or without a family history of breast cancer [National Collaborating Centre for Cancer, 2013]. However, NICE advises that women aged over 35 years with a family history of breast cancer should be informed of an increased risk of breast cancer associated with taking the oral contraceptive pill, given that their absolute risk increases with age. Women who are known carriers of a gene mutation associated with an increased risk of breast cancerAccording to the UKMEC for contraceptive use [FSRH, 2016]:There is no restriction for the use of the copper intrauterine device (UKMEC category 1: a condition for which there is no restriction for the use of the contraceptive method).The benefits generally outweigh the risks for the use of the levonorgestrel intrauterine device, the progestogen-only pill, depot medroxyprogesterone acetate, and the etonogestrel-only implant (UKMEC category 2: a condition for which the advantages of using the method generally outweigh the theoretical or proven risks).The use of a combined hormonal contraceptive (CHC) is classified as UKMEC category 3: a condition where the theoretical or proven risks usually outweigh the advantages of using the method. The provision of a method requires expert clinical judgement and/or referral to a specialist contraceptive provider, since use of the method is not usually recommended unless other more appropriate methods are not available or not acceptable.Evidence from one case-control study showed that ever use of oral contraceptives was associated with a 20% increase in breast cancer risk in women who had a BRCA1 mutation, but BRCA2 mutation carriers were not found to be at increased risk [National Collaborating Centre for Cancer, 2013]. NICE advises that for women with BRCA1 mutations, the conflicting effects of a possible increased risk of breast cancer under the age of 40 years and the lifetime protection against ovarian cancer risk from taking the oral contraceptive pill should be discussed [NICE, 2017].The recommendation to refer the woman to a specialist genetic service to discuss use of a CHC is based on advice from the Northern Genetics Service, as opinions are divided on whether or not the reduction in risk of ovarian cancer outweighs the increase in risk of breast cancer [Newcastle upon Tyne Hospitals NHS Foundation Trust, 2013].  Back to top Advice on hormone replacement therapy How should I manage a woman with a family history of breast cancer who wishes to take hormone replacement therapy? If the woman is at low risk of breast cancer (that is, she does not fulfil the referral criteria to secondary care), hormone replacement therapy (HRT) may be prescribed. For further information, see the CKS topic on Menopause.If the woman is at increased risk of breast cancer (that is, she fulfils the referral criteria to secondary care):Ensure that she has been referred to secondary care for assessment of her breast cancer risk.Inform her of the increase in breast cancer risk with type and duration of HRT, and refer her to secondary care for advice as to whether or not it is appropriate to prescribe HRT.Provide information on non-hormonal and non-pharmacological treatments, such as antidepressants (selective serotonin reuptake inhibitor), vaginal moisturisers and lubricants, cognitive behavioural therapy (CBT), hypnosis, acupuncture, and relaxation techniques, for the management of symptoms. For more information, see the section on Managing the menopause without HRT in the CKS topic on Menopause. Back to top Basis for recommendation Basis for recommendation Managing women at low risk of breast cancerThe basis for recommending hormone replacement therapy (HRT) in women at low risk of breast cancer, and the evidence for the benefits and risks associated with its use, can be found in the CKS topic on Menopause.Managing women at increased risk of breast cancerThese recommendations are based largely on the National Institute for Health and Care Excellence (NICE) guideline Familial breast cancer: classification, care and managing breast cancer and related risks in people with a family history of breast cancer  [NICE, 2017]. NICE commissioned the National Collaborating Centre for Cancer to produce the evidence review and develop the full NICE clinical guidelines [National Collaborating Centre for Cancer, 2013]. NICE advises that women with a family history of breast cancer who are considering taking, or already taking, HRT should be informed of the increase in breast cancer risk with type and duration of HRT. This recommendation is based on evidence from several studies, including a review of 51 epidemiological studies carried out in 21 countries, mainly North America and Europe, (n = 52,705 women with breast cancer and 108,411 women without breast cancer) [Collaborative Group on Hormonal Factors in Breast Cancer, 1997] and a prospective cohort study (the Million Women Study) which looked at the effects of HRT on the incidence of, and mortality from, breast cancer (n = 1,084,110 women aged 50–64 years) [Million Women Study Collaborators, 2003].CKS recommends seeking specialist advice about prescribing HRT to women who are at increased risk of breast cancer because the risks associated with HRT vary depending on the individual and require expertise to make an informed decision [Rees et al, 2009]. Supporting evidence Back to topSupporting evidence This CKS topic is based on the National Institute for Health and Care Excellence (NICE) guideline Familial breast cancer: classification, care and managing breast cancer and related risks in people with a family history of breast cancer [NICE, 2017].In 2013, NICE commissioned the National Collaborating Centre for Cancer to produce the evidence review and develop the full NICE clinical guidelines [National Collaborating Centre for Cancer, 2013]. In 2017, NICE made new recommendations on chemoprevention and replaced previous recommendations in the 2013 evidence review. New recommendations on chemoprevention can be found in the NICE guideline Familial breast cancer: classification, care and managing breast cancer and related risks in people with a family history of breast cancer  [NICE, 2017] and the 2017 addendum. How this topic was developed Back to topHow this topic was developed This section briefly describes the processes used in developing and updating this topic. Further details on the full process can be found in the About Us section and on the Clarity Informatics website. Back to top Search strategy Search strategy Scope of searchThis CKS topic is primarily based on the National Institute for Health and Care Excellence (NICE) guideline Familial breast cancer: classification and care of people at risk of familial breast cancer and management of breast cancer and related risks in people with a family history of breast cancer. A literature search was conducted for guidelines and systematic reviews on managing family history of breast cancer in primary care. Search datesAugust 2013 - December 2018Key search termsThe terms listed below are the core search terms that were used for EBSCOhost MEDLINE (searched 12th December 2018). These terms were combined with search filters for systematic reviews and guidelines in EBSCOhost MEDLINE. The strategy was adapted for The Cochrane Library databases. S11    S3 AND S10S10    S4 OR S5 OR S6 OR S7 OR S8 OR S9S9    (MH "Genes, BRCA2")S8    (MH "Genes, BRCA1")S7    AB (mutation carrier*) OR TI (mutation carrier*)S6    AB ( (familial or inherit* or hereditary or BRCA*) ) OR TI ( (familial or inherit* or hereditary or BRCA*) )S5    AB family history OR TI family historyS4    (MH "Genetic Predisposition to Disease+")S3    S1 OR S2S2    AB ( (breast* N2 (neoplasm* or cancer* or tumor* or tumour* or metasta* or carcinoma*)) ) OR TI ( (breast* N2 (neoplasm* or cancer* or tumor* or tumour* or metasta* or carcinoma*)) )S1    (MH "Breast Neoplasms+")Sources of guidelines National Institute for Health and Care Excellence (NICE) Scottish Intercollegiate Guidelines Network (SIGN) Royal College of Physicians Royal College of General Practitioners Royal College of Nursing NICE Evidence Health Protection Agency World Health Organization National Guidelines Clearinghouse Guidelines International Network TRIP database GAIN NHS Scotland National Patient Pathways New Zealand Guidelines Group Agency for Healthcare Research and Quality Institute for Clinical Systems Improvement National Health and Medical Research Council (Australia) Royal Australian College of General Practitioners British Columbia Medical Association Canadian Medical Association Alberta Medical Association University of Michigan Medical School Michigan Quality Improvement Consortium Singapore Ministry of Health National Resource for Infection Control Patient UK Guideline links UK Ambulance Service Clinical Practice Guidelines RefHELP NHS Lothian Referral Guidelines Medline (with guideline filter) Driver and Vehicle Licensing Agency NHS Health at Work(occupational health practice)Sources of systematic reviews and meta-analyses The Cochrane Library: Systematic reviews Protocols Database of Abstracts of Reviews of Effects Medline (with systematic review filter) EMBASE (with systematic review filter)Sources of health technology assessments and economic appraisals NIHR Health Technology Assessment programme The Cochrane Library: NHS Economic Evaluations Health Technology Assessments Canadian Agency for Drugs and Technologies in Health International Network of Agencies for Health Technology AssessmentSources of randomized controlled trials The Cochrane Library: Central Register of Controlled Trials Medline (with randomized controlled trial filter) EMBASE (with randomized controlled trial filter)Sources of evidence based reviews and evidence summaries Bandolier Drug & amp; Therapeutics Bulletin TRIP database Central Services Agency COMPASS Therapeutic NotesSources of national policy Department of Health Health Management Information Consortium(HMIC)Patient experiences Healthtalkonline BMJ - Patient Journeys Patient.co.uk - Patient Support GroupsSources of medicines informationThe following sources are used by CKS pharmacists and are not necessarily searched by CKS information specialists for all topics. Some of these resources are not freely available and require subscriptions to access content. British National Formulary(BNF) electronic Medicines Compendium(eMC) European Medicines Agency(EMEA) LactMed Medicines and Healthcare products Regulatory Agency(MHRA) REPROTOX Scottish Medicines Consortium Stockley's Drug Interactions TERIS TOXBASE Micromedex UK Medicines Information Back to top Stakeholder engagement Stakeholder engagement Our policyThe external review process is an essential part of CKS topic development. Consultation with a wide range of stakeholders provides quality assurance of the topic in terms of:Clinical accuracy.Consistency with other providers of clinical knowledge for primary care.Accuracy of implementation of national guidance (in particular NICE guidelines).Usability.Principles of the consultation processThe process is inclusive and any individual may participate.To participate, an individual must declare whether they have any competing interests or not. If they do not declare whether or not they have competing interests, their comments will not be considered.Comments received after the deadline will be considered, but they may not be acted upon before the clinical topic is issued onto the website.Comments are accepted in any format that is convenient to the reviewer, although an electronic format is encouraged.External reviewers are not paid for commenting on the draft topics.Discussion with an individual or an organization about the CKS response to their comments is only undertaken in exceptional circumstances (at the discretion of the Clinical Editor or Editorial Steering Group).All reviewers are thanked and offered a letter acknowledging their contribution for the purposes of appraisal/revalidation.All reviewers are invited to be acknowledged on the website.All reviewers are given the opportunity to feedback about the external review process, enabling improvements to be made where appropriate.StakeholdersKey stakeholders identified by the CKS team are invited to comment on draft CKS topics. Individuals and organizations can also register an interest to feedback on a specific topic, or topics in a particular clinical area, through the Getting involved section of the Clarity Informatics website.Stakeholders identified from the following groups are invited to review draft topics:Experts in the topic area.Professional organizations and societies(for example, Royal Colleges).Patient organizations, Clarity has established close links with groups such as Age UK and the Alzheimer's Society specifically for their input into new topic development, review of current topic content and advice on relevant areas of expert knowledge.Guideline development groups where the topic is an implementation of a guideline.The British National Formulary team.The editorial team that develop MeReC Publications.Reviewers are provided with clear instructions about what to review, what comments are particularly helpful, how to submit comments, and declaring interests.Patient engagementClarity Informatics has enlisted the support and involvement of patients and lay persons at all stages in the process of creating the content which include:Topic selectionScoping of topicSelection of clinical scenariosFirst draft internal reviewSecond draft internal reviewExternal reviewFinal draft and pre-publicationOur lay and patient involvement includes membership on the editorial steering group, contacting expert patient groups, organizations and individuals. Back to top Evidence exclusion criteria Evidence exclusion criteria Our policyScoping a literature search, and reviewing the evidence for CKS is a methodical and systematic process that is carried out by the lead clinical author for each topic. Relevant evidence is gathered in order that the clinical author can make fully informed decisions and recommendations. It is important to note that some evidence may be excluded for a variety of reasons. These reasons may be applied across all CKS topics or may be specific to a given topic.Studies identified during literature searches are reviewed to identify the most appropriate information to author a CKS topic, ensuring any recommendations are based on the best evidence. We use the principles of the GRADE and PICOT approaches to assess the quality of published research. We use the principles of AGREE II to assess the quality of published guidelines.Standard exclusions for scoping literature:Animal studiesOriginal research is not written in EnglishPossible exclusions for reviewed literature:Sample size too small or study underpoweredBias evident or promotional literaturePopulation not relevantIntervention/treatment not relevantOutcomes not relevantOutcomes have no clear evidence of clinical effectivenessSetting not relevantNot relevant to UKIncorrect study typeReview articleDuplicate reference Back to top Organizational, behavioural and financial barriers Organizational, behavioural and financial barriers Our policyThe CKS literature searches take into consideration the following concepts, which are discussed at the initial scoping of the topic.FeasibilityStudies are selected depending on whether the intervention under investigation is available in the NHS and can be practically and safely undertaken in primary care.Organizational and Financial Impact AnalysisStudies are selected and evaluated on whether the intervention under investigations may have an impact on local clinical service provision or national impact on cost for the NHS. The principles of clinical budget impact analysis are adhered to, evaluated and recorded by the author. The following factors are considered when making this assessment and analysis.Eligible populationCurrent interventionsLikely uptake of new intervention or recommendationCost of the current or new intervention mixImpact on other costsCondition-related costsIn-direct costs and service impactsTime dependenciesCost-effectiveness or cost-benefit analysis studies are identified where available. We also evaluate and include evidence from NICE accredited sources which provide economic evaluations of recommendations, such as NICE guidelines. When a recommended action may not be possible because of resource constraints, this is explicitly indicated to healthcare professionals by the wording of the CKS recommendation. Back to top Declarations of interest Declarations of interest Our policyClarity Informatics requests that all those involved in the writing and reviewing of topics, and those involved in the external review process to declare any competing interests. Signed copies are securely held by Clarity Informatics and are available on request with the permission of the individual. A copy of the declaration of interest form which participants are asked to complete annually is also available on request. A brief outline of the declarations of interest policy is described here and full details of the policy is available on the Clarity Informatics website. Declarations of interests of the authors are not routinely published, however competing interests of all those involved in the topic update or development are listed below. Competing interests include:Personal financial interestsPersonal family interestPersonal non-financial interestNon-personal financial gain or benefitAlthough particular attention is given to interests that could result in financial gains or losses for the individual, competing interests may also arise from academic competition or for political, personal, religious, and reputational reasons.An individual is not obliged to seek out knowledge of work done for, or on behalf of, the healthcare industry within the departments for which they are responsible if they would not normally expect to be informed.Who should declare competing interests?Any individual (or organization) involved in developing, reviewing, or commenting on clinical content, particularly the recommendations should declare competing interests. This includes the authoring team members, expert advisers, external reviewers of draft topics, individuals providing feedback on published topics, and Editorial Steering Group members. Declarations of interest are completed annually for authoring team and editorial steering group members, and are completed at the start of the topic update and development process for external stakeholders.Competing interests declared for this topic:None. References Back to topReferences ACOG (2015) Committee opinion no. 634: Hereditary cancer syndromes and risk assessment. Obstetrics and Gynecology 125(6), 1538-1543. [Free Full-text] Ahmed,M., Lalloo,F. and Evans,D.G. (2009) Update on genetic predisposition to breast cancer. Expert Review of Anticancer Therapy. 9(8), 1103-1113. [Abstract] Andrieu,N., Goldgar,D.E., Easton,D.F., et al. (2006) Pregnancies, breast-feeding, and breast cancer risk in the International BRCA1/2 Carrier Cohort Study (IBCCS). Journal of the National Cancer Institute. 98(8), 535-544. [Abstract] Antoniou,A.C., Shenton,A., Maher,E.R., et al. (2006) Parity and breast cancer risk among BRCA1 and BRCA2 mutation carriers. Breast Cancer Research. 8(6), R72. [Abstract] Bernier,M.O., Plu-Bureau,G., Bossard,N., et al. (2000) Breastfeeding and risk of breast cancer: a metaanalysis of published studies. Human Reproduction Update. 6(4), 374-386. [Abstract] Brohet,R.M., Goldgar,D.E., Easton,D.F., et al. (2007) Oral contraceptives and breast cancer risk in the international BRCA1/2 carrier cohort study: a report from EMBRACE, GENEPSO, GEO-HEBON, and the IBCCS Collaborating Group. Journal of Clinical Oncology. 25(25), 3831-3836. [Abstract] Cancer Research UK (2018a) Breast cancer risk. Cancer Research UK. www.cancerresearchuk.org [Free Full-text] (2018b) Breast cancer incidence (invasive) statistics. www.cancerresearchuk.org [Free Full-text] Chang-Claude,J., Andrieu,N., Rookus,M., et al. (2007) Age at menarche and menopause and breast cancer risk in the International BRCA1/2 Carrier Cohort Study. Cancer Epidemiology, Biomarkers & Prevention. 16(4), 740-746. [Abstract] Cibula,D., Zikan,M., Dusek,L. and Majek,O. (2011) Oral contraceptives and risk of ovarian and breast cancers in BRCA mutation carriers: a meta-analysis. Expert Review of Anticancer Therapy. 11(8), 1197-1207. [Abstract] Claus,E.B., Risch,N. and Thompson,W.D. (1994) Autosomal dominant inheritance of early-onset breast cancer. Implications for risk prediction. Cancer. 73(3), 643-651. [Abstract] Collaborative Group on Hormonal Factors in Breast Cancer (1997) Breast cancer and hormone replacement therapy: a collaborative reanalysis of data from 51 epidemiological studies of 52705 women with breast cancer and 108411 women without breast cancer. Lancet. 350(9084), 1047-1059. [Abstract] Collaborative Group on Hormonal Factors in Breast Cancer (2001) Familial breast cancer: collaborative reanalysis of individual data from 52 epidemiological studies including 58209 women with breast cancer and 101986 women without the disease. 358(9291), 1389-1399. [Abstract] Collaborative Group on Hormonal Factors in Breast Cancer (2002) 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. 360(9328), 187-195. [Abstract] Collaborative Group on Hormonal Factors in Breast Cancer (2002) Alcohol, tobacco and breast cancer: collaborative reanalysis of individual data from 53 epidemiological studies, including 58515 women with breast cancer and 95067 women without the disease. British Journal of Cancer. 87(11), 1234-1245. [Abstract] Eisen,A., Lubinski,J., Gronwald,J., et al. (2008) Hormone therapy and the risk of breast cancer in BRCA1 mutation carriers. Journal of the National Cancer Institute. 100(19), 1361-1367. [Abstract] Ellison,R.C., Zhang,Y., McLennan,C.E. and Rothman,K.J. (2001) Exploring the relation of alcohol consumption to risk of breast cancer. American Journal of Epidemiology. 154(8), 740-747. [Abstract] Emery,J., Lucassen,A. and Murphy,M. (2001) Common hereditary cancers and implications for primary care. Lancet. 358(9275), 56-63. [Abstract] FSRH (2016) UK medical eligibility criteria for contraceptive use - UKMEC 2016. Faculty of Sexual & Reproductive Healthcare.. www.fsrh.org [Free Full-text] Gabai-Kapara, E., Lahad, A. and Kaufman, B. et al. (2014) Population-based screening for breast and ovarian cancer risk due to BRCA1 and BRCA2. Proceedings Of The National Academy Of Sciences Of The United States Of America 111(39), 14205-14210. [Free Full-text] Harvie,M., Hooper,L. and Howell,A.H. (2003) Central obesity and breast cancer risk: a systematic review. Obesity Reviews. 4(3), 157-173. [Abstract] Hill,A.D., Doyle,J.M., McDermott,E.W. and O'Higgins,N.J. (1997) Hereditary breast cancer. 84(10), 1334-1339. [Abstract] IARC (2002) IARC handbook of cancer prevention. Weight control and physical activity.6th edn. Geneva: World Health Organization. Iodice,S., Barile,M., Rotmensz,N., et al. (2010) Oral contraceptive use and breast or ovarian cancer risk in BRCA1/2 carriers: a meta-analysis. European Journal of Cancer. 46(12), 2275-2284. [Abstract] Kosters,J.P. and Gotsche,P.C. (2003) Regular self-examination or clinical examination for early detection of breast cancer (Cochrane Review). The Cochrane Library. John Wiley & Sons Ltd. www.thecochranelibrary.com [Free Full-text] Kotsopoulos,J., Lubinski,J., Lynch,H.T., et al. (2007) Age at first birth and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers. Breast Cancer Research and Treatment. 105(2), 221-228. [Abstract] Lipworth,L., Bailey,L.R. and Trichopoulos,D. (2000) History of breast-feeding in relation to breast cancer risk: a review of the epidemiologic literature. Journal of the National Cancer Institute. 92(4), 302-312. [Abstract] Longnecker,M.P., Berlin,J.A., Orza,M.J. and Chalmers,T.C. (1988) A meta-analysis of alcohol consumption in relation to risk of breast cancer. Journal of the American Medical Association. 260(5), 652-656. [Abstract] Longnecker,M.P. (1994) Alcoholic beverage consumption in relation to risk of breast cancer: meta-analysis and review. Cancer Causes & Control. 5(1), 73-82. [Abstract] McGuire,V., John,E.M., Felberg,A., et al. (2006) No increased risk of breast cancer associated with alcohol consumption among carriers of BRCA1 and BRCA2 mutations ages