Fig. 3.1
The 10 most common cancers in females, UK, 2011 (Cancer Research UK, www.cancerresearchuk.org/cancer-info/cancerstats/incidence/commoncancers/ October 2014)
Breast cancer accounted for 15 % (11,684) of UK female deaths in 2011, but interestingly it is no longer the commonest cause of female cancer deaths, which is now attributable to lung cancer [9–11]. A number of factors are responsible for the decline in mortality rates over the past decade. These include: earlier detection via breast screening programmes; increased public awareness; improved treatments (surgical, radiotherapy/chemotherapy regimes and hormonal therapies) and improved delivery of specialist care by multi-disciplinary teams [12].
Lifetime Risk (Females)
Lifetime risk refers to the chance a person has of developing or dying from cancer over the course of his or her lifetime (from birth to death). Risk estimates are based upon current incidence and mortality rates but an individual’s risk may be higher or lower than the population risk as genetic and lifestyle factors are influential. Cancer research UK reported that in 2010 (UK) the lifetime risk of developing breast cancer is 1 in 8 for women and 1 in 868 for men [13].
Risk Factors for Breast Cancer
Risk factors are merely an indicator and not a certainty that an individual will develop the disease. Some women may have multiple risk factors and never have breast cancer, whilst many of the women diagnosed have no attributable risk factors. Some risk factors are unalterable (e.g. gender or age), but others are controllable and linked to the environment and personal lifestyle. Certain risk factors are more influential than others, and an individual’s risk for breast cancer will change over time.
Unchangeable Risk Factors
Gender
Being female is the main risk factor for developing breast cancer. Although men do develop breast cancer the incidence rates are very low in comparison and have remained stable over the last 40 years [4–6]. Cancer research UK reports that in the UK 397 men were diagnosed with breast cancer in 2010. As with females, breast cancer incidence is strongly associated with increasing age [4–6].
Age
In women, the strongest risk factor for breast cancer is age; the older a woman gets, the higher her risk. Data demonstrates that almost half (48 %) of female breast cancer cases are diagnosed in women in the 50–69 age group [4–8]. This contributed to the original rationale underpinning the UK NHS breast screening programme [14], which invites women in the 50–70 age group for screening every 3 years. At the time of writing this chapter, in England there is currently a trial “phasing-in” the age extension from 47 to 50 and 70 to 73. The trial aims to produce data on the incidence and mortality rates from extending the age range for screening.
Genetic Risk Factors
Family History
It is important to remember that the majority of breast cancers are not hereditary, as fewer than 15 % of women with breast cancer have a family member with the disease [15]. Analysis of data [15, 16] shows that having one first –degree relative (sister, mother or daughter) diagnosed with breast cancer almost doubles a woman’s risk of developing the disease compared to an individual with no family history. This risk increases further (3-fold) if two first degree relatives are affected and the age at diagnosis is also an important factor as risk is greater if the relative is under 50.
An increased risk does not mean that an individual will develop the disease as more than 85 % of women with a first degree relative with breast cancer will never develop the disease [15]. A very minor proportion of women are at a very high risk of familial breast or ovarian cancer and this is assigned to mutations in the breast cancer susceptibility genes Breast Cancer Gene 1 (BRCA1) and Breast Cancer Gene 2 (BRCA2) [17]. The estimated prevalence of mutations mean this will affect approximately 1 in 450 women who as a result have a high (45–65 %) chance of developing the disease by the age of 70 [18].
Mutations in the BRCA genes are identified as high-penetrance, and confer the greatest increase in risk (10-fold), but there are very rare genes e.g. Tumour Protein 53 (TP53) (Li Fraumeni syndrome) that also lie within this group [19]. There are also a number of intermediate-penetrance gene variants that give a 2–3 fold increase in risk such as Checkpoint kinase 2(CHEK2), Ataxia Telangiectasia Mutated (ATM), BRCA1 interacting protein C-terminal helicase 1 (BRIP1) and Partner And Localizer of BRCA2 (PALB2). A number of low-penetrance gene variants have also been identified [19].
Personal History of Breast Cancer
Women with a prior history of a breast cancer have an increased risk of developing a new cancer in the contralateral breast. Studies [20–22] report a variance from a 3- to almost 5-fold risk increase. This risk is not the same as the risk of recurrence (return) from the primary cancer.
Breast Density
There is strong evidence to show that there is an interdependent link between breast density and the risk of developing breast cancer [25, 26]. The greater the density of breast tissue, the greater the chance of developing breast cancer. Research shows that women with a Breast Imaging-Reporting and Data System (BI-RADS) breast density of category 4(d) (Appendix 1) have approximately a four times greater risk of breast cancer comparative to the category 1(a) group [27–29]. There are a number of contributory factors that affect breast density e.g. age, endogenous hormones [26, 30], menopausal status, body weight, pregnancy.) Further information about breast density can be found in Chap. 16.
Socio-economic Status
Data demonstrates that female breast cancer rates are much higher in women from developed countries compared to women from developing nations [31, 32], with rates rising in continents where incidence was historically much lower [33–35]. There are several causative factors for this. Life expectancy is greater in economically developed countries (risk of breast cancer increases with age) together with different lifestyles e.g. use of hormone replacement therapy (HRT), increasing body mass index (BMI), alcohol consumption [36, 37].
Historically South Asian women and those in lower socio-economic groups were considered at lower risk of developing breast cancer, but recent data [38] reports this is no longer the case.
Recent evidence shows that deprivation is one of the most significant factors associated with poor uptake rates at breast screening, which is anticipated to result in poorer outcomes [39].
Reproductive Factors That Influence Breast Cancer Risk
Menstrual Periods
Parity
Childbearing reduces the risk of breast cancer, but this is also relative to maternal age at first live birth and number of full-term pregnancies [42]. Having children lowers individual risk compared to a nulliparous woman [42–44].
Some studies suggest that breastfeeding can slightly lower breast cancer risk, but this is proportional to the amount of time spent breastfeeding [42].
Exogenous Hormones
Oral Contraceptives/HRT
Studies have found that women who currently or recently used oral contraceptives have a slightly greater risk of breast cancer than non-users, but the risk diminishes over time after stopping use. Ten years post use there does not appear to be a residual risk [45]. Similar findings are reported from studies that have looked at Depot-medroxyprogesterone acetate (DMPA; Depo-Provera®) the injectable form of birth control.
Using combined hormone therapy (oestrogen and progesterone) after the menopause is associated with an increased risk (66 %) of developing breast cancer compared to non-users [46]. This increase can be seen with as little as 2 years of use. Again, the increased risk appears to apply only to current and recent users with risk returning to that of the general population within 5 years of ceasing [46].
Previous Benign Breast Disease
Certain benign breast conditions confer an increased risk for breast cancer.
Lesions classified as non-proliferative infer no extra risk. They include:
Fibrosis and/or simple cysts
Mild hyperplasia
Non sclerosing adenosis
Duct ectasia
Benign Phyllodes tumour
Solitary papilloma
Fat necrosis
Other benign tumours (lipoma, hamartoma, haemangioma, neurofibroma)
Proliferative lesions without atypia appear to slightly raise (1½–2 fold increase) risk. They include ductal hyperplasia, fibroadenoma, sclerosing adenosis, papillomatosis and radial scar. Proliferative lesions with atypia imply a greater risk (3½–5 fold) and include atypical ductal hyperplasia (ADH) and Atypical lobular hyperplasia (ALH).
Ductal carcinoma in situ (DCIS) and lobular carcinoma in situ (LCIS) have the potential to develop into invasive carcinoma, more probable with high grade rather than low grade disease [47]. Previous in-situ disease is recognised to double an individual’s risk of developing an invasive breast tumour [48].
Medical Radiation Exposure
Exposure to ionising radiation is a known risk factor associated with any carcinoma [49]. Young female adults or children who received mantle radiotherapy to the chest area as treatment for Hodgkin’s Lymphoma have a significantly increased risk for breast cancer. Studies [49, 50] report a 12–25 fold increased risk dependent on the age at exposure, with the greater risk in adolescents.
Recent data concludes that breast cancer patients have a “small but significantly excess” risk of developing a second cancer close to prior radiotherapy treatment fields [51]. Studies also report an increased risk (3 fold) of breast cancer in females under the age of 30 who received diagnostic doses of radiation whilst undergoing chest x-rays for tuberculosis or pneumonia [49].
Risk associated with radiation exposure from 3 yearly breast screening mammograms is reported to be minimal [52].
Lifestyle Related Risk Factors
Being overweight or obese is one of the few risk factors that is amenable to change. However, the association between body weight and breast cancer risk is multifaceted.
Pre-menopausal women produce most of their oestrogen from the ovaries, with a small amount produced by fatty tissue. Post-menopause a woman’s oestrogen mainly comes from the conversion of hormones in fat tissue. Overweight post-menopausal women are reported to have a 10–20 % increased risk of breast cancer, which escalates to 30 % in women categorised as obese [53, 54].
However, the complexity lies in that the risk appears relative as to whether the weight gain is as a child or as an adult. Risk appears greater for women who gained excess weight as an adult but does not appear to have the same implications for those who have been overweight from childhood.
Physical Activity
Evidence supports that exercise can reduce an individual’s breast cancer risk. However, this appears to be relative to the intensity and duration of the exercise undertaken. The most significant findings are for vigorous activity in postmenopausal women where studies have reported a 15–20 % risk reduction [55, 56], believed to be due to the associated decreased levels of oestrogen and progesterone [57].
Alcohol Consumption
There is an association between alcohol consumption and an increased risk of developing breast cancer. A Lancet report in 2007 concluded that this association is causal [58], with relative risk increasing with the increasing amount of alcohol consumed.
Uncertain Risk Factors
Diet
Numerous studies have been undertaken to identify if there an association between dietary factors and breast cancer risk, but currently the results are conflicting [59, 60].
Smoking and Passive Smoke
Historically there has been no evidence to support a link between cigarette smoking and breast cancer. Larger studies undertaken in 2011 [64, 65] have demonstrated that long-term heavy smoking is associated with a higher risk of breast cancer particularly for certain cohorts i.e. women who started smoking when they were young (under the age of 20) and before their first birth.
There is no consistent evidence to authenticate an association between smoking and breast cancer after the menopause [65].
Night/Shift Work
Medications and Medical Conditions
Certain medications have been associated with reducing breast cancer risk, mainly aspirin and non-steroidal anti-inflammatory drugs [71–76]. Other medications e.g. diethylstilboestrol (synthetic oestrogen) and long-term use of anti-hypertensive medications suggest an increased risk [77, 78].
Appendix 1
The American College of Radiology BI-RADS [87]
1(a).
The breasts are almost entirely fatty
2(b).
There are scattered areas of fibroglandular density
3(c).
The breasts are heterogeneously dense, which may obscure small masses
4(d).
The breasts are extremely dense, which lowers the sensitivity of mammography
References
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Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. GLOBOCAN 2008 v1.2, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 10 [Internet]. Lyon: International Agency for Research on Cancer. 2010. http://globocan.iarc.fr. Accessed May 2011.
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Data were provided by the Welsh Cancer Intelligence and Surveillance Unit on request, April 2012. Similar data can be found here. http://www.wales.nhs.uk/sites3/page.cfm?orgid=242&pid=51358.
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