Breast cancer - UK incidence statistics

This page concentrates on female breast cancer incidence statistics by age,geographic variation, trends over time and prevalence. The ICD code for breast cancer is ICD9 174 (female), 175 (male) and ICD10 C50.

Breast cancer incidence by sex

Breast cancer is the most common cancer in the UK despite the fact that it is rare in men. In 2006 there were 45,822 new cases of breast cancer diagnosed in the UK: 45,508 (over 99%) in women and 314 (less than 1%) in men.

Table 1.11-4 shows the numbers and rates of new cases of breast cancer in the UK and its constituent countries. The lowest rates are recorded in Northern Ireland and this has been a consistent pattern since Northern Ireland cancer registration rates became available in 1993.19

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The lifetime risk of developing breast cancer

Breast cancer is by far the commonest cancer in women in the UK accounting for 31% of all cases in women. The next most common cancer in women is lung cancer, with 16,647 cases (11% of total) in 2006. So nearly a third of all new cancers in women are breast cancers. It has been estimated that the lifetime risk of developing breast cancer is 1 in 1,014 for men and 1 in 9 for women in the UK. These were calculated on February 2009 using incidence and mortality data for 2001-2005. 5

Breast cancer incidence statistics by age

Breast cancer risk is strongly related to age,with 81% of cases occurring in women aged 50 years and over. Nearly half (48%) of cases of breast cancer are diagnosed in the 50-69 age group ( Figure 1.11-4): these women and those aged 70 are targeted in the national screening programme. From 2009 onwards, the NHS Breast Screening Programme will extend the age range of women eligible for breast screening to ages 47 to 73 over time. The extension is due to be complete by 2012. For more information on breast cancer screening go to the screening section.

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Although very few cases of breast cancer occur in women in their teens or early 20s, breast cancer is the most commonly diagnosed cancer in women under 35. Among women aged 35-39 around 1,500 cases of breast cancer are diagnosed each year. Breast cancer incidence rates generally increase with age, with the greatest rate of increase prior to the menopause, supporting a link with hormonal status.

Geographic variation of breast cancer incidence

Worldwide, more than a million women are diagnosed with breast cancer every year, accounting for a tenth of all new cancers and 23% of all female cancer cases. 6 Breast cancer incidence rates vary considerably, with the highest rates in the North America and the lowest rates in Africa and Asia (Figure 1.2). 6

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Around 429,900 new cases of breast cancer occur each year in Europe and an estimated 182,460 in the USA 7, 37. The lowest European rates are in eastern and southern Europe and the highest are in northern and western Europe.( Figure 1.3).

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The risk for women who migrate from low to high risk countries typically increases suggesting a strong effect for lifestyle or environmental factors. For example, Japanese migrants to the USA experience rapidly increasing breast cancer rates. 8, 9

An analysis of cancer incidence and mortality from 1991 to 2000 within the UK and Ireland reported relatively little geographical variation for either breast cancer rate.10 At the regional and country level, the European age-standardised rates (EASR)11 for breast cancer incidence ranged from 97 per 100,000 in Ireland to 116 per 100,000 in the South East of England. In England rates were slightly higher than average in the south and slightly lower than average in the north but very few areas  differed by more than 10% from the average. 

In Ireland rates were generally more than 10% below the average. A more recent examination of incidence rates within the UK for 2005 also reported only modest variation in breast cancer incidence for the majority of cancer networks.12

Socio-economic variation in breast cancer incidence

Breast cancer is one of the few cancers where incidence rates are higher for more affluent women and there is a clear trend of decreasing rates from least to most deprived groups.13 An analysis of incidence rates in Scotland for patients registered from 2001-2005 showed a 6% difference between the rates in the least deprived (EASR 118.7 per 100,000) and the most deprived (EASR 111.0 per 100,000) areas. 14

In England, a study of incidence for patients diagnosed between 1998 and 2003 by socio-economic group and region, also reported modest differences between socio-economic groups with the highest rates for the most affluent groups.15 The most recent study in England comparing deprivation for cancer patients in two time periods, 1995-99 and 2000-04, reported that rates in the most deprived groups in 2000-04 were around 20% lower than in the most affluent.16 If all groups had the rates of the most affluent then there would be an additional 2,500 new breast cancer cases each year in England.16 These results are not unexpected as many of the risk factors for breast cancer, for example, late first pregnancy and lower parity are generally more prevalent in the more affluent groups in society.

Trends in breast cancer incidence

The incidence of breast cancer has been increasing for many years in economically developed countries 17,18. From the late 1970s until the introduction of breast screening, the increase in Britain was around 2% per annum 19. The introduction of the national screening programme in 1988 led to a transient additional increase in incidence as a prevalent pool of undiagnosed cancers were detected (Figure 1.41-3).

Over the thirty year period 1977-2006 in Britain, the European age-standardised incidence rate (EASR) increased by 63% from 75 per 100,000 in 1977 to 122 per 100,000 in 2006. Over the same time period the annual number of new cases of breast cancer almost doubled from 23,463 to 44,528 in Britain .(Figure 1.41-3).

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Figure 1.5 shows the breast cancer incidence trend for the UK. In the last ten years in the UK, the EASR has increased by 6% from 114 per 100,000 in 1997 to 121 per 100,000 in 2006, while the numbers of cases rose from 39,819 to 45,508, and increase of 14%.

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During the 1990s the increase in the use of hormone replacement therapy (HRT) is thought to have also contributed to the increase in incidence 20. Analysis of incidence trends by deprivation group showed that incidence rose more rapidly in affluent women than among deprived women between 1986 and 1999, and the higher use of HRT in affluent women may have contributed to this21.

The trends by age-group show clearly that the steep increase in incidence following 1988 was largely confined to women aged 50-64 who were invited to join the breast screening programme (Figure 1.61-3). The most recent rates show a downturn for this age-group. 

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A steep decrease in incidence since 2002 for women aged 50 or older has been noted in the USA and linked to the sudden drop in HRT use following publication of the Women's Health Initiative (WHI) Trial results 18, 22-24.  (The WHI trial was a randomised controlled trial of estrogen-plus-progestin use in post-menopausal women for prevention of chronic disease. The trial was stopped early in July 2002 because risks exceeded benefits).The most recent WHI study reports that the decrease in breast cancer incidence in the over 50s is most likely to be due to the reduced use of HRT rather than decreased uptake of screening and also that the risk of breast cancer after stopping HRT seems to fall very quickly 25. 

Similar trends have been seen in other countries 26. In Scotland a recent analysis of breast cancer incidence and HRT use also reports a reduction in incidence for women aged 50-64 and a dramatic decrease in HRT use consistent with this theory 27. In the UK as a whole, the use of hormonal preparations rose steeply from 1992 to reach a maximum in 2000-01 when approximately 25% of women aged 45-69 were using them; the percentage has fallen to half that in 2006 28. It has been estimated that due to the fall in the use of HRT, there were 1,400 fewer cases of breast cancer at ages 50-59 in the UK in 2005 than would have occurred if no such fall in use had happened 28.The recent steep rise in rates for women aged 65-69 is almost certainly caused by the introduction of national breast cancer screening for this age-group (Figure 1.7 38).

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Projections for Britain from 2005 until 2024 show that the EASR is expected to increase from 119 per 100,000 in 2000-04 to 124 per 100,000 in 2020-24. Over the same time period, the average number of cases per year will rise from 41,900 to 55,700 new cases, that is, more than double the number of cases registered in the late 1970s 29 (the projected number of cases in the UK in 2024 is 57,000).

The historically lower rates in central and Eastern Europe and the Far East have begun to rise rapidly30-32. For example, in Japan, where breast cancer incidence rates have more than doubled over the last 40 years, breast cancer is now the most common form of cancer in women, and rates are likely to continue rising 33.

China, with a fifth of the world’s female population, has already seen dramatic rises in incidence in some cities such as Shanghai and if these trends spread to the rest of the country, a substantial increase in the number of cases is predicted 34. These increases have been linked to changes in reproductive behaviour (in China the average birth rate fell from 5.9 births per woman in 1970 to 2.9 in 1979 and 1.7 in 2004 35) and lifestyle risk factors such as weight gain, alcohol consumption and the use of hormone replacement therapy.

Prevalence of breast cancer

As the incidence of breast cancer is high, and five-year survival rates are over 80%, many women are alive who have been diagnosed with breast cancer. The most recent estimate based on diagnoses up to the end of 2004 applied to the population in 2008 suggests that around 550,000 women are alive in UK who have had a diagnosis of breast cancer 36. This equates to more than 2% of the total female population and nearly 12% of the population aged 65 years and older.

Breast cancer histology

Nearly all invasive breast cancers are adenocarcinomas (derived from glandular tissue), either ductal (85%) or lobular (15%.)

Ductal carcinoma in situ (DCIS), a non-invasive cancer, is now detected much more frequently because of the widespread use of mammography.

 

Acknowledgements

Cancer Research UK would like to thank Dr David Brewster, Dr Gill Lawrence, Professor Julietta Patnick, Dr Paul Pharoah, Dr Gillian Reeves, Dr Elena Takeuchi and Professor Chris Twelves for their kind help and expert advice on the content of the breast cancer pages. We would also like to thank Dr Catherine Lagord for supplying the survival by stage data from the West Midlands. However the contents of the breast cancer pages are entirely the responsibility of Cancer Research UK.

We would also like to acknowledge the essential work of the cancer registries in the United Kingdom Association of Cancer Registries (UKACR). Without these cancer registries there would be no incidence or survival data.

Breast cancer - molecular biology and genetics

This page presents information on the molecular biology and genetics of breast cancer.

Intense research into the genetic basis of familial breast cancer led in the 1990s to the identification of the 'high risk' breast cancer susceptibility genes BRCA1 and BRCA2. 1, 2 However, faults in these genes are rare, and account for only a minority of familial breast cancer.

Most breast cancer families probably carry faults in one or more moderate or low-risk genes, and attention has shifted towards identifying these genes. Inheriting a faulty version of the gene CHEK2 may double a woman's risk, and alteration of CHEK2 may be involved in a substantial proportion of families with two cases of breast cancer. 3, 4

Most cases of breast cancer are 'sporadic' not familial, and are caused by gene damage acquired to breast cells during the woman's lifetime ('somatic' mutations). A wide variety of genes are commonly mutated or incorrectly regulated in sporadic breast cancers and have been implicated in the development and progression of the disease. These include genes encoding growth factors and receptors, intracellular signaling molecules, cell cycle regulators, apoptosis (cell death) regulators, and adhesion molecules.

Studies of these altered molecules are identifying new diagnostic and prognostic markers and unearthing new potential targets for therapy.

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The most frequent alterations include:

• overexpression of the epidermal growth factor receptors EGFR, HER-2/neu, ERBB3 and ERBB4;
• amplification of the MYC gene;
• mutation and overexpression of the intracellular signaling molecules h-Ras and c-Src;
• mutation and inactivation through other means of the cell cycle regulators p53 and RB1;
• overexpression of cyclin D1;
• reduced expression of the adhesion molecule E-cadherin

Recently a link was established between sporadic and inherited breast cancers with the discovery that the EMSY gene is amplified in a proportion of sporadic breast cancers. The EMSY gene codes for a protein that interacts with a highly conserved region of the BRCA2 protein, providing evidence for a shared disease pathway. 5

Amplification of the EMSY gene is also associated with a poor prognosis, indicating that this gene could also be a useful marker of disease severity.

The risk of acquiring the gene damage that causes breast cancer may itself be influenced by a woman's genetic makeup. Variant forms (polymorphisms) of many different genes, for example those involved in detoxifying environmental carcinogens, may be associated with a slightly increased (or decreased) risk of breast cancer. 6

A woman's overall risk is likely to be influenced by the precise combination of such low-risk gene variants that she has inherited.

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Breast cancer - UK mortality statistics

This page contains breast cancer mortality statistics by  sex age and trends over time.

Breast cancer mortality statistics by sex

In the UK in 2007 there were 12,082 deaths from breast cancer; 11,990 (99%) of these were in women and 92 (1%) were in men 1-3. Breast cancer accounts for around 16% of female deaths from cancer in the UK and was the most common cause of death from cancer in women until 1998; since then there have been more deaths from lung cancer.

The number of deaths from breast cancer and the mortality rates for the constituent countries of the UK are shown in Table 2.11-3.

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Breast cancer mortality statistics by age

The number of deaths and age-specific mortality rates for female breast cancer are shown in Figure 2.1.

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In younger women aged 35-54 years, breast cancer is the most common cause of all deaths from cancer.

Trends in breast cancer mortality

Breast cancer mortality rates in the UK have fallen dramatically since 1989 when 15,625 women died from the disease compared with 11,990 in 2007. Over the same period the breast cancer age-standardised death rates have fallen by 36% from 42 to 27 per 100,000 women, Figure 2.24.

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The age-standardised mortality rate for female breast cancer in all of the constituent countries of the UK increased until the late 1980s and then rapidly fell. Breast cancer mortality has declined in all age groups since the late 1980s ( Figure 2.3) 1-4.

Between 1989 and 2007 the breast cancer mortality rate fell by 41% in women aged 40-49 years; by 41% in women aged 50-64; by 38% in women aged 65-69; by 35% in women aged 15-39; and by 20% in women over 70.

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The reduction in breast cancer mortality rates is likely to have several different causes including screening, increasing specialisation of care and the widespread adoption of tamoxifen treatment since 1992.

Breast cancer - prevention

This page presents information on the prevention of breast cancer, including screening, lifestyle, surgery, and breast cancer prevention trials.

Breast cancer prevention - Breast Screening

Women aged 50-70 years are offered the opportunity of early detection of breast cancer through the NHS Screening Programme1

Breast cancer prevention - Lifestyle

Lifestyle changes which reduce the risk of developing breast cancer include avoiding obesity, taking regular exercise and initiating and prolonging breastfeeding. 2

Avoiding alcohol and exogenous hormones including oral contraceptives and hormone replacement therapy (HRT) would lower risk further, but these factors have effects beyond the breast and their risks and benefits may need to be assessed individually.

Because each of the risk factors has an independent effect on risk, the higher a woman's background risk, for example, the older she is, the more important her increase in risk is in absolute terms.

Breast cancer prevention - Surgery

Women at very high risk (for example BRCA1/ mutation carriers) can consider prophylactic surgery which reduces risk by approximately 90%. 3

Breast cancer prevention - Trials

Changes in patterns of reproduction in westernised countries, for example, having more children and doing so earlier in life, are not practicable and therefore many trials are looking at the possibility of reducing exposure to oestrogen through chemoprevention. 4

Breast cancer prevention trials show that taking tamoxifen reduces the risk of oestrogen receptor (ER) positive breast cancer by 30-40% 5-7 but side-effects include increased risk of endometrial cancer and thromboembolic events. A number of alternative strategies are being tested to reduce the side-effects of tamoxifen, for example, lowering the dose oftamoxifen 8, concomitant use of low-dose aspirin, and using alternative selective oestrogenreceptor modulators. 9

Other trials are investigating aromatase inhibitors 10 such as anastrozole, which appears to be better tolerated than tamoxifen and does not increase the risk of endometrial cancer and thromboembolism. However, there is a suggestion that it may increase the risk of osteoporosis and bone-fracture rate.

The IBIS-2 trial, which is currently recruiting, will investigate anastrozole versus a placebo in high risk postmenopausal women. Another group of substances under investigation are luteinising-hormone releasing hormones (LHRH). 11

Breast cancer - risk factors

This page contains information on breast cancer risk. A substantial proportion of the breast cancer cases experienced in developed countries can be explained by factors which influence exposure to oestrogen, including reproductive and hormonal factors, obesity, alcohol and physical activity 1.

Age and risk of breast cancer

The strongest risk factor for breast cancer (after gender) is age: the older the woman, the higher her risk. Risk by age is shown in Table 4.12.

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Reproductive history and breast cancer risk

Women in developed countries are at increased risk of breast cancer compared with women from less developed countries. Much of this variation can be explained by the fact that women in developed countries have fewer children and a limited duration of breastfeeding.

It is estimated that the cumulative incidence of breast cancer in developed countries would be reduced by more than half, from 6.3 to 2.7 per 100, if the average number of births(6.5 instead of 2.5 births) and lifetime duration of breastfeeding (breastfeed each child, on average, for 24 months instead of a lifetime mean of 8.7 months) prevalent in developing countries in the 1990s were to occur 3 ( Figure 4.1).

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Reproductive factors that influence breast cancer risk

• Age at menarche

  Early age at menarche has been consistently associated with an increased risk of breast cancer. Average age of menarche in developed countries fell from around 16-17 years in the mid 19th century to 12-13 today 4. Relative risk for premenopausal breast cancer is reduced by an estimated 7% for each year that menarche is delayed after age 12 years, and by 3% for postmenopausal breast cancer 5. Low risk countries such as China have a later average age at menarche (16-17 years). Nutrition in early life strongly influences age of menarche.

• Age at first birth

  The younger the woman is when she begins childbearing, the lower her risk of breast cancer. The relative risk of developing breast cancer increases by 3% for each year of delay 3. For example, a woman who has her first baby at age 28 would have a 3% lower risk of breast cancer than a woman who had her first baby at 29, all other factors being equal.

• Parity

  The effect of parity on reducing the risk of breast cancer has long been recognized. In the 18th century Bernado Ramazzini (1633-1714) reported the high rate of breast cancer in nuns compared with married women and speculated that this might be associated with their lack of children. In one meta-analysis nulliparity was associated with a 30% increase in risk compared with parous women 6. The higher the number of full-term pregnancies, the greater the protection. There is a reduction in risk of 7% for each birth after the first, in the absence of breast feeding 3.

• Breastfeeding

  Women who breastfeed reduce their risk compared with women who do not breastfeed 3. The longer a woman breastfeeds, the greater the protection: risk is reduced by 4.3% for each year a woman breastfeeds 3.

• Age at menopause

  Late menopause increases the risk of breast cancer 7. For each year menopause is delayed, there is an approximate 3% increase in breast cancer risk 8. Postmenopausal women have a lower risk of breast cancer compared to premenopausal women of the same age. This is true for both natural menopause or menopause induced through surgery 8.

Exogenous hormones and breast cancer risk

The Pill

The use of oral contraceptives (OCs) slightly increases the risk of breast cancer in current and recent users, but there is no significant excess risk ten or more years after stopping use ( Table 4.29).

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These estimates are based on a collaborative analysis of 54 studies in 25 countries, with data on over 50,000 women with breast cancer. Cancers diagnosed in women who have used OC tend to be less clinically advanced than those detected in never-users. OC users are generally younger women whose breast cancer risk is comparatively low, so the small excess risk in current users will result in a relatively small number of additional cases.

The formulation of OCs has changed considerably since use became widespread in the 1960s but current evidence suggests that this does not affect risk 9. The risk of oral contraceptive use in women is similar regardless of a woman’s family history, ethnic origin, years of education, age at menarche, height, weight, menopausal status and alcohol consumption 9.

Hormone Replacement Therapy (HRT)

HRT use increases the risk of breast cancer and reduces the sensitivity of mammography 10-13. The risk increase of breast cancer for current users of HRT is 66%. 13

The effect is substantially greater for oestrogen-progestagen combinations than for oestrogen only HRT. Risk increases with duration of use: the risk for current users of oestrogenprogestagen combinations for 10 or more years was 2.31 (CI 2.08-2.56) compared to 1.74 (CI 1.60-1.89) for 1-4 years of use. Risk decreases with cessation of use; past users have a similar risk to never users 13.

In the UK, use of HRT halved between 2000-01 and 2006, and it has been estimated that there were 1,400 fewer cases of breast cancer in women aged 50-59 in 2005 than there would have been if no such fall in use had happened. 45.

HRT is used by over 20 million women in western countries 14 to counteract menopausal symptoms and is an important source of exogenous oestrogen and in some cases progestagen exposure. A recent review concluded that the excess incidence of breast cancer, stroke and pulmonary embolism in postmenopausal women who use HRT for 5 years was greater than the reduction in incidence of colorectal cancer and hip fracture 14.

HRT should not be used for prevention of cardiovascular disease but the risks and benefits for treating menopausal symptoms should be evaluated on an individual basis.

Endogenous Hormones and breast cancer risk

Higher levels of endogenous hormones have long been hypothesized to increase breast cancer risk. A pooled analysis of nine prospective cohort studies found a statistically significant increased risk of breast cancer in postmenopausal women with higher levels of sex hormones 15. The risk was approximately double for women whose oestradiol levels were in the top quintile compared with women whose oestradiol levels were in the bottom quintile. Evidence for premenopausal women is inconclusive.

Bodyweight and breast cancer risk

Overweight and obesity, as measured by high body mass index (BMI), moderately increases the risk of postmenopausal breast cancer and is one of the few modifiable risk factors for breast cancer 16. BMI is calculated by dividing weight in kg by height in metres ². A BMI under 20 is classified as underweight, 26-30 as overweight, and over 30 as obese.

Estimates of the proportion of breast cancers caused by overweight and obesity in the UK range from 7% of postmenopausal breast cancer cases to 8% of all breast cancer cases. 17,46. In one pooled analysis the risk of developing breast cancer was increased by around 30% in postmenopausal women with a BMI >28kg/m2 compared to a BMI of less than 21kg/m2 16.Recently, the UK Million Women study reported a similar risk increase of 29% for women with a BMI of 30 or higher compared to a BMI of 22.5-24.9. 46

There is evidence that the effect of BMI on postmenopausal breast cancer is limited to women who do not use HRT 47. In a prospective mortality study the risk of breast cancer death increased with increasing BMI reaching a two-fold increased risk of death for the highest (>=40kg/m2 ) compared to lowest BMI category (< 24.9kg/m2) 18.

After the menopause, when the ovaries stop producing oestrogen, adipose tissue is the primary source of endogenous oestrogen so obese and overweight women are exposed to higher levels of oestrogen. Obesity is also associated with lower levels of sex hormonebinding globulin (SHBG) which increases the amount of bioavailable oestradiol 19. In premenopausal women, some but not all studies have observed that a higher BMI is associated with a slightly lower risk of breast cancer - possibly because it results in decreased exposure to endogenous oestrogens through increased anovulatory cycles.

Physical activity and breast cancer risk

A recent report from the International Agency for Research on Cancer concluded that physical activity has a preventive effect on breast cancer 20. This may be an indirect effect with exercise lowering BMI, or a direct effect on hormonal and growth factor levels.

The magnitude of this effect varies between studies; a typical result is a 30-40% reduction in the risk of breast cancer with a few hours per week of vigorous activity versus none 1.

Alcohol and breast cancer risk

A significant association between alcohol intake and breast cancer has been found, with an increase of risk of 7% for each additional 10 grams of alcohol consumed on a daily basis ( Figure 4.221).

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Around 4% of breast cancers in women in developed countries may be attributable to alcohol. Although alcohol and tobacco smoking are closely related social habits, there is no direct association between tobacco and breast cancer.

Diet and breast cancer risk

A diet high in fat has been positively associated with breast cancer in international correlation studies 22, animal studies 23 and case control studies 24. However, pooled analyses of cohort studies generally found no important association between fat intake and breast cancer risk 25-26 while a meta-analysis found a modest positive relation with both total and saturated fat intake 27.

A recent prospective study suggests these differences may be due to the difficulties of accurately recording fat intake 28. In this study the use of a detailed 7- day food diary revealed a significant association between saturated fat (found mostly in high fat milk, butter, meat, cakes and biscuits) and breast cancer risk, which the more commonly used food frequency questionnaire did not.

Overall, the evidence suggests fat intake, particularly animal fat, may cause a small increased risk of breast cancer but probably does not play as large a role as was once thought.

Height and breast cancer risk

Taller women have an increased risk of breast cancer 29. A pooled analysis estimated that the relative risk for women 1.75 metres or taller compared with women shorter than 1.6 metres was 1.22 for all women and 1.28 for postmenopausal women 16. There was an approximate increase in relative risk of 7% for each additional 5 centimetres in height for postmenopausal women and 2% for premenopausal women.

The underlying mechanism for the association between height and breast cancer risk is unclear, and it is likely that height may be a marker for other exposures that influence breast cancer risk 30.

Ionising Radiation and breast cancer risk

Ionising radiation is an established risk factor for breast cancer and excessive exposure to radiation should be avoided. The effect of radiation on the breast is strongly related to age at exposure ie the younger the woman is exposed the greater the excess risk.

A recent study estimated that exposure to diagnostic x-rays may be responsible for 29 cases per year of female breast cancer before the age of 75 in the UK, an attributable risk of 0.1% 31 Overall 0.6% of the cumulative risk of cancer to age 75 might be radiation-induced in the UK- approximately 700 cases of cancer each year. This was low compared to the other developed countries studied.

Another group at increased risk are women treated for Hodgkin’s disease by mantle irradiation where there is an approximate doubling of lifetime risk.51 Women treated in this way before age 35 are being recalled nationally and offered special surveillance.

Socio-economic status and breast cancer risk

Breast cancer is one of the few cancers to have a higher incidence in the more affluent social classes ( Figure 4.332). The age standardised incidence rate is 115.1 per 100,000 women in the least deprived quintile compared to 97.3 in the most deprived quintile. This is probably a reflection of other factors including reproductive history and early nutrition.

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Mammographic density and breast cancer risk

Mammographic density is related to the risk of breast cancer. (Density relates to the relative amounts of fat, connective tissue and epithelial tissue in the breast. Breasts with a higher proportion of fatty tissue are less dense. Cancer is less easily detected in denser breasts.) Women with denser breasts have 2-6 times the risk of breast cancer compared to women with less dense breasts 33. It is estimated that 20-30% of the variation in breast density is accounted for by menopausal status, weight and parity 34 and there is growing evidence that the more important determinant of breast density is inherited 34, 35.

Finding the gene or genes responsible for breast density may lead to a better understanding of the development of breast cancer 36, 37.

Benign breast disease and breast cancer risk

Benign breast disease 34 is a generic term describing all non-malignant breast conditions. As such it encompasses diseases associated with an increased risk of breast cancer and others that do not have a raised risk.

The commonest breast lump in young women is a fibroadenoma which is not associated with an increased risk of breast cancer.

Women in their 30s and 40s may develop cysts and those that suffer multiple cysts are at slightly increased risk of breast cancer.

Women who have had biopsies that showed proliferative breast disease without atypia have a 2-fold increased risk, while women with atypical hyperplasia have a 2-5 fold increased risk 37-39.

The presence of lobular carcinoma in situ increases the risk of developing cancer in either breast whereas DCIS may progress to invasive cancer within the affected breast.

Personal history of breast cancer

If a woman has had breast cancer, her risk of developing a second primary breast cancer is 2-6 times the risk seen in the general population of developing a primary breast cancer 40.

Family History of Breast Cancer

A woman with one affected first degree relative (mother or sister) has approximately double the risk of breast cancer of a woman with no family history of the disease; if two (or more) relatives are affected, her risk increases further 41, 42.

However, over 85% of women who have a close relative with breast cancer will never develop the disease, and more than 85% of women with breast cancer have no family history of it 42. In developed countries it is estimated that hereditary factors contribute around a quarter of inter-individual differences in susceptibility to breast cancer, while environmental and lifestyle factors contribute the remaining three-quarters 1.

A small proportion of women have a particularly strong family history of breast cancer and are at very high risk. Mutations in the breast cancer susceptibility genes BRCA1 and BRCA2 account for the majority of families with four or more affected members and 2-5% of all breast cancers 43. Women carrying such a mutation have a 50-80% chance of developing the disease.

Genetic testing for faulty BRCA genes is available on the NHS for women with a very strong family history. Increased susceptibility to breast cancer is also a feature of several rare, familial cancer syndromes ( Table 4.4).

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Since breast cancer affects one woman in nine there will be many women who have a mother or sister with the disease. But only if there are several family members with early onset breast cancer is there a likelihood of a significant inherited predisposition to the disease 44.

Breast screening statistics

This section presents information and statistics on breast screening from the NHS Breast Screening Programmes in the UK.

Summary of breast screening activity in the UK - 2004/2005

• More than 2 million women aged 50-70 years were invited for screening
• 1.7 million women were screened
• 83,000 women were recalled for further tests - 4.8% of women screened
• Nearly 14,000 cancers were detected - 17% of those undergoing further tests, 0.8% of all women screened
• 2004 was the first year that women aged 65 to 70 were invited for breast screening

In this section you can read about:

• A brief history of the breast screening programme
• Definition of terms used in breast screening
• Sensitivity and specificity of mammography
• Breast screening and Hormone Replacement Therapy
• The potential effect of breast screening
• Statistics from the breast screening programme
• Issues around breast screening

Information on breast cancer screening for patients

• CancerHelp UK, our patient information website answers your questions about mammography.

Find out more about why early detection of breast cancer is important and Cancer Research UK funded research into breast screening.

Further breast screening programme statistics can be found on the NHS Breast Screening Programme website.

Breast screening - definition of terms

This page presents information on the definition of terms used in breast screening, taken from the CancerStats report - Breast Screening - UK, published in 2003.

A screening test does not diagnose a particular condition, but sorts the population into test positive and test negative groups.

The sensitivity of a screening test is the proportion of the screened population that has the disease that tests positive. For instance, a sensitivity of 80% means that for every ten participants with the disease, eight will test positive and the other two will be false negatives. A test with poor sensitivity results in a high proportion of the population with the disease escaping detection. These people will be falsely reassured and could delay presenting important symptoms.

The specificity of a test is the proportion of the screened population that is disease free that tests negative. For instance, a specificity of 90% means that nine out of ten people who do not have the disease will have a negative result. One out of ten will have a false positive result and require further assessment before the possibility of disease can be eliminated. A test with poor specificity will have important consequences for the individual, including anxiety and unnecessary follow up.

An ideal screening test would have a high sensitivity (to reduce the number of false negatives) and a high specificity (to reduce the number of false positives). It is usually difficult to achieve this as there is a trade off between the two measures; tightening the criteria for one results in a decrease in the other.

Another feature of a screening test is the predictive value and there are two aspects to this. The positive predictive value of a test is the proportion of people who test positive who have the disease. The negative predictive value is the proportion of those who test negative who are disease free. The predictive value is influenced by both the sensitivity and specificity of the test, as well as the prevalence of the condition being screened for.

The relationships between specificity, sensitivity and predictive value are shown in Table 2.1.

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Coverage of breast screening is the proportion of women resident in the screening target area (excluding those who are ineligible for screening, for example, those who have had a bilateral mastectomy) who have had a recorded test result at least once in the previous three years.

The uptake of a screening programme is the proportion of women invited for screening for whom a test result is recorded.

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Breast screening - potential effects

This page is based on the CancerStats report Breast Screening - UK published in 2003.

The page presents information on the potential effect of breast screening including, registrations of carcinoma in situ, incidence of invasive cancer, mortality, survival and anxiety.

Registrations of carcinoma in situ

Ductal carcinoma in situ (DCIS) registrations have increased markedly since the introduction of breast screening, because it is a condition that is usually not palpable and therefore is mostly diagnosed by mammography. DCIS accounts for approximately 20% of screen-detected cancers.

Between 1995 and 1999 there were, on average, 2,732 registrations of carcinoma in situ in the UK per year which equates to a rate of 9.3 per 100,000 women.The peak age groups for numbers and rates of DCIS are the same as the screening age groups ( Figure 5.1).

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Critics of the breast screening programme have voiced concerns that identifying DCIS is overdiagnosis of breast cancer, as these lesions may never progress or threaten the woman’s life. 1 However, the majority of screen-detected DCIS is high grade (69%) and necrotic (87%), and there is growing and convincing evidence that the detection of high grade and necrotic DCIS by screening and its subsequent treatment prevents the development of high grade invasive cancer with poor prognosis. 2-4

Treatment of DCIS is usually wide area excision with or without radiotherapy. Recent results from a multi-national randomised controlled trial have shown the effectiveness of radiotherapy after complete local excision, but little evidence for the use of tamoxifen. 5 If the area of abnormality is extensive, a mastectomy may be more appropriate. Currently around 30% of screen-detected DCIS is treated with mastectomy. 6

Incidence of invasive cancer

The incidence of breast cancer in Britain has increased from an age standardised rate of 75 per 100,000 women in 1979 to 114 per 100,000 women in 2001. 7-10 Further details are in the Breast Cancer section. Introduction of the Breast Screening Programme in the UK in 1988 led to a transient additional increase in incidence, lasting four to seven years, for women aged 50-64 years, but the underlying increase in incidence predates screening, continues today, and is evident in all ages between 45 and 99 years 11 ( Figure 5.2). 7-10

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Mortality

Several analyses combining the results of published studies have been carried out to estimate the effect of mammography on mortality from breast cancer.

The most recent - a meta-analysis of seven randomised trials - concluded that there was a 15-20% reduction in risk of death from breast cancer in women attending mammography. The authors calculated that for 2,000 women attending screening over a period of 10 years, one life would be saved. At the same time, 10 women would be falsely diagnosed with cancer as a result of screening and undergo unnecessary treatment as a result. 30

A meta-analysis of nine randomised controlled trials and four observational studies showed that mortality from breast cancer is reduced by 26% in women aged 50-74 who are offered screening mammography (relative risk = 0.74, 95% confidence interval (CI) 0.66 to 0.83). 12 The same meta-analysis did not show a mortality reduction for women aged under 50 (relative risk = 0.93, 95% CI 0.76 to 1.13).

Another systematic review, published in 2000, concluded that screening for breast cancer with mammography is unjustified. 13 However, this review has been widely criticised for being far too stringent. 14-16

The reviewers excluded six out of eight randomised controlled trials on the basis of potential age imbalances between intervention and control groups, but the age differences were very small. The largest age difference was five months, and this was likely to be due to the cluster design of the trial (the Swedish Two County Trial). The authors of this trial have now adjusted for the differences in age and observed a significant reduction in breast cancer mortality associated with breast screening of 30%. 17

A recent analysis of mortality from breast cancer reported a 21% absolute reduction in observed death rates from breast cancer by 1998, compared with expected mortality rates in the absence of screening. The authors estimated that overall breast screening resulted in a 6.4% reduction in mortality, the rest of the decrease being due to improved treatment and earlier diagnosis independent of screening. 18

The controversy surrounding the effectiveness of breast screening continued with the publication in 2001 of an adapted version of the 2000 review. 19

This review claimed to strengthen and confirm the original findings questioning the impact of breast screening on mortality. 13

In a more recent review the International Agency for Research on Cancer (IARC) concluded that many of the criticisms of screening were unsubstantiated, and that breast screening of women aged 50-69 results in a 25% reduction in breast cancer mortality in women invited for screening (relative risk = 0.75, 95% CI 0.67 to 0.85).

The review also showed that screening women aged 40-49 does not significantly reduce mortality (relative risk = 0.81, 95% CI 0.65 to 1.01) 20 Amongst women who actually attend mammography, the mortality reduction has been estimated to be 35% for those aged 50-69 years at entry to screening. 20

The debate has continued: the methodology and conclusions of the 2000 and 2001 reviews have been recently challenged 21, 22 whilst the original authors continue to defend their position. 23

Survival

Breast cancer survival rates are worse the later the stage of the disease at diagnosis ( Figure 5.3). 24

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Over 20% of screen-detected cancers are non-invasive (DCIS), and a further 40% are tumours under 15mm. Invasive cancers detected while small are less likely than larger tumours to have spread to local lymph nodes or distant sites and therefore tend to be earlier stage cancers with a good prognosis. More details are given in the Breast Cancer section.

Anxiety

False positive results for breast screening can cause anxiety, as well as prompt further invasive investigations. A large UK study has shown that anxiety levels in women who are recalled and then found to be disease free are significantly higher during the year after their recall appointment than in women who receive negative results at initial screening. 25-27 For some women, anxiety persisted at three years after the recall appointment, and this could affect the attendance rates for subsequent screens. 28 The results about anxiety in false positive women have been confirmed in Sweden. 29

Issues around breast screening

This page presents information on various issues around breast screening, including frequency of screening, number of views taken, informed choice and screening women under 50 with a family history of breast cancer.

Frequency of screening

A recent randomised controlled trial to evaluate the optimum screening interval compared annual mammography with three-yearly mammography over a period of seven years. Over 76,000 women were involved and the results showed that shortening the screening interval from the current three years did not produce a statistically significant decrease in the predicted mortality from breast cancer. 1 Therefore the screening interval in the Breast Screening Programme will remain at three years.

Numbers of views taken at incident (repeat) screens

Originally the breast screening programme took one view of each breast at every appointment. Two view mammography was introduced for prevalent (first) screens following a randomised controlled trial that showed a 24% increase in cancer detection rates as a result of two view mammography at the first appointment. 3

Recent epidemiological evidence supports this result and has shown an increase of 45% in detection of small invasive cancers when double view mammography is used at prevalent screens, and a 42% increase at incident (subsequent) screens. 4 The programme has been extended so that two view mammography is now used at every screen.

Informed choice

As with the Cervical Screening Programme, the Breast Screening Programme has designed a patient information leaflet to facilitate informed choice. The leaflet outlines what breast screening can and cannot achieve, including an explanation about false positive and false negative results. 5

Copies of this leaflet can be obtained from the NHS Responseline on 08701 555 455, or email doh@prolog.uk.com

Breast screening for women under 50 with a family history of breast cancer

A large study is underway investigating the effectiveness of mammography in women who have a strong family history of breast cancer.

Ten thousand women aged 40-44 with a significant family history are being recruited and offered annual two-view mammography for five years. The incidence by size, node status and histological grade will be compared with a contemporaneous comparison group and a historical comparison group. 6

Breast screening in the UK - a brief history

Breast cancer is the most commonly diagnosed cancer in UK women, with over 44,000 new cases diagnosed in 2003. 1-4

Breast cancer accounts for 17% of female mortality from cancer in the UK, with 12,500 deaths each year. 5-7 There has been a dramatic reduction in breast cancer mortality since the late 1980s when over 15,000 women were dying each year 8 (see Breast Cancer section).

This page is based on the CancerStats Report - Breast Screening - UK, published in 2003.

The benefit of breast screening by mammography has been demonstrated (see Mortality section). In all randomised trials of women aged 50 and over, mortality from breast cancer is reduced in those offered screening compared with unscreened controls (although the reduction is not statistically significant in all trials). However, controversy continues over the effectiveness of breast screening programmes (see Effect of screening ).

In 1986, the Forrest Report 9 recommended the introduction of a National Health Service Breast Screening Programme (NHSBSP) offering three yearly mammography to women aged 50 to 64.

In 1988, the world’s first national breast screening programme was set up in England and more than 110,700 women between the ages of 50 and 64 were invited for screening.

It has been estimated that if 70% of eligible women attend screening, there would be a 25% reduction in breast cancer mortality rates in women invited for screening. The uptake target of 70% was included in the Health of the Nation White Paper in 1992 and remains the minimum standard for the NHS Breast Screening Programme. 10

All UK women aged 50-64 who are registered with a GP are invited for screening every three years. Since 2004, this has been extended to include women aged 65-70 years. Women aged over 70 can request mammography once every three years, but currently they are not routinely invited.

The screening process is organised by dedicated professionals at special screening sites (either fixed or mobile units). Unlike cervical screening, there is no financial incentive for GP practices to achieve a high uptake.

Until 2004, women were offered two view mammography at their first screen (prevalent screen) and a single oblique view mammogram in subsequent screens (incident screens).Two view mammography is now used at every screen by the end of 2003.

All screened women are sent written results. For some women, the mammogram is inconclusive and they are invited for further tests at assessment centres run by the screening programme’s multidisciplinary teams. Further investigations may include another mammogram, clinical breast examination, ultrasound, core biopsy, fine needle aspiration (cytology) or surgical biopsy.

The NHS Breast Screening Programme is the first NHS programme to be based on rigorous quality standards, both for the programme as a whole and for each specialist group (for example, surgeons and radiologists). Copies of the standards can be obtained from the Cancer Screening Programme. 11 Adherence to these standards has led to the high reputation of the breast screening programme.

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Breast screening and HRT

A systematic review of the relationship between Hormone Replacement Therapy (HRT) use and the effectiveness of mammography concluded that women using HRT are more likely to receive false negative screening results and are also more likely to receive a false positive recall. 1

However, the results of these studies had not been adjusted for crucial confounding factors such as age of the woman and menopausal status; the author of the review concluded that the size of the effect could not be estimated with confidence.

Results from the Million Women study - a large prospective study of women attending breast screening in the UK - show that current users of HRT are 64% more likely to receive a false positive recall than never users. 2

According to results from the same study, sensitivity of mammography (the proportion of breast tumours diagnosed within 12 months of screening detected through screening) is nine percentage points lower in current HRT users than in never users (83% versus 92%). 3

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Breast screening - performance of mammography

This page contains information on the performance of mammography taken from the CancerStats report - Breast Screening - UK published in 2003. Sections include sensitivity by age, specificity, positive predictive value and interval cancers. The Issues around Breast Screening page has information on two view mammography.

Sensitivity by age

To calculate sensitivity the number of true cancers must be known. The number of true cancers is estimated from the number of screen-detected cancers plus the number of cancers that are detected in a suitable time interval, often 12 months. The sensitivity will be lowered if the time since mammography is increased as additional cancers will be detected. These additional cancers will consist of those that were missed by mammography and true interval cancers that have developed since the last screening.

The sensitivity of mammography in women aged over 50 has been estimated to range from 68% to over 90%, with most trials and programmes achieving sensitivities of around 85%. In women aged 40-49 the sensitivity has been reported to be lower, with estimates between 62% and 76%. 1

Mammography is less effective in identifying cancers in women under 50 because breast tissue tends to be denser in pre-menopausal women. The sensitivity of mammography is much lower in women with dense breasts than those with predominantly fatty breasts. 2 Furthermore, cancers found in younger women tend to be more aggressive and grow faster. 3, 4

Specificity

The specificity of breast screening by mammography ranges between 82% and 97%. 1

Positive predictive value

Estimates of positive predictive value in the UK Breast Screening Programme range from 6% to 8% for prevalent screening, meaning that 6% to 8% of women recalled for further tests after their first screening have cancer. The positive predictive value is higher for incident screens and has been estimated as between 12% and 14%. 5

Interval cancers

A necessary condition for effective screening is that the incidence of cancer occurring in the interval between screens (interval cancers) is kept relatively low. Interval cancers can occur through failure to detect an abnormality at the time of screening (false negative result), or as a new event after a negative screen (true interval cancer). The effectiveness of a screening programme depends on both the sensitivity of the screening test and the frequency of screening. Less frequent screening will lead to an increase in the number of true interval cancers. As the overall interval cancer incidence approaches that of the unscreened population, the benefits of screening disappear.

Measures of interval cancers can be expressed in two ways: as the rate of interval cancers per women years, or as a proportion of the underlying incidence of breast cancer in the absence of breast screening. It has been assumed that the background incidence of breast cancer, without breast screening, is 22 per 10,000 person years for women aged 50-64. 6

Table 3.17-10 shows the standards set for the UK Breast Screening Programme and results from some individual programmes.

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The rates of interval cancers have improved over time, a likely result of the introduction in 1995 of two view mammography in prevalent screens and improvements in techniques and reading standards within the National Screening Programme.

Breast screening - statistics

This page presents breast screening statistics from the NHS Breast Screening programme including a summary of breast screening in the UK, statistics in detail, women aged 65+, treatment of screen detected cancers and total screening activity for women of all ages.

Summary of breast screening activity in the UK - 2004/2005

• More than 2 million women aged 50-70 years were invited for screening
• 1.7 million women were screened
• 83,000 women were recalled for further tests - 4.8% of women screened
• Nearly 14,000 cancers were detected - 17% of those undergoing further tests, 0.8% of all women screened
• 2004 was the first year that women aged 65 to 70 were invited for breast screening

Breast screening statistics are also available for England, Wales, Scotland and Northern Ireland.

Breast Screening statistics in detail

The UK breast screening programmes invited 2,074,572 women for breast screening in 2004/5 and almost three-quarters were screened. This figure includes 129,202 women who were screened after GP or self-referral.

Table 6.1 summarises breast screening activity in women aged 50 and over.

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Table 6.2 shows a small decrease in acceptance by age-group. Invited women aged 71 or over are too few in number for any conclusions to be drawn.

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Of the more than 1.7 million women who were screened, 4.8% were recalled for further investigations (83,028 women).

After further investigation a woman may be diagnosed with cancer or, a pre-cancerous lesion (DCIS), be given the all clear, or be placed on ‘early recall’. ‘Early recall’ occurs when a woman is not given a result but is asked to return for further tests before the routine three-yearly examination is due, most frequently after 6 or 12 months.

Breast screening for women aged 65+

In 2004, women aged 65-70 were invited for breast screening for the first time. More than a quarter of a million women aged over 65 are now screened in the UK. Women aged 65-70 are usually invited and women over 71 are screened on request.

Table 6.3 shows the screening activity for women in these age-groups.

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When we compare outcomes for women aged 50-64 and women aged 50-70 we can see that the older women have a higher rate of invasive cancer. This reflects their increased risk.

Table 6.4 compares outcomes for these two groups for women invited for screening and those who refer themselves for screening. Women who refer themselves are more likely to have breast cancer.

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Treatment of screen detected breast cancer

Figure 6.1 compares the rate of mastectomy (breast removal) to ‘lumpectomy’ (breast conservation). Most screen detected cancers are treated by lumpectomy.

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Total screening activity - all ages

Table 6.5 shows complete information for all women screened by the UK screening programme.

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Breast cancer - UK survival statistics

Survival rates for breast cancer have been improving for more than twenty years and more women are being successfully treated than ever before.

The information on breast cancer survival rates on this page is written for use by health professionals. If you are looking for information because you or someone you know has been affected by breast cancer, then the CancerHelp UK pages on breast cancer are likely to be more relevant and useful, particularly the section on statistics and prognosis.

This page includes breast cancer survival statistics including trends, survival by age and stage of diagnosis and patterns by deprivation

Understanding breast cancer survival statistics

In general, when talking about cancer survival rates, five-year survival is most commonly used. This is because one-year survival gives only a very short term view of prognosis and progress and for ten-year survival and beyond you have to look at people diagnosed a long time ago.

However, a new method of predicting survival rates has meant that we are now able to estimate long term survival rates for women with breast cancer.

A common misconception is to treat survival rates as ‘cure’ rates. However, there are very few types of cancer for which the five-year survival rate effectively represents a cure rate. For the vast majority of cancers survival rates continue to fall beyond five years after diagnosis, most notably for women with breast cancer, among whom survival rates continue to decline more than twenty years after diagnosis.

Breast cancer survival rates trends

Survival rates for breast cancer have been improving for more than 20 years. The estimated relative five-year survival rate for women diagnosed in England and Wales in 2001-2003 was 80%, compared with only 52% for women diagnosed in 1971-1975 ( Figure 3.1) 1, 2,14 The estimated relative twenty year survival rate for women with breast cancer has gone from 44% in the early 1990s to 64% for the most recent period.

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Breast cancer survival rates in the rest of the UK are similar. The latest survival statistics for Scottish women show that five-year relative survival rates have increased from 63.5% for patients diagnosed in 1981-85 to 79.7% for those diagnosed in 1996-99. 3

Breast cancer survival rates by age

As Figure 3.21 shows, breast cancer survival rates at 5, 10, 15 and 20 years are higher in women diagnosed in their 50s and 60s than rates for either younger or older women.

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The largest improvements in five-year survival have been for women aged 50-69 years, while the improvement in 1-year survival was similar in all age groups. 4[4]

Breast cancer survival rates by stage at diagnosis

The later the stage of breast cancer at diagnosis, the lower the survival rate ( Figure 3.35).

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The proportion of advanced stage breast cancer cases increases with age, and some, but not all studies show that older women are more likely to delay in the presentation of breast cancer 6.

Breast cancer survival rates and deprivation

Women with breast cancer who live in affluent areas have better survival rates than women in deprived areas 1-2. The most recent data for England and Wales has shown a statistically significant deprivation gap difference of 5.8% in five-year survival for women diagnosed between 1996 and 1999. Scottish data in Figure 3.43 shows a 6% difference in five-year survival between the least and most deprived groups of patients (76.7 v 70.4%).

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A study in Glasgow showed that women from deprived areas are more likely to present with locally advanced or metastatic disease 11-12. A follow up study of the Glasgow work concluded that women living in affluent areas did not receive better NHS care and that women from deprived areas seem to have greater co-morbidity 13.

Breast cancer - symptoms and treatment

This page presents information on the symptoms and treatment of breast cancer including in-situ carcinoma,early breast cancer and advanced breast cancer.

Breast cancer symptoms

Many breast cancers are detected by mammography before any symptoms are noticed.

Other signs include:

• breast lumps (although most of these are benign),
• change in size or shape of the breast,
• dimpling of breast skin,
• nipple inversion,
• change in the nipple,
• swelling or lump in the armpit
• and very rarely a blood-stained discharge from the nipple or rash around the nipple.

A recent meta-analysis concluded that breast self examination is not an effective method of reducing breast cancer mortality. 1 The NHS recommends that all women are 'breast aware': know what is normal for them and what signs of disease to look for 2 , and that women aged 50 or over attend for breast screening.

Treatment guidelines have been published to improve and standardise the treatment of breast cancer in the UK. 3-7

Surgery and radiotherapy are used to control local disease, and systemic treatments (chemotherapy and /or hormonal therapy) to combat frank or occult metastatic disease. Systemic treatments may also be administered up front as a primary treatment to reduce the size of the tumour prior to surgery.

Nearly all patients, whatever the stage of their disease, have some form of surgery. Other tests are carried out to assess the extent of the disease. The main stages of invasive breast cancer are shown in Table 6.1.

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A patient's treatment will depend upon a number of factors including the stage and grade of their tumour, hormone receptor (oestrogen and progesterone) status, menopausal status and general health.

Many breast cancer patients are elderly and there is growing concern that they may receive inadequate treatment on the grounds of age alone. The elderly are under-represented in clinical trials making it difficult to determine best practice for the growing numbers of elderly patients. 8-11

Less aggressive treatment may be appropriate for frail, elderly patients but a recent trial reported that older patients receiving tamoxifen alone for early breast cancer has an unacceptably high rate of local recurrence or relapse compared to those treated by surgery (modified radical mastectomy). 12 A parallel trial comparing tumour excision and tamoxifen with modified radical mastectomy showed that good local control could be achieved in selected patients treated with tumourectomy and tamoxifen, avoiding mastectomy and irradiation. 13

Another trial reported that elderly patients are less likely to receive conservative surgery than younger patients, yet their quality of life is better if they do. 14

Breast cancer treatment - Carcinoma In-Situ

The standard treatment of lobular carcinoma in situ is surveillance, whereas ductal carcinoma in situ (DCIS) is often treated by complete local excision as there is a strong possibility that it will progress to invasive carcinoma. 15

Cancer Research UK has supported two trials of treatment for DCIS: a European study showed the value of radiotherapy and the UK/ANZ DCIS trial reported on the benefit of radiotherapy over tamoxifen for women with completely excised ductal carcinoma in situ. 16-17

Breast cancer treatment - Early Breast Cancer (Stage I-III)

Early breast cancer is potentially curable. Surgery is carried out to remove the tumour with an increasing trend towards more conservative surgery and reconstruction of the breast.

The timing of surgery may be important: premenopausal women with early breast cancer seem to have a significantly better prognosis if their tumours are excised during the luteal phase I of the menstrual cycle. 18

During surgery, axillary lymph nodes are checked to see whether cancer has spread beyond the breast. New techniques of sampling lymph nodes may help to reduce the significant disability of lymphoedema of the arm.

A short course of radiotherapy is given to patients who have had conservative surgery or are considered at high risk of local recurrence. Around 6% of women treated with breast conserving surgery and radiotherapy have local recurrence, and if this is within the first two years they appear to have a worse prognosis than those with longer disease-free survival.

Some patients, for example young patients with large tumours, may receive chemotherapy before surgery (neo-adjuvant) to shrink the tumour, allowing more conservative surgery.

Women who have oestrogen sensitive (ER positive) tumours 19 receive some form of hormonal therapy to block the cancer-promoting effect of oestrogen. The use of tamoxifen was shown to significantly reduce the risk of recurrence and increase ten year survival in women with ER positive and ER unknown status tumours 20, 21 and its gradual widespread use is one of the main factors associated with the dramatic fall in mortality during the late twentieth century.

Trials are ongoing to establish even more effective drugs and regimens for pre- and postmenopausal patients, taking into account side-effects as well as survival times. The ATAC trial recently reported its early results comparing anastrazole alone, anastrazole plus tamoxifen, and tamoxifen alone for postmenopausal women and has shown the benefits of anastrozole over tamoxifen in disease-free survival in early breast cancer. 22

Most postmenopausal women receive tamoxifen for five years. In pre-menopausal women oestrogen production may be stopped by surgery (removing the ovaries), radiotherapy or drugs that reversibly suppress the ovaries (LHRH analogues) such as Goserelin.

Chemotherapy is usually given to women who have ER negative tumours although it may also be useful for some premenopausal ER positive patients. Standard treatment is usually with a combination of drugs and there is increasing evidence to suggest that one of these should be an anthracycline. 23 Clinical trials are ongoing to establish the best chemotherapy regimens.

Advanced breast cancer treatment

Most patients do not present with advanced breast cancer. For those that do, some form of systemic treatment will be considered to control the cancer and improve quality of life.

Hormonal therapies include tamoxifen, progestogens and aromatase inhibitors whereas chemotherapy is usually a combination of drugs including an anthracycline.

A monoclonal antibody treatment (Herceptin) has been shown to provide clinical benefit to patients with high levels of HER2 receptor although the accurate determination of HER2 status is still under discussion. 24 High levels of HER2 are associated with ER and PR negativity and poorer prognosis. When Herceptin is combined with chemotherapy survival is significantly improved. 25 Surgery and radiotherapy may also be useful in controlling local disease.