Breast cancer

Breast cancers can have different degrees of malignancy

Breast cancer is the uncontrolled growth of abnormal cells in one or both of the breasts, causing lump (tumour) growth. Certain lumps grow in place without affecting surrounding tissues (benign tumours) while others have the capacity to metastasize and compromise the functioning of other organs. These tumours are life-threatening and are called malignant (cancer). Pathologists distinguish benign and malignant tumours by looking at their microscopic appearance under the microscope.

Also see Causes and Risk factors.

In high-risk populations like Europe, the majority of breast cancers are epithelial tumours localised to the milk ducts (85%) or lobules (15%). Less than 1% are sarcomas and lymphomas arising in other tissues within the breast. Most ductal and lobular cancers of the breast have already spread beyond the epithelium of the milk ducts to the surrounding tissue when diagnosed, and are called invasive. Mammography can detect the cancer in an early stage when it is still non-invasive, see Interventions.

The ICD provides separate codes for malignant invasive- (ICD-9 code 174 in females, 175 in males; ICD-10 code C50) and non-invasive or in situ cancers (ICD-9 code 233.0; ICD-10 code D05).

Stage at first detection is crucial for prognosis

The stage of cancer at first diagnosis is the most important determinant of the outcome of the disease and allows doctors to decide on treatment regimens and make a prognosis. It describes the extent of growth and invasion of other tissues by the tumour. The most widely used staging systems are the TNM developed by the UICC and its re-groupings by the AJCC. Each group summarizes the behaviour (invasive or not), size of the tumour (in centimetres), whether and how many regional lymph nodes are involved and whether it involves other organs. Accurate staging requires that the patient undergoes a set of ad hoc examinations, such as for example chest x-rays to detect metastases to the lungs. For example, tumours up to 1cm in size that have not invaded regional lymph node or other organs are said 'early tumours' and belong to stage group I (AJCC/TNM); tumours that have extended to the skin of the breast or the chest wall (group IIIb) or other non-adjacent organs (group IV) are said advanced.

In addition to stage of disease, the expression of oestrogen receptors in the tumour tissue is an established prognostic marker in breast cancer. Breast cancer cases with positive receptor status tend to have a greater benefit from systemic hormonal therapy.

Also see Interventions.

Breast cancer is the most common cancer in women in the EU

The breast is by far the most common site of cancer in women in the EU (excluding non-melanoma skin cancer). It is also the most common female cancer in the world although incidence and mortality rates vary significantly between countries. This cancer is very rare in men.

In women, the number of new annual cases of breast cancer in Europe is at least twice that of new cancers at any other site (Ferlay et al., 2004). One in 10 women in the EU-27 will develop breast cancer before the age of 80 years (Curado et al., 2007).

Breast cancer incidence rates increase with age, rapidly among pre-menopausal and more slowly among post-menopausal women. This pattern of flattening after menopause is not observed for other tumours, which strongly suggests that reproductive hormones play an important role in the development of breast cancer. In the EU more than 70% of the cases occur after the age of 49 years (Curado et al., 2007).

Incidence has been rising for decades but first signs of stabilisation have been observed

Population-based cancer registries have consistently documented a continuing rise of incidence rates since the 1960s. Incidence is still on the increase but the first slow-downs have been observed since 2002. It has been estimated that there were 319,000 newly diagnosed cases in the EU-25 in 2006 (Ferlay et al., 2007).

Mass screening temporarily led to increased incidence

In the 1990s mass screening by mammography further boosted the increase of registered incidence wherever it was introduced, by enabling earlier and more complete detection of cases. The degree of increase depended on the coverage and intensity of the programmes. The increase itself was temporary. The benefit of screening is that diagnosis in an earlier stage permits a more effective treatment.

The North-South gradient across Europe is diminishing

Before the introduction of mass screening in the 1990s, breast cancer incidence was the highest in Northern Europe, intermediate in Central Europe and the lowest in Southern and Eastern European countries. Estimates for 2006 show that geographical differences have been shrinking, due to rapid increases in incidence rates in the South. See Estimated incidence of breast cancer throughout Europe in 1990 and 2006.

Breast cancer more prevalent in affluent communities

When looking at the worldwide situation, we see that the risk of breast cancer is greater both in the more affluent countries of the world and in higher socio-economic groups within countries (Faggiano et al., 1997). See Estimated incidence of breast cancer throughout the world in 2002.

Possible involvement of hormone replacement therapy

In the US breast cancer incidence fell suddenly in 2003 after having been flat for several years. It was suggested that this could be due to the sudden decline in users of HRT (Ravdin et al., 2007) following the publication of a clinical trial which demonstrated an increase of breast cancer in users of HRT (Rossouw et al., 2002). Women in European countries also discontinued HRT following this publication, but no such dramatic decline has been observed here as yet.

Also see Estimated incidences, survival rates and trend in mortality of breast cancer throughout Europe (interactive - click on Indicators to select desired topic).

Mortality is declining throughout Europe

Until the late 1980s few countries in Europe had reliable population-based cancer registries. Consequently mortality was the only available indicator of the cancer burden until recently. From 1950 to the late 1980s breast cancer mortality was constantly on the increase everywhere in Europe, with a few exceptions (Sweden, Norway). This unfavourable trend was reverted in the 1990s, with downturns or at least levelling off of the rates being observed in most European countries by 2004. Since the incidence rates do not generally mirror this downward trend, this decreasing mortality can be attributed to improved access of the population to early diagnosis and optimal treatment.

In 2004, mortality was still on the increase in Latvia, Lithuania, Romania and Greece; and a clear decrease was not yet visible in Poland, Bulgaria and Estonia.

Also see Trends in mortality from breast cancer. ASR (SDR) per 100.000 of the population in selected countries, 1970-2005.

In Eastern Europe cancer (all sites) has become the most common cause of death in women aged 20-64 years, since death rates from cardiovascular diseases began to fall in the 1990s (Zatonski & Didkowska, 2008); in 2002-2003 22% of all female cancer deaths in this region were due to breast cancer (IARC).

Survival depends on the quality of the health system

Most breast cancers detected early can be cured if properly managed. By 2004 the geographic distribution of mortality from breast cancer across Europe appears to be more influenced by differences in the efficacy of the health systems than by differences in the background risk of the disease. In 2004 for example, Austria and Lithuania had the same age-adjusted mortality rates, despite the incidence of breast cancer being 50% greater in Austria. Also see Interventions.

Despite its relatively good prognosis, breast cancer is still the leading cause of cancer death in women in all but three EU-27 countries. In women lung cancer causes more deaths than breast cancer in Denmark, Hungary and the United Kingdom. See the EUphact Lung cancer.

The status of cancer control in Europe has been reviewed under the Slovenian Presidency (Coleman et al., 2008). The report highlights the gap between the EU-15 and the countries of Eastern Europe that joined the EU at a later stage (Zatonski & Didkowska, 2008), showing how disproportionately high cancer mortality is in the new member states.

Also see Estimated incidences, survival rates and trend in mortality of breast cancer throughout Europe (interactive - click on Indicators to select desired topic).

More than half of the cases occur before the age of 65 years

On average, 20% to 30% of breast cancer cases in Europe occur in young women below the age of 50 years; 33% occur at age 50-64 and the remaining in elderly women (Curado et al., 2007). It is therefore a disease that affects a large number of women in the most demanding years of their lives professionally and within the family.

Breast cancer prognosis has improved

Treatment is very effective for early cancers. 5-year survival among cases detected when the tumour is less than 2 cm in size and only a few lymph nodes are involved can be as high as 85%. 99% of the very early in situ cancers are cured if properly treated (Lee et al., 2006; Sainsbury et al., 2000). Prognosis and survival are less favourable the greater the size of the tumour and the deeper the involvement of other tissues.

Generally speaking, the 5-year relative survival of breast cancer patients has increased in European countries in recent years see Survival of female breast cancer patients diagnosed in 1990-1994 and in 1995-1999. Age-adjusted relative 5-year survival for cases diagnosed in 1995-1999 ranged from 69.3% in the Czech Republic to 84.3% in Sweden. On average, the 5-year relative survival of breast cancer patients diagnosed in 1995-1999 in Europe was 79.5% (Berrino et al., 2007). This figure may be an optimistic estimate for the pool of the EU because countries and regions where organized screening is in place are over-represented in the Eurocare working group gathering the data.

Also see Interventions.

Breast cancer has a large impact on patients

Intention-to-cure treatment may take 6 to 12 months during which the patient’s ability to attend to her normal activities is deeply disrupted. It is estimated that every day in the EU-25 countries at least 1.1 million women required treatment and health care for breast cancer in 2006.

Premature deaths have impact on the population level

Years of life lost due to premature death (YLL) is an important measure of health outcome (Lopez et al., 2006). The WHO estimated that in 2002, 60% of the YLL due to breast cancer in the WHO EURO region, which includes the Russian Federation and the countries of Central Asia, occurred before age 60 years and 82% before age 70 years.

No comparable expenditure measures for breast cancer care

There are no comparable measures of expenditure for breast cancer care and of indirect costs due to the disease, in the EU or Europe. Spending on health varies significantly within the EU-25 (Eurostat, 2007) but expenditure is not the main determinant of health outcomes, even for diseases, the fate of which depends a lot on management quality, as in the case of breast cancer (Smith, 2002). Outcomes can be improved by more effective use of resources and high quality standards (Haward, 2008; Perry et al., 2006).

Also see Estimated incidences, survival rates and trend in mortality of breast cancer throughout Europe (interactive - click on Indicators to select desired topic).

Reproductive factors are associated with the risk of breast cancer

Full-term pregnancies reduce the risk of breast cancer; this protection is greater the younger one is when first giving birth. Breastfeeding further reduces breast cancer risk, with parous women who also breastfeed their children benefiting from an additional 10% reduction in risk. Early age at first menstruation and late age at menopause increase the probability of developing breast cancer (Collaborative Group on Hormonal Factors in Breast Cancer, 2002).

Exogenous hormones increase breast cancer risk

Users of oral contraceptives that combine estrogens and progestogen experience a small increase in risk of breast cancer during the years of usage. Since the excess risk is present only during use, it does not persist after a few years of cessation, and since the users are young women, it is estimated that the associated excess risk has a small impact on the overall incidence of the disease (IARC, 2007).

The other important source of exogenous hormones is HRT in post-menopausal women. Several large epidemiological studies have shown that HRT increases the risk of breast cancer in users. The excess risk declines after cessation and reaches that of never users about 5 to 9 years later. The relative risks of being diagnosed breast cancer while taking combined HRT was estimated at 1.2 compared with never users. The relative risk was back to 1.0 (indicating no excess risk) 10 years after use ceased (Collaborative Group on Hormonal Factors in Breast Cancer, 1997). The excess risk for users is relatively small but it applies to the age groups in which breast cancer incidence rates are high. The additional cases caused may therefore be significant (IARC, 2007).

Alcohol consumption and overweight increase the risk for breast cancer

Wide differences in nutritional habits between high-risk (e.g. Europe) and low-risk populations (e.g. Japan and India) have supported the idea that some components of diet could explain differences in breast cancer incidence. However, the recent expert review on Nutrition and Cancer by the World Cancer Research Fund (WCRF/AICR, 2007) identified only two nutritional factors unequivocally linked to the risk of breast cancer: alcohol consumption and overweight.

The WCRF/AICR review estimated a 10% increase in risk for every 10 g of ethanol consumed per day. In postmenopausal women, the incidence of breast cancer increases by 13% for every increase of 5 BMI units. Additionally, postmenopausal women who are obese (BMI> 30) have a 30% greater probability to develop the disease compared to those with normal weight. Conversely, overweight in pre-menopause confers a 15% reduced incidence for every increase by 5 BMI units. It should be noted that breast cancer incidence increases with age so that two thirds of the cases occur at postmenopausal ages. Therefore, the additional cases related to overweight in postmenopausal women, outweighs those prevented in younger women.

Regular intense physical activity probably contributes to reducing the risk of breast cancer; it certainly helps maintain a healthy body weight. The WCRF/AICR concludes, however, that the evidence on any relationship between other food items/groups (cereals, vegetables, fruits, meat, etc.), macronutrients (proteins, carbohydrates, fats and oils, etc.) or a variety of micro-nutrients and anti-oxidants and breast cancer is inconclusive.

Host factors, including genetic susceptibility, are important

Family history:

Women who have had a first-degree family member (parents, siblings or children) diagnosed with breast cancer, are nearly two times as likely to develop breast cancer themselves. If two or more first-degree family members have developed breast cancer, the risk is increased by three to four times (Collaborative Group on Hormonal Factors in Breast Cancer, 2001). The occurrence of several cases in a family, diagnosed at a young age or in both breasts may indicate the presence of a genetic predisposition in the family and therefore imply a high risk of the disease.

Genetic susceptibility:

40% to 85% of women carriers of certain mutations in the BRCA1 or BRCA2 genes develop breast cancer during their life. Luckily genetic susceptibility is rare in most populations. Therefore, these conditions explain only about 5% of breast cancer cases (Ferla et al., 2007).

Multiple tumours of the breast:

Women who have had breast cancer are three to four times more likely to develop cancer in their other breast. This means that 15 to 20% of women who survive breast cancer are diagnosed as having breast cancer for a second time within the following 20 years.

Benign breast tumours:

Benign breast tumours do not spread to other organs; they are removed surgically and have no clinical consequences. Women who have had a benign lump removed have an increased risk of developing a malignant cancer later, in particular when the benign tumour had certain microscopic features called Atypical Hyperplasia (AH). 4-8% of benign lumps, depending on the woman’s age, present AH features (Dupont & Page, 1985; Carter et al., 1988; Hartmann et al., 2005).

Primary prevention can help reduce a person's risk of contracting breast cancer

Several of the known risk factors for breast cancer are amenable to the following primary prevention measures:

1. breastfeeding children as long as possible;
2. limiting the consumption of alcoholic beverages to one drink per day;
3. avoiding prolonged use of exogenous sex-steroid hormones;
4. avoiding overweight particularly in post-menopause.

Mammography is the most effective type of breast cancer screening

Mammography has been proven to be a more effective method of early detection of small tumours than the traditional methods of clinical examination or self-examination (IARC, 2002b). With regular mammography, the average tumour size on detection is less than 1.5 cm, compared with 3.5 cm for occasional clinical examination, or 2 cm for regular clinical examination. Detecting a tumour when it is smaller than 1 cm gives a woman a 90% chance of survival (Louwman et al., 2008). Also see Consequences for individual and society.

The EPGBC calls for every woman in Europe to have access to the same first-class early detection, diagnosis, treatment and aftercare, irrespective of where she lives, her social status and her level of education. They establish requirements for mammography screening, treatment and the setting up of breast units according to European guidelines. The EPGBC also state that women between the ages of 50 and 69 must have the right to attend high-quality mammography screening at two-year intervals in dedicated and certified centres paid for by health insurance schemes.

In the 1990s mass screening by mammography was introduced as part of organized programs. Population-based screening ensures that all eligible women are invited to use the service. These programs substantially improved the awareness of the disease and the access to optimal treatment for the population at large. The declining mortality rates in many European countries are most likely connected to this development. The status of mammography screening in the EU and an evaluation of its impact are reviewed in a recent report on cancer control in the community (Coleman et al., 2008).

Some of the sub-clinical tumours detected by screening would take too long to become a threat. Treating all sub-clinical tumours the same as invasive ones may result in some over-treatment. This is an adverse effect of mass screening that health providers must be made aware of. There are ongoing clinical trials to develop less invasive and disabling treatments for sub-clinical cancers including in situ tumours. These may eventually help to clear concerns about over-treatment, as in the case of cancers of the cervix, colon and rectum.

Treatment options and survival rates depend on stage

Treatment of breast cancer involves surgical removal of the tumour followed by a combination of radiotherapy, chemotherapy, hormonal therapy, or immunomodulation, depending on the stage of the disease and other prognostic factors.

Tumours detected at an early stage (I or II) may opt for breast-conserving surgery combined with radiotherapy. More advanced cases require mastectomy and radiotherapy to control local recurrence. Most cases, unless unsuitable due to other clinical conditions, also receive systemic adjuvant treatment with chemotherapy and/or hormonal therapy. Also see Definition and scope.

Improved treatment is reflected in improved survival rates. See Survival of female breast cancer patients diagnosed in 1990-1994 and in 1995-1999.

Recent reviews by the EBCTCG have shown that over a few decades treatment for breast cancer has become more and more effective, in particular by its combination with the early detection of tumours. They have also shown that all of the treatment options widely available in Europe contribute to the long-term improvement in the disease prognosis (Clarke et al., 2005, EBCTCG, 2005).

Cases presenting at an advanced stage (IIIb and IV) receive palliative care aiming at reducing pain and suffering.

Cancer survival

Disease-specific mortality

Life expectancy

Healthy life expectancy

Health Inequalities

Lung cancer

Breastfeeding

Alcohol use

Overweight

Physical activity

IARC worldwide cancer statistics

HFA-DB WHO Health for all database

Eurostat Statistical Office of the European Communities

Eurocare Statistics on cancer survival in Europe

Health-EU Portal, cancer

ENCR European Network of Cancer Registries

IARC International Agency for Research on Cancer

Evaluation of carcinogenic risks to humans

WCRF Expert report on diet, nutrition and cancer

UICC International Union Against Cancer

AJCC cancer staging

European Cancer Leagues

Trend in mortality (SDR/ASR) from breast cancer per 100.000 of the population in selected countries, 1970-2005 (interactive)

Estimated incidence of breast cancer throughout the world in 2002

Estimated incidence of breast cancer throughout Europe in 1990 and 2006

Survival of female breast cancer patients diagnosed in 1990-1994 and in 1995-1999

Estimated incidences, survival rates and trend in mortality of breast cancer throughout Europe (interactive - click on Indicators to select desired topic)

The map shows rates estimated for the different countries based on existing sources of information. These vary widely in terms of coverage, quality and reliability.

Information about the sources of data and the methods of estimation used per country is available at IARC.

The Greenland estimate (not included in GLOBOCAN 2002) was derived from Friborg et al., 2003.

Also see Boysen et al., 2008.

The 1990 national rates of the EU-15 member countries were measured by population-based cancer registries in Sweden, Finland, Denmark, UK and Ireland. For the other member states national figures were obtained by modelling national mortality rates and regional incidence rates, or by combining and modelling mortality and site-specific survival rates as described in Black et al., 1997.

National rates between 2000 and 2002 were available from registries in Sweden, Finland, Estonia, Latvia, Lithuania, Denmark, UK, Ireland, Netherlands, Austria, Czech Republic, Slovakia, Bulgaria, Slovenia, Malta. For the other EU-27 member states national figures were obtained by modelling national mortality rates and regional incidence rates as described in the referenced article. Modelling was applied to project rates to 2006 as described in Ferlay et al., 2007.

Also see Estimated incidences, survival rates and trend in mortality of breast cancer throughout Europe (interactive - click on Indicators to select desired topic).

The national estimates shown above for Austria, Denmark, Finland, Ireland, Latvia, Malta, Slovenia, Sweden and UK were produced by population-based registries. For the other countries represented the proportion of population covered by the estimation varied between 1% and 58% (Berrino et al., 2007)

The data shown above were taken from Sant et al., 2003 and Berrino et al., 2007.

Also see Estimated incidences, survival rates and trend in mortality of breast cancer throughout Europe (interactive - click on Indicators to select desired topic).