Breast Cancer

Background Information

What is breast cancer?

Breast cancer occurs when the cells in the breast undergo uncontrolled division and growth, resulting in development of a tumour.¹ Breast tumours may be benign (non-cancerous or malignant (cancerous).¹ If left untreated, cancer cells can metastasise to the lymph nodes, from where they can spread out to further areas of the body, forming secondary tumours in organs such as the lungs and liver, or the bones.¹ Breast cancer is classified in stages depending on the extent of tumour growth and metastasis.¹

Aetiology and risk

There are several factors which have been shown to affect the risk of breast cancer in the population. These include both endogenous and exogenous elements.²

Hormonal status

Hormones have a link to breast cancer through their influence on age at menarche and menopause, both of which have a bearing on a woman’s risk of developing the disease. Endogenous hormones, such as the oral contraceptive pill and hormone replacement therapy (HRT), can also affect a woman’s risk of breast cancer.²

Genetic predisposition

About 10% of the breast cancer cases which occur in developed countries are due to genetic predisposition.³ The lifetime risk of developing breast cancer for people carrying the breast cancer susceptibility genes, BRCA1 and BRCA2, is 80-85%.⁴ Women with a family history of breast cancer are also at increased risk of the disease. Having one first-degree relative with breast cancer increases the risk by about 80%, two first-degree relatives raises risk approximately 3-fold and in those with three or more first-degree relatives affected by breast cancer the risk is elevated 4-fold.⁵

Lifestyle factors

Diet, obesity, use of alcohol and tobacco, child-bearing age and breastfeeding are all lifestyle factors which have been shown to possess a relationship to the risk of breast cancer.²

Radiation

As with many other cancers, radiation exposure is known to influence breast cancer risk.²

Incidence and impact

It is estimated that around one in every nine women will develop breast cancer during their lifetime, making it the most common type of cancer to affect women in the Western world.¹ On a global level, more than 700,000 women are diagnosed with breast cancer every year.¹ Overall, this disease accounts for a tenth of all new cancers and a fifth of all female cancer cases.¹ Incidence rates vary considerably, with the highest rates found in America and the lowest rates in Africa and Asia.^1,6 Although breast cancer is more common in older women, around a quarter of patients are under the age of 50 when diagnosed.¹

Breast cancer in Europe

On a yearly basis in Europe, over 200,000 women are confronted with a diagnosis of breast cancer.⁶ In 2000, there were 350,000 new breast cancer cases in Europe, making it responsible for 26.5% of all new cancer cases among European women and the cause of 17.5% of all cancer deaths.² There are substantial differences in both breast cancer incidence and mortality across Europe.² The regions of highest incidence are Western and Northern Europe, while Southern and Eastern Europe have lower incidence rates.² This makes the risk of getting breast cancer in Western Europe 60% greater than in Eastern Europe. Equally, the highest mortality rates are also observed in Northern and Western Europe.²

[Incidence of, and mortality from, breast cancer: Europe 2000²]

See http://www.encr.com.fr/breast-factsheets.pdf for PDF version of above graphic

The highest incidence rates in Europe are to be found in France, Denmark, Sweden and the Netherlands, where between approximately 90 to 120 new cases occur for every 100,000 females.⁷ In contrast, Latvia and Lithuania have the lowest incidence of breast cancer. In 2000, these Baltic countries reported less than 55 new incidents of breast per 100,000 females.⁷

Incidence and prevalence of breast cancer in countries surveyed as part of the GAEA initiative⁸

Country	Incidence	Mortality	Prevalence
	Cases	Deaths	5 year
Austria	4635	1637	19840
France	41957	11643	188924
Germany	55689	17994	233237
Hungary	5411	2340	20026
Italy	36634	11345	164067
Spain	15855	5914	69993
Sweden	6583	1516	29186
Switzerland	4954	1404	21990
UK	40928	13303	156741

Treatment of breast cancer

The aim of breast cancer treatment is removal of the tumour and any additional cancerous cells, coupled with prevention of recurrence. Most women are offered surgery as the initial treatment, followed by additional therapy to eliminate any residual cancer cells and reduce the risk of the cancer recurring.¹

Surgery¹

The type of surgery chosen depends on a number of factors such as the size, stage and location of the tumour, as well as the size of the woman’s breasts. The main surgical procedures for breast cancer consist of:

o Breast conserving surgery where the tumour and a small amount of surrounding tissue are removed, leaving the remainder of the breast intact.

o Mastectomy is undertaken in cases where the cancer is large or where tests have revealed abnormal changes in the breast tumour. In this instance, the entire breast is removed.

Treatment post-surgery⁹

After surgery, a woman may need additional radiotherapy, chemotherapy or hormone therapy, either alone or in combination, or no further treatment. Decisions on the type and course of post-surgical treatment, if any, hinge on the size, stage and spread of the cancer as well as other factors such as the oestrogen receptor and HER-2 status of the tumour (and all the risk factors mentioned previously).

o Radiotherapy is used in women that have had a lumpectomy, in order to remove any residual breast cancer cells left behind after surgery. Treatment spans a period of several weeks and involves a course of x-ray therapy five days a week. It is a localised treatment, which means it only kills cancer cells in the specific area where it is directed. This is usually the affected breast, or area from where the breast was removed, and sometimes also the area of the lymph nodes in the armpit (axilla) and above the collarbone.

o Chemotherapy is used post-surgery to remove any remaining cancer cells, including those that may have spread to other areas in the body, and has been shown to significantly reduce the risk of cancer recurrence. Treatment with chemotherapy continues for between three and six months, with therapy given according to well-proven standard protocols.

o Adjuvant Endocrine Therapy (also known as hormone therapy) are designed to prevent the growth of hormone-sensitive breast cancers. They exert their effects either through the blockade of oestrogen production or by preventing oestrogen from reaching its target receptors on cancer cells. Adjuvant endocrine therapy is now an essential tool in the fight against breast cancer as it decreases the risk of recurrence by at least one third.¹⁰

o Targeted molecular therapy, i.e. treatment with trastuzumab (Herceptin^®), which is now approved for adjuvant treatment.

In advanced or metastatic (secondary) breast cancer, the cancer cells have metastasized, or spread to other parts of the body. Research indicates that one of the most common sites for breast cancer metastases is to the bone. Bone metastasis is connected with a decrease in a patient’s quality of life and increased morbidity.

The majority of women with metastatic breast cancer, from 65-75%,^11,12,13,14 eventually develop bone metastasis. The earlier any metastasis is diagnosed, the more likely it can be effectively managed. Bone metastases are one of the most debilitating complications for patients suffering from breast cancer and seriously impact a patient’s day to day activities, the quality of their life and that of their caregivers.

There are specific drugs which can help slow down the destruction of the bones by the cancer. These are called bisphosphonates. They provide an effective option to reduce and delay the risk of developing bone complications from breast cancer. Bone complications (also called skeletal-related events or SREs) such as pathological fracture, spinal cord compression, surgery or radiation to bone to prevent or treat a fracture cause severe pain and debilitation, limit functionality and may require hospitalisation.

The most widely used bisphosphonate is called zoledronic acid (Zometa^®).  It is licensed for treating cancers that have spread to the bones.  It is given via a drip into a vein and the treatment has to be repeated every three to four weeks.   

Since 1978 the St Gallen conferences have focused on developing consensus opinions for the adjuvant management of breast cancer and these are now recognised as the leading international treatment guidelines for adjuvant therapy.^15,16

The St Gallen classification of patients with primary breast cancer into risk groups^15,16

Risk Factor	Low Risk *	Intermediate Risk*	High Risk†
Nodal Status	Negative	Negative	Negative or Positive
Tumour Size	≤1 cm	1-2 cm	>2cm
Grading	1	1-2 cm	2-3cm
Receipt Status	ER+ and / or PR+ **	ER+ and / or PR+	ER- and PR -
Age	≤ 35	≤35	<35

Survival statistics

Despite the general upward trend in breast cancer incidence, mortality rates have been decreasing overall. Deceleration of the increase in mortality and the beginning of a decline began in the 1970s in several Western European countries such as Sweden, the Netherlands and the UK.² However, in some countries, mainly Eastern and Southern Europe, the increase in mortality continued into the 1990s.²

[Breast cancer mortality in Europe 1995-1999²]

See http://www.encr.com.fr/breast-factsheets.pdf for PDF version of above graphic

Reduced breast cancer mortality can be attributed, in part, to the diagnosis of the disease at an early stage. Today, more than 90% of breast cancers diagnosed are ‘early’ breast cancers.¹⁷ Mortality has also improved due to the significant advances in breast cancer therapy which have led to greater chances of survival for sufferers. Chemotherapy, oophorectomy and hormone therapies such as tamoxifen and aromatase inhibitors all reduce annual rates of tumour recurrence and death in postmenopausal women and can substantially improve long-term survival.¹⁸

In Europe, the average 5-year survival of women diagnosed with breast cancer increased up to the end of the 1980s.¹⁹ However, there were substantial differences among the various countries, with survival in breast cancer cases diagnosed during 1985-1989 ranging from 81% in Swedish women to 58% in Slovakia and Poland.¹⁹ The highest European survival rates were observed in young women aged 40-49 years.²⁰ Survival depends strongly on stage at diagnosis and implemented therapy. In Europe, there are substantial differences in staging of breast cancer at the time of diagnosis, which has had strong implications for implemented therapy and survival.⁵ For instance, 34% of cases in France but only 8.5% in Estonia were in stage T1N0M0 at diagnosis. Large differences in methods of treatment are also apparent.⁵ Conservative surgery was used in 63% of cases in England and 57% in France, but only in 8% in Estonia and 13% in Spain.²¹ Overall, in 2000, breast cancer was responsible for 130,000 deaths in Europe.⁵

As of late 2005, Cancer Research UK, the UK’s leading cancer charity, estimated the 10-year survival for women diagnosed with breast cancer to be 72%.²² A further 64% of women were predicted to live for at least 20 years following diagnosis.²² Looking at outlook by stage and grade, it was predicted that 85 to 89% of women with small early breast cancers will live for at least 10 years after diagnosis.²² Survival statistics for larger cancers or those that have spread to the lymph nodes are more complicated, with estimates for 10-year survival ranging from 20 to 78%.²² For breast cancer which has metastasised, the outlook is poorer. Around one in five women (20%) with breast cancer which has spread will live for at least five years after their diagnosis, but only around 4% are predicted to live for more than 10 years.²²

– Ends –

References

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