Breast Cancer

Deffination:

The breast is a gland that consists of breast tissue supported by connective tissue (flesh) surrounded by fat.

The easiest way to understand how the inside of the breast is formed is by comparing it to an upturned bush. Its leaves are known as lobules and they produce milk that drains into ducts that are the branches of the breast tree. These in turn drain into 12 or 15 major or large ducts which empty onto the surface of the nipple, just like the branches of a tree drain to the trunk.

Breast cancer develops from the cells that line the breast, lobules and the draining ducts.

Cancer cells that remain confined to the lobule and the ducts are called ‘in situ’ or ‘non-invasive’. They are sometimes also referred to as pre-cancers in recognition of the fact that these cells have not yet gained the ability to spread to other parts of the body, which is the feature that most people associate with cancer.

An invasive cancer is one where the cells have moved outside the ducts and lobules into the surrounding breast tissue.

How common is breast cancer?

Breast cancer is the most prevalent cancer among women and affects approximately one million women worldwide.

Breast cancer accounts for 30 per cent of all female cancers in the UK and approximately 1 in 9 women in the UK will get breast cancer sometime during their life.

What are the risk factors leading to the development of breast cancer?

Age

The incidence of breast cancer increases with age and doubles every 10 years until the menopause when the rate of increase slows.

Approximately a quarter of breast cancers affect women under the age of 50, a half occur between the ages of 50 and 69 and the remaining quarter develop in women who are 70 years or older.

Geographical variation

There is quite a difference in incidence and death rate of breast cancer between different countries. The biggest difference is between Eastern and Western countries.

Recent, age-adjusted figures show that the rate of breast cancer per 100,000 women is 24.3 in Japan and 26.5 in China compared to 68.8 in England and Wales and 72.7 in Scotland and 90.7 in North America in white females.

However, studies of women from Japan who emigrate to the US show that their rates of breast cancer rise to become similar to US rates within just one or two generations, indicating that factors relating to everyday activities are more important than inherited factors in breast cancer.

Reproductive factors

Women who start menstruating early in life or who have a late menopause have an increased risk of breast cancer. Women who have natural menopause after the age of 55 are twice as likely to develop breast cancer as women who experience the menopause before the age of 45.

Age at first pregnancy

Having no children and being older at the time of the first birth both increase the lifetime incidence of breast cancer. The risk of breast cancer in women who have their first child after the age of 30 is about twice that of women having their first child before the age of 20.

The highest risk group are those who have their first child after the age of 35 and these women have an even higher risk than women who have no children. These observations indicate a ‘menstrual cycle effect’. During the monthly cycle a woman’s fluctuating hormone levels cause several changes within breast tissue, which are repeated every month.

These changes possibly encourage or amplify abnormalities in the cell repair processes within breast tissue, which can in some cases lead to breast cancer later in life.

Women who have fewer menstrual cycles before their first pregnancy, either through being older when they start menstruating or younger when they first get pregnant, run less chance of such an abnormality occurring.

Inherited risk

Up to 10 per cent of breast cancer in Western countries is due to an inherited factor. This factor can be passed on from either parent and some family members pass on the abnormal gene without developing cancer themselves.

It is not yet known how many breast cancer genes there are, but to date, two specific breast cancer genes have been identified (BRCA1 and BRCA2).

Previous breast disease

Women with certain benign changes in their breasts are at increased risk of breast cancer. These women present with a breast lump, have an operation and the breast tissue removed shows severe overgrowth of the cells lining the breast lobule.

The technical name for this type of breast condition is ‘severe atypical epithelial hyperplasia’. Although benign in itself, its occurrence in a particular woman multiplies her risk of developing breast cancer during her life by a factor of four.

Radiation

Doubling of the risk of breast cancer was observed among teenage girls exposed to radiation during the second world war.

Another study of women who received radiation to the chest as a result of repeated X-rays for tuberculosis, found that there was a risk among women who were first X-rayed between the ages of 10 and 14 years. Fortunately, as TB itself has been prevented, this risk is less relevant today.

Other studies have shown that women with Hodgkin’s disease who received radiation therapy to the chest have an excess risk of breast cancer. As they are surviving to older age they are now developing not only unilateral but bilateral breast cancer.

The increase in risk depends on the dose and the age at which they received radiation. Data has also suggested that there is increased risk of breast cancer in the other breast in patients having radiation to one breast.

Lifestyle

Although there is a close correlation between the incidence of breast cancer in a country and the dietary fat intake of that country, more detailed studies have shown that there does not appear to be a particularly strong or consistent relationship between fat intake in any individual and their risk of developing breast cancer.

Weight

Being overweight is associated with a doubling of the risk of breast cancer in postmenopausal women whereas amongst premenopausal women obesity is associated with reduced breast cancer incidence.

Alcohol intake

Some studies have shown a link between the amount of alcohol people drink and the incidence of breast cancer, but this relationship is not consistent and may be influenced by dietary factors other than alcohol.

Hormones

Women who take the contraceptive pill are at a slight increased risk while they take the Pill and they remain at risk for 10 years after coming of the Pill.

The increased risk is, however, very small and cancers diagnosed in women taking the oral contraceptive Pill are less likely to have spread than those cancers diagnosed in women who have never used the oral contraceptive.

The duration of use, age at first use, dose and type of hormone within the contraceptive appears to have no significant effect on breast cancer risk.

Women who begin taking the Pill before the age of 20 appear to have a higher risk than women who begin taking oral contraceptives at an older age.

Hormone replacement therapy

Among current users of hormone replacement therapy (HRT) and those who have stopped using it one to four years previously, there is an increased risk of breast cancer.

The risk increases 1.023 times for each year of HRT use. This increased risk is very similar to the effect of a delay in the menopause by one year. The risk of breast cancer in a woman who has not used HRT increases 1.028 times for each year she is older at the menopause.

HRT using a combination of oestrogen and progestogen has been shown to be associated with a slightly higher risk of breast cancer than oestrogen-only HRT.

Cancers diagnosed in women taking HRT tend to be less advanced clinically than those diagnosed in women who have not used HRT. Current evidence suggests that HRT does not increase breast cancer mortality.

What are the symptoms of breast cancer?

* Generally, breast cancers are not painful and women do not feel unwell with them.

* Breast cancer is now commonly diagnosed by breast screening in women who have no symptoms. Approximately 6 in every 1000 women between the ages of 50 and 64 who attend for screening will be found to have breast cancer the first time they attend screening.

* A lump in the breast. In many cases, the woman herself will first suspect the disease because she notices a lump or an area of lumpiness or irregularity in her breast tissue. This may happen when she is examining her breasts or while washing or applying lotion to her breasts, or the lump may be visible.

Other signs of breast cancer include:

* a change in the skin: there is often dimpling or indentation of the skin with the formation of wrinkles. The nipple might be pulled in or there may be a discharge from the nipple.

* occasionally the nipple itself changes. A rash can affect the nipple or the nipple may weep.

* the breast may swell and become red and inflamed or the skin may change and become like the skin of an orange. In some breast cancers this is due to a blockage of the drainage of fluid from the breast.

* patients sometimes present with a lump under the arm which is a sign that the cancer has spread to the lymph glands.

How is breast cancer diagnosed?

If a woman has any breast symptoms it is very important that she consult her doctor so that the cause of these symptoms can be found. If breast cancer is found at an early stage this improves the chances of recovery. As a rule, the doctor will ask her a number of questions.

* Does the lump vary in relation to her menstrual cycle?

* What previous breast problems has she had?

* Is there any breast cancer in her family?

* How many children has she had?

Physical examination

The doctor will look at her breasts, first with her arms by her sides, then above her head and, finally, with her arms pressing on her hips.

By looking carefully at the outline of the breast in various positions, the doctor can often see changes in the outline of the breast, which will help identify the site and cause of any problems.

Next, her breasts are examined while she is lying flat with her arms folded under her head.

If, during this examination, the doctor finds a lump, he or she will concentrate on this area examining with the fingertips and measuring the lump.

After checking her breasts, the doctor usually carefully examines the lymph glands under the patient’s arm pit and those in the lower part of her neck.

Should the patient need any further investigations, the breast specialist in the breast clinic will organise any tests that are necessary.

Mammograms

If the patient is over 35 and has not had a breast X-ray within the past year, the doctor may arrange for one to be performed. Breast X-rays are known as mammograms.

Mammograms are a good way of identifying abnormalities in the breast, but they don’t always tell whether they are benign or malignant.

Further tests are sometimes necessary and these tests include ultrasound and fine needle aspiration cytology (FNAC).

Ultrasound scanning

X-rays do not pass easily through the breasts of young women. Ultrasound scanning, which is familiar to many women by its use to look at babies during pregnancy, can also be used in the breast to tell whether a lump is fluid or solid.

Ultrasound is not useful as a screening test. It is useful if an abnormal shadow is seen on the mammogram because ultrasound is an accurate way of judging whether any abnormality is benign and straightforward or whether it is more likely to be serious.

Needle tests (FNAC)

Inserting a needle into the lump will show whether it is full of fluid (a cyst) or solid. The needle can allow a sample of cells to be removed for examination under the microscope (a process called cytology) and this is a very accurate method of finding out whether the lump is benign or malignant.

If there is an abnormality on the mammogram, but no lump to feel, then using either the X-ray machine or the ultrasound machine, it is possible to guide the needle into the area of abnormality and to obtain enough cells or tissue to obtain a definite diagnosis. The very fine needles used for this procedure give rise to its name.

Having the lump removed

After investigation, the doctor may decide the lump is benign and that it can be left alone. Alternatively the doctor may suggest that the lump should be removed. This is called an excision biopsy and it can be performed either while the patient is awake under local anaesthesia or, more commonly, under a general anaesthetic.

Before any operation, the patient will be asked to sign a consent form agreeing to the removal of the lump. It is important for the patient to know that the doctor performing the operation will only remove the lump and will not take any more tissue away without explaining any further procedure to the patient first and being given her consent.

What are the types of breast cancer?

Breast cancer was originally described according to its appearances, so words like scirrhous (meaning woody) were used and still appear in the literature.

More recently, breast cancer has been classified according to its appearances when under the microscope.

Early pathologists classified breast cancers into ‘invasive ductal’ cancers and ‘invasive lobular’ cancers believing that invasive ductal cancers arose in ducts and invasive lobular cancers in the lobules. However, it is now clear that all invasive ductal and invasive lobular cancers arise either in the terminal duct or the lobule. As the terms invasive ductal and lobular are in such common usage and as they have different appearances under the microscope they are still used.

A more logical classification divides tumours into those of ’special’ and ‘no special’ type. Invasive carcinoma of no special type is also commonly referred to as invasive ductal carcinoma. It is the most common type and accounts for up to 85 per cent of all breast cancers.

Special types of tumour have particular microscopic features and these include invasive lobular carcinoma, invasive tubular, cribriform, medullary and mucinous cancers, with other types being uncommon. Many of the special type cancers have a better prognosis - in other words the patient has a higher chance of survival.

When a cancer is examined under the microscope, it is usually possible to assess how aggressive it is: in other words how far and how fast it is likely to spread. The tumour may be assigned to one of three grades ranging from grade I to grade III in order of seriousness. For instance, a grade I cancer is non-aggressive and unlikely to cause harm. In contrast, grade III tumours are aggressive and likely to cause harm, but can sometimes be controlled with effective treatment.

How is breast cancer treated?

The treatment of the disease depends on the tumour type and the stage of disease - how far it has spread to involve either lymph glands or other organs in the body. There are various ways a cancer can be staged and classified.

A simple way of staging or classifying breast cancer is to divide it into three groups.

Early or operable breast cancer

This describes cancer that is confined to the breast and/or the lymph glands in the axilla (arm pit) on the same side of the body

Locally advanced breast cancer

This has not apparently spread beyond the breast and axillary lymph glands but involves the skin or the chest wall of the breast.

These cancers tend to have a worse outlook than early breast cancer and are usually best initially treated by drug therapy or radiotherapy rather than surgery. In locally advanced breast cancer the skin of the breast can either be directly involved by cancer or it is swollen or red. These changes occur because cancer cells get into the fluid channels that drain the breast (lymphatics) and block them, which causes the skin of the breast to be swollen and look like the skin of an orange (peau d’orange).

Locally advanced breast cancers were initially treated with surgery but this treatment was successful in only about 30 per cent of patients.

In the remainder, the cancer recurred in the areas immediately next to where the surgery was performed

Advanced breast cancer

This is where the cancer has spread beyond the breast and arm pit to other parts or organs of the body such as lymph glands in the neck, bone, lungs, liver and brain.

Other tumours in the breast

A rare form of tumour in the breast arises from the supporting tissue and is called a sarcoma. These types of tumour are rare and account for much less than 1 per cent of all malignant tumours within the breast. These are usually best treated by surgery.

How does breast cancer develop?

Initially, carcinoma cells are confined within the lobule and adjacent ducts. These are known as non-invasive cancers or ‘carcinoma in situ’.

As with invasive disease, there are two main types - ductal carcinoma in situ (DCIS) and lobular carcinoma in situ (LCIS).

Under the microscope these look different and, clinically, these two types of non-invasive cancer behave differently and require different treatments. Certain types of DCIS develop characteristic tiny particles of calcium within them. These particles show up as tiny white dots on a mammogram.

DCIS is much more common than LCIS. DCIS accounts for over one fifth of all types of cancer detected by breast screening.

DCIS is treated by surgery which may be followed by radiotherapy and hormonal treatment. LCIS when diagnosed is usually treated by simple follow up with regular mammograms or with hormonal tablets (tamoxifen).

Only rarely is surgery used for LCIS.

DCIS is considered to be a pre-malignant breast disease. It is not early breast cancer, but if left untreated DCIS cells eventually spread into the surrounding connective tissue of the breast to form an invasive cancer. The time period in which DCIS changes into an invasive cancer appears to be over months and years rather than days or weeks.

When an invasive cancer has developed, it is at this stage that there is a risk that cancer cells can spread to nearby lymph glands, the most common lymph glands affected being in the axillary (armpit) region.

Cancer cells can also enter the blood stream through the blood vessels that supply the cancer and then move to other organs of the body where they grow and cause problems in these organs. The most common sites for breast cancer to spread to are the bones, lungs, liver and brain. Sarcomas if they spread do so mainly through the bloodstream.

Can breast cancer be prevented?

One particular medicine used to treat breast cancer, tamoxifen (eg Nolvadex D), has been shown in an American study to reduce the risk of developing breast cancer by approximately 50 per cent in women at high risk of developing the disease. Research with tamoxifen and some other breast cancer medicines is still being carried out to determine if these are suitable options for preventing breast cancer. However, tamoxifen is associated with some rare but serious side effects that may make it unsuitable as a preventive measure.

Screening, as currently practised can reduce the mortality but not the incidence of breast cancer (and then only in the age group that is screened).

Once a woman reaches the age of 50, she will be invited to take part in a breast screening programme. In the UK, this means having a mammogram every three years up to the age of 64, although the upper age limit of routine screening is currently being extended to 70 years throughout the UK.. The aim of screening by mammography is to pick up cancer while it is still small before it has a chance to spread.

There are various reasons why women are not normally screened below the age of 50:

* breast cancer is less common in younger women.

* mammography is less likely to detect breast cancer in young women because the breast tissue is denser which can make breast cancer much more difficult to detect.

* there is no evidence that breast screening below the age of 50 is cost effective.

How is breast cancer treated with surgery and radiotherapy?

Early breast cancer can be treated by a combination of local treatments to control the local disease and adjuvent treatments to kill any cells which may have spread.

Local treatments consist of surgery and radiotherapy.

Surgery

Surgery can be an excision of the tumour with surrounding normal breast tissue (breast conservation) or removal of the whole breast (mastectomy). Clinical trials comparing mastectomy and breast conservation have shown that the two produce identical results.

If the lump is relatively small it is usually possible for the surgeon to remove it along with a small amount of surrounding normal tissue. This is called lumpectomy, wide local excision or breast-conserving surgery.

With a larger lump, this breast-conserving operation may not be possible because so much of the breast tissue would have been taken away that it would badly distort the breast.

Once the lump and surrounding tissue is removed it needs to be examined under the microscope. In some women, the surrounding tissue is abnormal and a further operation is necessary.

A mastectomy (removal of the whole breast) may be necessary if:

o the cancer is too large to remove and leave a reasonable looking breast after surgery.

o there is more than one lump in the breast.

o the cancer is directly underneath the nipple.

o the patient has previously had a lumpectomy or wide excision and the tissue round the cancer is abnormal.

As well as removing the lump or breast, the surgeon will also usually remove some or all axillary lymph glands, which are found under the arm. There are about 20 of these lymph glands and they are the most common place for cancer to spread.

Knowing whether this has happened and, if so, how many glands are affected is important in both assessing the severity of the cancer and deciding on follow up treatment.

If the surgeon needs to check whether the cancer has spread to these glands, then removing either a single gland which drains the cancer or a few of these glands is all that is needed. If however the surgeon wants to find out exactly how many lymph glands are affected, then it is necessary to remove all 20 lymph nodes from the axilla.

If it has been decided to treat the patient by mastectomy, the surgeon will probably discuss with her the possibility of having her breast rebuilt at the same time. The results of breast rebuilding or reconstruction are usually more successful if this is performed straight away rather than left until many months or years later.

There is no evidence that immediate breast reconstruction makes any recurrence of the cancer more likely. If the cancer does return, reconstruction does not make it harder to detect.

Radiotherapy

Studies have shown that all patients treated by breast conserving surgery (lumpectomy or wide excision), should receive radiotherapy to the breast following surgery. This is given every day, Monday to Friday, over three to five weeks.

After mastectomy, radiotherapy is given to patients who are considered to be at risk of recurrence. Radiotherapy kills cells that are growing and has greater effects on cancer than on surrounding tissue.

After a few days of radiotherapy, the patient’s skin may look red and feel a bit sore, rather like they have spent too long in the sun.

Towards the end of treatment, there may also be some blistering of the skin. The radiotherapy staff will give all the necessary advice about how to look after the treated skin.

How is breast cancer treated with medicines?

Medicines act on cancer cells, including those which have spread. We know that in some women there are small numbers of cancer cells that have spread beyond the breast but cannot be detected by scans. Medicines can kill these cells or prevent them from growing for many months and years after surgery with or without radiotherapy. This is called adjuvant treatment.

In some patients with larger but operable breast cancers, the medicines can be used before surgery to shrink the cancer. This allows some women who would initially have required a mastectomy to be treated by less extensive surgery. If the cancer has already spread at the time it is first diagnosed or a patient who is treated for early breast cancer develops a recurrence of the cancer at some other site in the body, then the only practical way of treating these two groups of patients is by medicines.

The medicines for treating breast cancer fall into two groups: hormones and chemotherapy. Whether the patient receives hormone therapy or chemotherapy will depend on the size of the tumour, type of tumour (including the grade) and whether the tumour has spread to involve the lymph glands.

Hormones

Most breast cancer is sensitive to the female hormone oestrogen. Sensitive cancer cells need oestrogen to stay alive and removal of oestrogen from the body or stopping any circulating oestrogen getting to the cancer cells is very effective at controlling or killing hormone-sensitive breast cancers. It is possible to determine whether a tumour is sensitive to hormones by performing a chemical test on the tumour.

Tumours can be classified into oestrogen sensitive and oestrogen insensitive tumours.

In premenopausal women who are still having regular menstrual periods, about half of all breast cancers are hormone sensitive. Over two thirds of tumours in postmenopausal women whose periods have stopped are oestrogen sensitive.

The most commonly used medicine against oestrogen sensitive tumours is tamoxifen (eg Nolvadex D). This medicine is an anti-oestrogen in its effect on breast cancers and works by stopping oestrogen getting to the cancer cells. It appears to be a very safe medicine but can cause side effects which can be distressing and these include flushing (similar to those women experience during the menopause), vaginal dryness and vaginal discharge.

Many women complain of weight gain on tamoxifen, but, in randomised studies, women taking tamoxifen put on a similar amount of weight to those women who were not receiving drug treatment. There is an increased incidence of eye problems and disturbance of vision. This is reversible if the medicine is stopped.

The most serious possible side effects of tamoxifen are that it can slightly increase the incidence of cancer of the lining of the womb, and slightly increase the risk of a blood clot in the leg (deep vein thrombosis). However the risks of both these side effects are very low. Tamoxifen has been widely used throughout the world and is a very safe medicine for pre and postmenopausal women. Few women have to stop the medicine because of side effects. Women who have had surgery for early breast cancer are commonly given tamoxifen following the surgery to reduce the risk of recurrence of the cancer.

The production of oestrogen in postmenopausal women requires an enzyme called aromatase. A new class of medicines for treating breast cancers blocks this aromatase enzyme. These medicines are called aromatase inhibitors and include letrozole (Femara), anastrazole (Arimidex) and exemestane (Aromasin). They are very effective in postmenopausal women with oestrogen sensitive tunours. The side effects include flushings, nausea and lack of appetite. Occasionally, women have to stop the medicine because of the constant feeling of sickness.

In premenopausal women the major source of oestrogen is the ovaries. Either removing the ovaries or using an injectable medicine called goserelin (Zoladex), which stops the ovaries from producing oestrogen are effective treatments in hormone sensitive breast cancer. The medicine which stops the ovaries working has to be injected once a month. Side effects of this type of medicine or removal of the ovaries include the rapid onset of menopausal symptoms.

Chemotherapy

Chemotherapy involves being given a combination of anti-cancer medicines, often up to three at a time. The prime target for such medicines is cancer cells that are actively growing and dividing. Unfortunately, anticancer medicines are not able to recognise cancer cells specifically and they also kill normally dividing cells such as the blood and hair cells. The art of the science behind successful cancer chemotherapy is combining medicines which are chosen to minimise the damage to blood cells while maximising damage to cancer cells.

Chemotherapy may be preferable for more advanced cancer that is not hormone responsive and for aggressive disease, particularly if the cancer has spread to other sites, such as the liver. It is sometimes administered prior to surgery in order to shrink a tumour. As outlined above, this sometimes means that the surgeon is able to perform less extensive surgery in patients whose cancers respond.

Cancer chemotherapy is usually given through an intravenous drip in the hand or arm on an outpatient basis. Treatments vary but each session usually lasts between one and two hours and is repeated every three weeks. Patients may be frightened because they have heard about very unpleasant side effects such as nausea, vomiting and hair loss. In fact, by no means everyone will experience all or even any of these problems. Some of the anti-cancer drugs that are in common use cause little or no hair thinning and anti-sickness medicine given with the chemotherapy works well.

A common complaint in people receiving chemotherapy is of weight gain. This is due to the anti-sickness pills which are taken after the chemotherapy. Once the chemotherapy is finished, providing the patient remains active, they should return to their initial weight. One of the less well-known side effects of chemotherapy is to cause premature menopause. This means that periods are likely to stop at a much earlier age if you have had this type of treatment. Bringing forward the menopause is particularly likely to occur in women in their late 30s and 40s, but even younger women can find that their periods temporarily stop during chemotherapy.

Treatment for locally advanced breast cancer

Some patients whose cancer is locally advanced because it has grown directly into the skin overlying the breast are suitable for surgery and are treated in an identical way to patients with early or operable breast cancer. The majority of patients with locally advanced breast cancer are treated with drug therapy followed by surgery and/or radiotherapy. Some patients with locally advanced breast cancer are treated by radiotherapy initially which can be followed by drug therapy and/or surgery.

Drug therapy can consist of either hormonal therapy in slower growing hormone sensitive cancers or chemotherapy in hormone sensitive or more rapidly growing cancers.

Outlook for patients with operable or early breast cancer

There are various factors which relate to survival in breast cancer.

These include:

* tumour size - the smaller the tumour the more likely a patient is to survive.

* spread to axillary lymph nodes - the single best factor which predicts a person’s survival is the presence or absence of cancer cells in the lymph glands. The more lymph glands which are affected, the worse is the outcome.

* the tumour type.

* the grade (whether it is a grade I which has a good prognosis or a grade III which has a poorer prognosis).

* whether tumour cells are seen by the pathologist in lymph channels or blood vessels.

* whether the tumour is slow growing or fast growing.

* whether it expresses hormone receptors.

* the genetic abnormalities in the cancer.

Outlook for patients with locally advanced breast cancer

The outlook is worse than for patients who present with operable breast cancer. Local recurrence of the disease after treatment is a problem even in patients who have had drug treatment, surgery and radiotherapy. Control rates of disease are however much better than they used to be when surgery was the initial treatment. The outlook is better in patients who have a good response to their initial drug treatment. In approximately 10 per cent of patients who receive chemotherapy, the drug treatment is so effective than when surgery is performed, no breast cancer cells can be identified in the breast or the lymph glands.

Outlook for patients with metastatic breast cancer

Metastasis is the process of further spread of the cancer within the body, away from the site at which the cancer starts. People whose cancers have already spread have a much worse outlook than those whose disease is apparently localised. There are differences in survival, depending on the site affected.