Stages and types of breast cancer

Are there different types of breast cancer?

Many women do not realise that breast cancer is not just one disease that is treated in a standard way with the same predictable outlook for each person who gets it. There are many different types of breast cancer and there are many aspects of this disease that play a part in determining the best treatment and whether the outlook is likely to be better or worse than for another patient with the disease.

Factors that need to be considered include:

• The size of the tumour

• What the tumour looks like under the microscope

• Whether there has been spread to the lymph nodes

• Whether the cancer is hormone sensitive

• Whether the cancer has certain growth factors on its surface or whether the cancer is HER2 positive.

Breast cancer can be classified into two main types:

• Non-invasive

• Invasive

Non-invasive cancers

Breast cancers develop from the cells that line the breast lobules (leaves of the breast tree) and draining ducts (or branches). Cancer cells that are confined to the lobules and ducts are called in situ or non-invasive.

These are sometimes referred to as pre-cancer and can be split into two types based on their appearance under the microscope. The two types are:

1 Ductal carcinoma in situ (DCIS)

2 Lobular carcinoma in situ (LCIS).

Another term for LCIS is lobular neoplasia.

It was thought originally that lobular carcinoma in situ arose in the lobules (leaves of the breast tree) and ductal carcinoma in situ arose in the ducts (branches of breast tree). We now know that this is not true, in that all cancers arise in the lobule alone or in the final branch of the ducts and the lobule, the so-called terminal duct lobular unit.

Ductal carcinoma in situ (DCIS)

This condition is often referred to by its initials, DCIS, rather than the full name ductal carcinoma in situ. The cells lining the milk ducts that carry the milk to the nipple can overgrow to such an extent that they look cancerous, but they remain confined to the milk duct channels.

DCIS is sometimes called pre-invasive, non-invasive or intraductal cancer. It used to be quite rare but has become much more common since the introduction of breast screening. Although DCIS can sometimes present as a lump, most women with DCIS have no signs or symptoms and they only know that they have it because it has been found on a mammogram.

DCIS usually shows on the mammogram as a localised area of microcalcification and the flecks of calcium are very small. Occasionally women with DCIS find a breast lump or have nipple discharge.

If DCIS is left untreated it is likely that, as time passes, cancer cells will spread and invade from the ducts into the surrounding tissue to form a true invasive cancer. Although DCIS should be treated to stop it developing into invasive cancer, provided that it is removed completely, it cannot cause any harm.

Not every woman who has DCIS will go on to develop invasive cancer. There are different types of DCIS and they can be separated into different groups based on the cell pattern and appearance under the microscope.

The most common classification is into three groups based on the resemblance of the cells in the DCIS to the normal cells lining the milk ducts. These three groups are:

1 low grade

2 intermediate grade

3 high grade.

Low-grade DCIS

These cells resemble normal cells in many ways, although they are clearly abnormal. They have the slowest rate of growth.

Intermediate-grade DCIS

These cells have some features of normal cells. They have a growth rate between that of low-grade and high-grade DCIS.

High-grade DCIS

The DCIS cells in this group are larger and do not resemble the normal cells lining the milk ducts. They have the highest growth rate and have a tendency to be larger than other types of DCIS. They also sometimes outgrow their blood supply and so some areas within the DCIS die – this is called necrosis.

After removal of an area of low-grade DCIS there appears to be a low rate of the DCIS coming back and a low rate of development of cancer in the same area of the breast. In comparison, high-grade DCIS is more likely to recur after removal and is more likely to develop into an invasive cancer than low-grade DCIS if left untreated.

If a cancer develops in an area of low-grade DCIS it is likely to be a low-grade (less aggressive) cancer. One that develops after the treatment of a high-grade DCIS tends to be a high-grade (worse than low-grade) invasive cancer.

How is DCIS treated?

Surgery is the main treatment for DCIS. Provided that all the DCIS is removed from the breast, this should be a cure.

Breast-conserving surgery

If the DCIS is localised to a small portion of the breast, breast-conserving surgery (complete removal of the DCIS with some surrounding normal tissue) is usually possible.

With breast-conserving surgery alone there is a risk that further DCIS or an invasive cancer will develop in future and this most commonly occurs in breast tissue immediately at the edge of where the surgery has been performed.

Radiotherapy

For this reason most women with DCIS who have breast-conserving surgery are advised to have radiotherapy after their surgery because this markedly reduces the risks of further disease developing in the breast. There are some women, however, with small low- and intermediate-grade cancers who are satisfactorily treated by breast-conserving surgery to remove the DCIS alone.

Mastectomy

Although breast-conserving surgery is possible for small and medium-sized areas of DCIS, if there is more extensive disease in the breast over an area of more than four centimetres, or more than one area of the breast is affected by DCIS, then a mastectomy is usually advised.

Patients with DCIS who have a mastectomy are ideal candidates for breast reconstruction. Patients can have skin-sparing mastectomy where most of the skin is left intact and the scars from surgery are kept to a minimum.

If a mastectomy is performed, the surgeon will often remove some of the lymph glands in the armpit to check that the nodes are clear. To identify the lymph glands that are most likely to be affected a procedure called sentinel node biopsy (see page 116) is performed.

The reason is that, when a large area of DCIS is removed, and examined under the microscope, there will occasionally be small areas where the cancer has become invasive. Checking the lymph glands and knowing that these are clear means that the cancer is very unlikely to have spread beyond the breast.

This armpit surgery does not significantly increase the likelihood of developing problems after the operation, but it does avoid having to go back for a second operation in those women where invasion is identified after examination of the tissue removed by the surgeon.

There is conflicting evidence whether tamoxifen is beneficial for women with DCIS. Currently studies are under way to see whether the new aromatase inhibitors (see page 142) can help in this condition. It does appear likely that tamoxifen reduces the chances of more DCIS or invasive cancer developing in women who have hormone receptor-positive DCIS.

Lobular carcinoma in situ (LCIS) or lobular neoplasia

Lobular neoplasia, also known as lobular intraepithelial neoplasia (LIN), is the new term that is used to include two conditions that were considered separately:

1 atypical lobular hyperplasia

2 lobular carcinoma in situ.

This condition is diagnosed by the pathologist after a breast biopsy. Normally only one layer of cells lines the breast lobule. When there are two or more layers of cells this is called hyperplasia. As the number of layers of cells increase the breast lobule expands and increases in size. When the whole lobule and draining ducts are expanded by abnormal round or regular cells the pathologist considers this to be lobular neoplasia. It is much less common than DCIS.

This is not a cancer but its presence in the breast means that there is an increased risk of developing breast cancer later in life. Even with this increased risk most women who have lobular neoplasia do not develop breast cancer.

It is not necessary to remove all the lobular neoplasia because what lobular neoplasia tells us is that the person is at increased risk of getting breast cancer, but any cancer that does develop can occur anywhere in either breast. For this reason careful follow-up is recommended with regular mammograms for 10 to 15 years.

Patients with lobular neoplasia are also suitable for some of the clinical trials looking at drugs to try to prevent breast cancer. In an American study, patients who had lobular neoplasia and took tamoxifen for five years halved their risk of developing breast cancer over this period.

How is lobular neoplasia diagnosed?

Lobular neoplasia is usually discovered as a chance finding in a woman who has had a breast biopsy of a lump or an abnormality detected by screening. Sometimes lobular neoplasia can cause calcification but it is most often found by chance when a breast biopsy is looked at under the microscope.

How is lobular neoplasia treated?

Most women with lobular neoplasia do not require any treatment. Only if you have lobular neoplasia and a very strong family history of breast cancer will your doctor suggest further surgery.

As women with lobular neoplasia are at increased risk of breast cancer, regular screening is recommended, usually once a year for 10 to 15 years after the diagnosis.

Invasive cancers

A cancer is classified as invasive if the cells have moved beyond the ducts and lobules into the surrounding tissue. Non-invasive cancer can develop into invasive cancer if left untreated.

Invasive cancers have the ability to spread locally in the breast and they may enter lymph channels in the breast and spread to lymph glands, usually under the arm; this is the most common place that breast cancer spreads to.

Sometimes invasive cancers cells get into the bloodstream, either from the lymph nodes or by direct growth into blood vessels in the breast. Once in the bloodstream they can spread to any part of the body, the bones, lung, liver and brain being most commonly affected.

There are different ways of classifying invasive cancers; the one that is in most common use splits cancers into:

1 Special type tumours: the special type of invasive breast cancers include:

• tubular

• cribriform

• mucinous or mucoid

• papillary

• medullary

• lobular

2 Tumours of no special type (NST), also called invasive ductal cancers.

Special types of tumours

Invasive tubular cancer

This is an uncommon type of cancer. About two to three per cent of breast cancers are of this type. It is much more commonly found in women whose cancer is diagnosed through screening.

The cancer under the microscope consists of tubes of cells, which is why it gets its name. Tubular cancer has a very good outlook and few people ever die as a result of this type of cancer. As it has a very good outlook, it usually requires less treatment and women with this type of cancer almost never need chemotherapy.

Invasive cribriform cancer

This is even rarer than tubular cancer. The pattern under the microscope is rather like Swiss cheese with groups of cells and lots of holes in the centre. These cancers are very closely related to invasive tubular cancers and have the same excellent outlook.

Invasive mucinous or mucoid cancer

In this type of tumour the cancer cells produce a thick jelly-like material called mucin. These cancers are usually well rounded on X-ray and are slightly more common in older women.

They have a very good outlook. Sometimes, however, if left untreated they can become quite large. They are also known as colloid cancers.

Papillary cancers

These cancers have finger-like projections, which are lined by the cancer cells. As with medullary and mucinous cancers, they can sometimes appear as very well-defined lumps with smooth edges. Sometimes it can be difficult to tell whether these cancers are invasive or not. Women with this type of cancer tend to do better than women with cancers of no special type.

Invasive medullary cancer

This type of cancer is uncommon in women who have no family history of breast cancer but is more common in women who carry a BRCA-1 gene mutation. They tend to be soft and rounded lumps in the breast.

They are not always easy to pick up on X-ray and have some of the appearances of a benign lump on mammogram. Women with medullary cancers tend to have a slightly better outlook than women who have cancers of no special type.

Invasive lobular cancer

Between five and ten per cent of all cancers are classified by the pathologist as of invasive lobular type. They are called lobular because it was thought that this type of cancer arose in the lobules, whereas ordinary cancers of no special type (also called invasive ductal cancers) were thought to arise in the ducts.

It is now known that this is incorrect and all cancers arise from within the terminal duct lobular unit. Invasive lobular cancers are, however, still classified separately and the old name persists because not only do they look very different under the microscope, but they also behave differently to cancers or cancers of no special type.

In invasive lobular cancer the cancer cells push through normal tissue with the cells spreading in lines that are interspaced between the normal breast tissue. Rather than forming a lump, this type of spread often forms just a thickening.

Invasive lobular carcinoma (ILC) is a type of cancer that surgeons find most difficult to diagnose. It is much more difficult to feel and the edges of the cancer are difficult to define. They do not always show up on mammograms and needle tests can sample the normal tissue and miss the cancerous cells in between. ILC also tends to cast less of a shadow on ultrasound than cancers of no special type.

For all these reasons invasive lobular cancers are often larger at diagnosis than cancers of no special type. As a result of this, invasive lobular cancers have often also spread to lymph glands by the time that a diagnosis is made.

It is not always possible to tell how large an invasive lobular cancer is by examining the lump and this can be a problem for the surgeon because he or she may think that the cancer is small and localised, but when the surgeon tries to remove the lump they find that the cancer is more extensive.

In almost half of patients with invasive lobular cancer who have a lumpectomy, further surgery is needed to get all the cancer out. MRI is sometimes helpful at estimating the extent of disease.

Patients with invasive lobular cancer are thought to have a slightly higher risk than average of developing a cancer in the opposite breast compared with patients whose cancers are of no special type.

Cancers of no special type (also known as invasive ductal cancers)

Most cancers, approximately 85 per cent, are classified as invasive cancers of no special type, and they are commonly called invasive ductal cancers because they were thought to arise in the ducts, in contrast to invasive lobular cancer which was thought to arise in the lobule.

It is unfortunate that, when pathologists decided to give names, they used terms that we now know are not an accurate reflection of the origin of the different cancer types.

There is a whole range of cancers of no special type and they can be split into groups based on their grade (that is, how abnormal the cells look under the microscope) and whether they have receptors for hormones and certain growth factors on their surface.

Different types of invasive cancers of no special type

Rather than being one disease, invasive breast cancers of no special type are a range of different diseases. It is probably easier to explain if you compare breast cancers with dogs.

At one end of the spectrum there are small low-grade tumours that have an excellent outlook and will rarely if ever kill; these cancer cells look similar to normal breast cells which is why they are classified as low grade or grade 1, and these cancers behave much like a small well-trained family pet.

At the other end of the spectrum there are large cancers that have spread and cause problems elsewhere in the body, which look very different from normal cells and are considered high grade or grade 3 under the microscope and often grow quickly; these cancers behave more like an untrained rottweiler.

These large grade 3 cancers are still treatable and modern-day treatments can be very effective. Aggressive cancers often respond very well to treatments such as chemotherapy. The aim is to find out about your individual tumour and then tailor the treatment to suit you and your cancer.

Hormone and growth factor receptors

The hormones oestrogen and progesterone play important roles in breast cancer. Oestrogen receptors, called ERs after the American spelling of estrogen, are present in approximately 75 per cent of breast cancers. ER is expressed in much greater amounts in cancer cells than in normal breast cancer tissue. ER is thus an important target for treatment and depriving cancer cells of oestrogen causes the cancer cells to stop growing, and the cancer will eventually shrink. The majority of cancers that express ER also have receptors for progesterone and these are called PgRs. The presence of ER and PgR indicates that the cancer is likely to benefit from removing oestrogen compared with a cancer that has no ER or PgR (ER and PgR negative), where there is no benefit from hormone treatment.

Growth factors in cancer cells control the rate of growth of the cancer. The most important group of growth factors are the human epidermal growth factor receptors, also known as the HER group. There are four HER receptors, the most important of which is HER2. Blocking HER2 with a new type of drug called trastuzumab (see page 161), also known as Herceptin, reduces growth and leads to cancers shrinking and in some patients results in eradication of the cancer. About 15 to 20 per cent of all cancers have a lot of HER2 receptors and thus rely on HER2, and are candidates for treatment with trastuzumab. Treatments that block HER1 have been developed. A new oral drug, lapatanib (see page 162), blocks HER1 and HER2 together and pertuzumab (see page 162) blocks HER1, HER2 and HER3.

Currently all breast cancers are checked for ER and HER2. Some breast units routinely check for PgR but some check for PgR only in ER-negative cancers to make sure that they are not likely to benefit from hormone treatment. The amount of ER is reported as well as a simple ER positive (+ve) or ER negative (–ve).

A commonly used scale classified both ER and PgR between 0 and 8. Zero is negative. There is no score of 1, the score 2 indicating a very low level of receptors.

Most cancers have high levels of ER or PgR and have scores of 6, 7 or 8. Cancers with scores of 6, 7 or 8 are known as ER rich.

HER2 is reported as positive or negative but two tests are needed in borderline cases and it can sometimes take 10 to 14 days to get a HER2 result.

Cancers are classified as hormone sensitive, which means that they are ER+, PgR+; there are few if any ER–, PgR+ cancers. About 20 per cent of cancers are hormone resistant, that is they are ER–, PgR– cancers.

Cancers are considered triple negative (ER–, PgR–, HER2–) if all three markers are negative on testing.

Triple-negative cancers, which are often seen in women carrying an abnormal BRCA-1 gene (see page 210), tend to have a worse outcome, although about half do respond very well to chemotherapy.

HER2-positive cancers used to have a worse outlook than HER2-negative cancers before the widespread use of trastuzumab. This drug dramatically improves outcome in HER2-positive disease so that there is now little difference in prognosis between patients with HER2+ and those with HER2– cancers.

Lymphatic system and lymph node spread

The lymph system is a network of lymph channels and glands involved in fighting off infection. If a germ gets into the body it passes through the lymph channels to the lymph glands where the cells that are involved in killing the germs are stored.

The white blood cells in the lymph glands either kill the germs themselves or produce substances called antibodies, which are released into the bloodstream to kill the germs.

The main flow of lymph from the breast is to the lymph glands under the arm. The area under the arm is called the axilla and the lymph glands under the arm are called the axillary lymph glands or axillary lymph nodes.

It is important to know whether a cancer is localised to the breast or whether it has spread to the lymph glands or other parts of the body. Doctors describe cancers by their extent of spread and classify breast cancer into stages. Another more simple classification is to separate breast cancer into three groups:

• early breast cancer

• locally advanced breast cancer

• metastatic breast cancer.

Lymphatic drainage within the breast

Blood and lymph vessels form a network throughout each breast. Breast tissue is drained by lymphatic vessels that lead to axillary nodes and internal mammary nodes (which lie along each side of the breast bone). This is important in terms of breast cancer, as cancer cells can break away from the main tumour and may spread to other parts of the body through the lymphatic system.

Early breast cancer

This is cancer that is confined to the breast and/or the lymph nodes of the armpit on the same side of the body.

Locally advanced cancer

This is cancer that has not apparently spread beyond the breast and armpit but has a series of signs to suggest that it is not suited to treatment initially by surgery.

In locally advanced breast cancer either the skin of the breast is abnormal and swollen or red, or the cancer is growing directly into the skin or the muscles and ribs of the chest wall.

If these cancers are treated by surgery alone, this treatment will be successful only in less than half of patients at controlling the cancer and stopping spread to the rest of the body. In the other half the cancer comes back despite the surgery, often in areas next to where the surgery was performed.

These cancers are usually best treated by drug therapy to shrink the cancer, followed by surgery and/or radiotherapy.

Metastatic breast cancer

This is cancer that has spread beyond the breast and armpit or to other parts of the body, such as the bones, liver, lungs and even the brain. These cancers are best treated by drugs that reach cancer cells wherever they are in the body sometimes combined with local radiotherapy.

Staging

Breast cancer can be grouped into stages – commonly called staging – and there are five main stages ranging from stage 0 to stage 4. This groups cancers together that have a similar risk and very often similar treatment.

Stage 0: very early disease

This stage indicates that there is only non-invasive cancer in the breast such as DCIS or Paget’s disease (see page 90) together with underlying DCIS. Stage 0 therefore includes only carcinoma in situ.

There are two types of stage 0 disease or carcinoma in situ:

1 Ductal carcinoma in situ known as DCIS, sometimes called intraductal carcinoma, non-invasive cancer or pre-cancer

2 Lobular cancer in situ (LCIS), sometimes also called lobular neoplasia.

The abnormal cells in stage 0 disease have not spread outside the duct or the lobule to invade the surrounding breast tissue.

Stage 1: early disease

To classify as stage 1:

• the cancer has to measure less than two centimetres across (approximately three-quarters of an inch)

• the cancer is localised to the breast; this means that it has not spread to the lymph glands or anywhere else in the body.

Stage 2: early disease

To classify as stage 2:

• the tumour must measure less than two centimetres across and have spread to the axillary lymph glands or

• the tumour must measure between two and five centimetres and the lymph glands may or may not be involved or

• the tumour must measure larger than five centimetres (two inches) but have no evidence of spread to the lymph glands under the arm.

Stage 3: locally advanced breast cancer

To qualify as stage 3 there must be no evidence of spread beyond:

• the skin overlying the breast

• the lymph node areas

• the chest wall.

This stage is split into three groups: stages 3a, 3b and 3c.

Stage 3a

• The tumour in the breast must be smaller than five centimetres, and the cancer has spread to the lymph glands under the arm and grown beyond the edges of the lymph gland into the surrounding tissues, such as the underlying muscles or the skin, so that the lymph glands are stuck to these tissues or

• The tumour must measure over five centimetres and the lymph glands under the arm are affected, or stuck to surrounding tissues.

Stage 3b

• The tumour must have grown directly into the skin overlying the breast, which can result in an ulcer or bleeding or

• The tumour must have grown from the breast to involve the underlying muscles and ribs of the chest wall or

• The tumour must have spread to the lymph glands under the breast bone – known as the internal mammary nodes – or

• An inflammatory breast cancer is present. This is a rare of type cancer. The next section in this chapter describes this condition (see page 89).

Inflammatory cancer is diagnosed when the breast is red, swollen and inflamed. The cancer cells from these inflammatory cancers block lymph channels that drain fluid from the breast; this causes a reaction in the tissues which results in the local redness and inflammation.

Stage 3c

• The lymph glands under the breast bone and under the arm are affected by spread from the cancer or

• The lymph glands above the collar bone, known as the supraclavicular nodes, are involved with cancer.

Stage 4: metastatic disease

Stage 4 is when the cancer has metastasised (spread) beyond the breast and axillary nodes to other parts of the body. Patients sometimes but not commonly have stage 4 disease when they first present to hospital.

If the cancer returns it is usually in some other part of the body and many years after apparently effective treatment for breast cancer.

When cancer recurs the most common site is recurrence in the breast or on the chest wall, known as local recurrence. This is not stage 4 disease.

Only when the cancer comes back and affects other parts of the body beyond the breast and axilla such as the bones, lungs, liver and brain is it classed as stage 4 disease. Even when cancer has spread to these sites the cancer is still treatable.

Unusual types of breast cancer

Inflammatory breast cancer

What is inflammatory breast cancer?

An inflammatory breast cancer is one in which the cancer cells produce swelling of the whole breast and cancer cells grow along and block lymph channels in the breast and skin. As a result the breast looks swollen, red and inflamed (this is how the condition gets its name).

Signs and symptoms

The symptoms often develop quite suddenly. The breast may be painful and looks red and inflamed.

The breast feels warm and swollen, and there are often ridges or marks on the skin where the bra presses against the skin. Other symptoms may include a lump or thickening of the breast, discharge from the nipple or a lump underneath the arm.

Treatment

Usually a combination of treatments is needed, including chemotherapy, radiotherapy, hormone therapy and surgery. For most types of breast cancer surgery is usually the first treatment, but for inflammatory breast cancer chemotherapy or radiotherapy is usually given first. Chemotherapy is sometimes combined with trastuzumab if the cancer is HER2 positive (see page 212).

Usually between four and eight doses of chemotherapy are given. The effect of treatment will usually be assessed after four doses of chemotherapy.

It is usual to get some reduction in the swelling, redness and tenderness of the breast after chemotherapy is started.

Occasionally the chemotherapy can result in complete disappearance of all cancer at the end of treatment. After chemotherapy the next treatment is usually surgery and/or radiotherapy.

Paget’s disease

Paget’s disease of the nipple is uncommon. Fewer than five per cent of women with breast cancer have Paget’s disease. It can also affect men. In Paget’s disease cancer cells grow from the ends of the milk ducts into the skin of the nipple.

The features of Paget’s disease are a red scaly nipple. One way in which a doctor can distinguish between Paget’s disease and eczema – a chronic skin

condition commonly affecting the nipple – is that Paget’s disease always affects the nipple first, whereas eczema affects the area around the nipple, known as the areola, first.

Paget’s disease also usually affects only one breast whereas eczema often affects both. In Paget’s disease the rash can feel itchy and there is often leakage of material from the surface of the nipple.

About half of patients with Paget’s disease have an underlying lump. Most patients with cancer and Paget’s disease have either DCIS in the ducts underneath the nipple or an invasive cancer somewhere in the breast.

To tell whether an abnormal area on the nipple is Paget’s disease, a small biopsy of the skin is taken and sent to the laboratory.

Treatment

If Paget’s disease is associated with DCIS or cancer in the underlying breast, treatment is directed at this as described in the next chapter, except that the nipple is always removed.

For Paget’s disease that is present on its own, treatment involves surgery to remove the nipple, usually followed by radiotherapy.

Follow-up usually involves annual examination and mammograms.

Lymphoma and sarcoma of the breast

Within the breast there is lymphoid tissue and supporting tissues and occasionally a tumour can develop in these tissues. This is rare. Malignant growths arising in lymphoid tissue are known as lymphomas and malignant growths from fat and fibrous tissue are known as sarcomas.

Metastasis to the breast

Very unusually a cancer at another site, for example a cancer in the lung or skin, can spread to the breast. Over 99 per cent of cancers in the breast start in the breast and are breast cancers. Breast cancers have particular appearances under the microscope and so, if your doctor tells you that you have breast cancer, you can be confident that the growth started in the breast.

KEY POINTS

• There are several different types of breast cancer, some of which have a better outlook than others

• Treatment for ductal carcinoma in situ (DCIS) should prevent cancer developing; most women with DCIS can be treated by breast-conserving surgery but where DCIS involves a large part of the breast then mastectomy may be needed

• Important considerations for all breast cancers are whether they have spread to the armpit lymph nodes or to elsewhere in the body

• Tests are carried out after a breast cancer is diagnosed to check how far the disease has progressed

• Inflammatory breast cancer, where the breast is red and swollen, is usually treated with chemotherapy first

• In Paget’s disease the nipple is red and scaly. If there is no underlying cancer it is treated by removing the nipple