5 Cancer of the breast

Take the chapter quiz before and after you read this chapter.

Open chapter quiz

Contents

• Objectives
• Case studies
• Introduction to breast cancer
• Types of breast cancer
• Clinical presentation of breast cancer
• Imaging changes in breast cancer
• Case studies

Objectives

When you have completed this chapter you should be able to:

• Name the different types of breast cancer.
• Understand the concept of grading and hormonal status.
• Understand staging.
• Know how breast cancer is usually diagnosed.

Case study 1

A 60 year old woman presents with a 2 cm mass in one of her breasts. Her mammogram shows a lump, which looks malignant, and her cytology also suggests a malignancy. She has no lymph nodes palpable in her axilla. Core biopsy shows a grade 1 ductal carcinoma. It is found to be ER positive

1. What stage is her cancer?
2. What does grade 1 mean?
3. What does ER +ve mean?
4. Are you surprised that the cells are ER +ve?
5. Why is it important to know if a breast cancer is ER +ve?
6. What are HER2 receptors?

Case study 2

A 42 year old obese mother of two young children presents with a bloody nipple discharge. On examination she has an 8 cm lump in her right breast. She has enlarged lymph nodes in her right axilla. The rest of her general examination is normal. A core biopsy is done and a diagnosis of breast cancer is made.

1. What stage is her cancer?
2. What organs are likely to have metastases?
3. What staging investigations should she have?
4. What are prognostic factors?
5. Which are good prognostic factors?

Case study 3

A 40 year old woman notices that she has a 1 cm lump in her breast that does not disappear after her menstrual period. Following an ultrasound scan she has a core biopsy which shows a ductal carcinoma in situ.

1. What is ductal carcinoma in situ?
2. Are there other forms of carcinoma in situ?
3. What will happen if ductal carcinoma in situ is not treated?
4. Are there other conditions which are associated with an increased risk of cancer?
5. What other investigations should she have?

Case study 4

An elderly woman presents with a red, swollen breast and peau d’orange skin changes. She also has what appears to be an inverted nipple on that side. On examination she has a large breast lump with enlarged lymph nodes in her axilla. Her other breast is normal but her liver is enlarged and she has severe back pain.

1. What is the diagnosis?
2. What are peau d’orange skin changes?
3. What is the problem with her nipple?
4. What type of breast cancer is this likely to be?

Introduction to breast cancer

5-1 What is cancer?

Cancer is a disease caused by cells that can multiply uncontrollably and then break off and spread both locally and beyond the breast to other areas of the body (metastasize). There are many types of cancer. Cancer can originate from many organs in the body.

Cancer is a disease caused by cells which multiply uncontrollably and can break off to spread to different sites in the body.

Note

Other words that are used to indicate that a lump is cancerous: invasive, carcinoma, malignant, neoplastic and non-benign.

Cancer implies an invasive lump. It is confusing as the terms ductal carcinoma in situ and lobular carcinoma in situ are non-invasive forms of cancer. Whenever cancer is used in this text, it refers to invasive cancer.

5-2 Is breast cancer always a primary cancer?

Over 99% of the time a cancer in the breast is a primary cancer. This means that it starts in the breast and has not spread to the breast from other parts of the body.

5-3 Where does the breast cancer start?

The commonest type of breast cancer starts in the ducts. Other types start in the lobes and rarely in the tissue in between.

The commonest type of breast cancer starts in the ducts.

5-4 Is there a stage before breast cancer?

Yes: It is called carcinoma in situ.

The commonest form is ductal carcinoma in situ or DCIS. This means that the malignant cells are still in the ducts and have not yet moved into the surrounding breast tissue. It is therefore not an invasive cancer yet.

Ductal carcinoma in situ will progress to invasive cancer over time as the malignant cells break through the wall of the duct and then spread into the surrounding fatty tissue. Therefore this invasive cancer will form in the area of the DCIS.

Over time ductal carcinoma in situ (DCS) will become an invasive ductal cancer.

Lobular carcinoma in situ (LCIS) is very complicated and far less common. If LCIS is found anywhere in either breast, it means the woman is more likely to develop a breast cancer at some stage in her life although it may not actually be in the same place where the LCIS has formed.

Figure 5-1: Stages from normal duct to invasive ductal cancer

5-5 Are there any non-cancerous conditions associated with an increased risk of breast cancer?

Yes:

• Atypical ductal hyperplasia. This means that ductal cells are multiplying much faster than usual but have not yet become a carcinoma in situ as shown in the picture above. Sometimes only atypical duct hyperplasia will be seen if a ductal carcinoma in situ or a cancer has been missed with the biopsy.
• A new fibroadenoma which develops in a woman over 40 years. This implies that her breasts are more proliferative (busier) than they should be.

5-6 What are the risk factors that increase the chance of getting a breast cancer?

In 90% of cases, the cause for a woman developing breast cancer is unknown. There are, however, a number of known risk factors:

• Sex: women are a 100 times more likely to develop breast cancer than men.
• Age: the older a women, the more likely she is to get breast cancer
• Family history: 5% of women have a gene abnormality (BRCA 1 or 2 mutation). They have a 50-85% risk of developing a breast cancer.
• Previous radiotherapy to the chest wall: patients who have had radiation for a lymphoma have an increased chance of breast cancer.
• Personal history of breast cancer. If a woman has had one breast cancer, she is at a higher risk than normal of developing another breast cancer.
• Having a personal history of having had atypical ductal hyperplasia or a new fibroadenoma over the age of 40.

In 90% of cases the cause of breast cancer is unknown.

5-7 How common is breast cancer in the general population?

It depends which population is being referred to. In a western population, the lifetime incidence is 1:9 (12%). In the developing world, it is lower. This difference is partly due to the fact women in the western world live longer than those in developing countries and also because some women with breast cancer in developing countries do not get a diagnosis. However, that is not the whole story and further research is necessary to explain the difference.

Numbers in South Africa are inaccurate but the incidence is quoted as being 1:25. This is set to increase as women are living longer.

Breast and cervical cancer are the two commonest forms of cancer in women.

The incidence of breast cancer in South Africa is expected to increase as women live longer.

5-8 How does breast cancer spread beyond the breast?

Breast cancer can spread via the lymphatic system to the local lymph nodes and also via the blood system to distant organs. Usually it spreads to the lymph nodes under the arm first (axillary lymph nodes).

Breast cancer usually spreads to the axillary lymph nodes first.

If the breast cancer cells are spread via the blood stream, they will follow the blood flow from the breast to the next organ or be trapped where the blood vessels become narrow. In practice, this means the lungs, liver, bone or brain. Cancer cells may go to the brain.

Figure 5-2: Lymphatic breast drainage to axillary and internal mammary nodes.

Figure 5-3: Sites for spread of breast cancer

5-9 What makes a cancer more likely to spread?

The biology of the breast cancer determines its behaviour. Breast cancer can be very slow growing or very fast growing. However, most cancers are in between.

Figure 5-4: Method of cancer spread

5-10 Do all cancers behave in the same way?

No. Breast cancer describes many different diseases and that is what makes the understanding and the treatment both difficult and interesting. Slow growing cancers tend to cause problems locally with ulceration in the breast and don’t really spread beyond the breast. Other cancers are fast growing and although they are still small, cells break off and travel to either the lymph nodes or to a distant organ.

5-11 What does prognosis mean?

Prognosis is the probable outcome for a person with a particular disease, i.e. the natural history of the disease without treatment. A good prognosis means the patient will probably remain well. Good prognostic factors for breast cancer are:

• Size of primary (the smaller the better).
• The grade (the lower the grade the better).
• The stage (if it has not spread to the nodes the prognosis is better).
• The receptor status (the presence or absence of surface receptors on the cancer cells affects the prognosis).
• The metastatic status (i.e. whether the disease has spread around the body); a cancer that has metastasized (spread to other organs) does worse than a tumour that is still in the breast and lymph node.
• Lymphovascular invasion (spread into the lymphatics and blood stream even if there are no clinical metastases yet).
• The response to treatment.

Most women with breast cancer get treated so the outcome depends on the response to treatment, as well as the natural history of the disease.

The prognosis is affected by the natural history of the disease and the response to treatment.

5-12 What does the grade mean?

The grade of the cancer describes how active (‘busy’ or aggressive) a cancer is and how ‘cohesive’ (sticky) the cells are. The higher the grade, the faster the cells are multiplying and the less cohesive the cells are. The faster the cancer grows the more likely it is to metastasize if treatment is not given. Breast cancer is graded from 1 to 3 with grade 1 being the least aggressive and 3 the most aggressive. The lower the grade the better the prognosis.

The grade of a cancer indicates the risk of it spreading.

5-13 What does the stage mean?

The stage describes:

• The size of the cancer
• Whether it has spread to the lymph nodes (nodal status)
• Whether it has spread to other parts of the body

Therefore staging is based on the size of the primary tumour in the breast (T), the spread to the nodes (N) and whether it has spread (metastasized) via the blood stream (M).

There are 4 stages of breast cancer with stage 1 describing early cancer (small tumour with no spread to nodes or other organs) and stage 4 describing advanced cancer that has spread around the body. The earlier the stage, the better the prognosis.

The stage of a breast cancer indicates whether a cancer has spread and, if so, how far it has spread.

5-14 What does hormone receptor status mean?

Most cells in the body have receptors on their surface to which specific hormones can attach. Hormones are chemicals that circulate in the blood stream and can change the behaviour of a cell far away from the gland where the hormone is produced. Normal breast cells have receptors for both the female hormones estrogen and progesterone. This allows the behaviour of cells in the normal breast to be altered at different times of the menstrual cycle and also during pregnancy.

Cancer cells may or may not have receptors to estrogen and progesterone. If they have receptors they are called ER/PR positive cancers (Estrogen/Progesterone sensitive cancers). The most important receptor is the ER receptor. Cells with estrogen receptors are called ER +ve.

Note

The lower the grade, of cancer, the more likely it is to have hormone receptors. Nearly all grade 1 cancers are ER +ve.

Cancers that are ER +ve have a better prognosis than those that are ER −ve and more importantly, the receptor which is present on some breast cancer cells allows hormone treatment to be used for the cancer.

ER positive cancers have a better prognosis.

5-15 What other receptors may cancers cells have?

Breast cancer cells may also have HERS2 receptors. HER2 +ve tumours (with HERS2 receptors) do worse than HER2 −ve tumours (without HERS2 receptors). Aggressive cancers with HER2 receptor will allow treatment with Herceptin which attaches to the receptor and slows the tumour growth. Treatment with Herceptin is known as targeted therapy. Newer types of treatment are targeting different receptors.

Tumours without estrogen, progesterone or HERS2 receptors are called triple negative and have the worst prognosis. They grow fast and spread quickly. Neither hormone nor Herceptin treatment is effective with these tumours.

Note

HER2 stands for human epidermal growth factor receptor type 2. If present it allows the growth factor to attach and stimulate rapid cell multiplication making the tumour more aggressive.

5-16 Does a cancer start in one place in the breast only?

Cancers may be single or may be multiple.

5-17 What change does normal breast tissue go through before a breast cancer develops?

This is controversial but there are different changes that occur before the development of a breast cancer. Often, atypical hyperplasia progresses to ductal carcinoma in situ and then cancer. However, more recent research has shown that cancers do not always follow a clear-cut path.

Types of breast cancer

5-18 What types of breast cancer are there?

There are 2 common types of breast cancer:

• Ductal
• Lobular

There are also other less common types:

• Inflammatory
• Tubular
• Papillary
• Colloid
• Mucinous

Ductal and lobular are the commonest types of breast cancer.

Although there are different types of breast cancer, the treatment principles remain similar.

Malignancies in the breast may also start from the connective tissue. These usually fall under “sarcomas”. They are uncommon and will not be discussed here.

5-19 What is ductal cancer?

Ductal cancer is the common type of breast cancer and accounts for about 75% of all the breast cancers seen. It starts in the ducts. Ductal cancer can be low grade and slow growing or high grade and highly aggressive.

Ductal cancer can be either low or high grade.

5-20 What is lobular cancer?

Lobular carcinoma starts in the lobes (lobules) and is nearly always low grade. It can be difficult to diagnose as the cancer sometimes is not seen on mammograms while on cytology it can look like normal breast tissue.

Lobular cancer is nearly always low grade but can be difficult to diagnose.

5-21 What is inflammatory cancer?

Inflammatory breast cancer is an aggressive type of cancer that presents with redness and swelling of the breast. There is always lymph node involvement and unless the patient is very fat, a lymph node will be felt. The typical history is that a woman noticed that her breast is red. It is not generally painful which helps distinguish it from an infection.

Clinical presentation of breast cancer

5-22 What factors in the clinical assessment would point to a diagnosis of breast cancer?

History:

• Age: the older the woman, the more likely it is to be breast cancer
• Family history of breast cancer particularly if the relatives were younger than 40 at the time of diagnosis or if there are many relatives with breast cancer
• Family history of other cancers, particularly prostate or ovarian cancer
• History of a lump either under the arm or in the breast. The lump is generally painless.
• Bloody discharge from the nipple
• Change in the nipple appearance: Paget’s disease of the nipple

Examination:

• A lump that is not clearly defined. It may feel like a thickening. However, some cancers can feel well defined like cysts or fibroadenomas.
• Thickening of the breast
• Skin dimpling
• Redness of the skin
• Peau d’orange skin changes (due to skin oedema)
• Nipple changes: either bloody discharge, inversion of the nipple or Paget’s disease (looks like eczema)

Peau d’orange means skin of an orange. If present, the skin over the breast has obvious indentations which is due to alteration in lymphatic flow.

(Paget’s disease is the name given to changes in the nipple which are a sign of breast cancer. These nipple changes may look like eczema. To start with, the nipple appears dry and flaky. Later, the nipple becomes flatter and may ulcerate. The only reliable way to tell the difference between eczema and Paget’s disease is to do a biopsy. The name Paget’s disease is confusing as it is not a separate disease or different kind of cancer. It is an uncommon sign of cancer.)

Imaging changes in breast cancer

5-23 What does breast cancer look like on a mammogram?

A mammogram is nearly always done if a cancer is suspected. Cancers are white on a mammogram and may have malignant microcalcifications (small specks of calcium). It is important to do a mammogram to look at the rest of the breast. It should give an indication as to whether a cancer is single or multifocal.

A cancer usually looks white on a mammogram.

5-24 Are mammograms always reliable?

No. About 10% of cancers are not seen on a mammogram.

10% of cancers are not seen on a mammogram.

5-25 When is a mammogram unreliable in diagnosing breast cancer?

Mammography is especially unreliable in:

• Young women
• Women with dense breasts
• Women with prostheses
• Women with lobular cancer
• Cancers that are far back in the breast or at the bottom of the breast

In some cases, the primary cancer does not show up clearly (e.g. in inflammatory cancer) but the malignant lymph node does show up.

5-26 What does breast cancer look like on an ultrasound?

Cancers may appear on ultrasound as a black irregular mass. An ultrasound should be done if a woman has a palpable mass but a normal mammogram or if the breasts are dense. Ultrasound should be the first imaging done on a young woman under 35 years of age.

5-27 What changes are seen on cytology?

The cancer cells look abnormal with little cytoplasm and large abnormal nuclei when compared to normal cells (see figure 3-8).

5-28 What should be done once the diagnosis of breast cancer is made?

The stage of the cancer must be decided upon. This will need further investigations to look for spread via the blood stream to other organs. Staging is important because it helps to determine both treatment and outcome.

5-29 To which organs does breast cancer spread and who should be tested?

The commonest places for breast cancer to spread to are the:

• Liver
• Lungs
• Bones

If a woman has any symptoms that may suggest spread (e.g. cough or bony pain) she should have appropriate tests.

All women with a cancer greater than 5 cm, palpable lymph nodes or a triple negative cancer should have a CT scan of chest, abdomen and pelvis to check for spread. A bone scan is indicated if she has a raised serum calcium or any lesions on her CT scan.

If a CT scan is not available, a chest X-ray, liver ultrasound and bone scan can be done instead.

5-30 What must be known about the breast cancer before deciding on the appropriate treatment?

A full description of the breast cancer is needed:

• What type of cancer does the women have i.e. the biology of the tumour
• What is the size of the primary tumour (the lump in the breast)
• Whether the cancer has spread to the lymph nodes
• Whether the cancer has spread to the rest of the body

A detailed assessment of the breast cancer is needed before deciding on appropriate treatment.

Case study 1

A 60 year old woman presents with a 2 cm mass in one of her breasts. Her mammogram shows a lump, which looks malignant, and her cytology also suggests a malignancy. She has no lymph nodes palpable in her axilla. Core biopsy shows a grade 1 ductal carcinoma. It is found to be ER positive.

1. What stage is her cancer?

She has a stage 1 cancer as it is small and has not spread to the lymph nodes.

2. What does grade 1 mean?

Grade 1 means that this is a slow growing, non-aggressive tumour. It has probably taken years to reach the size of 2 cm.

3. What does ER +ve mean?

It means that there are estrogen receptors on the cancer cells.

4. Are you surprised that the cells are ER +ve?

No, as nearly all grade 1 cancers are ER +ve.

5. Why is it important to know if a breast cancer is ER +ve?

Because these cancers respond well to hormonal treatment.

6. What are HER2 receptors?

Receptors for Herceptin on the cancer cells. If they are present targeted therapy can be used.

Case study 2

A 42 year old obese mother of two young children presents with a bloody nipple discharge. On examination she has an 8 cm mass in her right breast. She has enlarged lymph nodes in her right axilla. The rest of her general examination is normal. A core biopsy is done and diagnosis of breast cancer is made.

1. What stage is her cancer?

At least stage 2 or 3 as she has a large tumour with spread to the local lymph nodes. It would be stage 4 if the cancer has spread via the blood stream to other organs.

2. What organs are likely to have metastases?

Lung, liver or bones.

3. What staging investigations should she have?

A CT scan of her chest, abdomen and pelvis. A bone scan is indicated if she has a raised serum calcium or any lesions on her CT scan.

4. What are prognostic factors?

Prognostic factors are characteristics about the cancer that will give some indication as to how good the outcome is likely to be.

5. Which are good prognostic factors?

• A small tumour
• No lymph node involvement
• A low-grade cancer
• No metastases
• A good response to treatment

Case study 3

A 40 year old woman notices that she has a 1 cm lump in her breast that does not disappear after her menstrual period. Following an ultrasound scan she has a core biopsy which shows a ductal carcinoma in situ.

1. What is ductal carcinoma in situ?

Malignant cells which have not yet spread beyond the walls of the duct. This is a common form of carcinoma in women who have screening mammograms. It is often referred to as DCIS.

2. Are there other forms of carcinoma in situ?

Lobular carcinoma in situ or LCIS.

3. What will happen if ductal carcinoma in situ is not treated?

It will become an invasive ductal cancer.

4. Are there other conditions which are associated with an increased risk of cancer?

• Atypical ductal hyperplasia
• A new fibroadenoma in a woman over 40 years of age

5. What other investigations should she have?

She needs a mammogram as DCIS shows up much better on a mammogram than on an ultrasound scan.

Case study 4

An elderly woman presents with a red, swollen breast and peau d’orange skin changes. She also has what appears to be an inverted nipple on that side. On examination she has a large breast lump with enlarged lymph nodes in her axilla. Her other breast is normal but her liver is enlarged and she has severe back pain.

1. What is the diagnosis?

She almost certainly has breast cancer. Her enlarged liver and back pain suggests that she already has metastases.

2. What are peau d’orange skin changes?

The skin over the tumour becomes oedematous and looks like the skin of an orange.

3. What is the problem with her nipple?

She probably has cancer behind her nipple causing inversion.

4. What type of breast cancer is this likely to be?

Inflammatory breast cancer.