6 Treatment of breast cancer

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Contents

• Objectives
• Case studies
• Introduction to breast cancer treatment
• Surgery in breast cancer treatment
• Mastectomy
• Breast reconstruction after mastectomy
• Axillary surgery
• Chemotherapy
• Hormone (endocrine) treatment of breast cancer
• Targeted therapy
• Radiotherapy
• Case studies

Objectives

By the end of this chapter, you should be able to:

• Understand the principles of different treatment methods.
• Know the difference between neoadjuvant therapy and adjuvant therapy.
• Understand the different possibilities for breast and axillary surgery.
• Understand when chemotherapy, hormone therapy, targeted therapy and radiotherapy are used.

Case study 1

A young premenopausal woman with small breasts presents with a small breast cancer. She is unmarried and worried that treatment will leave her disfigured. After discussion by a multidisciplinary team she is offered a choice of local and systemic management.

1. What does local management mean?
2. What local treatments are available?
3. What is systemic management?
4. What types of systemic treatment can be used?

Case study 2

A 45 year old mother of two children has a breast lump found on a mammogram. A diagnosis of cancer is confirmed on histology. Examination of the other breast and both axillae is normal. She chooses to have surgery and a sentinel node biopsy is found to be positive. She is offered adjuvant radiotherapy after surgery.

1. What is a sentinel node biopsy?
2. What is an axillary clearance?
3. What are the complications of axillary node clearance?
4. What is adjuvant radiotherapy?

Case study 3

A 55 year old postmenopausal woman presents with a 2 cm ductal carcinoma in the upper outer quadrant of her left breast. It shows up on the mammogram and there are no other masses. There are no nodes that can be seen on ultrasound scan or felt in her armpit. The cancer is ER +ve.

1. Would she be suitable for a wide local excision if that was her preference?
2. Will she be advised to have hormone therapy?
3. Is she suitable for an aromatase inhibitor?
4. How do these drugs work?

Case study 4

An elderly woman presents with a large 6 cm breast lump which is found to be an invasive ER −ve, PR −ve, HER2 +ve ductal cancer. She has lymph nodes palpable in her axilla. She is advised to have neoadjuvant chemotherapy before surgery.

1. What is neoadjuvant chemotherapy?
2. How does this differ from adjuvant chemotherapy?
3. Will she be advised to have an aromatase inhibitor?
4. If it is available to her, would she be advised to have Herceptin?

Introduction to breast cancer treatment

6-1 What is the aim of treatment?

To prolong life, improve the quality of life and wherever possible cure the patient. This is done by:

1. Treating the primary (local) breast tumour
2. Removing any lymph nodes that have cancer
3. Preventing systemic spread of the cancer via the blood stream to other parts of the body.
4. Providing systemic treatment if the cancer has spread.

The aim of breast cancer treatment is to prolong life and cure the patient whenever possible.

6-2 What types of management are available for treating breast cancer?

There are two types (modalities or methods) of management:

• Local management
• Systemic management

6-3 What does local management mean?

Local management describes treatment to the breast and the axilla (armpit).

6-4 What types of local management are available?

• Surgery
• Radiation

6-5 What does systemic management mean?

Systemic management is treatment to the whole body. It must be remembered that systemic management can also treat the primary (local) breast cancer.

6-6 What types of systemic management are available?

• Hormone (endocrine) therapy
• Chemotherapy
• Targeted therapy

6-7 What factors should be taken into account when deciding on which type of treatment to use?

1. The stage of the cancer:
   • If the cancer is very early, surgery is the most effective treatment.
   • If the cancer has already spread around the body then systemic treatment is the most important. Additional local treatment may be advised in certain circumstances.
2. The patient herself:
   • Her general fitness
   • Her preference
3. The biology of the cancer:
   • More aggressive cancers (grade 3) will be treated with chemotherapy
   • Endocrine therapy should only be used for ER +ve cancers
   • Herceptin should only be given to HER2 +ve cancers
4. The individual preference of the doctors
5. Local availability of treatment options

The earlier the stage of breast cancer, the more important surgery is.

6-8 In what order are the different types of treatment given?

Traditionally, if surgery is going to be done, it is the first treatment carried out. However, over the last two decades, that has changed. Systemic treatment may now be given before the surgery or after surgery depending on factors in each patient.

6-9 What does neoadjuvant therapy mean?

Primary therapy. Neoadjuvant therapy is systemic treatment which is given before surgery. In most cases this means chemotherapy given before surgery. Herceptin and hormone therapy can also be given as neoadjuvant therapy before surgery.

Neoadjuvant therapy is systemic treatment which is given before surgery.

6-10 What are the advantages of neoadjuvant therapy?

There are some advantages:

• The primary cancer can be used as an ‘index’ to judge the response to treatment, i.e. how it responds to neoadjuvant therapy.
• It may allow the type of surgery that is planned to be changed. For example, a large cancer can be reduced in size by chemotherapy making a wide local excision possible rather than a mastectomy.

Therefore neoadjuvant therapy helps to make the surgery easier or more successful.

6-11 What does adjuvant therapy mean?

Adjuvant therapy is generally given after surgery. It is treatment given ‘in case’ the surgery has not removed all the cancer cells when there is no clinical evidence of spread of cancer cells beyond the primary tumour. The aim is to increase the chance of long-term survival. Adjuvant therapy may include:

• Chemotherapy
• Radiotherapy
• Hormonal (endocrine) therapy
• Targeted therapy with Herceptin

The aim of adjuvant therapy is to improve the chance of long-term survival.

6-12 What are the advantages of doing surgery first?

The advantage of doing surgery first is that a lot more is known about the tumour before any treatment is started. The whole cancer can be seen and the lymph node involvement can be accurately assessed. Many patients feel better if their primary is removed.

Surgery in breast cancer treatment

6-13 What surgery is done?

Surgery is done on the breast and on the axillary nodes. Although some names for operations include both the axilla and the breast, they will be considered separately here.

6-14 What does oncoplastic surgery mean?

Onco (cancer) plastic (aesthetic) surgery is the term used to describe doing a breast cancer operation and leaving the most acceptable breast shape possible and minimising the asymmetry.

Aesthetic means acceptable or pleasing. The management of the cancer must always come before the aesthetic appearance.

6-15 Surgery for the primary tumour of the breast

The operations for the primary tumour in the breast fall into 2 types:

• Wide local excision
• Mastectomy

Surgery to the breast is either wide local excision or mastectomy.

6-16 What other terms are used for a wide local excision?

Wide local excision is sometimes referred to as:

• Breast conservation surgery/therapy
• Lumpectomy
• Tumourectomy
• Quadrantectomy
• Partial mastectomy
• Tumour excision

Although terms may differ slightly, they basically mean the same thing.

Figure 6-1: Wide local excision of a breast lump

6-17 What is a wide local excision?

Wide local excision (WLE) is the removal of the cancer with a margin of normal breast tissue around the cancer. The margins of the tumour MUST be clear of any disease, i.e. there must be no cancer cells in the tissue removed around the cancer.

6-18 What are the problems with wide local excision?

Problems are:

• Some women will have a higher rate of recurrence than if they had a mastectomy.
• Radiotherapy has to be given post­operatively. If the patient cannot have radiotherapy, she should have a tumour excision. (There are some exceptions)
• The breasts may be very lopsided (not the same size and shape after surgery).
• The asymmetry increases with age (only the normal breast will continue to get bigger).

6-19 What are the advantages of wide local excision?

Advantages are:

• The woman keeps her breast.
• The nipple can often be kept.

Mastectomy

6-20 What is a mastectomy?

A mastectomy is removal of all the breast tissue.

With a mastectomy all the breast tissue is removed.

6-21 Who should be advised to have a mastectomy rather than a wide local excision?

There are cancer (oncological), individual and cosmetic reasons:

1. Cancer reasons for mastectomy:
   • Multiple tumours: If the cancer starts from more than one area in the breast, there is a higher rate of recurrence if a wide local excision is done.
   • Widespread ductal carcinoma in situ (a large area of precancer).
   • Strong family history: If there is a strong family history, the woman has a higher chance of developing another breast cancer.
   • Cancers bigger than 5 cm.
   • Cancers that are not seen on imaging. If a cancer is not seen on a mammogram or ultrasound scan, an MRI is usually performed. If the primary cancer is not seen, there may be other cancers within the breast that are also not seen.
2. Individual reasons for mastectomy:
   • A woman is unable to have radiotherapy postoperatively. There are many reasons for this but the commonest is that she has already had radiotherapy for another cancer, e.g. lymphoma.
   • Patient preference. Some women feel safer with a mastectomy while others choose a mastectomy to avoid radiotherapy.
3. Cosmetic reasons:
   • What affects the cosmetic outcome more than anything after a wide local excision is the amount of tissue removed from the breast. If more than 20% of the breast is removed, there will be obvious asymmetry unless tissue is also removed from the opposite breast (breast reduction)
   • If the cancer is under the areola, it will have to be removed if a wide local excision is done

6-22 What types of mastectomy are there?

There are a number of different types of mastectomy. The names given to these different types of mastectomy are confusing:

• Skin-sparing mastectomy: all the breast tissue is removed but the skin overlying the breast is kept. This is only done if a reconstruction is being performed at the same time as the mastectomy.
• Skin-reducing mastectomy: the breast tissue is removed together with the overlying skin. The woman is left with a flat chest.
• Nipple-sparing mastectomy: the skin and the nipple are left but the underlying breast tissue is removed. This is only done when there is a planned reconstruction.
• Simple mastectomy: removal of the breast tissue and no operation on the lymph nodes.
• Modified radical mastectomy: this describes a simple mastectomy with removal of the lymph nodes as well but the underlying muscle is not removed.
• Radical mastectomy: this is the original operation done in the 1950s and should not be performed anymore as it is a disfiguring operation. The breast was removed together with the overlying skin and the underlying muscle (pectoralis major).

6-23 How painful is a mastectomy?

A mastectomy without reconstruction (simple mastectomy) is not a physically painful operation but can be psychologically challenging. The operation for the lymph nodes is generally more painful. Reconstructive surgery can be painful.

Breast reconstruction after mastectomy

6-24 Who should have a reconstruction?

Generally, it is a woman’s choice.

6-25 When are breast reconstructions done?

They can be immediate, delayed or started with an expander at the time of surgery. Many women decide to have no reconstruction initially. However, they may want a reconstruction later:

• Immediate reconstruction: this is done at the time of the cancer surgery.
• Delayed reconstruction: initially a skin-reducing mastectomy is performed. All cancer management is finished (this may include radiotherapy) and then a reconstruction is started from scratch sometime later.
• Expander placement: at the time of the cancer surgery, an expander may be placed under the muscle or skin. The skin is then gradually stretched up over the next few months and the final surgery is done when all cancer treatment has finished. This allows some skin to be removed at the time of surgery and eventually, the reconstruction is done using the chest wall skin.

Figure 6-2: Use of an expander after mastectomy

6-26 What types of reconstruction are there?

There are two types of reconstruction:

1. Autologous reconstructions which use the patient’s own tissues:
   • Abdominal fat can be used: Transverse Rectus Abdominus Myocutaneous (TRAM) flap uses the fat from the abdomen to make a new breast. If microsurgery is used, it is called a Deep Inferior Epigastric Perforator (DIEP) flap.
   • Muscle can be used. The Latissimus Dorsi (LD) flap uses the muscle from the women’s back to create a new breast.
2. Prosthetic reconstructions using a silicone prosthesis.

Figure 6-3: Examples of autologous reconstruction: TRAM flap and DIEP flap.

Figure 6-4: Latissimus Dorsi (LD) flap

Figure 6-5: Examples of a prosthetic reconstruction. On the right, silicone-containing prostheses

Axillary surgery

6-27 What types of operations are done on the axilla (armpit)?

Removal of the lymph nodes. A variable number may be removed:

• Removing lymph nodes known to have cancer is called an axillary node clearance.
• Testing of the lymph nodes to see if there is cancer is called a sentinel lymph node biopsy.

6-28 Who should have their lymph nodes removed?

In general, if the cancer has spread to the lymph nodes, they need to be removed.

6-29 What are the problems of removing lymph nodes?

The more lymph nodes that are removed, the more complications are likely to occur:

• Numbness down the arm. A nerve that supplies sensation to the inside of the arm is damaged if all the nodes are removed
• Swelling of the arm (lymphoedema)
• Seroma (build up of fluid in the axilla)

Axillary clearance may lead to complications such as lymphoedema.

6-30 What is a sentinel lymph node biopsy?

The whole breast drains to between one and three lymph nodes in the axilla: these are called the sentinel nodes (sentinel means guard). A sentinel lymph node biopsy is therefore a biopsy of the first lymph nodes to which cancer cells in the breast will spread. If there are no cancer cells in these nodes then it can be assumed there is no spread of cancer to the lymph nodes higher up in the axilla.

6-31 Who should have a sentinel lymph node biopsy?

Women who do not have clinical or radiological evidence of cancer spread to the axillary nodes at the time of surgery, i.e. no enlarged axillary lymph nodes.

A sentinel lymph node biopsy is done to assess whether there has been cancer spread to the axillary lymph nodes.

6-32 How is the sentinel node found?

Before surgery, the breast is injected with either an iron oxide, a radioactive substance or a blue dye. This travels along the path of the lymphatics the cancer would take if it spread to the axillary lymph nodes. At the time of surgery, these nodes can now be easily identified and removed. Sometimes they are tested for the dye or radioactivity in theatre. Sometimes they are just removed and tested later.

6-33 What are the advantages in doing a sentinel lymph node biopsy?

The sentinel nodes are examined to assess whether they contain cancer cells. If they do not contain cancer cells then additional nodes further up the axilla do not need to be removed. The fewer the nodes removed, the fewer the postoperative complications.

Chemotherapy

6-34 What is chemotherapy?

Chemotherapy is the use of drugs (chemicals) to treat cancer. Chemotherapy interferes with all the stages of cancer development:

• Rapid, uncontrolled reproduction (proliferation) of new cells
• Loss of normal function of the cells (de-differentiation)
• Invasion into the surround tissues
• Spread around the body (metastases)

Chemotherapy has no means of distinguishing healthy cells from cancer cells so is associated with a lot of side effects as healthy cells are also damaged. There are many different regimes of chemotherapy and the type given depends on many factors.

6-35 What are the main principles behind the decision to give a particular type of chemotherapy?

The following factors need to be considered:

• If it is given as adjuvant therapy and the intention is to cure the patient then chemotherapy with strong side effects may be given.
• If it is given when a woman already has metastatic cancer (spread around the body) and it is clear that she cannot be cured, chemotherapy with less side effects is given to slow the spread of the cancer.
• Most chemotherapy given as adjuvant therapy will result in the women losing her hair.
• If a second course of chemotherapy has to be given, different drugs are generally used.
• More than one drug is given in neoadjuvant or adjuvant therapy but a single drug may be given to women for palliative care.
• Using more than one drug may make the tumour shrink faster but gives more side effects.

6-36 When is chemotherapy given?

• When the cancer has been removed but there is a high risk of recurrence (the cancer coming back in the same place or at another place in the body): adjuvant therapy is given.
• When there is a need to reduce the size of the cancer to allow surgical removal of the cancer: neoadjuvant therapy is given.
• When the cancer is incurable: it may be given to prolong the woman’s life or to improve the quality of life. When it is given to improve the symptoms of the cancer, it is known as palliative chemotherapy.

6-37 How is the decision made to give adjuvant chemotherapy?

It should be a multidisciplinary decision. That means it should be a decision made by a group of professionals: oncologists, radiotherapists and surgeons. Once the type of cancer (including the grade and hormone sensitivity) and the stage are known the prognosis and likely response to treatment can be worked out. Based on this, a woman may be advised to have chemotherapy.

In general, a young fit patient will be advised to have adjuvant chemotherapy if any one of the following is present:

• A grade 3 cancer
• A triple negative cancer
• A HER2 +ve cancer
• A cancer affecting axillary lymph nodes
• A cancer bigger than 3 cm

The decision about what treatment a woman should have must be made by a multidisciplinary team.

6-38 Who is advised to have neoadjuvant chemotherapy?

• Patients with inflammatory carcinoma.
• Women with inoperable cancer.
• Women who wish to have a wide local excision but cannot as their cancers are too large.
• Nearly all women with a triple negative or HER2 positive cancer unless the cancer is very small.

6-39 When is palliative chemotherapy given?

• When cure is not possible.
• When the aim is to prolong quality survival. That means that it is better to increase survival but the quality of the women’s life is really important.

For palliative chemotherapy a single drug may be given.

Hormone (endocrine) treatment of breast cancer

6-40 Who should have hormone treatment for breast cancer?

Anyone who has a breast cancer that has estrogen (oestrogen) receptors on their cancer cells, i.e. any ER +ve cancers or HER2 +ve cancers. If the cancer cells have receptors for estrogen, then the woman’s own estrogen can stimulate the growth of the cancer. If the estrogen can be blocked or the source removed, the cells will not survive. Hormone treatment is not effective if the cells do not have estrogen receptors, i.e. ER –ve.

Hormone treatment is used in women with estrogen receptor positive breast cancer cells.

6-41 How does hormonal treatment work?

There are 2 types of drugs used in hormone treatment:

• Drugs that stop the action of estrogen by blocking or destroying the receptors
• Drugs that stop all estrogen production

Both types of drug will prevent the ER +ve cancer cells from multiplying.

6-42 Which drug blocks the estrogen receptors?

Tamoxifen. Although tamoxifen blocks estrogen receptors on ER +ve breast cancer cells, and thereby prevents cell growth, it stimulates growth in other types of cell such as bone and endometrial cells.

Tamoxifen blocks estrogen receptors on estrogen receptor positive breast cancer cells.

6-43 How long do drugs that block the estrogen receptors take to work?

They take 4 to 6 weeks to start working.

6-44 Where does estrogen come from?

• In premenopausal women, nearly all the estrogen comes from the ovaries.
• Although the ovaries stop working after menopause some estrogen can still be produced using a different pathway in fat cells.

6-45 Which drugs prevent estrogen production by the body?

• In premenopausal women, the ovaries can be turned off with goserelin (Zoladex)
• In postmenopausal women, aromatase inhibitors can be used (anastrozole, letrozole and exemestane). These drugs stop the production of estrogen from other hormones. They are effective only if the ovaries have stopped working.

Aromatase inhibitors stop estrogen production in postmenopausal women.

6-46 Which drugs should be chosen for hormone treatment?

The choice of drugs depends on whether the woman is premenopausal or postmenopausal:

• In premenopausal women only tamoxifen and goserelin can be used.
• In postmenopausal women, a combination of tamoxifen and aromatase inhibitors are given. They are never given together. This results in few side effects.

6-47 How long should the drugs be given?

Traditionally, they have been given for 5 years and are started after chemotherapy and radiotherapy have finished. Recently it has been shown that many women should have hormone treatment for 10 years.

6-48 How effective is hormone treatment?

It will decrease the risk of getting a recurrence from the breast cancer by 50% and decrease the risk of another breast cancer by 50%.

Targeted therapy

6-49 What is Herceptin?

Herceptin is the trade name for trastuzumab. It is an example of a drug used in targeted therapy. Herceptin binds to the HER2 receptor on the outside of some breast cancer cells and slows their growth and multiplication. It has very few side effects as very few normal cells have receptors for Herceptin.

There are other newer targeted therapies that can be used for HER2 positive cancers.

6-50 Why is Herceptin not given to everyone?

• Only some breast cancers are HER2 +ve (i.e. have the receptor that Herceptin can bind to). Herceptin does not work on HER2 –ve cancer cells.
• It is very expensive.

Radiotherapy

6-51 What is radiotherapy?

Radiotherapy is the use of high-energy rays (such as X-rays) to destroy cancer cells. It is only effective at the site where it is given. Therefore it is an example of local treatment.

Radiotherapy kills any cancer cells which have been left behind after surgery.

6-52 How is radiotherapy used in breast cancer?

Radiotherapy is used for both adjuvant and therapeutic treatment.

6-53 When is radiotherapy given for adjuvant treatment?

Adjuvant radiotherapy is given after surgery:

• Radiotherapy is nearly always given to the breast area if a wide local excision has been done rather than a mastectomy.
• It is given after a mastectomy if the cancer was big or had spread to a lot of lymph nodes.
• It is sometimes used when there is only ductal carcinoma in situ.

Radiation to the breast is nearly always needed after wide local excision.

6-54 What effect does adjuvant radiotherapy have?

It will reduce the chance of the cancer coming back locally on the chest wall or in the axilla and improves survival.

Adjuvant radiotherapy reduces the risk of cancer recurring on the chest wall and axilla.

6-55 Who should not have adjuvant radiotherapy?

• Women who have had previous radiotherapy (e.g. lymphoma patients)
• Pregnant women
• Women with a weak heart or lungs: the radiotherapy may reduce function of either so make them a little worse. If function is normal, the slight decrease will not be noticed.
• Women with a frozen shoulder

6-56 How is adjuvant radiotherapy given?

• A CT scan is taken of the area and the breast is marked with a special pen.
• It is generally given to the armpit and to the supraclavicular nodes.
• An extra dose is given to the site of the original breast cancer.

6-57 When is adjuvant radiotherapy given?

Generally it is started about 1-2 months after surgery or chemotherapy. Chemotherapy is generally given first if it is needed.

6-58 When is therapeutic radiotherapy given?

• Therapeutic radiotherapy is given to treat inoperable breast cancer and to metastatic breast cancer.
• It is very effective in treating bone pain caused by cancer.
• It will also strengthen bone weakened by cancer and prevent it from fracturing.

Case study 1

A young premenopausal woman with small breasts presents with a small breast cancer. She is worried that treatment will leave her disfigured. After discussion by a multidisciplinary team she is offered a choice of local and systemic management.

1. What does local management mean?

Local management is the treatment given to the breast and axilla.

2. What local treatments are available?

Surgery (wide local excision or mastectomy) and radiotherapy if wide local excision is used.

3. What is systemic management?

This is treatment which is given to the whole body.

4. What types of systemic treatment can be used?

• Hormone therapy (tamoxifen or goserelin in a premenopausal woman)
• Chemotherapy
• Targeted therapy

Case study 2

A 45 year old mother of two children has a breast lump found on a mammogram. A diagnosis of cancer is confirmed on histology. Examination of the other breast and both axillae is normal. She chooses to have surgery and a sentinel node biopsy is found to be positive. She is offered adjuvant radiotherapy after surgery.

1. What is a sentinel node biopsy?

It is a biopsy taken at the time of surgery to determine whether there are cancer cells in the sentinel nodes. This is the first lymph node or nodes to be reached by cancer cells spreading from the breast to the axilla.

2. What is an axillary clearance?

This is removal of axillary nodes. It is done if cancer cells have spread to these nodes.

3. What are the complications of axillary node clearance?

• Numbness of the upper arm
• Lymphoedema
• Seroma

4. What is adjuvant radiotherapy?

Radiotherapy to the breast and axilla after surgery to reduce the risk of local recurrence of cancer.

Case study 3

A 55 year old postmenopausal woman presents with a 2 cm ductal carcinoma in the upper outer quadrant of her left breast. It shows up on the mammogram and there are no other masses. There are no nodes that can be seen on ultrasound scan or felt in her armpit. The cancer is ER +ve.

1. Would she be suitable for a wide local excision if that was her preference?

Yes, as long as there is no reason for her not to have radiotherapy.

2. Will she be advised to have hormone therapy?

Yes, as she has an ER +ve tumour.

3. Is she suitable for an aromatase inhibitor?

Yes, she could have either tamoxifen or an aromatase inhibitor as she is postmenopausal.

4. How do these drugs work?

Tamoxifen blocks the action of estrogen on any remaining cancer cells while an aromatase inhibitor blocks the formation of estrogen from other hormones.

Case study 4

An elderly woman presents with a large 6 cm breast lump which is found to be an invasive ER −ve, HER2 +ve ductal cancer. She has lymph nodes palpable in her axilla. She is advised to have neoadjuvant chemotherapy before surgery.

1. What is neoadjuvant chemotherapy?

This is chemotherapy that is given before surgery. It will reduce the size of the tumour, making surgery possible.

2. How does this differ from adjuvant chemotherapy?

Adjuvant chemotherapy is given after surgery with the aim of curing the patient by killing any remaining cancer cells which may remain in the body.

3. Will she be advised to have an aromatase inhibitor?

No. Her cancer is ER −ve so it will not work.

4. If it is available to her, would she be advised to have Herceptin?

Yes. Her cancer is HER2 positive.