Breast Oncology

Question 1

Assessment of breast lump

Answer 1

-TRIPLE
-History and clinical examination
-Imaging (USS, mammography, tomosynthesis)
-Pathology (FNA, core biopsy)

Question 2

Breast cancer overview

Answer 2

-One in eight women will develop breast cancer in their lifetime.
-In Scotland each year around 4700 women and 30 men are diagnosed with breast cancer.
-Five out of six women diagnosed in the UK today will be alive in five years time

Question 3

Risk factors for breast cancer

Answer 3

-Female (99% of breast cancers)
-Increased oestrogen exposure (earlier onset of periods and later menopause)
-More dense breast tissue (more glandular tissue)
-Obesity
-Nulliparity, 1st pregnancy >30
-Smoking
-Family history (first-degree relatives, premenopausal)
-BRCA1, BRCA2
-Not breastfeeding
-Ionising radiation
-p53 gene mutations
-Previous surgery for benign disease

-The combined contraceptive pill gives a small increase in the risk of breast cancer, but the risk returns to normal ten years after stopping the pill.
-Hormone replacement therapy (HRT) increases the risk of breast cancer, particularly combined HRT (containing both oestrogen and progesterone).

Question 4

Breast cancer genetics

Answer 4

-BRCA refers to the BReast CAncer gene. The BRCA genes are tumour suppressor genes. Mutations in these genes lead to an increased risk of breast cancer (as well as ovarian and other cancers).

-The BRCA1 gene is on chromosome 17. In patients with a faulty gene:
=Around 70% will develop breast cancer by aged 80
=Around 50% will develop ovarian cancer
=Also increased risk of bowel and prostate cancer

-The BRCA2 gene is on chromosome 13. In patients with a faulty gene:
=Around 60% will develop breast cancer by aged 80
=Around 20% will develop ovarian cancer

-There are other rarer genetic abnormalities associated with breast cancer (e.g., TP53 and PTEN genes)

Question 5

Describe male breast cancer

Answer 5

-<1% of breast cancer and < 1% of all male cancers.
-Guidelines are essentially the same as female breast cancer

Question 6

Types of breast cancer

Answer 6

-Invasive
=Ductal (75-80%) No Special Type
=Lobular (10-15%)
=Medullary, mucinous, tubular, micropapillary, metaplastic, inflammatory, Paget’s
=Phyllodes, angiosarcoma

-In situ (no spread beyond local tissue)
=Ductal carcinoma in situ (DCIS)

-Rare:
=Medullary breast cancer
=Mucinous breast cancer
=Tubular breast cancer
=Multiple others

Question 7

Overview of Ductal Carcinoma In Situ

Answer 7

-Pre-cancerous or cancerous epithelial cells of the breast ducts
-Localised to a single area
-Often picked up by mammogram screening
-Potential to spread locally over years
-Potential to become an invasive breast cancer (around 30%)
-Good prognosis if full excised and adjuvant treatment is used

Question 8

Overview of Lobular Carcinoma In Situ

Answer 8

-A pre-cancerous condition occurring typically in pre-menopausal women
-Usually asymptomatic and undetectable on a mammogram
-Usually diagnosed incidentally on a breast biopsy
-Represents an increased risk of invasive breast cancer in the future (around 30%)
-Often managed with close monitoring (e.g., 6 monthly examination and yearly mammograms)

Question 9

Overview of Invasive Ductal Carcinoma

Answer 9

-NST means no special/specific type, where it is not more specifically classified (e.g., medullary or mucinous)
-Also known as invasive breast carcinoma of no special/specific type (NST)
-Originate in cells from the breast ducts
-80% of invasive breast cancers fall into this category
-Can be seen on mammograms

Question 10

Overview of Invasive Lobular Carcinomas

Answer 10

-Around 10% of invasive breast cancers
-Originate in cells from the breast lobules
-Not always visible on mammograms

Question 11

Overview of Inflammatory breast cancer

Answer 11

-1-3% of breast cancers
-cancerous cells block the lymph drainage resulting in an inflamed appearance of the breast. This accounts for around 1 in 10,000 cases of breast cancer.
-Presents similarly to a breast abscess or mastitis
-Swollen, warm, tender breast with pitting skin (peau d’orange)
-Does not respond to antibiotics
-Worse prognosis than other breast cancers

Question 12

Describe Paget’s Disease of the Nipple

Answer 12

-Looks like eczema of the nipple/areolar
-Erythematous, scaly rash
-Indicates breast cancer involving the nipple, present in 1-2% of patients with breast cancer
=In half of these patients, it is associated with an underlying mass lesion and 90% of such patients will have an invasive carcinoma. 30% of patients without a mass lesion will still be found to have an underlying carcinoma. The remainder will have carcinoma in situ.
-May represent DCIS or invasive breast cancer
-Requires biopsy, staging and treatment, as with any other invasive breast cancer

Question 13

Presentation of breast cancer

Answer 13

-Lumps that are hard, irregular, painless or fixed in place
-Lumps may be tethered to the skin or the chest wall
-Nipple retraction
-Skin dimpling or oedema (peau d’orange)
-Lymphadenopathy, particularly in the axilla

Question 14

Referral criteria for breasts cancer

Answer 14

The NICE guidelines (updated January 2021) recommend a two week wait referral for suspected breast cancer for:

=An unexplained breast lump in patients aged 30 or above
=Unilateral nipple changes in patients aged 50 or above (discharge, retraction or other changes)

The NICE guidelines recommend also considering a two week wait referral for:

=An unexplained lump in the axilla in patients aged 30 or above
=Skin changes suggestive of breast cancer

The NICE guidelines suggest considering non-urgent referral for unexplained breast lumps in patients under 30 years.

Question 15

Biomarkers for breast cancer

Answer 15

-Oestrogen / progesterone receptors (ER/PR)
=Found within nuclei of cells, act as transcription factors
=75% of breast cancers have some ER activity

-Human Epidermal Growth Factor receptor 2 (HER2)
=Cell surface receptor involved in cell growth and differentiation
=Over expressed in 10-15% of breast cancers

-Ki-67
=Marker of cell proliferation
=Higher levels associated with better response to neoadjuvant chemo, but overall prognosis poorer

-Gene expression profiling involves assessing which genes are present within the breast cancer on a histology sample. This helps predict the probability that the breast cancer will reoccur as a distal metastasis (away from the original cancer site) within 10 years.
=The NICE guidelines (2018) [DG34] recommend this for women with early breast cancers that are ER positive but HER2 and lymph node negative. It helps guide whether to give additional chemotherapy.

Question 16

FBC in Breast cancer

Answer 16

Patients with a clinical/pathological diagnosis of inflammatory breast cancer without distant metastasis should have an FBC and platelet count
=may show anaemia, thrombocytopenia, leukopenia/neutropenia

-An FBC, a comprehensive metabolic panel, liver function tests, and an alkaline phosphatase test should be considered only if the patient is a candidate for preoperative or adjuvant systemic therapy

Question 17

Imaging in breast cancer

Answer 17

-Younger women generally have more dense breasts with more glandular tissue.

-Ultrasound scans are typically used to assess lumps in younger women (e.g., under 30 years). They are helpful in distinguishing solid lumps (e.g., fibroadenoma or cancer) from cystic (fluid-filled) lumps.

-Mammograms are generally more effective in older women. They can pick up calcifications missed by ultrasound.

-MRI scans may be used:
=For screening in women at higher risk of developing breast cancer (e.g., strong family history)
=To further assess the size and features of a tumour

Question 18

Lymph node assessment in breast cancer

Answer 18

-Women diagnosed with breast cancer require an assessment to see if cancer has spread to the lymph nodes. All women are offered an ultrasound of the axilla (armpit) and ultrasound-guided biopsy of any abnormal nodes.

-A sentinel lymph node biopsy may be used during breast cancer surgery where the initial ultrasound does not show any abnormal nodes.
=Sentinel node biopsy is performed during breast surgery for cancer. An isotope contrast and a blue dye are injected into the tumour area. The contrast and dye travel through the lymphatics to the first lymph node (the sentinel node). The first node in the drainage of the tumour area shows up blue and on the isotope scanner. A biopsy can be performed on this node, and if cancer cells are found, the lymph nodes can be removed.

Perform surgery using sentinel lymph node biopsy (SLNB) rather than axillary lymph node clearance to stage the axilla for people with invasive breast cancer if they have:
=no evidence of lymph node involvement on ultrasound, or
=a negative ultrasound-guided needle biopsy

Question 19

Staging investigations of breast cancer

Answer 19

-Breast cancer usually spreads to regional lymph nodes first, then common sites of metastasis are
=Lung
=Liver
=Bone
=Brain

-Investigations
=Ultrasound of axilla +/- biopsy or FNA of suspicious nodes (mammogram >40 years)
=Bloods – FBC, U&Es, LFTs, calcium

-If locally advanced disease, multiple involved nodes or abnormal bloods
=CT chest / abdomen + bone scan

TNM staging

Lymph node assessment and biopsy
MRI of the breast and axilla
Liver ultrasound for liver metastasis
CT of the thorax, abdomen and pelvis for lung, abdominal or pelvic metastasis
Isotope bone scan for bony metastasis

Question 20

Metastasis in breast cancer

Answer 20

L – Lungs
L – Liver
B – Bones
B – Brain

Question 21

Principles of breast cancer management

Answer 21

-Surgery
-Adjuvant therapies
=Radiotherapy
=Endocrine therapy
=Chemotherapy
=Targeted therapies
=Other

Question 22

Describe breast cancer surgery

Answer 22

-Breast
=Main principle is to do the least necessary.
=Both invasive and pre-invasive disease should be removed with a margin of surrounding normal tissue, aiming for a microscopic margin at least 1mm.

-Options
=Simple wide local excision
=Wide local excision as part of breast reduction
=Mastectomy (with or without reconstruction)
=Therapeutic mammoplasty?
=Implant-based reconstruction?
=Autologous reconstruction?
=Lipomodelling (improve cosmesis following breast conserving surgery or reconstruction, own fat harvested from abdomen or thighs, processed, re-injected into breast or skin flaps to give volume)
=Axillary: undertaken at same time, axillary nodal clearance reserved for proven nodal involvement, if no evidence of lymph nodes on USS sentinel lymph node biopsy

Tumour Removal

The objective is to remove the cancer tissue along with a clear margin of normal breast tissue. The options are:

Breast-conserving surgery (e.g., wide local excision), usually coupled with radiotherapy
Mastectomy (removal of the whole breast), potentially with immediate or delayed breast reconstruction

Axillary Clearance

Removal of the axillary lymph nodes is offered to patients where cancer cells are found in the nodes. Usually, the majority or all lymph nodes are removed from the axilla. This increases the risk of chronic lymphoedema in that arm.

Question 23

Presence of axillary lymphadenopathy

Answer 23

-Women with no palpable axillary lymphadenopathy at presentation should have a pre-operative axillary ultrasound before their primary surgery
=if negative then they should have a sentinel node biopsy to assess the nodal burden

-In patients with breast cancer who present with clinically palpable lymphadenopathy, axillary node clearance is indicated at primary surgery
=this may lead to arm lymphedema and functional arm impairment

Question 24

Wide local excision vs mastectomy

Answer 24

-Wide local excision
=Solitary lesion
=Peripheral tumour
=Small lesion in large breast
=DCIS <4 cm

-Mastectomy
=Multifocal tumour
=Central tumour
=Large lesion in small breast
=DCIS >4 cm

Question 25

Overview of chronic lymphoedema

Answer 25

-Lymphoedema is a chronic condition caused by impaired lymphatic drainage of an area. Lymphoedema can occur in an entire arm after breast cancer surgery on that side, with removal of the axillary lymph nodes in the armpit.

-The lymphatic system is responsible for draining excess fluid from the tissues. The tissues in areas affected by an impaired lymphatic system become swollen with excess, protein-rich fluid (lymphoedema).

-The lymphatic system also plays an important role in the immune system. Areas of lymphoedema are prone to infection.

-There are specialist lymphoedema services that can help manage patients. Non-surgical treatment options include:
=Massage techniques to manually drain the lymphatic system (manual lymphatic drainage)
=Compression bandages
=Specific lymphoedema exercises to improve lymph drainage
=Weight loss if overweight
=Good skin care

Question 26

Adjuvant therapies for breast cancer

Answer 26

-Radiotherapy
=Key in breast conservation
=Also given to chest wall, axilla, SCF, and T4 disease
=Some limitations (previous RT, arm mobility, side effects)

-Chemotherapy
=Where justified with improved survival risk
=Online prognostication tools available, also gene profiling prognostication tests
=Adjuvant or neoadjuvant

-Hormone therapy (ER positive disease only)
=Tamoxifen, aromatase inhibitors, ovarian suppression

-Targeted therapies
=E.g. Trastuzumab (Herceptin) in HER2 positive cancers

-Bisphosphonates
=For the prevention of bone recurrence and improved overall survival in postmenopausal women

Question 27

Overview of radiotherapy in breast cancer

Answer 27

Whole breast radiotherapy is recommended after a woman has had a wide-local excision as this may reduce the risk of recurrence by around two-thirds. For women who’ve had a mastectomy radiotherapy is offered for T3-T4 tumours and for those with four or more positive axillary nodes

Radiotherapy is usually used in patients with breast-conserving surgery to reduce the risk of recurrence. High-dose radiation is delivered from multiple angles to concentrate radiation on a targeted area. Patients will have a course of radiotherapy after surgery, for example, with a session of radiotherapy every day for 3 weeks.

Common radiotherapy side effects include:
=General fatigue from the radiation
=Local skin and tissue irritation and swelling
=Fibrosis of breast tissue
=Shrinking of breast tissue
=Long term skin colour changes (usually darker)

Question 28

Overview of chemotherapy in breast cancer

Answer 28

Oncologists will guide chemotherapy. Chemotherapy is used in one of three scenarios:

=Neoadjuvant therapy – intended to shrink the tumour before surgery
=Adjuvant chemotherapy – given after surgery to reduce recurrence
=Treatment of metastatic or recurrent breast cancer

Question 29

Hormone treatment in breast cancer

Answer 29

Patients with oestrogen-receptor positive breast cancer are given treatment that disrupts the oestrogen stimulating the breast cancer.

There are two main first-line options for this:
=Tamoxifen for premenopausal women
=Aromatase inhibitors for postmenopausal women (e.g., letrozole, anastrozole or exemestane)

Tamoxifen is a selective oestrogen receptor modulator (SERM). It either blocks or stimulates oestrogen receptors, depending on the site of action. It blocks oestrogen receptors in breast tissue, and stimulates oestrogen receptors in the uterus and bones. This means it helps prevent osteoporosis, but it does increase the risk of endometrial cancer.

Aromatase is an enzyme found in fat (adipose) tissue that converts androgens to oestrogen. After menopause, the action of aromatase in fat tissue is the primary source of oestrogen. Aromatase inhibitors work by blocking the creation of oestrogen in fat tissue.

Tamoxifen or an aromatase inhibitor are given for 5 – 10 years to women with oestrogen-receptor positive breast cancer.

Other options for women with oestrogen-receptor positive breast cancer, used in different circumstances, are:
=Fulvestrant (selective oestrogen receptor downregulator)
=GnRH agonists (e.g., goserelin or leuprorelin)
=Ovarian surgery

Question 30

Targeted treatments in breast cancer

Answer 30

Trastuzumab (Herceptin) is a monoclonal antibody that targets the HER2 receptor. It may be used in patients with HER2 positive breast cancer. Notably, it can affect heart function; therefore, initial and close monitoring of heart function is required.

Pertuzumab (Perjeta) is another monoclonal antibody that targets the HER2 receptor. It may be used in patients with HER2 positive breast cancer. This is used in combination with trastuzumab (Herceptin).

Neratinib (Nerlynx) is a tyrosine kinase inhibitor, reducing the growth of breast cancers. It may be used in patients with HER2 positive breast cancer.

Question 31

Breast screening principles

Answer 31

-Breast cancer falls into the WHO criteria for a screening programme:
=Disease has a recognised early stage (DCIS)
=that is identifiable (90% of DCIS has microcalcification on mammography),
=by a simple, acceptable and cost-effective test(mammography),
=is treatable,
=and treatment at early stage improves outcome

-Downsides:
=Anxiety and stress
=Exposure to radiation, with a very small risk of causing breast cancer
=Missing cancer, leading to false reassurance
=Unnecessary further tests or treatment where findings would not have otherwise caused harm

Question 32

Follow up in breast cancer

Answer 32

The NICE guidelines (2018) recommend all patients treated for breast cancer have surveillance mammograms yearly for 5 years (longer if they are not yet old enough for the regular breast screening programme).

Patients treated for breast cancer are given an individual written care plan, including details on:

=Designated contacts and details
=Adjuvant treatment review dates
=Surveillance dates
=Advice on identifying recurrence
=Support service details

Question 33

UK breast screening programme

Answer 33

-Women are sent an appointment for a two view mammogram
-In Scotland, women aged 50-70 years old, every 3 years
-In England, women aged 47-73 years old, every 3 years (as atrial)
-Also offered to certain women at a younger age who are deemed at increased risk of developing breast cancer due to family history, known genetic mutation, previous mantle radiotherapy etc

Question 34

Who are high-risk patients?

Answer 34

There are different recommendations for screening patients with a higher risk due to a family history of breast cancer. These are in the NICE guidelines (2013, updated 2019).

There are specific criteria for a referral from primary care for patients that may be at higher risk due to their family history. For example:

=A first-degree relative with breast cancer under 40 years
=A first-degree male relative with breast cancer
=A first-degree relative with bilateral breast cancer, first diagnosed under 50 years
=Two first-degree relatives with breast cancer

Question 35

Red flags in family history of breast cancer

Answer 35

-age of diagnosis < 40 years
-bilateral breast cancer
-male breast cancer
-ovarian cancer
-Jewish ancestry
-sarcoma in a relative younger than age 45 years
-glioma or childhood adrenal cortical carcinomas
-complicated patterns of multiple cancers at a young age
-paternal history of breast cancer (two or more relatives on the father’s side of the family)

Question 36

Management of high-risk patients

Answer 36

Secondary care breast clinic or a specialist genetic clinic.

-Patients require genetic counselling and pre-test counselling before performing genetic tests. This is to discuss the benefits and drawbacks of genetic testing, such as the implications for family members and offspring.

-Annual mammogram screening is offered to women with increased risk, between specific age ranges, depending on their level of risk (potentially starting from aged 30, if high risk).

-Chemoprevention may be offered for women at high risk, with:
=Tamoxifen if premenopausal
=Anastrozole if postmenopausal (except with severe osteoporosis)

-Risk-reducing bilateral mastectomy or bilateral oophorectomy (removing the ovaries) is an option for women at high risk. This is suitable for only a small number of women and requires significant counselling and weighing up risks and benefits.

Question 37

Breast cancer drug types

Answer 37

-Letrozole (Femara)
-Tamoxifen
-Trastuzumab
-Zoledronic acid
-Goserelin
-Capecitabine

Question 38

What is letrozole?

Answer 38

-Hormonal therapy drug used to treat breast cancer.
-It is usually used when you have been through a natural menopause.
-It may also be used when someone is premenopausal and having treatment to stop the ovaries working (temporary menopause).
-Sometimes it might be used to treat breast cancer in men.

Question 39

When is letrozole used?

Answer 39

-Before surgery, to try to reduce the size of the cancer and avoid removal of the breast (mastectomy)
-After other treatments, to reduce the risk of breast cancer coming back
-To control breast cancer that has come back or spread to other parts of the body (secondary breast cancer).

Question 40

How does letrozole work?

Answer 40

-Letrozole reduces the amount of a type of hormone called oestrogen in the body. Hormones are substances that our bodies make. They help control how cells and organs work.

-The hormone oestrogen can encourage some breast cancers to grow. This type of breast cancer is called oestrogen receptor-positive (ER-positive) breast cancer. Letrozole can be used in ER-positive breast cancers to stop breast cancer cells from growing when someone has been through the menopause.

-Oestrogen is produced mainly in the ovaries before the menopause. After the menopause, the ovaries no longer produce oestrogen. But a small amount of oestrogen is still produced in the fatty tissues, muscle and skin. This happens using a type of protein (an enzyme) called aromatase. Letrozole works by blocking this enzyme to reduce the amount of oestrogen in the body. It is a type of drug called an aromatase inhibitor.

-If you have not been through the menopause, you may have other types of hormone therapy

Question 41

Common letrozole side effects

Answer 41

-Hot flushes and sweats
-Fatigue
-Muscle or joint pain
-Feeling sick, indigestion, abdominal pain
-Raised cholesterol
-Change in appetite
-Hair thinning
-Mood changes
-Skin changes
-Headaches
-Feeling dizzy
-Weight gain
-Vaginal bleeding or dryness
-Diarrhoea
-Constipation
-Osteoporosis
-Bone thinning
-Raised BP
-Fluid build up

Question 42

Less common side effect of letrozole

Answer 42

-Heart problems
-Risk of infection
-Eye problems
-Difficulty sleeping
-Memory and concentration issues
-Effect on liver
-Dry mouth
-Changes to taste
-Blood clot risk

Question 43

When is Tamoxifen used?

Answer 43

Tamoxifen is a hormonal therapy drug used:

=to reduce the risk of breast cancer coming back and to prevent a new cancer developing in the other breast – you take it for a number of years
=to treat secondary breast cancer.

-Tamoxifen is also sometimes used to:

=reduce a woman’s risk of breast cancer developing if they have a higher risk because of family history
=treat other types of cancer
=treat or prevent breast tenderness and swelling (gynaecomastia) – this can be a side effect of some hormonal therapies used for prostate cancer.

Question 44

How does Tamoxifen work?

Answer 44

Hormones are chemicals that our bodies make. Hormones act as messengers and help control how cells and organs work. Hormonal therapies are drugs that change the way hormones are made or how they work in the body.

Many breast cancers rely on the hormone oestrogen to grow. This type of breast cancer is called oestrogen receptor-positive (ER-positive) breast cancer. Tamoxifen blocks oestrogen from reaching the cancer cells.

Question 45

Common side effects of Tamoxifen

Answer 45

-Hot flushes and sweats
-Vaginal dryness
-Vaginal bleeding and effects on periods
-Nausea
-Fatigue
-Mood changes
-Skin changes
-Hair thinning
-Oedema
-Leg cramps and muscle pain
-Headaches
-Diarrhoea and constipation
-Cataracts
-Pins and needles
-Blood clot or stroke
-Womb cancer
-Liver effects

Question 46

What is trastuzumab?

Answer 46

Trastuzumab belongs to a group of targeted therapy drugs known as monoclonal antibody. Trastuzumab is often given in combination with chemotherapy and other cancer drugs.

Some cancer cells have too much of a protein called HER2 – this is called HER2 positive cancer. HER2 encourages cancer cells to grow. Cells taken during a biopsy or surgery to remove the cancer are tested for HER2.

Trastuzumab can be used to treat HER2 positive cancer. It works by locking on to the HER2 protein to help stop the cancer cells from dividing and growing.

Question 47

Common side effects of trastuzumab

Answer 47

-Risk of infection
-Bruising and bleeding
-Anaemia
-Heart problems
-Nausea
-Sore mouth and throat
-Loss of appetite
-Changes to taste
-Indigestion
-Diarrhoea, constipation
-Muscle or joint pain
-Watery sore eyes

Question 48

What is zoledronic acid?

Answer 48

Zoledronic acid belongs to a group of drugs called bisphosphonates. It can be used to:

=help protect the bones from the effects of some treatments for early breast cancer
=reduce the risk of early breast cancer spreading to the bones – this is called adjuvant treatment
=reduce a raised calcium level in the blood caused by cancer that has spread to the bones
=treat bone weakness or pain caused by myeloma or by breast cancer that has spread to the bones.
Early breast cancer means the cancer has not spread beyond the breast or nearby lymph nodes.

Cancer that has spread to the bones is called secondary bone cancer. It happens when cells from the original (primary) cancer spread to form a new tumour in the bone. This is called secondary cancer or metastasis.

Myeloma is a cancer of a type of blood cell called plasma cells. The abnormal plasma cells build up inside bones, causing pain and weakness.

Question 49

How does zoledronic acid work?

Answer 49

Zoledronic acid reduces the activity of the osteoclasts. This can help reduce pain and strengthen the bone. For breast cancer, it can reduce the risk of cancer spreading to the bones.

Zoledronic acid also reduces the amount of calcium that is lost from the bones. This helps calcium levels in the blood return to normal.

Question 50

Side effects of zoledronic acid

Answer 50

-Flu like symptoms
-Pain in thigh, hip, groin
-Anaemia
-Fatigue
-Headaches
-Red or sore eyes
-Blood in urine

Question 51

Overview of Goserelin

Answer 51

-LH blocker: stops ovaries from making oestrogen
-For women post menopause, ER positive
-Depot injection

Question 52

Overview of capecitabine

Answer 52

-Chemotherapy drug