Women’s Health - New Breast (mainly cancer)

Question 1

How common is breast cancer

Answer 1

Breast cancer is the most common form of cancer in the UK. It mostly affects women and is rare in men (about 1% of UK cases). Around 1 in 8 women will develop breast cancer in their lifetime.

56,000 new cases annually

Question 2

Basic breast anatomy

Answer 2

The breast is made up of the following main components:

Most of the breast is adipose (fatty) tissue.

Lobules are part of the glandular system; they are glands that produce breast milk. Lobules are found in groups which together form a lobe.

Ducts are small tubes that carry breast milk from the lobules to the nipple.

Breast cancers most commonly arise in the ducts that transport milk from the lobules to the nipple. These are known as ductal cancers. Some breast cancers can develop in the lobules, which are known as lobular cancers.

Question 3

Risk factors for breast cancer

Answer 3

Age- biggest risk factor
Female (99% of breast cancers)
Increased oestrogen exposure (earlier onset of periods and later menopause)
More dense breast tissue (more glandular tissue)
Obesity
Smoking
Family history (first-degree relatives)
COCP - oestrogen again.
HRT - oestrogen stimualtes proliferation of the breast epithelium. Women should be on the lowest dose of HRT for the shortest period of time to get them over the worst symptoms of menopause

Question 4

What is ductal carcinoma in situ and how does it differ from invasive carcinoma histologically and behavoirally?

Answer 4

DCIS is pre-invasive disease and a pre-curor to invasive breast cancer. It involves neoplastic proliferation of epithelial cells - confined to duct without
invasion through basement membrane.

Most DCIS cases are completely asymptomatic and are detected
by breast screening - microcalcifications on mammography, but occasionally it can present as a lump. The lining epithelium of the breast ducts becomes thickened as the cells proliferate and eventually appear full of cells, often with central necrosis. Cytologically the cells appear malignant but they have not yet acquired the ability to invade the basement membrane and therefore cannot metastasise. Treatment primarily involves wide excision and radiotherapy
or rarely mastectomy if the disease is more extensive.

LCIS - The other type of pre-invasive breast cancer is lobular carcinoma in situ. This is where there is neoplastic ploriferation of epithelial cells that is confined to the terminal ductal lobular units.

Question 5

What is invasive breast cancer and what are the different histological types

Answer 5

Invasive carcinoma means that the cells have penetration through basement membrane. There are two common histological types of invasive breast cancer –
ductal (70%) and lobular (10%).

1. Invasive ductal carcinoma (commonest - 75%). Neoplastic proliferation of epithelial cells that invades through the ductal basement membrane.
2. Invasive lobular carcinoma - harder to feel, less likely to be visible on mammography, more diffuse and therefore more difficult to excise and more prone to be bilateral or multi-focal.

Rarer subtypes include **tubular, mucinous **and medullary but
the treatment is largely the same regardless. Tubular and mucinous
tumours tend to be grade 1 (better differentiated) and therefore have a
better prognosis than the more usual types. **Medullary may be of high
grade. **Other rare subtypes include phyllodes tumour, spindle cell
tumours, primary breast sarcomas and lymphomas of the breast.

**INVASIVE/MALIGNANT BREAST CANCER (80%) IS DIFFERENT FROM METASTATIC BREAST CANCER (25% of cases - spread to other organs) **

Question 6

What is padget’s disease of the nipple

Answer 6

• This is an eczematous change of the nipple (Erythematous, scaly rash) due to an underlying malignancy (invasive or in-situ).
• should be suspected in apparent nipple eczema that does not resolve with two weeks of steroid/anti fungal cream.
• Indicates breast cancer involving the nipple, may represent DCIS or invasive breast cancer
• Requires biopsy, staging and treatment, as with any other invasive breast cancer

Question 7

What are the BRCA genes and on what chromosomes are they found.

Answer 7

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).

mnemonic - 1+2 = 3, 17+13 = 30

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 8

What is the UK breast cancer screening programme?

Aim of the screening programme?

Minor point but some key downsides to screening

Answer 8

**The NHS breast cancer screening program offers a mammogram every 3 years to women aged 50 – 70 years.
**

Screening aims to detect breast cancer early, which improves outcomes. Roughly 1 in 100 women are diagnosed with breast cancer after going for a mammogram.

There are some potential downsides to screening:

Overdiagnosis - Unnecessary further tests or treatment of cancers would never caused symptoms in the womans lifetume.
Anxiety and stress
Exposure to radiation, with a very small risk of causing breast cancer
Missing cancer, leading to false reassurance

Generally, the benefits far outweigh the downsides and breast cancer screening is recommended.

Question 9

Who is considered high risk for developing breast cancer and what is their management ?

Answer 9

The following patients are considered high risk and should be referred to secondary care:

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

Management:
- Patients require genetic counselling and genetic testing
- annual mamograms, potentially starting from age 30
- Chemoprevention may be offered for high risk women - Both reduced oestrogen - Tamoxifen if premenopausal and Anastrozole (aromatase inibitor) 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 10

KEY - Once a patient has been referred for specialist services under a two week wait referral for suspected breast cancer usually for a breast lump. How are they assessed for breast cancer?

Answer 10

They should initially receive a triple diagnostic assessment comprising of:

Clinical assessment (history and examination)
Imaging (ultrasound or mammography)
Biopsy (fine needle aspiration or core biopsy)

Question 11

Presentation of breast cancer

Answer 11

Clinical features that may suggest breast cancer are:

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

Question 12

What imaging can be used to investigate breast lumps. What is involved and when is each suitable.

Answer 12

Ultrasound scans cannot be used as a screening tool but can be used to assess lumps in younger women (e.g., under 40 years). They are helpful in distinguishing solid lumps (e.g., fibroadenoma or cancer) from cystic (fluid-filled) lumps.

Mammograms are used as both a screening tool and an investigation for lumps. They are generally more effective in older women - below the age of 40, but remember screening starts at 50 (or for women on HRT) the breast tissue is usually too dense to pick up any cancer and therefore they are less useful. They can pick up calcifications missed by ultrasound.

The breast is compressed in 2 planes, the first is cranio-caudal (CC) with the plates horizontal. This view gives a good image of the medial part of the breast and the deeper part near the chest wall. The second view is with the breast squeezed obliquely, the medio-lateral oblique, (MLO) view. This gives a better view of the axillary tail and
lateral breast.

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 13

How are breast lumps biopsied?

Answer 13

Core Biopsy - under local anaesthetic and ultrasound guidance, a needle mounted to a spring loaded biopsy gun removes an apple core of tissue from the lump.

Formerly fine needle aspiration cytology was used - lower sensitivity and specificity - cytology but not histology (looks at aspirated cells not sections of tissues).

Question 14

Investigations for axillary lymph node involvement and management in breast cancer

Answer 14

Women diagnosed with breast cancer require an assessment to see if cancer has spread to the lymph nodes (up to 40% of women with breast cancer will have cancer in their axillary nodes at diagnosis) . All women are offered an ultrasound of the axilla (armpit) and ultrasound-guided biopsy of any abnormal nodes.

If no cancer is seen, a sentinel lymph node biopsy may be used during breast cancer surgery where the initial ultrasound does not show any abnormal nodes to confirm that the nodes are clear. 25% of cases the nodes seem normal on ultrasound but cancer is detected on histology after sentinel node biopsy.

If the USS scan/SNB does show signs of cancer in the nodes then full ANC is the management.

SO THE KEY BIT TO MEMORISE IS EVERYONE GETS AN USS. Positive -> ANC, negative ->

The purpose of surgery to the axillary lymph nodes is twofold. It aims to remove any breast cancer deposits within the glands and so provide local disease control and also to provide valuable prognostic information which will determine whether any additional or
adjuvant treatments are needed post-operatively.

Sentinel Lymph Node Biopsy:

Sentinel node biopsy is performed during breast surgery for cancer. An isotope contrast (technitium) 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. These first nodes are removed and sent for histology to determine if the axilla is involved.

ANC:

If a women if known to have axillary invovlement from USS or from sentinal node biopsy then Axillary node clearance surgery is usually performed. Axillary clearance involves removal of all of the lymph nodes in the axilla. This has a low rate of axillary recurrence (good local control and prognostic information) but can lead to seroma, nerve damage and lymphoma.

Radiotherapy:

Some women with low risk axillary disease are offered radiotherapy to the axilla instead of surgical management.

Question 15

What 3 receptors are targetted in breast cancer therapy

Answer 15

Breast cancer cells may have receptors that can be targeted with breast cancer treatments. These receptors are tested for on samples of the tumour and help guide treatment. There are three types of receptors:

Oestrogen receptors (ER)
Progesterone receptors (PR)
Human epidermal growth factor (HER2) - Rx with trastuzumab

Triple-negative breast cancer is where the breast cancer cells do not express any of these three receptors. This carries a worse prognosis, as it limits the treatment options for targeting the cancer.

Question 16

Where does breast cancer most commonly metastasise to

Answer 16

25% of breast cancers are metastastic

You can remember the notable locations that breast cancer metastasis occur using 2 Ls and 2 Bs:

L – Lungs
L – Liver - bad prognosis
B – Bones
B – Brain - bad prognosis

Notably, breast cancer can metastasise to anywhere in the body, like melanoma.

Question 17

How is breast cancer staged

Answer 17

The TNM system is used to stage breast cancer. This scores the size and spread of the tumour (T), nodes (N) and metastasis (M).

T= tumour size/diametre
N = spread to lymph nodes
M = spread to another part of the body

Staging is different to grading - Tumour grade varies from grade 1, where the cells are well differentiated with a
low mitotic rate (and look very similar to normal breast glands down the
microscope) to grade 3 where the reverse is true, and the cells look very abnormal and have many more mutations in the genes.

Question 18

What are the 2 options for breast cancer surgery

Answer 18

The objective is to remove the cancer tissue along with a clear margin of normal breast tissue. The 2 options are:

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

Extra information:
- Removal of the axillary lyph nodes is offered when cancer cells are found in the nodes, there is a risk of chronic lyphaodema in that arm

BACKGROUND
The purpose of surgery in breast cancer is primarily to gain local control of the disease and to determine the prognostic features of the primary cancer.

The biological features and stage of the cancer will often have determined whether a patient has micro-metastases at the time of surgery and surgery will have no influence on this distant disease. These micro-metastases are the reason for giving systemic therapy (adjuvant chemotherapy, trastuzumab and endocrine therapy) after surgery depending on the prognostic features of the primary cancer. Micro-metastases, if present, may not develop into symptomatic metastases for many years. Once metastatic disease has developed, breast cancer becomes incurable (i think this means if you allow the micro-metastasis to establish).

Question 19

Key - what are the two possible management options for the axillar

Answer 19

If USS shows axillary nodes are clear of disease then it’s a sentinel node biopsy to confirm it’s all clear

If USS shows disease then full axillary node clearance is used

Sidenote: 2 options for breast are lumpectomy and mastectomy.

Question 20

When is chemotherapy used in breast cancer treatment - 3 reasons

Answer 20

Chemotherapy is used in one of three scenarios:

Neoadjuvant therapy – intended to shrink the tumour before surgery

Adjuvant chemotherapy – given after surgery to prevent recurrence (aim is to target micro-metastases or microscopic disease at the primary site).

Treatment of metastatic or recurrent breast cancer

Question 21

Breast cancer - what are the two options for hormone treatment

Answer 21

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.

TOM TIP: It is worth committing tamoxifen and aromatase inhibitors (e.g., letrozole) to memory, their relationship to menopausal status and their basic mechanism of action. These are good facts for examiners to test you on.

Question 22

Mamary Duct ectasia cheat sheet
what is it?
presentation?
how is it managed?

Answer 22

Mammary duct ectasia is a benign condition of unknown aetiology where there is dilation of the large ducts in the breasts and they fill with debris.

There is inflammation in the ducts, leading to intermittent discharge from the nipple. The discharge may be white, grey or green. It ususally occours in perimenaupause.

Management:
Ix is to exclude breast cancer with tripple assessment.

Management is usually expectant, it can cause infections (periductal mastitis) and surgery may be required in problematic cases.

Question 23

Mastitis/Breast infeciton

Two causes?

What is infectious mastitis and what is the causative organism?

What is a breast abcess?

Management?

Answer 23

Mastitis refers to inflammation of breast tissue. It can be divided into two groups

• lactational - a complication of breast feeding. There is an obstruction in the flow of milk and the breasts become engorged with milk.
• non-lactional - usually associated with duct ectasia

Mastitis can be with or without infection. Bacteria can enter at the nipple and back-track into the ducts, causing infection and inflammation. Mastitis caused by infection may precede the development of an abscess. The commenst orgnanism by far is staph. aureus.

Mastitis presents with:
Breast pain and tenderness (unilateral)
Erythema in a focal area of breast tissue
Local warmth and inflammation
Nipple discharge
Fever

The key feature that suggests a breast abscess is a swollen, fluctuant, tender lump within the breast. Fluctuance refers to being able to move fluid around within the lump using pressure during palpation. Where there is infection without an abscess, there can still be hardness of the tissue, forming a lump, but it will not be fluctuant as it is not filled with fluid.

Management of lactational mastitis:
- lactional mastitis caused by bloackage - expressing with a breast pump (alongside analgesia) usually is sufficient.
- if infeciton is suspected or conservative managment fails - Antibiotics - flucloxacillin or erythromycin 1st line.

Management of non-lactational mastitis:
- Ix - US to confirm the diagnosis and culture of drained fluid.
- Antibiotics for non-lactational mastitis need to be broad-spectrum - co-amoxiclav or erythromycin+ metronidazole.
- drainage with repeated needle aspirations (surgical incision is avoided).

Question 24

What causes breast pain and how is it managed?

Answer 24

Breast pain (mastalgia) is common. It can be:

Cyclical – occurring at specific times of the menstrual cycle (luteal phase)

Non-cyclical – unrelated to the menstrual cycle, usually in women 40-50. Usually no cause is found but can be caused by COCP, pregnancy or infeciton.

Pain is not typically considered a symptom of breast cancer. After a proper assessment and without other features of breast cancer (e.g., a lump or skin changes), patients with mastalgia can generally be reassured, with ocassional simple analgesia.

Ix - breast pain diary is helpful

Most women just need simple reassurance and management with simple anagelsia and wearing a supportive bra.

Hormonal treatments (e.g., danazol and tamoxifen) are only under specialist guidance when breast pain is severe because they cary signifcant side effects.

Question 25

What are fibroadenomas?
management?

Answer 25

Fibroadenomas are common benign tumours of stromal/epithelial breast duct tissue. They are not cancerous and do not predispose to cancer. They are more common in younger women, aged between 20 and 40 years and respond to female hormones. They are typically small and mobile within the breast tissue. They are sometimes called a “breast mouse”, as they move around within the breast tissue.

Their natural history is that 1/3rd will shrink, 1/3rd will stay the same size and 1/3rd will enlarge over time. Women are usually reassured and only advised to have surgical removal if they are large or prominent.

On examination, fibroadenomas are:

Painless
Smooth
Round
Well circumscribed (well-defined borders)
Firm
Mobile (moves freely under the skin and above the chest wall)
Usually up to 3cm diameter

Question 26

What is breast nodularity/fibrocystic breast changes

Answer 26

This is really a variation of “normal”. Some ladies have ‘lumpy’ breasts, which is often cyclical i.e. more prominent premenstrually.

Symptoms can affect different areas of the breast, or both breasts, with:

Lumpiness
Breast pain or tenderness (mastalgia)
Fluctuation of breast size

Management is to re-examine after some time to see if the lump disappears. Mastalgia is managed the same as before - reassurance and wearing a supportive bra.

Question 27

What are the three most common causes of benign breast lumps

Answer 27

fibrocystic breast change/nodularity
fibroadenoma
cysts

Question 28

What are breast cysts and how are they managed

Answer 28

Breast cysts are benign, individual, fluid-filled lumps. They are the most common cause of breast lumps and occur most often between ages 30 and 50, more so in the perimenopausal period. They can be painful and may fluctuate in size over the menstrual cycle.

Breasts cysts require further assessment to exclude cancer, with imaging and potentially aspiration or excision (blood stained fluid is bad sign). Aspiration can resolve symptoms in patients with pain.

Question 29

What is gynaecomastia?

physiology?

causes?

Answer 29

Gynaecomastia refers to the enlargement of the glandular breast tissue in males. It must be differnetiated from pseudogynaecomastica - deposition of fat in overweight men.

It is caused by an imblance between oestrogen and androgens (testosterone). Gynaecomastia may be physiological in adolescents, where there can be proportionally higher oestrogen levels around puberty. This resolves after a few years, as the hormone levels balance.

Causes
- In men older than 50 - male breast cancer should be exlcuded via biopsy
- obesity - aromatase increases oestrogen
- testicular cancer (particularly leydig cell)
- liver failure
- hyperthyrodism
- others…

Management is reversal of the cause.

TOM TIP: It is worth remembering the link between gynaecomastia and Leydig cell testicular tumours. About 2% of patients presenting with gynaecomastia have a testicular tumour. An examination question might describe a patient presenting with gynaecomastia and ask what additional examination should be performed. The answer will be a testicular examination. Also, examine for signs of liver failure and hyperthyroidism.

Question 30

What is an intraductal papilloma?
Investigations?
management?

Answer 30

An intraductal papilloma is a warty lesion that grows within one of the ducts in the breast. It is the result of the proliferation of epithelial cells. Intraductal papillomas are benign tumours; however, they can be associated with atypical hyperplasia or breast cancer.

The typical presentation:
- clear or blood-stained nipple discharge - the main oen
- a palpable lump
- pain or tenderness

Patient require tripple assessement to exlude breast cancer - examination, mamogram and biopsy.

Intraductal papillomas require complete surgical excision. After removal, the tissue is examined for atypical hyperplasia or cancer that may not have been picked up on the biopsy.

Question 31

What causes galactorrhoea? 4

Answer 31

Galactorrhoea refers to breast milk production not associated with pregnancy or breastfeeding. Breast milk is produced in response to the hormone prolactin.

There is a long list of causes of hyperprolactinaemia, but the key causes to remember are:

• Idiopathic (no cause can be found)
• Prolactinomas (hormone-secreting pituitary tumours) - can cause bitemproal hemionopia
• Endocrine disorders, particularly hypothyroidism and polycystic ovarian syndrome
• Medications, particularly dopamine antagonists (i.e., antipsychotic medications)

Other conditions can cause nipple discharge that is not breast milk:

Mammary duct ectasia
Duct papilloma
Pus from a breast abscess

Ix:
- serum prolactin
- pregnancy test
- TFTs and LFTs
- MRI scan if pituary tumour is suspected

Managment is dopamine agonists (bromocryptine) and transphenoidal reseciton of pituitary adenomas.