Cancer

Question 1

Define breast cancer?

Answer 1

Breast carcinoma refers to a malignant tumour originating from the cells of the breast tissue. It exhibits different subtypes each with unique cellular properties and clinical implications. The carcinomas can be invasive, indicating they have broken through the basement membrane of the tissue of origin and have the potential to metastasize, or non-invasive (in situ), suggesting they are confined to the initial location.

Question 2

What are the two most common types of breast cancer?

Answer 2

Most breast cancers are either ductal (arising from the epithelial lining of the ducts) or lobular (originating from epithelial cells in the terminal ducts of the lobules).

Question 3

Name some risk factors for breast cancer?

Answer 3

Being female
99% of breast cancer cases occur in women
Increased hormone exposure
Early menarche or late menopause
Nulliparity or late first pregnancy
Oral contraceptives or Hormonal Replacement Therapy
Susceptibility gene mutations
Most commonly BRCA mutations (BRCA1/BRCA2)
Advancing age
Caucasian ethnicity
Obesity and lack of physical activity
Alcohol and tobacco use
History of breast cancer
Previous radiotherapy treatment

Question 4

What two things can breast cancer be based on?

Answer 4

Origin cell type or on the hormone receptors present on the surface of the breast cancer

Question 5

What are the different origin cell types of breast cancer:

Answer 5

Invasive ductal carcinoma (IDC): This is the most common type, accounting for about 80% of all breast cancers. It starts in a milk duct, breaks through the wall of the duct, and invades the fatty tissue of the breast.

Invasive lobular carcinoma (ILC): This type begins in the milk-producing glands (lobules) and can spread to other parts of the body. It presents with a thickened area of breast tissue alongside changes to the nipple or to the skin. It is difficult to detect using a mammogram and most women have a MRI scan of their breast to confirm/exclude the diagnosis.

Ductal carcinoma in situ (DCIS): This is a non-invasive or pre-invasive cancer where the cells are confined to the ducts in the breast and have not spread into the surrounding breast tissue.

Lobular carcinoma in situ (LCIS): This is not a cancer but an area of abnormal cell growth that increases a person’s risk of developing invasive breast cancer later.

Paget’s disease of breast: Infiltrating carcinoma of nipple epithelium.

Question 6

What are the hormone receptor classifications of breast cancer?

Answer 6

Inflammatory breast cancer (IBC): This is a rare but aggressive type of breast cancer that causes the lymph vessels in the skin of the breast to become blocked.

Triple-negative breast cancer (TNBC): This type lacks estrogen receptors, progesterone receptors, and does not have an excess of the HER2 protein on the cancer cell surfaces. It tends to be more aggressive and has fewer targeted treatments available.

HER2-positive breast cancer: This is a cancer that tests positive for a protein called human epidermal growth factor receptor 2 (HER2), which promotes the growth of cancer cells. It tends to be more aggressive than other types of breast cancer, but it may respond well to targeted therapies that can block HER2.

Question 7

What are the signs and symptoms of breast cancer?

Answer 7

Unexplained breast mass in patients aged 30 and above, with or without pain

In those aged 50 and older, nipple discharge, retraction/inversion, or other concerning symptoms
This can also include eczema-type changes surrounding the nipple as seen in Paget’s disease of the breast

Skin changes suggestive of breast cancer
This includes skin retraction, peau d’orange appearance or ulceration of the skin above an underlying mass.

Unexplained axillary mass in those aged 30 and above

Question 8

Explain the breast screening in the UK:

Answer 8

In the United Kingdom, the NHS Breast Screening Programme provides free breast screening services for all women registered with a GP. The programme invites women between the ages of 50 and 70 for breast screening every three years, with the first invitation to screening usually sent to women before they turn 53.

This screening process involves a mammogram, which is an X-ray of the breasts that can help detect breast cancers early, often before they can be felt. The aim of breast cancer screening is to find cancer at an early stage when treatment is most effective.

Question 10

What is the criteria for the 2 week wait in breast cancer?

Answer 10

Criteria for 2-week wait:
Age 30 or more with unexplained breast lump (with or without pain)
Age 50 or more with nipple discharge, retraction or other changes
Consider a 2-week wait if a patient is 30 or over with skin changes suggestive of breast cancer or an unexplained lump in the axilla
NB: a non-urgent referral should be considered for patients under the age of 30 with an unexplained breast lump.

Question 11

What is the triple assessment for breast cancer?

Answer 11

Clinical examination: of the breast and surrounding lymph nodes

Radiological examination:
Ultrasound is used for women under the age of 40 or those with higher breast density.
A mammogram is commonly used for women over 40 years.
If there are concerns of metastatic disease, a CT or PET scan may be done.

Biopsy: often a core needle biopsy or fine needle aspirate (FNA)
Fine needle aspiration (FNA): Often combined with mammography, however, has a high rate of false negatives.
Core needle biopsy: method of choice, can be combined with imaging to aid accuracy.
DCIS biopsy will show cellular atypia and hyperchromatic nuclei involving the ducts, but not passing the basement membrane
In invasive breast cancer, these abnormal cells will pass the basement membrane
In lobular carcinoma, the abnormal cells will be found within the lobular acini

Question 12

Name some further investigations for breast cancer?

Answer 12

Biopsies to determine
Oestrogen and progesterone receptor status
Epidermal growth factor receptor status
Routine blood tests (i.e. LFTs)
CXR
MRI is not routinely used. It is used for women with:
Discrepancy between the extent of disease between clinical examination and imaging
Dense breast tissue limiting mammography
Invasive lobular carcinoma to evaluate tumour size when planning breast-conserving surgery
BRCA1/2 testing is done for women < 50 years with triple-negative breast cancer regardless of family history

Question 13

What are the two main types of management for breast cancer?

Answer 13

Surgical management: Wide local excision (WLE) or mastectomy, with sentinel node biopsies for invasive cancers and possible axillary node clearance for positive nodes. Breast reconstruction can be done concurrently or later.

Radiotherapy: Adjuvant radiotherapy is commonly offered following WLE to reduce recurrence. It may also be given to patients with higher-stage cancers post-mastectomy.

Question 14

What is the staging for breast cancer?

Answer 14

If cancerous cells are found in 4-9 local lymph nodes (axillary or internal mammary), an N2 score is given. If fewer than 4 are affected, then the score is N1. If more than 9, or it has spread to supra- or infra-clavicular lymph nodes, the score will be N3.

Question 15

What is Suggested for hormone receptor-negative and HER2 over-expressing patients

Answer 15

chemotherapy:

Neoadjuvant chemotherapy may be given to downstage tumours before surgery. This commonly includes an anthracycline (i.e. doxorubicin) and a taxane (i.e. paclitaxel)

Question 16

What is given to HER2-positive patients with tumour size T1c and above in combination with surgery, chemotherapy and radiotherapy

Answer 16

Trastuzumab (Herceptin)

A well documented side effect of Trastuzumab ( Herceptin) is cardiotoxicity resulting in heart failure

Question 17

What is given for HER2-negative, hormone receptor-positive breast cancer?

Answer 17

Abermaciclib (selective inhibitor of cyclin-dependent kinases 4 and 6)

Question 18

What is given for triple-negative breast cancer?

Answer 18

Pembrolizumab

Question 19

What is given for BRCA positive, HER2 negative high-risk early breast cancer?

Answer 19

Olaparib (PSTP inhibitor)

Question 20

When is hormonal therapy given in breast cancer?

Answer 20

for oestrogen-positive breast cancer:
Anastrozole (aromatase inhibitor) for postmenopausal women
Tamoxifen (oestrogen receptor antagonist) for premenopausal patients
Bisphosphonates: May be used for reducing occurrence in node-positive cancers.
Zoledronic acid has been shown to improve disease-free survival in postmenopausal women with node-positive invasive breast cancer.
Bisphosphonates are also advised for treatment-induced menopause in women treated with aromatase inhibitors

Question 21

Name some complications of breast carcinomas?

Answer 21

Fatigue
Bone metastases
Brain metastases
Psychological difficulties: Anxiety, depression and damage to the individual’s self-esteem.
Recurrence:
Local: recurrence in the same breast as the original tumour
Regional: recurrence in the axillary or sub-clavicular lymph nodes draining the breast cancer
Distant: recurrence once already metastasized to other parts of the body (i.e. liver, lungs, brain, bone)

Question 22

Name some complications of chemotherapy?

Answer 22

Chemotherapy drugs are powerful medications that aim to destroy rapidly dividing cells, such as cancer cells. However, they can also affect healthy cells, leading to a range of side effects, including fatigue, hair loss, easy bruising and bleeding, infection, anaemia, nausea and vomiting, appetite changes, peripheral neuropathy, and problems with concentration or memory.
Chemotherapy agents can have specific side effects such as:
Doxorubicin is associated with cardiac toxicity (e.g. cardiac arrhythmias, myopericarditis)
Paclitaxel is associated with lung fibrosis.

Question 23

Name some side effects of hormone therapy drugs, such as tamoxifen and aromatase inhibitors, are used to treat hormone receptor-positive breast cancers

Answer 23

Common side effects include hot flushes, vaginal dryness or discharge, menstrual changes, fatigue, mood changes, and osteoporosis. In rare cases, tamoxifen can increase the risk of serious conditions like endometrial cancer and blood clots.

Question 24

What are the side effects of targeted drug therapies such as trastuzumab (Herceptin), pertuzumab (Perjeta), and ado-trastuzumab emtansine (Kadcyla), are designed to interfere with specific proteins or processes that contribute to cancer growth.

Answer 24

Side effects include:
Infections
Bruising and easy bleeding
Anaemia
Cardiac (i.e. arrhythmias)
Insomnia
GI side effects (i.e. diarrhoea, vomiting, constipation, appetite loss, weight loss)
Runny nose
Conjunctivitis
Hair loss
Nail changes
Hand foot syndrome: the palms and plantar surfaces become sore, peel, crack and blister.
Hepatotoxicity

Question 25

A poor prognosis of breast cancer is associated with:

Answer 25

Advancing age
Being male
Stage III or IV
Tumour size
Tumour grade
Hormone receptor-negative tumours (oestrogen or progesterone receptor-negative)
HER 2 positive tumours

Question 26

Define a pathological fracture

Answer 26

Pathological fractures refer to fractures that occur in diseased or compromised bone tissue. They are typically provoked by an innocuous trauma that would not ordinarily result in a fracture, particularly in younger individuals.

Question 27

Name some causes of pathological fractures:

Answer 27

Tumours: These can be Primary or Secondary (metastatic, the most common cause of pathological fractures)
- Osteosarcoma (sunburst pattern on X-ray)
- Chondrosarcoma
- Ewing’s tumour (onion skin appearance on X-ray)
Metabolic disorders:
Osteoporosis (the most common metabolic cause)
Hyperparathyroidism
Bone diseases:
Paget’s disease

Question 28

What are the signs and symptoms of pathological fractures?

Answer 28

Localized pain that may be severe and out of proportion to the injury
An unexpected fracture after minor trauma
Deformity at the fracture site
Impaired function of the affected limb

Question 29

What are the investigations for pathological fractures?

Answer 29

Radiographic evaluation: To identify the fracture and any associated bony abnormalities
Bone scans: To detect metabolic abnormalities and tumors
Lab tests: Including serum calcium, phosphate, parathyroid hormone, and alkaline phosphatase to diagnose metabolic diseases
Biopsy: May be necessary for the diagnosis of tumors

Question 30

What is the management for pathological fractures

Answer 30

Treating the underlying disease: This may involve medications, surgery, or other therapies specific to the condition causing the fracture.
Fracture repair: This can include immobilization, surgery, or other interventions as appropriate to the nature and location of the fracture.

Question 31

Which cancers spread to the bone?

Answer 31

Prostate Loves To Kill Bone - Prostate Lungs Thyroid Kidneys Breast

Question 32

An 88 year old woman presents to the emergency department with sudden onset lower back pain whilst getting up from her chair. The pain feels dull and there is no radiation to her legs and no changes in bladder and bowel function. The patient has COPD and her medications include calcium supplements and frequent courses of steroids.
On examination, she has a BMI of 19. Standing and walking with the aid of her stick is possible but painful. She has a kyphotic posture and is tender over T12. A spinal x-ray is requested.
What is the most likely finding on the x-ray?

Answer 32

In elderly individuals with a history of steroid use, low BMI, and osteoporosis, a sudden onset of back pain may indicate an anterior vertebral body wedge fracture.

Question 33

How does Ewing sarcoma present:

Answer 33

Ewings sarcoma most commonly affects males between 10-20 years. A classical finding on the x-ray would be a lytic lesion with a lamellated or ‘onion type’ periosteal reaction. Ewing sarcoma can present with pain and swelling in the groin following trauma, as described in the stem. It can also present with stiffness, lumps, fever and fatigue. Pain with Ewings sarcoma may be intermittent and worsen at night.

Question 34

What is Paget’s disease?

Answer 34

Paget’s disease of the bone is a disease associated with brittle, abnormally shaped, weak bones. This is due to increased bone formation and bone resorption, meaning that bone turnover is very dysregulated and uncontrolled. Unlike normal bone in which the bone remodelling cycle is in balance, the increased bone turnover in Paget’s disease results in abnormal bone formation and reduced structural integrity.

Question 35

What are the risk factors for Paget’s disease?

Answer 35

Age >50
English, Scottish and central European
Male predominance in age group 45–74
Family history of Paget’s disease
Certain viral infections e.g. respiratory syncitial virus

Question 36

What is the aetiology of Paget’s disease?

Answer 36

The pathogenesis of Paget’s disease involves increased osteoclast activity initially, followed by heightened osteoblast activity. This leads to disorganised bone breakdown and formation. Eventually, in some patients, the condition ‘burns out’ and bone resorption and formation reduces, leaving an abnormal bone structure which is composed of a mixture of lamellar and woven bone.

Question 37

What are the signs and symptoms of Paget’s disease?

Answer 37

Most cases are asymptomatic and identified as isolated increases in ALP with no other cause
Key symptoms however would include:
Patient reporting bony deformity, including frontal bossing
Compression of nerves due to bone expansion, with symptoms dependent on the location of the compression, including hearing loss, cranial nerve palsies, carpal tunnel, and visual impairment *NB hearing loss can be caused by vestibulocochlear nerve compression or ossicle ossification
High output heart failure symptoms, including shortness of breath and ankle swelling
Redness of skin overlying the bone involved and a deep, boring pain in the affected bones. A dramatic increase in pain/night pain should raise clinical suspicion of osteosarcoma, a possible complication.
Kidney stone symptoms
Joint pain due to joint destruction
Pathological fractures sustained by the patient either in the past or as a presenting complaint

Bounding pulse and tachycardia due to high output
Positive Tinel and Phalen’s due to carpal tunnel
Collapsing pulse
Bossed skull
Visual loss, cranial nerve abnormalities
Hearing aids
Features of heart failure
Bowing of the legs/bony deformity
Hot skin overlying the bone involved
Evidence of previous pathological fractures
Fundoscopy reveals optic atrophy and angioid streaks

Question 38

What are the investigations for Paget’s disease?

Answer 38

X-ray: Early findings may include osteolysis. Later findings can show increased bone size and sclerosis, osteolytic lesions, and pathological fractures.
Blood tests: Elevated ALP levels indicate bone resorption and can be used for monitoring disease activity. Calcium and phosphate levels typically remain normal.

Question 39

What is the management for Paget’s disease?

Answer 39

Management of Paget’s disease involves:
Pain management with analgesics
Use of bisphosphonates such as alendronic acid or pamidronic acid to inhibit osteoclast activity
Treatment typically lasts for 6 months, after which bone activity may return to normal
Regular monitoring every 6 or 12 months to check for disease recurrence

Question 40

What are the complications of Paget’s disease?

Answer 40

Pathological fracture
High output heart failure
Nerve entrapment - deafness, optic nerve atrophy, carpal tunnel, cord compression, spinal canal stenosis
Osteoarthritis
Osteosarcoma
Kidney stones
Bone deformity