20. Breast Cancer And Breast Cancer Screening

Question 1

What are the risk factors for breast cancer?
(5)

• commonest cause of death

Answer 1

RISK FACTORS

1. Age
   - Rare before age 25
   - Risk increases with age
2. Fam Hx
   - Up to 10% of cases due to genetic predisposition
   - BRCA1 gene mutations (chromosome 17)
   - BRCA2 gene mutations (chromosome 13)
   - Risk increases two-fold with affected 1st degree relative <50yrs
3. Hormonal Factors
   - Age at menarche and menopause
   - Age at 1st pregnancy
   - Use of oral contraceptive
   - Postmenopuasal oestrogen therapy
4. Radiation exposure
5. Lifestyle factors: alcohol, smoking, obesity

Question 2

Describe the pathology of breast cancer.

How is breast cancer classified?
(2)

What is carcinoma in situ?

What is Paget’s Disease of Nipple?

What is invasive breast carcinoma?

Answer 2

CLASSIFICATION

1. Anatomical location: ductal / lobular
2. Pathological characteristics: invasive / non-invasive

CARCINOMA IN SITU
- Ductal carcinoma in situ can become invasive over time
- Many subtypes exist
- Comedo necrosis carries a worse prognosis
—> Comedo necrosis: “plug” = breast duct plugged by cancer cells

PAGET’S DISEASE OF NIPPLE

• Form of ductal carcinoma arising in the excretory ducts
• Associated with underlying DCIS or invasive cancer (less common)
• Characterised by: ulceration of nipple, surrounding hyperaemia and an underlying lump in 50%

INVASIVE
- Ductal – 80% // Lobular – 10%
- Relatively better prognosis is associated with:
o Invasive cancers displaying a tubular pattern
o In mucin producing tumors

Question 3

What are the signs of breast cancer?
(9)

What are the symptoms of breast cancer?
(7)

Answer 3

• Palapable breast lump
• Pain not usually feature, but rare patients present with metastatic breast cancer

SIGNS

1. Skin dimpling
2. Visible mass
3. Assymetrical nipples
4. Peau d’orange
5. Recent nipple inversion or skin change
6. Nipple discharge – particularly if bloody
7. Skin ulceration (advanced cases)
8. Arm swelling
9. Change in size or shape

SYMPTOMS

1. Breathing difficulties
2. Bone pain or pathological fractures
3. Symptoms of hypercalcaemia
4. Abdominal distension
5. Jaundice
6. Localizing neurologic signs
7. Altered cognitive function

Question 4

What is triple assessment?

3

Answer 4

1. History and Physical Exam
   - Accurate history of presenting symptom and risk factor profile
   - Physical exam to assess tumour characteristics and spread (axillary nodes, distant metastases)
   - Exam findings:
   o S2: benign findings
   o S3: findings are most likely benign but could be malignant
   o S4: findings are concering for malignancy
   o S5: most likely malignant findings
2. Radiological Assessment
   - Mammogram
   o Detects 80 - 90 % of breast cancers
   o Detects tumours that are not clinically palpable
   o Generally, if the woman is <35 years old US, is performed as first line
   o 50-64y every 2 years
   o Screening women > 50 years reduces mortality by up to 30%

• Wire guided biopsy
  o Occasionally required to allow sampling of a radiological abnormality in order to provide a definitive tissue diagnosis
  o Needle placed under x-ray guidance into the area of abnormality
  o Needle acts as a guide to the surgeon
  o Performed under general anaesthetic
• Ultrasound
  o Useful in younger patients
  o Provides additional information on tumour characteristics
  o Generally, if the woman is <35 years old, US is performed as first line

3. Cytology
   - Fine needle aspiration cytology (FNAC)
   o Performed in the out-patient clinic
   o Aspirate from lump assessed by cytologist
   o Demonstration of presence or absence of malignant cells
   o Doesn’t distinguish invasive and non-invasive

• Core Biopsy ** performed more than FNA**
  o Performed under local anaesthetic
  o Small sample of tissue from the lump
  o Allows histological as opposed to cytological diagnosis
  o Differentiates invasive and non-invasive
  o Performed under x-ray guidance

-	Results of cytology and core biopsy: 
o	C1 or B1: no diagnosis possible
o	C2 or B2: benign
o	C3 or B3: atypia, probably benign
o	C4 or B4: suspicious for malignancy
o	C5 or B5: malignant

Question 5

How is breast cancer staged?

4

Answer 5

1. Clinical findings
2. Pathological analysis
3. Imaging studies assessing metastatic disease: chest x-ray, liver ultrasound, bone scan
4. TNM or staging classification **

Question 6

Describe the TNM classification.

Answer 6

T1: lesion less than 2cm
T2: lesion btwn 2-5cm
T3: lesion +5cm
T4: tumour involves local structures (skin or chest wall)

N0: no palpable axillary nodes
N1: ispilateral nodes which contain tumour
N2: fixed ispilateral axillary nodes

M0: no systemic metastases
M1: distance metastases present or where supraclavicular nodes are involved

Question 7

Describe the staging classification.

Answer 7

Stage I: tumour less than 2cm with on spread of disease

Stage II: tumour btwn 2-5cm with mobile palpable lymph nodes

Stage III: tumour +5cm or locally advanced diseased involing chest wall or skin or fixed axillary nodal disease

Stage IV: metastatic disease

Question 8

What are the treatment options for breast cancer?

2

Answer 8

1. Surgery

2. Adjuvant therapy

Question 9

Describe the surgical options for breast cancer.
(2)

What is sentinel node biopsy?

Answer 9

1. Surgery to Breast
   - Breast conserving surgery vs. mastectomy
   - Factors:
   o Patient preference
   o Tumour size
   o Tumour location
   o Presence of multifocal disease
   - Breast conserving surgery always followed by radiotherapy – reduces risk of local recurrence
2. Surgery to Axilla
   - Stages the axilla
   - Reduces the risk of reccurrence in the axilla
   - Axillary clearance vs. sentinel node biopsy
   - Axillary clearance:
   o Removal of all axillary lymph node
   o 75% of patients node negative, so axillary clearance not needed
   o SE’s:
   —> Lymphoedema 20-40%
   —> Arm / axillary numbness 80%

SENTINEL NODE BIOPSY

• Sentinel node: first draining lymph node
• Identified using blue dye and radiolabelled isotop
• If positive: patient undergoes axillary clearance
• If negative: no further surgery

Question 10

Describe adjuvant therapy.

3

Answer 10

1. Hormonal therapy
   - Patients with oestrogen receptor positive tumours
   - Tamoxifen: anti-oestrogen, reduces relapse
   - Aromatase inhibitors: more effective in post-menopausal patients
   - Herceptin: antibody directed at Her2neu receptor present in the breast cancer cell in 20% of patients
2. Radiotherapy
   - Routine after breast conserving surgery
   - Selected patients after masectomy that are at high risk for chest wall recurrence
3. Chemotherapy
   - Consider in all node positive patients
   - In selected node negative patients, is considered at high risk of recurrence
   - Tx: CMF – cyclophosphamide, methotrexate, 5-fluorouracil

Question 11

What is breast cancer screening?

What is the outcome?

What is leading-time bias?

What is length bias?

What are characteristics of the disease?
(5)

What are characteristics of the screening test?
(5)

Answer 11

• Application of a test to detect a potential cancer where no S+S of cancer are present
• Detect cancer prior to its systemic spread, alter natural history of the disease, and defer death

OUTCOME: reduced mortality in the screened population when compared to the mortality rate in an equivalent unscreened population

LEADING-TIME BIAS: apparent increase in survival time without reduction in mortality

LENGTH BIAS: clinical outcome observations that aren’t adjusted for rate of progression of disease

CHARACTERISTICS OF DISEASE

1. High morbidity, mortality, costs
2. High incidence, prevalence
3. Known natural history and biology
4. Pre-clinical phase with high prevalence
5. Treatment of early stage disease

CHARACTERISTICS OF SCREENING TEST

1. Able to detect disease in pre-clinical phase
2. Effective (sensitive and specific)
3. Safe
4. Simple and inexpensive
5. Acceptable to individuals