Breast Cancer Flashcards

1
Q

What are the risk factors for breast cancer?

A

¥ Age: Increased incidence the older women are
¥ Previous breast cancer
¥ Family history of breast cancer: 1st degree relative doubles risk
¥ Genetic: BRCA1 and BRCA2
¥ Early menarche and late menopause
¥ Late or no pregnancy
¥ HRT (combined: extra 19 cancers per 1000 oestrogen alone– 5 extra cancers per 1000 )
¥ OCP
¥ Alcohol (>14 units per week)/ Weight / smoking/ NSAID
¥ Post Radiotherapy treatment for Hodgkin’s disease
¥ breast feeding and physical activity are protective

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2
Q

What is the presentation of breast cancer?

A

¥ Asymptomatic: Breast Screening (50-70 yrs)

¥ Symptomatic: Outpatient Clinic
Lump (36%)
Mastalgia (persistent unilateral pain) (17.5%)
Nipple discharge (blood-stained) (5%)
Nipple changes (Paget’s disease, retraction) (3%)
Change in the size or shape of the breast (1%)
Lymphoedema (Swelling of the arm)
Dimpling of the breast skin

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3
Q

What does the triple assessment for breast assessment comprise of?

A

Clinical: hx and examination

Radiological: Mammography/USS

Cyto-Pathological: FNA (cytology) Core biopsy (histo-pathology, grading/hormone markers)

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4
Q

Describe the history examination in assessment of breast conditions?

A
History:
•	Present Complaint
•	Previous Breast Problems
•	Family History
•	Hormonal Status
•	Drug History

Examination
• BOTH breasts
• Axillae
• SCF

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5
Q

Describe the imaging that takes place in the triple assessment of breast

A
  • Mammogram if over 40
  • USS if under 40

Mammography is most sensitive of breast imaging modalities
o Sensitivity is reduced in young women due to presence of increased glandular tissue (<40yrs)
o Microcalcification is due to debris within the duct wall or lumen and is sole feature of 33% screen-detected cancers
USS
o Useful in the assessment of breast lumps
o Complements mammography
o Able to differentiate solid and cystic lesions
o Guidance for fine needle aspiration and core biopsies
o To assess tumour size and response to therapy
o In the diagnosis of malignancy it has a sensitivity and specificity of 75% and 97% respectively
o Cysts and solid lesions have typical appearances

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6
Q

What different malignant pathology is seen in the breast?

A
Invasive:
•	80% Ductal Carcinoma
•	10% Lobular Carcinoma
•	10% Others
o	(Mucinous 5%
o	Papillary <5% 
o	Medullary <5%) 

Non invasive:
• DCIS - ductal carcinoma in situ
• LCIS - lobular carcinoma in situ

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7
Q

Lobular carcinoma in situ:

  • what is this?
  • is it multifocal?
  • is it bilateral?
  • if find this what has to be done and why?
A

¥ Intra-lobular proliferation of characteristic cells
Ð Small-intermediate sized nuclei
Ð Solid proliferation
Ð Intra-cytoplasmic lumens/vacuoles
Ð ER positive = has estrogen receptors
Ð E-cadherin negative (deletion & mutation of CDH1 gene on Chr 16q22.1) this is an adhesion molecule and this is lost

¥ frequently multifocal and bilateral

If find:

LN on core biopsy
¥ Proceed to excision or vacuum biopsy to exclude higher grade lesion

LN on vacuum or excision biopsy
¥ Follow up
¥ Clinical trials

This is because 15-20% of LCIS on core biopsy have a higher grade lesion on open diagnostic biopsy

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8
Q

Ductal carcinoma in-situ:

  • is this common?
  • where does this arise?
  • does it arise in single or multiple ducts?
A

Ð 15-20% of breast malignancies are DCIS (formerly 5%)

Ð Arises in TDLU – terminal ductal lobular unit

Ð Characteristically unicentric (single duct system)

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9
Q

DCIS:

  • what is seen on cytology?
  • where does it extend to?
  • what is it called when it involves lobules?
  • what is pagets disease of the breast?
A

¥ Cytologically malignant epithelial cells

¥ Confined within basement membrane of duct

¥ May involve lobules (cancerisation)

¥ May involve nipple skin (Paget’s)
=High grade DCIS extending along ducts to reach the epidermis of the nipple
=Still in situ carcinoma (ie non-invasive)

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10
Q

What is the management of DCIS?

A

Ð Diagnosis:
-grade/histological type/presence of necrosis

Ð Surgery - (Trials of mammographic follow-up in low risk DCIS)

Ð Radiotherapy

Ð Chemoprevention (trial)

Surgery is mainstay of treatment but trials exist which research whether low risk DCIS are better treated by watchful waiting

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11
Q

What is microinvasive carcinoma and how is this treated?

A

¥ Rare
¥ DCIS (high grade) with invasion of <1mm
¥ Treat as high grade DCIS

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12
Q

What is an invasive carcinoma defined as?

A

¥ Malignant epithelial cells which have breached the BM
¥ Infiltration of normal tissues
¥ Risk of metastasis and death

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13
Q

How does invasive breast carcinoma spread?

A

¥ Local invasion (T)
Ð Stroma of breast
Ð Skin
Ð Muscles of chest wall

¥ Lymphatics (N)
Ð Regional draining lymph nodes

¥ Blood-borne (M)
Ð Bone, liver, brain, lungs, abdominal viscera, female genital tract

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14
Q

Describe breast carcinoma grading

A

o Grading: measure of the tumour differentiation - how similar is the tumour to the parent tissue?
♣ Very similar = well differentiated = good prognosis
♣ Very different = poorly differentiated = poor prognosis
♣ For breast carcinoma it’s an objective assessment of:
o Tubular differentiation (1-3)
o Nuclear pleomorphism (1-3)
o Mitotic activity (1-3)

Score 3/4/5 = grade 1
Score 6/7 = grade 2
Score 8/9 = grade 3

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15
Q

Describe staging of breast carcinoma

A

TNM

♣ Direct invasion of adjacent tissues
• T0 - T4 Local tumour growth (size of tumour and extent of involvement of adjacent structures)

♣ Lymphatic spread
• N0 - N3 Regional lymph nodes

♣ Blood-borne spread
• M0 - M1 Distant metastasis

Tests to investigate how far the cancer has spread:
¥ Blood tests: FBC, UE’s, LFTs, Ca 2+/PO2-
¥ CXR
¥ AUSS - if indicated
¥ Bone scan (Nuclear Medicine)- if indicated
if NPI over 5 – go for full stagins

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16
Q

What hormonal receptors are looked for and why?

A

ER (PgR) (if positive ER/PR expression = better prognosis)
• ER expression predicts response to anti-oestrogen therapy
o Oophorectomy
o Tamoxifen: pre and post menopausal
o Aromatase inhibitors (Letrozole): post menopausal
o GnRH antagonists - (Goserilin [Zoladex])

♣ HER 2: human epidermal growth factor receptor 2 (if this is positive = worse prognosis)
• HER 2 overexpression and amplification seen in ~15%
• HER 2 overexpression or amplification predict response to Trastuzamab (Herceptin)

17
Q

What are the prognostic factors in breast carcinoma?

A

♣ Tumour size – the bigger the tumour the worse prognosis
♣ Lymph node status – the more nodes the worse prognosis
♣ Lymphovascular invasion = bad prognosis
♣ ER +ve good prognosis
♣ HER 2 +ve worse prognosis

18
Q

What prognostic indices can be used for breast carcinoma?

A

¥ Nottingham Prognostic Index: Histopathology only (grade & stage)

  • 0.2 x tumour diameter (cm)
  • Tumour grade (1-3)
  • Lymph node status (1-3)

¥ Adjuvant! Online
Ð Histopathology + ER + clinical factors

¥ PREDICT
Ð Histopathology + ER + clinical factors + HER2 + mode of detection

19
Q

What are the surgical options for treatment of breast carcinoma?

A

¥ Breast
Mastectomy (Mx) traditional or oncoplastic (+reconstruction)
Wide Local Excision (WLE)
+/- reconstruction

¥ Axilla
Axillary Node Clearance (ANC)
Axillary Node Sampling (ANS)
Sentinel Lymph Node Biopsy (SNBx)

20
Q

if doing a WLE for breast carcinoma what is the margin aimed for?

A

Clear margin 1mm or more, aim for 1cm

-if can’t palpate lesion, use a wire

21
Q

Who recieves radiotherapy?

  • how is this delivered?
  • what are the complications?
A

¥ All patients after WLE as adjuvant treatment
¥ After Mx if there is local involvement - 4+ nodes, involved margins <1mm
¥ palliative to bony mets/skin deposits/brain mets…etc

¥ 40 Gy –50 Gy over 3 weeks or 5 weeks
¥ Boosts reduce local recurrence

¥	Complications:  immediate- longterm
Skin reaction- Skin  telangiectasis
Radiation pneumonitis
Cutaneous Radio-/ Osteonecrosis    
Tiredness
possibly mild dysphagia if doing SCF
22
Q

What chemotherapy options are used for breast carcinoma? when do benefits of this increase?

A

Traditional :
¥ CMF Combinations
¥ Taxane Combinations
¥ Anthracycline-containing Combinations using Doxorubicin or Epirubicin

¥ Benefits greatest in younger women
¥ Benefit increases with increasing adverse prognostic factor (LN pos., ER neg., <35yrs, HER2 pos.)

23
Q

Hormone therapy for ER+ve tumours:

  • what are the options
  • what are the side effects?
A

Tamoxifen or aromatase inhibitors
surgical oophorectomy

Side effects:
Reduced libido, impotence, lethargy, hot-flushes, weight gain, osteoporosis, depression, muscle-wasting, endometrial cancer, DVT

24
Q

Tamoxifen:

  • how is this given
  • how does this work?
  • when is this most effective?
A
¥	20mg once daily over 5 yrs (new studies!)
¥	Blocks directly on recept.
¥	Antagonistic action in breastCa
¥	Effective in all age groups
¥	Less effective in HER2+
¥	More effective given after chemothx
25
Q

Aromatase inhibitors:

  • what are these called?
  • how do these work?
  • when is this most effective
  • what is the risk factor?
A

¥ Inhibiting estrogen synthesis - so pushes people into menopause
¥ Only effective in post menopausal women
¥ Improve disease free survivial (switch thx)
¥ More effective in HER2+ women
!Osteoporosis

26
Q

What immunotherapy is given to HER+ve tumours?

A

trastuzumab

27
Q

When may bisphosphonates be used?

A

bony mets