Breast Cancer Flashcards
What are the risk factors for breast cancer?
¥ 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
What is the presentation of breast cancer?
¥ 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
What does the triple assessment for breast assessment comprise of?
Clinical: hx and examination
Radiological: Mammography/USS
Cyto-Pathological: FNA (cytology) Core biopsy (histo-pathology, grading/hormone markers)
Describe the history examination in assessment of breast conditions?
History: • Present Complaint • Previous Breast Problems • Family History • Hormonal Status • Drug History
Examination
• BOTH breasts
• Axillae
• SCF
Describe the imaging that takes place in the triple assessment of breast
- 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
What different malignant pathology is seen in the breast?
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
Lobular carcinoma in situ:
- what is this?
- is it multifocal?
- is it bilateral?
- if find this what has to be done and why?
¥ 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
Ductal carcinoma in-situ:
- is this common?
- where does this arise?
- does it arise in single or multiple ducts?
Ð 15-20% of breast malignancies are DCIS (formerly 5%)
Ð Arises in TDLU – terminal ductal lobular unit
Ð Characteristically unicentric (single duct system)
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?
¥ 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)
What is the management of DCIS?
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
What is microinvasive carcinoma and how is this treated?
¥ Rare
¥ DCIS (high grade) with invasion of <1mm
¥ Treat as high grade DCIS
What is an invasive carcinoma defined as?
¥ Malignant epithelial cells which have breached the BM
¥ Infiltration of normal tissues
¥ Risk of metastasis and death
How does invasive breast carcinoma spread?
¥ 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
Describe breast carcinoma grading
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
Describe staging of breast carcinoma
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
What hormonal receptors are looked for and why?
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)
What are the prognostic factors in breast carcinoma?
♣ 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
What prognostic indices can be used for breast carcinoma?
¥ 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
What are the surgical options for treatment of breast carcinoma?
¥ 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)
if doing a WLE for breast carcinoma what is the margin aimed for?
Clear margin 1mm or more, aim for 1cm
-if can’t palpate lesion, use a wire
Who recieves radiotherapy?
- how is this delivered?
- what are the complications?
¥ 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
What chemotherapy options are used for breast carcinoma? when do benefits of this increase?
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.)
Hormone therapy for ER+ve tumours:
- what are the options
- what are the side effects?
Tamoxifen or aromatase inhibitors
surgical oophorectomy
Side effects:
Reduced libido, impotence, lethargy, hot-flushes, weight gain, osteoporosis, depression, muscle-wasting, endometrial cancer, DVT
Tamoxifen:
- how is this given
- how does this work?
- when is this most effective?
¥ 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
Aromatase inhibitors:
- what are these called?
- how do these work?
- when is this most effective
- what is the risk factor?
¥ 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
What immunotherapy is given to HER+ve tumours?
trastuzumab
When may bisphosphonates be used?
bony mets
