Cancer 3- Breast Cancer

Question 1

Basic Pathology of breast cancer
Two most frequent subtypes and other

Pathology report should include 
1) 
2)  
3) IHC which includes (Allred) + 2 more 
3a) Negative, weak, intermittent, strong 
3b) (+2) means, (+3) means, FISH means 
What chromosome is it on? 

what is Allred score?

What is the BRCA gene?

Where is BRCA 1 gene found?
% lifetime risk for ovarian and breast cancer

Where is BRCA 2 gene found?
% lifetime risk for ovarian and breast cancer

BRCA gene also assoc. with 3

Test for BRCA gene when 4

Answer 1

• Ductal carcinoma (70-75%)
• Lobular carcinoma (12-15%)
• 18 other subtypes (0.5-5%)

DCIS, LCIS, IDC (invasive), ILC

1) Presence/ absence of DCIS
2) Grade: Low- always reverts back on own, Med- either way, High- mostly turns invasive
3) IHC (immuno-histo-chemistry) - shows via staining if they have ER (Allred score), HER2, PR

3a) Proportion of cells which are ER +ve (Oestrogen Receptive)
0 no cells Intensity score (separate)
1 <1% Negative
2 10% Weak
3 11-13% Intermittent
4 34-66% Strong
5 67-100%

3b) HER2 expression (it is an oncogene) or HER2 gene amplification
(+2) means ambiguous
(+3) means >10% of the cells harbous complete membrane staining
FISH if the number of HER2 gene copies >6 or the HER2: Chromo 17 (CEP17) ratio is >2 and HER2 copies >4

HER2 causes:

• potent proliferation
• anti-apoptosis signals

What is BCRA gene?

• Tumour suppressor gene which repairs double stranded breaks in DNA by homologous recombination repair (HR)
• Usually mutated and non-functional in breast cancer

BRCA 1- Chrmosome 17
15-4-% ovarian 85% breast
BRCA 2- Chromosome 13
10-20% ovarian 85% breast

BRCA also assoc with: Pancreas, Prostate, Melanoma

Test for BCRA when:

• Strong fam hisotry of breast, ovarian, pancreatic, prostate
• Breast cancer before 50yo
• Triple negative breast cancer (TNBC) before 60yo
• Personal history of ovarian cancer second to breast

Question 2

 Perform a competent examination of the breast

- Steps ***

Question 3

Explain the triple assessment of breast lumps and the rationale behind it

 Explain the principles of surgical treatment of cancer of the breast

 Explain the relevance of the assessment of the axilla in the management of breast cancer

• Two possibilities:
• 1
• 3

Answer 3

Triple Assessment:

• History + Physical exam
• Mammogram/ image (USS <35yo and mam> 35yo)
• Fine needle aspiration or core biopsy

Surgery

• Total mastectomy if greater than 4cm
• Lumpectomy in breast conserving surgery

Axilla Assessment
- If axilla shows met then ‘Axillary node clearance’
- Axilla doesnt show met then ‘Sentinal lymph node biopsy SLNB’
what?
Where tumour injected with radioactive substance + blue dye and probe given to closest lymph node to see if radioactive or blue and if so axillary node clearance.

Question 4

 Explain hormonal treatments for cancer of the breast. Name the commonly used hormones.
Pre- menopausal - MOA (1 eg and 2 side effects)

Post-menopausal (1eg + MOA)

Selective oestrogen rec degrader 1
Steroidal aromatase inhibitor 1

 Describe, in general terms, adjuvant radiotherapy and chemotherapy in the treatment of breast cancer

Radiotherapy - when?
Chemo- when and what 3 things given?

Breast Screening age and how often

Answer 4

Pre- menopausal: Tamoxifen (prevent estradiol from entering breast cell tumour/ oestrogen blocker)
Tamoxifen:
- inc thromboembolic complications
- can’t get pregnant on it

Post-menopausal: Aromatase inhibitors such as anastrozole or LATRAZOLE (decrease testosterone/ fat to estradiol/ oestrogen)- prevents conversion of androgens to oestrogen
side effect:
-Decrease bone density

Selective oestrogen rec degrader- Fulvestrant
Steroidal aromatase inhibitor- Exemestane

Radiotherapy- receommended if INVASIVE after WLE
Chemo- Adjuvant eg. epirubicin + cyclophosphamide + methotrexate

Screening: 50-69yo mammogram every 3 years