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Breast Cancer
Risk factors
a. Hereditary:
 BRCA 1 gene
17 q
Female breast cancer > Male breast cancer
Ovarian m/c
Cancer associated with Breast, ovarian, prostate, pancreatic, colon
Triple negative
 BRCA 2 gene
Male breast cancer > Female breast cancer
Prostate cancer m/c
Luminal types B >A
 P53 gene
Li-Fraumeni syndrome
Breast cancer
Brain Cancer
Leukaemia
Sarcomatous tumour
Triple negative
 CHEK 2 gene
Breast
Thyroid
Renal
b. Sporadic:
 m/c
 p53 gene mutation
 Related to Estrogen
 Early menarche, late menopause
 HRT, OCP
 Increased alcohol consumption
 Protective factors : Coffee/ Caffeine, Exercise, Lactation

Classification:

a. Molecular Classification
b. Histological Classification

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a. Molecular Classification

 Based on gene expression profiling

Luminal A Luminal B Triple Claudin low Her 2 new

negative/Basal enriched
type

ER+ ER+ ER- Associated with ER-

PR+ PR+ PR- tight junction PR-
HER-2 neu - HER-2 neu + HER-2 neu - HER2neu +

 Most common type is Luminal A

 Luminal A has low proliferation
 Luminal B has high proliferation
 How do we know about proliferation: By Ki 67 marker
 If Ki 67 marker is low: low proliferation
 If Ki 67 marker is high: high proliferation
 Luminal A and Luminal B are associated with BRCA -2 mutation
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 BRCA -1 mutation seen with Triple negative
 P53 mutation seen with Triple negative
 Best prognosis for the patient is Luminal A

Treatment

 If patient is ER +, PR +  Targeted therapy

 If patient is ER -, PR -  Chemotherapy
 Her-2 neu positive  Targeted therapy (Trastuzumab /Herceptin)

Note- How to analyse ER, PR, HER -2neu = Immunohistochemistry (Brown colour)

 ER, PR will come brown in nucleus

 HER-2neu  Membranous positivity

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Extra edge:

HER 2 neu IHC

0  HER 2 neu negative
1  HER 2 neu negative
2  HER 2 neu equivocal
3  HER 2 neu positive
HER 2 neu equivocal – Confirmation is carried out by FISH (Fluorescent in-situ hybridization)
In this we look for ratio: Her 2 neu - CEP 17 Chromosome enumeration probes
If the ratio is >2.2  Her 2 neu +
If the ratio is <2.2  Her 2 neu -

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B. Histological classification:

1. Epithelial tumours
a. Non-invasive
DCIS – Ductal Carcinoma insitu
LCIS – Lobular carcinoma insitu
Paget’s Disease
b. Invasive
IDC- Infiltrating ductal carcinoma
ILC- Infiltrating lobular carcinoma
2. Stromal tumours
a. Fibroadenoma
b. Phyllodes tumour

Note- Insitu: Intact basement membrane

 DCIS – Ductal Carcinoma insitu is of two types:

a. Comedo type

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b. Non Comedo type

Cribriform DCIS (Sieve like)

Solid DCIS
Papillary DCIS

 Note: Both DCIS and LCIS has 25 % -30 % chance of going into invasive cancer

Paget’s disease
 Can occur in vulva and breast
 Breast – 1-4 % of all tumours

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 
Paget’s cells:
ER +, PR +/ HER 2 +
Poor prognosis
Mucin +/ PAS +

IDC- Infiltrating ductal carcinoma

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 m/c site upper outer quadrant

 least common site – lower inner quadrant
 Variants of IDC- Infiltrating ductal carcinoma
Tubular carcinoma – Good prognosis
Mucinous/ Colloid carcinoma – Good prognosis
Medullary carcinoma:
 Triple negative tumour
 Poor prognosis
 Microscopy examination:
 Solid sheets
 Lymphoplasmacytic infiltrate
Inflammatory carcinoma
 Worst prognosis

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 Classical orange peel appearance: Peau de orange appearance

 Why this appearance: due to dermal lymphatic involvement

ILC- Invasive Lobular carcinoma

 b/l (Clinical application: Always examine both breast)

 multicentric
 Indian file pattern
 Signet ring shape

Prognostic factor of breast cancer:

1. TNM Staging
Tx size
L.N involvement
 First / Sentinel L.N: Axillary L.N
Metastasis

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 Good prognosis: Early stage – Stage 1
Bad prognosis: Late stage – Stage 4

2. Nottingham Bloom Richardson scoring:

Tubule formation
Nuclear pleomorphism
Mitotic rate
3. Molecular classification:
Luminal A – good prognosis
Triple negative/ Her 2 neu – poor prognosis
4. Histological classification
Tubular carcinoma and mucinous carcinoma – good prognosis
Medullary carcinoma and inflammatory carcinoma – poor prognosis
Inflammatory carcinoma - worst pro gnosis
5. Aneuploidy
Poor prognosis

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2. Stromal tumours

a. Fibroadenoma:

 u/l or b/l
 Radiologically and clinically: Breast mouse (extremely mobile)
 Gross: well circumscribed Gray white slit like spaces
 Microscopic examination: increased stroma
 Intracanalicular pattern


 Peri canalicular pattern

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b. Phyllodes tumour

 Aka: Cystosarcoma phyllodes

 Phyllodes means leaf like
 Diagram: 48.18
 Genetics: Gain 1q, HOX B13

Fibroadenoma Phyllodes tumour

Stroma: + + Stroma: + + + +
Cellular + Cellular + + +
Mitosis - Mitosis + +
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Miscellaneous

 Lymphoma in breast: DLBCL: Diffuse large B cell lymphoma