Pathological Subtypes of Breast Cancer

There are over 12 subtypes of breast cancer - though most of them are rare
- Invasive carcinoma (No Special Type) is by far the most common followed by Invasive lobular
- the remaining subtypes are quite rare

1) Invasive carcinoma: No Special Type
- majority 70-80%
Subtypes:
- Luminal A (ER +ve, HER2/neu -ve)
- Luminal B (Triple +ve)
- Normal Breast-Like (ER +ve, HER2/neu -ve)
- Basal-Like (ER -ve, PR -ve, HER2/neu -ve)
- HER2 positive (ER -ve, HER2/neu +ve; associated with brain mets)

2) Invasive Lobular Carcinoma
- increased bilateral

3) Medullary Carcinoma
- 6th decade of life
- slightly better prognosis than NST carcinomas despite negative histological features
- high nuclear grade, aneuploidy, absence of hormone receptors, high proliferative rate
- rapidly growing with smooth borders and thereforeon imaging can resemble a benign lesion

4) Mucinous (Colloid) Carcinoma
- older women
- grow slowly
- ER +ve, LN mets uncommon
- slightly better prognosis vs. NST

5) Invasive Papillary Carcinoma
- <1% of invasive ca
- ER +ve
- favorable prognosis
- much different outcome compared to micropapillary carcinoma

6) Micropapillary Carcinoma
- ER -ve, HER2/neu _ve
- LN mets
- poor prognosis

7) Metaplastic carcinoma
- rare type of breast cancer (<1% of cases)
- Matrix-producing carcinomas
- Triple negative
- LN mets infrequent but poor prognosis

Source:
Robbins

Neoadjuvant Therapy for Breast Cancer

Standard of care foe bulky breast or axillary disease:
- primary tumor 2-5cm
- <2cm but metastatic axillary LNs

Early skeptisism for this approach is unfounded: concern initially that pts would have poorer operative outcomes due to wound complications

McCready and Colleagues:
- ALN retains prognostic value after neoadjuvant Rx
- Not clear if neoadjuvant Rx impacts survival (but it's at least equivalent overall survival)
- 80% of pts have ~50% shriknage of tumor
- only 2-3% have signs of progression during neoadjuvant Rx

If there is complete pathologic regression there is a survival benefit

NSABP B-18:
- 4 cycles of doxorubicin and cyclophosphamide
- 5 year survival of complete response pts ~50%
- however, only 12% of pts achieve this kind of response

Advantages:
- Down size tumor in 80% of pts
- Determine which are chemo-responsive

HER-2

HER-2
- gene responsible for encoding a transmembrane typrosine kinase (growth stimulating activity)
- when over-expressed in breast cancer causes more rapid growth and aggressive behaviour of tumor cell
- over-expressed in ~30% of breast cancers
- over-expression is an independent predictor of worse prognosis
- Herceptin: monoclonal antibody targetting HER-2 membrane receptor

BRCA

BReast CAncer 1 and 2
- higher incidence of breast and ovarian cancer
- Autosomal dominant with incomplete penetration
- 85% chance of developing breast cancer over lifetime; majority will present before age 50
- risk of ovarian cancer BRCA-1 40%, BRCA-2 20%
- 10% of males with BRCA-2 develop breast cancer

Li-Fraumeni Syndrome

mutations of p53 gene
- breast cancer
- sarcoma
- brain tumors
- adrenocortical carcinomas
- leukemia

Breast Cancer in Pregnancy

Breast cancer 2nd most common malignancy in pregnancy
(1:3,000 pregnancies)
Diagnosis:
- Mammography can be performed if fetus shielded
- U/S
Treatment:
- mastectomy usually operation of choice (radiation contraindicated in all trimesters)
- lumpectomy can be performed very late stages of pregnancy
- Tc99 can be used for SLNB
- avoid isosulfan blue dye and vital blue dyes
- chemotherapy acceptable in 2nd and 3rd trimester but avoid in 1st trimester

Locally Recurrent Breast Cancer

Local recurrence after mastectomy - 10%
Treatment:
-local excision plus irradiation
- use of systemic therapy is contraversial
Prognosis:
-almost always accompanied by distant metastatic disease
- Long-term prognosis poor 20 yr survival <10%

Male Breast Cancer

<1% of breast cancers
Risk factors:
- (increased estrogen levels): cirrhosis, Klinefelter sydnrome
- radiation
- BRCA2
most common tumor type is infiltrating ductal cancer
- stage for stage same as female breast cancer but detected later
management:
- mastectomy SLNB +/- ALND
- large majority are ER positive and adjuvant treatment should be offered the same as females

BiRADS classification

0: incomplete assessment
1: negative (normal breast)
2: benign finding
3: likely benign finding (short-interval follow-up suggested)
4: suspicious finding (biopsy suggested)
5: highly suspicious of malignant finding

Breast Cancer Staging

T1: <2cm
T2: 2-5 cm
T3: >5 cm
T4a: invades into pec major or chest wall
T4b: invades into skin
T4c: inflammatory breast cancer

N0: no nodes
N1: palpable mobile LN
N2: palpable fixed LN
N3: supraclavicular LN

Stage	T1	T2	T3	T4
N0	1	2a	2b	3b
N1	2a	2b	3a
N2	3a
N3	3c