1. Hormone Receptors (ER & PR)
(a) Estrogen Receptor (ER)
Function:
ER is a nuclear receptor that binds estrogen, leading to gene transcription that promotes cell growth & proliferation.
Found in luminal epithelial cells of the breast.
Types of ER:
ERα (Most relevant in breast cancer) → Drives tumor growth.
ERβ (Less common, anti-proliferative effects) → Role not well understood.
Clinical Significance:
ER-positive tumors (~70% of breast cancers) → Generally less aggressive and have a better prognosis.
Therapeutic Target:
Tamoxifen (Selective Estrogen Receptor Modulator - SERM) → Blocks ER in breast tissue (used in premenopausal women).
Aromatase Inhibitors (Letrozole, Anastrozole, Exemestane) → Reduce estrogen synthesis (used in postmenopausal women
(b) Progesterone Receptor (PR)
Function:
PR is regulated by ER → Its presence indicates a functional ER pathway.
Involved in hormone-driven cell proliferation.
Clinical Significance:
PR positivity reinforces ER positivity → Better response to hormone therapy.
PR-negative but ER-positive tumors → Less responsive to hormonal treatment.
Therapeutic Target:
PR is not directly targeted, but its presence supports the use of anti-ER therapy.
2. Human Epidermal Growth Factor Receptor 2 (HER2)
Function:
HER2 is a tyrosine kinase receptor in the epidermal growth factor receptor (EGFR) family.
Promotes cell proliferation, survival, and angiogenesis when overexpressed.
HER2-Positive Breast Cancer (~15-20% of cases)
More aggressive, high recurrence rates, and poor prognosis.
HER2 amplification leads to uncontrolled growth.
Detection Methods:
Immunohistochemistry (IHC) → Measures HER2 protein expression.
HER2 0-1+ (Negative)
HER2 2+ (Equivocal, needs confirmation with FISH)
HER2 3+ (Positive, eligible for targeted therapy)
Fluorescence In Situ Hybridization (FISH) → Confirms gene amplification.
Therapeutic Target:
Trastuzumab (Herceptin) → Monoclonal antibody that blocks HER2 activation.
Pertuzumab → Enhances the effect of trastuzumab.
Lapatinib → Tyrosine kinase inhibitor (used in metastatic cases).
3. Triple-Negative Breast Cancer (TNBC)
Definition:
Lacks ER, PR, and HER2 receptors.
Most aggressive subtype, high recurrence risk, high metastasis rate.
Common in:
BRCA1 mutation carriers.
Young, African-descent women.
Treatment Approach:
No targeted therapy → Chemotherapy is the mainstay (Anthracyclines, Taxanes).
Immunotherapy (PD-1 inhibitors like Atezolizumab) in advanced case
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