Breast

# Female Breast Cancer: Hormones and Heredity

## Introduction: The Most Common Cancer in Women
With 2.3 million new cases annually, breast cancer represents 25% of all female cancers. The disease spectrum ranges from indolent **ductal carcinoma in situ (DCIS)** to aggressive **triple-negative breast cancer (TNBC)**. Five-year survival exceeds 90% for localized disease but plummets to 30% for metastatic cases. Recent genomic classifications now guide personalized treatment approaches beyond traditional histology.

---

## Causes and Risk Factors: Estrogen and DNA Repair

### Hormonal Drivers
- **Endogenous Estrogen**: Early menarche (<12), late menopause (>55)
- **Exogenous Hormones**: HRT >5 years increases risk 26%
- **Reproductive Factors**: Nulliparity or first pregnancy >30

### Genetic Factors
- **BRCA Mutations**: 72% lifetime risk for BRCA1, 69% for BRCA2
- **CHEK2/PALB2**: Moderate-risk alleles (2-4× increased risk)
- **Dense Breast Tissue**: 4-6× higher risk

---

## Prevention Strategies: From Surveillance to Surgery

### Risk-Reduction Approaches
- **Pharmacologic Prevention**:
  - Tamoxifen (50% reduction in high-risk women)
  - Aromatase inhibitors for postmenopausal women

- **Surgical Prevention**:
  - Bilateral prophylactic mastectomy (90% risk reduction)
  - Salpingo-oophorectomy for BRCA carriers (50% risk reduction)

### Screening Innovations
| Risk Category | Screening Protocol |
|---------------|-------------------|
| Average Risk | Annual mammography 40-54 yrs; Biennial 55+ |
| High Risk (≥20% lifetime) | Mammography + breast MRI annually |
| BRCA Carriers | Mammography + MRI starting at age 25 |