Breast Cancer¶
Chapter 84 | Breast Cancer
KEY CLINICAL POINTS¶
- Breast cancer is the most common nonskin cancer in women, with ~310,000 new cases in the U.S. in 2024 and a 5-year relative survival rate of 91%.
- Key risk factors include female gender, age >55, family history, BRCA mutations, and hormone replacement therapy.
- Staging is based on AJCC TNM criteria, with survival rates varying by stage (Stage I: >99%, Stage IV: 29%).
- Treatment is tailored by molecular subtypes (Luminal A/B, HER2+, TNBC) and includes surgery, endocrine therapy, targeted agents, and chemotherapy.
- Metastatic breast cancer is managed with systemic therapies, including CDK4/6 inhibitors, PARP inhibitors, and immunotherapy.
1. DEFINITION & OVERVIEW¶
Breast cancer is a malignant neoplasm arising from epithelial cells in the breast. It is classified as in situ (DCIS/LCIS) or invasive, with subtypes defined by receptor status (ER/PR/HER2) and molecular profiles.
Table 84-1: Five-Year Breast Cancer Relative Survival Rate (%) by Stage and Race/Ethnicity¶
| STAGE | ALL | WHITE | BLACK | AIAN | HISPANIC | API |
|---|---|---|---|---|---|---|
| I | >99 | >99 | >99 | >99 | >99 | >99 |
| II | 93 | 93 | 89 | 93 | 92 | 94 |
| III | 75 | 77 | 64 | 72 | 74 | 77 |
| IV | 29 | 31 | 20 | 35 | 29 | 34 |
1.1 Molecular Subtypes¶
Invasive breast cancer is categorized into four major subtypes: Luminal A (ER+/PR+/HER2-), Luminal B (ER+/PR+/HER2- with high proliferation), HER2-positive (ER-/PR-/HER2+), and Triple-Negative (ER-/PR-/HER2-).
1.2 Staging Systems¶
Staging follows AJCC TNM criteria (8th edition). Stage I: localized; Stage II: regional; Stage III: locally advanced; Stage IV: distant metastases (M1).
2. EPIDEMIOLOGY¶
Breast cancer is the most common cancer in women globally. In the U.S., ~310,000 new cases in 2024, with ~42,250 deaths. Incidence peaks in non-Hispanic whites, while mortality is highest in non-Hispanic Black women.
2.1 Risk Factors¶
Non-genetic: female gender, age >55, late menopause, early menarche, obesity (postmenopausal). Genetic: BRCA1/2 mutations, Li-Fraumeni syndrome, PALB2, ATM, PTEN mutations.
2.2 Demographics¶
Incidence highest in non-Hispanic whites, lowest in Asian/Pacific Islanders. Mortality rates vary by race/ethnicity, with highest in non-Hispanic Black women.
3. ETIOLOGY & PATHOPHYSIOLOGY¶
Prolonged estrogen exposure drives most breast cancers. Mutations in DNA repair genes (BRCA1/2, TP53) lead to genomic instability. HER2 overexpression and hormone receptor dysregulation drive tumor growth.
3.1 Genetic Mutations¶
BRCA1/2 mutations confer 50–80% lifetime risk of invasive breast cancer and 30% risk of ovarian cancer. Other mutations (TP53, PALB2, ATM) increase risk in specific syndromes.
3.2 Hormonal Factors¶
Estrogen and progesterone receptor signaling promote proliferation. Hormone replacement therapy (HRT) increases risk, while postmenopausal obesity exacerbates estrogen exposure.
4. CLINICAL FEATURES¶
Common presentations include breast mass, skin changes, nipple retraction, or axillary lymphadenopathy. Metastases may occur in bones, lungs, liver, or brain.
4.1 In Situ vs. Invasive¶
DCIS (ductal carcinoma in situ) is confined to ducts; LCIS (lobular carcinoma in situ) is a marker for future invasive disease.
4.2 Metastatic Patterns¶
Common sites: bones, lungs, liver, brain. Metastatic disease may present with bone pain, pleural effusion, or neurological symptoms.
5. DIFFERENTIAL DIAGNOSIS¶
Differential includes fibroadenoma, fibrocystic changes, mastitis, and gynecomastia. Imaging (mammography, ultrasound) and biopsy are critical for distinction.
5.1 Benign Lesions¶
Fibroadenoma, cysts, and intraductal papilloma may mimic malignancy on imaging.
5.2 Inflammatory Breast Cancer¶
Distinctive presentation with erythema, swelling, and skin dimpling due to lymphatic invasion.
6. INVESTIGATIONS & DIAGNOSIS¶
Diagnosis combines imaging (mammography, ultrasound, MRI), biopsy, and biomarker testing (ER, PR, HER2). Staging includes CT, PET, and bone scans for metastases.
Table 84-1: Five-Year Breast Cancer Relative Survival Rate (%) by Stage and Race/Ethnicity¶
| STAGE | ALL | WHITE | BLACK | AIAN | HISPANIC | API |
|---|---|---|---|---|---|---|
| I | >99 | >99 | >99 | >99 | >99 | >99 |
| II | 93 | 93 | 89 | 93 | 92 | 94 |
| III | 75 | 77 | 64 | 72 | 74 | 77 |
| IV | 29 | 31 | 20 | 35 | 29 | 34 |
6.1 Diagnostic Workup¶
Suspicious findings undergo imaging (mammography, ultrasound, MRI) followed by core biopsy. MRI is more sensitive than mammography for dense breasts.
6.2 Biomarker Testing¶
ER, PR, HER2 status and genomic assays (Oncotype DX, MammaPrint) guide treatment decisions.
7. MANAGEMENT & TREATMENT¶
Treatment is tailored by subtype and stage. Surgery (lumpectomy/mastectomy), radiation, endocrine therapy, targeted agents, and chemotherapy are core modalities.
Table 84-1: Five-Year Breast Cancer Relative Survival Rate (%) by Stage and Race/Ethnicity¶
7.1 Early-Stage Management¶
Breast-conserving therapy (lumpectomy + radiation) or mastectomy. Endocrine therapy (tamoxifen, aromatase inhibitors) for ER+/PR+ tumors.
7.2 Metastatic Disease¶
Systemic therapies include CDK4/6 inhibitors (abemaciclib, ribociclib), PARP inhibitors (olaparib), and immunotherapy (pembrolizumab for TNBC).
8. PROGNOSIS & COMPLICATIONS¶
5-year survival >99% for Stage I, 29% for Stage IV. Complications include cardiotoxicity (from anthracyclines), osteoporosis (from aromatase inhibitors), and lymphedema.
8.1 Survival Rates¶
Stage I: >99%, Stage II: 93%, Stage III: 75%, Stage IV: 29% (U.S., 2012–2018).
8.2 Long-Term Effects¶
Cardiotoxicity, osteoporosis, lymphedema, and cognitive dysfunction may occur with treatment.
9. SPECIAL CONSIDERATIONS¶
Management in pregnancy requires balancing maternal and fetal safety. Fertility preservation is critical for premenopausal women. Germline testing is recommended for BRCA carriers.
9.1 Pregnancy¶
Surgery safe in second/third trimesters; radiation delayed until after delivery. Chemotherapy (e.g., doxorubicin) may be used in second/third trimesters.
9.2 Fertility Preservation¶
Ovarian suppression with GnRH agonists or cryopreservation of oocytes recommended for premenopausal women.
10. KEY POINTS & CLINICAL PEARLS¶
- Breast cancer is the most common cancer in women, with 5-year survival >91% in the U.S. 2. Staging guides treatment and prognosis. 3. Molecular subtypes dictate therapy (e.g., HER2-targeted agents for HER2+ tumors). 4. Endocrine therapy is foundational for ER+/PR+ tumors. 5. Metastatic disease requires systemic therapy with CDK4/6 inhibitors or PARP inhibitors.