Management of Breast Carcinoma

1. Initial Assessment & Staging

• Full history and physical examination
• Bilateral breast imaging (mammogram + ultrasound), MRI if indicated
• Core needle biopsy for histology, receptor status (ER, PR, HER2), and grade

• T - primary tumor size and local extension
• N - regional lymph node involvement
• M - distant metastases

• Sabiston Textbook of Surgery, p. 1392

2. Molecular Subtypes (Governs Systemic Therapy)

3. Surgical Management

Breast Surgery Options

• Six randomized trials showed equivalent survival to modified radical mastectomy for early-stage disease
• Must achieve negative margins
• Requires postoperative radiation in most cases
• Contraindications: multifocal disease, prior chest radiation, ongoing pregnancy, poor cosmesis, patient preference

• Indicated when BCS is contraindicated or patient preference
• Types include total (simple) mastectomy, modified radical mastectomy (breast + axillary nodes, sparing pectoralis), and skin/nipple-sparing variants
• Discuss immediate or delayed reconstruction (implant vs. autologous tissue)
• BRCA mutation carriers may opt for bilateral mastectomy given high contralateral risk

Historical note: Halsted radical mastectomy (1880s) removed breast + pectoralis muscles + axillary nodes and was standard until 1970s. NSABP B-04 showed no survival advantage of radical over total mastectomy at 25-year follow-up.

• Sabiston Textbook of Surgery, p. 1393

Axillary Management

• Clinically negative axilla: Sentinel lymph node biopsy (SLNB) - minimally invasive staging. Avoids full axillary dissection if sentinel nodes are negative
• Clinically positive axilla / significant sentinel node burden: Level I-II axillary lymph node dissection (ALND)
• De-escalation trends: Randomized data now support omitting SLNB in older women with small, biologically favorable, clinically node-negative tumors on adjuvant endocrine therapy; omitting ALND for low sentinel node burden + planned radiation

4. Radiation Therapy

After BCS

• Standard: whole breast radiation (WBR) daily x 4-6 weeks
• Hypofractionated schedules (3 weeks or 5-fraction) - equivalent outcomes, shorter duration
• Partial breast irradiation - not shown superior to WBR in trials
• Regional nodal irradiation extended to axillary/internal mammary nodes based on pathology
• Omission of RT is safe in women >65 years with low-risk ER+ tumors on endocrine therapy

Post-Mastectomy Radiation Therapy (PMRT)

• Recommended for: tumor >5 cm, ≥4 positive axillary nodes (strong indication), 1-3 positive nodes or close margins (also considered)
• Reduces locoregional recurrence and improves OS
• Harrison's Principles of Internal Medicine, 22E, p. 680

5. Systemic Therapy

Neoadjuvant vs. Adjuvant

1. Locally advanced disease (T3, T4 / N2, N3) - to downsize
2. HER2+ tumors - chemotherapy + anti-HER2 agents
3. Triple-negative breast cancer (TNBC) ≥2 cm or node-positive
4. Desire to convert to BCS
5. Premenopausal women with node-positive disease

• Bailey and Love's Short Practice of Surgery, 28th Edition

A. Endocrine (Hormonal) Therapy

• Harrison's Principles of Internal Medicine, 22E

B. Cytotoxic Chemotherapy

• Anthracyclines: Doxorubicin (Adriamycin), Epirubicin
• Taxanes: Paclitaxel (weekly or q3-weekly), Docetaxel
• Alkylating agents: Cyclophosphamide
• Antimetabolites: 5-Fluorouracil, Capecitabine, Methotrexate
• Platinum salts: Carboplatin, Cisplatin (especially TNBC/BRCA-mutated)

• AC-T: Doxorubicin + Cyclophosphamide → Paclitaxel
• TC: Docetaxel + Cyclophosphamide (lower-risk patients)
• CMF: Cyclophosphamide + Methotrexate + 5-FU (older regimen, less used now)

C. HER2-Targeted Therapy

• For small tumors (node-negative, <3 cm): weekly paclitaxel x12 weeks + trastuzumab ± pertuzumab (excellent outcomes)
• For larger/node-positive HER2+: neoadjuvant TCHP (Taxane + Carboplatin + Trastuzumab + Pertuzumab)

D. Immunotherapy

• Pembrolizumab (anti-PD-1): FDA-approved for early-stage and metastatic TNBC
  • Neoadjuvant: added to chemotherapy for TNBC ≥2 cm or node-positive
  • Post-surgery: continued to complete 1 year
  • Patients achieving pCR: continue pembrolizumab alone

E. PARP Inhibitors (Targeted Therapy for BRCA-Mutated Disease)

• Olaparib: Oral PARP inhibitor for high-risk early HER2-negative breast cancer with germline BRCA1/2 mutation
• Talazoparib: Used in metastatic BRCA-mutated HER2-negative breast cancer

6. Special Situations

DCIS (Ductal Carcinoma In Situ)

• BCS + radiation is standard (reduces ipsilateral recurrence)
• Mastectomy for multifocal DCIS or patient preference
• SLNB: considered if mastectomy performed or if high-grade DCIS (risk of occult invasion)
• Adjuvant tamoxifen reduces contralateral breast events in ER+ DCIS

Locally Advanced Breast Cancer (LABC) - Stage III

• Neoadjuvant chemotherapy first, then surgery (usually mastectomy + ALND), then radiation
• Sequence: NACT → Surgery → RT → Adjuvant systemic therapy

Inflammatory Breast Cancer (IBC)

• Present with rapid onset, peau d'orange skin, warmth, erythema
• Always treated with neoadjuvant chemotherapy first (never primary surgery)
• Classified as T4d regardless of tumor size
• Remains classified as IBC even after complete response to NACT

Breast Cancer in Pregnancy

• Surgery (mastectomy preferred over BCS) can be performed in all trimesters
• Chemotherapy can be given in 2nd and 3rd trimesters
• Radiation and endocrine therapy deferred until after delivery
• HER2-targeted therapy (trastuzumab) - contraindicated during pregnancy (oligohydramnios)

BRCA Mutation Carriers

• Bilateral mastectomy reduces contralateral breast cancer risk
• Risk-reducing salpingo-oophorectomy for BRCA1/2 reduces ovarian cancer risk and helps with endocrine status

Male Breast Cancer

• Rare (~1% of all breast cancers); typically ER+
• Treatment mirrors female breast cancer; mastectomy typically preferred; tamoxifen is mainstay of endocrine therapy (AIs less effective without oophorectomy equivalent)

7. Metastatic Breast Cancer (Stage IV)

• ER+/HER2-: Endocrine therapy + CDK4/6 inhibitor (e.g., palbociclib, ribociclib, abemaciclib) as first-line; subsequent lines include fulvestrant, everolimus + exemestane, PI3K inhibitors (alpelisib for PIK3CA-mutated tumors)
• HER2+: Trastuzumab + pertuzumab + taxane (first-line); T-DXd (second-line); T-DM1, lapatinib-based regimens
• TNBC: Pembrolizumab (if PD-L1+) + chemotherapy; sacituzumab govitecan (TROP2 antibody-drug conjugate); platinum-based chemo for BRCA-mutated; olaparib/talazoparib
• Bone metastases: Zoledronate or denosumab for skeletal-related event prevention
• Oligometastatic disease: Select patients may benefit from local ablative therapy

8. Follow-Up of Survivors

• History and physical examination: every 3-6 months for first 3 years, then annually
• Annual mammography (ipsilateral and contralateral)
• No routine CT/bone scans or blood tests unless symptomatic
• Bone health: Bisphosphonate (zoledronate 6-monthly x3 years) for those on aromatase inhibitors or LHRH agonists
• Symptom management on endocrine therapy:
  • Hot flashes: venlafaxine, gabapentin
  • Vaginal dryness: topical estrogen, lubricants
  • AI-associated arthralgia: switching AI, NSAIDs, duloxetine, exercise
  • Peripheral neuropathy (taxane-related): gabapentin
• Harrison's Principles of Internal Medicine, 22E, p. 680

Summary Algorithm

Sources: Harrison's Principles of Internal Medicine 22E (2025) | Sabiston Textbook of Surgery | Bailey and Love's Short Practice of Surgery 28th Edition | Current Surgical Therapy 14e