8.1 Breast, Lung, Colorectal & Prostate Cancer

Solid tumor oncology for internal medicine requires a comprehensive understanding of evidence-based cancer screening guidelines, molecular subtype-driven therapies, and the prompt diagnosis and management of life-threatening oncologic emergencies.

1. Common Solid Tumors: Screening & Management

Breast Cancer

• Screening (USPSTF 2024 Updated Guidelines): Biennial screening mammography for all average-risk women aged 40 to 74 years. High-risk women (known BRCA1/2 mutation, lifetime risk > 20% by Tyrer-Cuzick model, or prior mantle chest radiation between age 10–30) should undergo annual breast MRI starting at age 25–30 plus annual mammography.
• Molecular Subtypes & Biomarkers:
  • Hormone Receptor-Positive (ER+/PR+, HER2-negative): ~70% of cases.
    • Premenopausal: Tamoxifen (Selective Estrogen Receptor Modulator [SERM]) x 5–10 years. Adverse effects: hot flashes, thromboembolism, endometrial cancer (in postmenopausal women). Add ovarian function suppression (GnRH agonist Leuprolide) for high-risk patients.
    • Postmenopausal: Aromatase Inhibitors (AIs: Anastrozole, Letrozole, Exemestane) x 5–10 years. Blocks peripheral conversion of androgens to estrogens. Adverse effects: arthralgias, accelerated bone loss/osteoporosis (mandates baseline DEXA scan, calcium/vitamin D, and bisphosphonates if T-score < -2.0).
    • Targeted Adjuvant Therapy: CDK4/6 Inhibitors (Abemaciclib) in high-risk node-positive ER+/HER2- early breast cancer.
  • HER2-Positive (HER2+ by IHC 3+ or FISH amplified):
    • Targeted therapy with Trastuzumab + Pertuzumab combined with chemotherapy.
    • Safety Monitoring: Trastuzumab causes non-dose-dependent, reversible left ventricular systolic dysfunction. Mandates baseline and serial echocardiography every 3 months; hold therapy if LVEF drops > 10% or below 50%.
  • Triple-Negative Breast Cancer (TNBC: ER-, PR-, HER2-): Aggressive biology, higher prevalence in BRCA1 mutation carriers. Managed with neoadjuvant chemo-immunotherapy (Pembrolizumab + Platinum/Taxane/Anthracycline).
  • BRCA1/BRCA2 Mutation Carriers: Adjuvant PARP Inhibitors (Olaparib) for high-risk HER2-negative disease. Offer risk-reducing bilateral salpingo-oophorectomy (BSO, recommended at age 35–40 for BRCA1, 40–45 for BRCA2) and risk-reducing bilateral mastectomy.

Lung Cancer

• Screening (USPSTF 2021 Guidelines): Annual Low-Dose Chest CT (LDCT) in adults aged 50 to 80 years who have a ≥ 20 pack-year smoking history and currently smoke or have quit within the past 15 years. Discontinue screening once a person has not smoked for 15 years or develops a health condition that substantially limits life expectancy.
• Non-Small Cell Lung Cancer (NSCLC: ~85% of cases):
  • Subtypes: Adenocarcinoma (peripheral, most common in non-smokers) vs. Squamous Cell Carcinoma (central, cavitary, associated with hypercalcemia/PTHrP).
  • Mandatory Broad-Panel Molecular Profiling (NGS): Test all advanced non-squamous NSCLC for actionable driver alterations:
    • EGFR Mutations (Exon 19 del, L858R): Osimertinib (3rd generation irreversible EGFR TKI, superior CNS penetration).
    • ALK Rearrangements (EML4-ALK fusion): Alectinib or Brigatinib (1st-line ALK TKIs).
    • ROS1 Fusions: Crizotinib or Entrectinib.
    • BRAF V600E Mutations: Dabrafenib + Trametinib.
    • KRAS G12C Mutations: Sotorasib or Adagrasib.
    • RET Fusions: Selpercatinib; MET Exon 14 Skipping: Capmatinib.
  • PD-L1 Tumor Expression (TPS): In tumors lacking driver mutations: If PD-L1 TPS ≥ 50%, first-line therapy is single-agent Pembrolizumab; if PD-L1 < 50%, combination platinum-doublet chemotherapy + Pembrolizumab.
• Small Cell Lung Cancer (SCLC: ~15% of cases):
  • High-grade neuroendocrine tumor strongly linked to heavy tobacco use. High propensity for early hematogenous and CNS dissemination.
  • Paraneoplastic Syndromes: SIADH (euvolemic hyponatremia), Lambert-Eaton Myasthenic Syndrome (LEMS: antibodies against presynaptic P/Q-type voltage-gated calcium channels → proximal leg weakness that improves with repeated muscle contraction, autonomic dysfunction, hyporeflexia), and ectopic Cushing Syndrome (ACTH production).
  • Management: Limited Stage (concurrent Cisplatin + Etoposide + Radiation + Prophylactic Cranial Irradiation [PCI]); Extensive Stage (Platinum + Etoposide + anti-PD-L1 immunotherapy [Atezolizumab or Durvalumab]).

Colorectal Cancer (CRC)

• Molecular Testing in Metastatic CRC (mCRC): Test all mCRC for KRAS, NRAS, and BRAF mutations, Mismatch Repair (dMMR / MSI-H) status, and HER2 amplification.
• Anti-EGFR Monoclonal Antibodies (Cetuximab, Panitumumab): Indicated ONLY in RAS wild-type (KRAS and NRAS wild-type) tumors (activating RAS mutations downstream confer absolute resistance to EGFR blockade; left-sided primary tumors derive greatest benefit).
• Immune Checkpoint Inhibitors (Pembrolizumab, Nivolumab + Ipilimumab): Highly effective first-line therapy for tumors with dMMR / MSI-H (defective DNA mismatch repair creates thousands of neoantigens sensitive to PD-1 blockade).

Prostate Cancer

• Screening: Individualized shared decision-making regarding PSA screening in men aged 55 to 69 years; routine screening not recommended in men aged ≥ 70 years.
• Risk Stratification & Localized Disease: Active Surveillance (serial PSA, DRE, multiparametric prostate MRI, repeat biopsies) is preferred for low-risk disease (Gleason 6 / Grade Group 1, PSA < 10, T1c–T2a). Definitive radical prostatectomy or radiation + short-term ADT for intermediate/high risk.
• Advanced & Metastatic Prostate Cancer: Standard backbone is Androgen Deprivation Therapy (ADT) using LHRH agonists (Leuprolide, Goserelin; require antiandrogen bicalutamide co-administration to prevent initial testosterone flare) or GnRH antagonist (Relugolix oral or Degarelix SC; no flare) PLUS novel Androgen Receptor Signaling Inhibitors (ARSIs: Enzalutamide, Apalutamide, Darolutamide) or Abiraterone Acetate + Prednisone (CYP17 inhibitor).