Systematic Anti - Cancer Therapy - SACT

What is SACT?

Systemic Anti-Cancer Therapy, including chemotherapy, targeted therapy, and immunotherapy, used to treat or control cancer.

What is the goal of adjuvant chemotherapy?

To eradicate micrometastatic disease, reducing recurrence risk and improving survival after surgery.

What is the goal of neoadjuvant chemotherapy (NACT)?

To shrink tumors before surgery, especially in ER-negative, HER2+, or triple-negative breast cancer.

Which patients are typically offered NACT?

• Node-positive

• Triple-negative (ER-/PR-/HER2-)

• HER2+ tumors

• Large tumors (>5cm)

What are common adjuvant regimens?

• Taxane + anthracycline (e.g., EC → Docetaxel)

• Benefits: Reduced cardiac toxicity vs. anthracycline alone.

• Risks: Neuropathy, neutropenia, hypersensitivity.

What is a key regimen for triple-negative NACT?

• Paclitaxel + Carboplatin → followed by EC (Epirubicin/Cyclophosphamide).

How is HER2+ NACT treated?

• EC → Docetaxel + Trastuzumab (± Pertuzumab)

• Alternative: TCHP (Docetaxel/Carboplatin/Trastuzumab/Pertuzumab).

What is the role of platinum agents (e.g., Carboplatin)?

Alkylating agents used in triple-negative or BRCA-mutated cancers to enhance DNA damage.

How does Trastuzumab (Herceptin) work?

Monoclonal antibody blocking HER2 receptors, improving survival in HER2+ breast cancer.

What is the PERSEPHONE trial finding?

6 months of Trastuzumab is non-inferior to 12 months, with less cardiotoxicity.

When is Pertuzumab added?

For node-positive HER2+ disease, combined with Trastuzumab (Phesgo).

What is Kadcyla (T-DM1)?

Trastuzumab + chemotherapy drug (emtansine), used if residual disease post-NACT.

Key side effects of HER2-targeted therapy?

• Cardiotoxicity (monitor LVEF)

• Infusion reactions

• Neuropathy

Which immunotherapy is used for triple-negative BC?

Pembrolizumab (Keytruda) + chemotherapy, given neoadjuvantly and continued post-surgery.

What is the evidence for Pembrolizumab?

Improves pathological complete response (64.8% vs. 51.2%) in PD-L1+ tumors.

Key side effects of immunotherapy?

• Immune-related toxicities (e.g., pneumonitis, colitis)

• Fatigue, skin reactions

How do CDK4/6 inhibitors work?

Block cell cycle proteins (CDK4/6), halting cancer growth in HR+/HER2- disease.

Which patients get adjuvant Abemaciclib?

HR+/HER2-, high-risk (≥4 nodes OR 1–3 nodes + grade 3/tumor ≥5cm).

What did the PALLAS trial show?

Palbociclib did not improve outcomes over endocrine therapy alone in early BC.

Side effects of CDK4/6 inhibitors?

• Diarrhea

• Neutropenia

• Fatigue

How do PARP inhibitors work?

Block DNA repair in BRCA-mutated cells, causing cancer cell death ("synthetic lethality").

Which patients get Olaparib?

BRCA1/2+, HER2-, high-risk post-chemotherapy (per OlympiA trial).

Side effects of PARP inhibitors?

• Anemia

• Nausea

• Fatigue

What tools assess chemotherapy benefit in HR+ disease?

• Oncotype DX: Predicts recurrence risk and chemo benefit.

• PREDICT Tool: Estimates survival based on tumor features.