What is the standard chemotherapy regimen and dosage for triple negative breast cancer?

Standard Chemotherapy Regimens for Triple Negative Breast Cancer

For triple negative breast cancer (TNBC), the standard chemotherapy regimen consists of sequential anthracycline and taxane-based therapy, with specific regimens including dose-dense AC (doxorubicin/cyclophosphamide) followed by paclitaxel, or TAC (docetaxel/doxorubicin/cyclophosphamide). 1

First-Line Regimens

Preferred Regimens:

• Dose-dense AC followed by paclitaxel:

  • Doxorubicin 60 mg/m² IV, day 1
  • Cyclophosphamide 600 mg/m² IV, day 1
  • Cycled every 14 days for 4 cycles with filgrastim support
  • Followed by paclitaxel 175 mg/m² by 3-hour IV, day 1, every 14 days for 4 cycles 1

• TAC regimen:

  • Doxorubicin 50 mg/m² IV, day 1
  • Docetaxel 75 mg/m² IV, day 1
  • Cyclophosphamide 500 mg/m² IV, day 1
  • Cycled every 21 days for 6 cycles with filgrastim support 1

• TC regimen:

  • Docetaxel 75 mg/m²
  • Cyclophosphamide 600 mg/m² IV, day 1
  • Cycled every 21 days for 4 cycles 1

Neoadjuvant Setting

The treatment paradigm has shifted toward neoadjuvant therapy for early TNBC, as pathological complete response (pCR) is directly linked to improved survival outcomes 2.

Pembrolizumab-Based Regimen:

• Current standard of care for stage II or III TNBC:
  • Pembrolizumab 200 mg IV every 3 weeks
  • Combined with sequential chemotherapy:
    • Initial 4 cycles of Paclitaxel + Carboplatin
    • Followed by 4 cycles of Anthracycline (doxorubicin or epirubicin) + Cyclophosphamide 1
  • After surgery: pembrolizumab 200 mg IV every 3 weeks for up to 9 additional cycles

Post-Neoadjuvant Treatment for Residual Disease

For patients with residual disease after neoadjuvant therapy:

• Continue pembrolizumab for nine courses (if given in neoadjuvant setting)
• Consider capecitabine for patients with gBRCA1/2-wildtype:
  • Dosage: 1,250 mg/m² orally twice daily on days 1-14 of a 21-day cycle
  • Duration: six to eight cycles 3, 1

Important Considerations

1. Sequential vs. Concomitant Administration:

   • Sequential use of anthracyclines and taxanes is superior to concomitant use and is much less toxic 3
   • Both anthracycline/taxane and taxane/anthracycline sequences are acceptable 3

2. Cardiac Monitoring:

   • Essential when using anthracycline-containing regimens 1
   • Consider baseline and follow-up cardiac function assessments

3. Timing with Radiotherapy:

   • Chemotherapy should be given before radiotherapy (except with CMF regimens) 1

4. Dose Adjustments:

   • Older patients may require dose adjustments but should receive full doses whenever feasible 1
   • The capecitabine dosage of 1,250 mg/m² twice daily is associated with higher toxicity in patients ≥65 years old 3

5. Common Side Effects:

   • Hand-foot syndrome is the most frequent adverse event with capecitabine (73.4% of patients), with 11.1% experiencing grade 3 events 3
   • Monitor for immune-related adverse events with pembrolizumab, particularly thyroid dysfunction 1

Emerging Evidence

Recent research shows that incorporating dose-dense AC into a modified KEYNOTE-522 regimen is safe and effective, with comparable efficacy regardless of chemotherapy sequencing. However, administering dose-dense AC first is significantly associated with higher rates of treatment delays and cytopenias 4.

The addition of immune checkpoint inhibitors like atezolizumab to neoadjuvant chemotherapy has shown significant improvement in pathological complete response rates with an acceptable safety profile 5.

By following these evidence-based regimens and considering patient-specific factors, optimal outcomes can be achieved in the treatment of triple negative breast cancer.