Neoadjuvant Chemotherapy (NAC) Among Women with Operable Breast Cancers at the time of Diagnosis

• Among women with operable breast cancers at the time of diagnosis:
  • Neoadjuvant chemotherapy (NAC) is increasingly used:
    • To gain information about the tumor’s response to treatment, with pathologic response rates correlating with long-term prognosis
• The most accepted definition of pathologic complete response (pCR) includes:
  • No residual invasive disease in the breast or sampled axillary nodes:
    • Although this definition varies, residual in situ disease does not affect the risk of distant recurrence
• Response to preoperative treatment:
  • Differs by tumor biology:
    • With hormone-receptor positive breast cancer patients having the lowest overall pCR rate
• For some women with residual disease, including those with HER2-positive and triple-negative breast cancers:
  • This allows for use of additional adjuvant therapy:
    • That improves cancer outcomes including receipt of:
      • TDM-1 (trastuzumab emtansine, KATHERINE Trial)
      • Xeloda (Capecitebine, CREATE-X Trial)
      • Eligibility for ongoing clinical trials
• Notably, recent changes to the American Joint Committee on Cancer Staging System includes:
  • Pathologic stage after neoadjuvant chemotherapy as part of the updated system
• When pCR is achieved in both the breast and axillary nodes:
  • Survival is driven by response to chemotherapy compared to initial presenting stage
• Choosing a NAC regimen depends on tumor biology:
  • In HER2-positive patients:
    • Chemotherapy should be combined with HER2-targeted therapies:
      • Taxane + carboplatin + trastuzumab, pertuzumab (TCHP)
  • For HER2-negative patients:
    • Anthracycline-based drugs including:
      • Doxorubicin and cyclophosphamide followed by a taxane
    • Higher risk HER2-negative breast cancers (node-positive hormone-receptor positive patients and triple-negative patients):
      • Typically receive anthracycline and taxane-based regimens with or without carboplatin
    • Notably, results from the CALGB 40603 trial suggested that for triple-negative breast cancer:
      • The addition of carboplatin to NAC:
        • Resulted in a 14% increase in eligibility for breast conservation

References

1. Fayanju OM, et al. The Clinical Significance of Breast-only and Node-only Pathologic Complete Response After Neoadjuvant Chemotherapy. Annals of Surgery. 2018; 268(4): 591-601.

2. von Minckwitz, G et al. Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer. NEJM. 2018; 380(7): 617-628.

3. Masuda N, et al. Adjuvant Capecitabine for Breast Cancer After Preoperative Chemotherapy. NEJM. 2017; 376:2147-59.

4. Golshan M, et al. Impact of neoadjuvant chemotherapy in stage II-III triple negative breast cancer on eligibility for breast-conserving surgery and breast conservation rates: surgical results from CALGB 40603 (Alliance). Annals of Surgery. 2015; Sep; 262(3):434-9.