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.

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