Neoadjuvant Chemotherapy (NAC) Offers Several Advantages in Locally Advanced Breast Cancer

• The administration of neoadjuvant chemotherapy (NAC) offers several advantages in locally advanced breast cancer:
  • It allows for down staging the disease:
    • Which can potentially allow for less extensive surgery in the breast and axilla
  • It also provides information regarding the responsiveness of the cancer to systemic therapy while the tumor remains in vivo:
    • Which can guide the course of therapy
• Administering chemotherapy in the neoadjuvant vs. adjuvant setting:
  • Does not change overall survival:
    • As demonstrated in the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-18 and NSABP B-27 trials
• The patient’s response to chemotherapy:
  • Does offer prognostic information:
    • Particularly in patients with hormone receptor negative (HR-) disease
    • Patients who achieve pathologic complete response (pCR):
      • Which is typically defined as no residual invasive disease in the breast or axilla:
        • Appear to have improved event-free survival (EFS) and overall survival (OS) compared with patients with residual disease:
          • This finding was demonstrated by a recent meta-analysis that included 36 studies including 5,768 patients with HER2 positive breast cancer
          • This correlation was strongest in patients with HR- disease
          • Further, among patients with HER2 positive disease that do not have a pCR:
            • The degree of residual cancer burden appears to correlate with outcomes
              • Patients with HER2 positive tumors:
                • May complete up to one year of HER2-targeted therapy:
                • With trastuzamab ± pertuzamab.
• When planning surgery:
  • The pre-treatment volume does not need to be excised if the tumor has responded to chemotherapy:
    • However if multifocal disease is present:
      • The satellite lesion(s) should be localized and excised with the index lesion
      • When considering the appropriateness for breast conservation following NAC:
        • The distance between the lesions, location, and breast size must be considered
        • Placement of clips in the index lesion and any satellite lesions prior to initiation of NAC is critical for appropriate surgical planning post-NAC

• References
  • Rastogi P, Anderson SJ, Bear HD. Preoperative chemotherapy: updates of National Surgical Adjuvant Breast and Bowel Project Protocols B-18 and B-27. J Clin Oncol. 2008; 10;26(5):778-785.
  • Broglio KR, Quintana M, Foster M, et al. Association of pathologic complete response to neoadjuvant therapy in HER2-positive breast cancer with long-term outcomes: a meta-analysis. JAMA Oncol. 2016;2(6):751-760.
  • Symmans WF, Wei C, Gould R, et al. Long-term prognostic risk after neoadjuvant chemotherapy associated with residual cancer burden and breast cancer subtype. J Clin Oncol. 2017;35(10):1049-1060.
  • Boughey JC, Peintinger F, Meric-Bernstam F, et al. Impact of preoperative versus postoperative chemotherapy on the extent and number of surgical procedures in patients treated in randomized clinical trials for breast cancer. Ann Surg. 2006;244(3):464-470.

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