Neoadjuvant Chemotherapy (NAC)

Neoadjuvant chemotherapy (NAC):
- Refers to the delivery of systemic treatment prior to surgery
Preoperative chemotherapy was initially utilized in women with locally advanced or inflammatory cancers:
- To improve operability
Among women with early-stage breast cancers:
- The NSABP B-18 and B-27 randomized clinical trials:
  - Demonstrated no difference in:
    - Disease-specific or overall survival between those who received neoadjuvant versus adjuvant chemotherapy
  - Neoadjuvant chemotherapy:
    - Improved rates of breast conservation:
      - 68% versus 60%
More recent observational data have demonstrated:
- No increased risk in surgical complications among women who underwent neoadjuvant chemotherapy
NAC has more recently been used to:
- Downstage the axilla in patients with biopsy-proven lymph node involvement with hopes to avoid completion lymphadenectomy and decrease the risk of lymphedema
Additionally, NAC has been used in women with operable breast cancers:
- To theoretically treat micro-metastatic disease prior to local therapy and to allow assessment of the in vivo tumor response to certain chemotherapy regimens
Notably, results from the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) meta-analysis included:
- Patient-level data from 4,756 women enrolled in clinical trials 1983 to 2002:
  - Results demonstrated a higher risk of in-breast recurrence after neoadjuvant chemotherapy:
    - At 15 years, women treated with NAC had a 21% risk of local recurrence (vs. 16% in the surgery-first patients):
      - This was attributed to a higher rate of breast conservation, but with no difference in distant recurrence or breast cancer-specific overall survival
References
- Fisher B, Bryant J, Wolmark N, Mamounas E, Brown A, Fisher ER, et al. Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. J Clin Oncol. 1998;16(8): 2672-2685.
- Boughey J, Peintinger F, Meric-Bernstam F, Perry AC, Hunt KK, Babiera GV, 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.
- Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomized trials. Lancet Oncol. 2018;19(1):27-39.