Breast Conserving Surgery (BCS) after Neoadjuvant Chemotherapy

  • Neoadjuvant chemotherapy:
    • Usually has been administered in cases of:
      • Inoperable or locally advanced breast cancer:
        • To downsize the primary tumor and nodal disease:
          • To facilitate local-regional therapy:
            • With surgery and / or radiation
    • Given the success of this approach in locally advanced disease:
      • Combined with the known benefits of adjuvant systemic therapy:
        • Neoadjuvant chemotherapy has also been assessed for the management of patients with operable breast cancer
  • A well-recognized role of neoadjuvant chemotherapy:
    • Is the ability to improve surgical options for patients by:
      • Downsizing tumors and increasing the chances for breast conservation 
  • In the landmark National Surgical Adjuvant Breast and Bowel Project (NSABP) B-18 trial:
    • 1523 patients with primary operable breast cancer
    • Were randomized to either preoperative or postoperative systemic therapy with:
      • Four cycles of standard doxorubicin (60 mg/m2) plus cyclophosphamide (600 mg/m2) (AC) given every three weeks
    • The administration of preoperative therapy in this trial:
      • Increased the proportion of patients able to receive breast conservation surgery by 12%:
        • The breast conservation therapy rate increased from:
          • 60% to 68%
    • This result has been confirmed in other studies:
      • Suggesting that neoadjuvant chemotherapy can:
        • Enable downsizing of tumors and reduce mastectomy rates in favor of breast conservation therapy
    • Critical to the success and widespread adoption of this approach was:
      • The demonstration of comparable distant disease control with neoadjuvant chemotherapy vs adjuvant chemotherapy
    • In the NSABP B-18 trial:
      • At a mean of 9.5 years of follow-up:
        • No significant differences were seen in:
          • Disease-free and overall survival rates between the two randomized groups:
            • 69% vs 70%, P = .80; 55% vs 53%, P = .50, respectively
    • Similar results have been observed in other randomized studies, and a recent pooled meta-analysis demonstrated that:
      • Both approaches provide equivalent survival outcomes for patients:
        • Consequently, neoadjuvant chemotherapy is a safe alternative to adjuvant therapy, especially in patients in whom breast conservation therapy is desired
  • Data from multiple studies has shown that when the same regimens are utilized:
    • No survival advantage has been identified between neoadjuvant and adjuvant chemotherapy
  • The two landmark trials that established that there is no survival advantage between neoadjuvant and adjuvant chemotherapy were the:
    • NSABP B-18:
      • Roughly 1500 patients treated with adriamycin and cyclophosphamide, 16 years follow-up
    • NSABP B-27:
      • Approximately 2300 patients treated with adriamycin, cyclophosphamide, and a taxanes, 8.5 years follow-up
  • Evolving evidence is demonstrating that:
    • The degree of pathologic response:
      • Correlates with both disease-free survival (DFS) and overall survival (OS) outcomes
      • These has been shown to be breast cancer subtype dependent:
        • With the more aggressive subtypes, like triple negative breast cancers (TNBC) and HER2 positive breast cancers:
          • Having a much higher pathologic response rates compared to hormone receptor positive cancers
        • TNBC have a pathologic complete response (pCR) rate of :
          • 34%
        • HER2 positive hormone receptor negative cancers have a pCR rate of:
          • 50%
        • HER2 positive hormone receptor positive cancers have a pCR rate of:
          • 30%
        • Hormone receptor positive cancers have a pCR rate of:
          • 7% to 16%
      • This data will help refine adjuvant therapy options in patients with TNBC and HER2 positive breast cancers
  • An advantage of neoadjuvant chemotherapy is that:
    • It allows for down-staging of the disease making breast conservation surgery (BCS) a possible option in patients with large tumors and it reduces the need for axillary node dissection (Table 1):
      • In these trials tumor shrinkage was seen in 79% of patients with 36% have a clinical complete response rate (cCR) and 43% having a clinical partial response rate (cPR
      • The NSABP B-18 identified that the patients who had the largest tumors (5 cm or greater):
        • Had the best benefit of neoadjuvant therapy in terms of BCT (Table 2)
  • Multiple studies have shown:
    • That BCT after neoadjuvant chemotherapy is safe and did not result in higher rates of local or regional recurrence:
      • The long-term results of NSABP B-18 and B-27 showed no difference in local and regional recurrence after neoadjuvant chemotherapy by surgery type (Table 3)
    • More recent data from MD Anderson Cancer Center, in a series of 751 patients (between 2005 to 2012) in which all participants received appropriate preoperative Taxane based chemotherapy and appropriate HER2 targeted therapy:
      • All women undergoing BCT had excellent outcomes across all molecular subtypes with 5-year local and regional recurrence free survival between 93% and 97% (Table 4)
      • The highest pCR rate (72.4%) was seen in patients whose tumors where hormone receptor negative / HER2 positive and the lowest pCR (16.5%) was seen in patients whose tumors where hormone receptor positive / HER2 negative
      • One important point to note from the study is that:
        • Not achieving a pCR in the hormone receptor positive / HER2 negative patients was not associated with an inferior outcome however:
          • In the high-risk hormone receptor negative subtypes not achieving a pCR does result in higher rates of local and regional failure (Table 4), something that will also occur if the patients would have undergone mastectomy instead of BCT
  • A study from the National Cancer Data Base (NCDB) from 2006 to 2011 of 354,202 patients with stage I to stage III breast cancer (47.8% of the study population underwent BCT) shows:
    • That the use of neoadjuvant chemotherapy in patients undergoing BCT is gradually increasing, from approximately 14% in 2006 to approximately 20% in 2018:
      • The use of neoadjuvant chemotherapy requires a multi-disciplinary approach

Table 1. Neoadjuvant Therapy and Breast Conservation Therapy (BCT)

Trial% BCT Neoadjuvant Therapy% BCT Surgery First
Royal Marsden 89%78%
Institut Curie82%77%
NSABP B-18 67%60%

Table 2: NSABP B-18 Breast Conservation Therapy (BCT) in Neoadjuvant Therapy

Tumor SizePlanned LumpectomyLumpectomy Performed
All Patients65%67%
Equal or Less than 2 cm89%81%
2.1 cm to 5 cm68%71%
Equal or Greater than 5 cm3%22%

Table 3: Combined Analysis of the NSAB B-18 / 27

Surgery10-Year Incidence of Local or Regional RecurrenceLocalRegional
Breast Conservation Surgery10.3%8.1%2.2%

Table 4: Neoadjuvant Chemotherapy and BCT – pCR and LRR by Subtype

VariableHR+/HER2- (n=369)HR+/HER2+ (n=105)HR-/HER2+ (n=58)HR-/HER2- (n=219)
pCR Rate16.5%45.7%72.4%42.0%
5-yr LRR-Free Survival:
No pCR
5-yr LRR-Free Survival97.2%96.1%94.4%93.4%

#Arrangoiz #BreastSurgeon #CancerSurgeon #SurgicalOncology #BreastCancer #CASO #CenterforAdvancedSurgicalOncology #PalmettoGeneralHospital

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