Neoadjuvant systemic therapy (NST) for breast cancer has a proven role in the modern treatment of breast cancer. The usual intent of such therapy is to downsize responsive tumors to improve operability and increase chances of successful breast conserving surgery (BCS). Indeed, randomized trials have shown that NST increases rates of BCS compared to a “surgery-first” strategy. Although BCS is more often achieved with a NST strategy than a “surgery-first” strategy, data from the NSABP B18 trial suggested that certain patients receiving NST and were converted from needing mastectomy to BCS experienced higher rates of locoregional recurrence (LRR) than was expected based on rates seen in trials of BCS not involving NST. These data raised concern that the NST-BCS approach may be associated with unacceptably high rates of local breast cancer recurrence.
The present study reports the long-term (median FU 7+ years) outcomes of NST-BCS in 652 patients treated at the MD Anderson Cancer Center (MDACC), the largest series of such patients reported to date. The tumor downstaging in this series was impressive. Of 607 patients presenting with clinical stage II/III disease, chemotherapy downstaged 313 patients (52%) to pathological stage 0/I disease and there was a 20% pathologic complete response rate. The results of the study demonstrate that overall, a strategy of NST-BCS is associated with acceptable rates of LRR (5- and 10-year LRR-free survival rates of 93% and 90%, respectively). The authors also demonstrated favorable 5- and 10-year LRR-free survival rates in patients with clinical stage II or III disease who were most likely marginally eligible or ineligible for BCS and received neoadjuvant chemotherapy [93% (95% CI, 91–95) and 90% (95% CI, 87–93), respectively). These data confirm that a selective approach to NST-BCS in patients with large tumors can achieve excellent local-regional control.
In a non-randomized fashion the authors also compared the results of the NST-BCS group with a contemporary group of 2331 patients having surgery first. The LRR rates in the “surgery-first” group were better; however, when controlled for presenting tumor stage there was no difference in LRR between the “surgery-first” group and the NST-BCS group indicating that tumor biology rather than choice of surgery was the driving factor behind LRR as long as negative margins were achieved. In multivariate analysis, an age less than 50 years, clinical stage III, tumor grade 3, estrogen receptor (ER)-negative disease, estrogen receptor-positive disease without receipt of endocrine therapy, lymphovascular invasion, multifocal disease on pathology, and close/positive margins were associated with LRR in both groups. Choice of surgical strategy (“surgery-first” vs NST-BCS) was not significant with respect to LRR. Lastly, the authors made the expected observation that patients in the NST-BCS experienced higher rates of distant relapse and disease-specific death than did those in the surgery first group, consistent with the greater percentage of patients with clinical stage II or III disease in the NST-BCS cohort.
So what does this mean? The key to this paper and the important aspect of the work lay in figures 3 A-E. Although the presence of significant adverse factors progressively increases the risk of LRR, there is no combination of adverse risk factors that makes a strategy of NST-BCS better or worse than a strategy of “surgery-first”. The key is that resection with negative margins must be achieved. The unanswered question is whether patients with a higher number of risk factors will have better local control with mastectomy.Questions:
1. What factors drive a decision for BCS versus mastectomy following NST?
2. Stage for stage, would one expect a difference in distant relapse-free survival?
3. Are there subtypes of breast cancer better suited to a strategy of NST-BCS?
4. How should axillary nodes be handled in patients receiving NST?
Please feel free to comment on any or all of the questions above. We look forward to hearing from you, the Annals readers.