Cancers | Free Full-Text | De-Escalation Surgery in cT3-4 Breast Cancer Patients after Neoadjuvant Therapy: Predictors of Breast Conservation and Comparison of Long-Term Oncological Outcomes with Mastectomy

The use of chemotherapy in the neoadjuvant setting has substantially increased in recent years [13,29]. Notably, this approach has greatly facilitated the shift from mastectomy to BCS as a surgical option, particularly in patients with initially diagnosed cT3-4 BC who were previously deemed unsuitable for breast conservation. Despite the substantial progress in systemic therapies that have improved the rates of complete response in primary tumors, recent neoadjuvant trials have reported lower rates of breast conservation [30]. This occurs even though most patients eligible for BCS after NAT often end up undergoing mastectomy [21,22,26,31,32,33,34]. In a large retrospective analysis involving 916 patients with BC treated with NAT, Li et al. [35] showed that patients with cT3 tumors were nearly six times more likely to undergo mastectomy than patients with cT1 tumors (OR: 5.74, 95%CI: 2.07–15.97, p = 0.003). Additionally, in a recent meta-analysis involving 36 studies and 12,311 patients with BC, Criscitiello et al. [36] demonstrated that achieving a complete response does not necessarily lead to an increased adoption of BCS in patients treated with NAT. In our study, we aimed to identify the predictors of breast conservation after NAT in cT3-4 tumors and to evaluate the long-term oncological outcomes, specifically in terms of recurrence and survival. This evaluation was conducted to determine whether opting for breast conservation after NAT compromises prognosis in any way.

According to multivariate analysis, three independent factors with a statistically significant correlation with the surgical choice after NAT were found to be important predictors of breast conservation in cT3-4 BC, including absence of vascular invasion, a smaller tumor, and achieving ypT0. The decision to proceed with mastectomy in patients with cT3-4 BC after NAT and potentially aggressive tumor features (vascular invasion, larger, and failure to achieve a complete response) is often driven by concerns over the risk of increased local recurrence and lower survival rates. Such concerns were highlighted by a 2018 meta-analysis conducted by the Early BC Trialists’ Collaborative Group (EBCTCG) [37], which reviewed ten randomized trials over a median period of nine years. This analysis revealed an increased rate of local recurrences at 10 and 15 years among patients who had BCS for tumors downsized by NAT in comparison to those who underwent BCS in the adjuvant setting for tumors of similar sizes (17.9% versus 13.2% and 21.4% versus 15.9%, respectively, log-rank p p = 0.002) [38,39]. Moreover, there was a lack of information on axillary surgery and radiotherapy data.

On the other hand, our study suggests that the choice of surgical treatment, be it BCS or mastectomy, does not significantly influence the long-term oncological outcomes in patients with BC undergoing NAT, as corroborated by numerous other studies. Gwark et al. [20] retrospectively analyzed 1641 patients with BC who received NAT before surgery, of whom 839 (51.1%) underwent BCS + radiotherapy and 802 (48.9%) underwent mastectomy. Patients who underwent mastectomy had larger tumors (p p = 0.005). For the breast conservation and mastectomy groups, the unadjusted 5-year DFS, DDFS, and OS rates were 87.0% and 73.1%, 89.5% and 77.0%, and 91.8% and 81.0%, respectively (all p 21] analyzed the results of 561 patients with BC treated with NAT, 362 (64.5%) with BCS and 199 (35.5%) with mastectomy. Mastectomy patients had larger tumors (p p = 0.004). The unadjusted 5-year OS was 95.3% and 85.9% (p 22] performed a retrospective study of 411 patients with non-metastatic, locally advanced BC who received NAT followed by surgery. The estimated 5-year DFS, DDFS, and OS rates of BCS and mastectomy groups were 63.9%, 71.0%, and 79.3% and 57.9%, 58.3%, and 71.5%, respectively. After adjusting for age, cT stage, cN stage, and radiotherapy, the BCS and mastectomy groups were found comparable in terms of DFS, DDFS, and OS. A recent meta-analysis [40] including 14 studies and 19,819 patients suggested that BCS after NAT is actually associated with significantly decreased risk of death (OR: 0.78, 95%CI: 0.69–0.89, p p = 0.002), and DDFS (OR: 0.70, 95%CI: 0.53–0.94, p = 0.020) compared to mastectomy. Additionally, Werutsky et al. [41] conducted a pooled analysis of 10,075 primary patients with BC treated with NAT, revealing 5-year loco-regional recurrence rates of 7.8% in the BCS group and 11.3% in those undergoing mastectomy. In the I-SPY2 trial, a prospective, randomized study, Mukhtar et al. [42] evaluated the relationship between NAT response, assessed via the residual cancer burden (RCB) method, and loco-regional recurrence in 1462 patients with BC who received surgical treatment (BCS or mastectomy) from 2010 to 2021. With a median follow-up of 3.5 years, loco-regional recurrences were observed in 5.4% of BCS patients and 7.0% of mastectomy patients (p = 0.18). Patients with RCB 2/3 post-NAT had a notably reduced loco-regional free survival compared to those with RCB 0/1, irrespective of the surgical method. There was no significant difference in loco-regional-free survival between BCS and mastectomy patients with RCB 0/1 after NAT. Moreover, many other studies have consistently demonstrated that BCS does not compromise recurrence and survival rates in patients with BC treated with NAT [43,44,45,46,47].