Doxorubicin and paclitaxel are well known as the most effective neoadjuvant and adjuvant treatments for breast cancer [4, 8]. Our analysis is one of the few studies reporting 10-year outcomes for patients treated with the AP regimen. This study presents a Vietnamese experience of neoadjuvant treatment for stage III breast cancer with a combination of paclitaxel and doxorubicin. It demonstrates the effectiveness of this regimen and identifies reliable long-term prognostic factors affecting patient outcomes. These predictive factors will be a valuable tool to inform oncologists in similar contexts to help them in adjusting management and follow-up plans. Our study demonstrates that the AP regimen is a promising neoadjuvant chemotherapy regimen for patients with stage III breast cancer. Neoadjuvant chemotherapy in this study achieved high clinical responses, with clinical CR and PR rates of 29.4 and 65.1%, respectively. The overall response rate was 94.5%. Stable disease was observed in four patients (3.2%), while disease progression was observed in three patients (2.4%). Other neoadjuvant chemotherapy studies have consistently shown a low risk of progressive disease during chemotherapy (less than 5%) [4, 5, 8]. Of 37 patients with a clinical CR, 15 breast cancer patients (40.5%) achieved pCR.

Many studies around the world have determined that the main goal of neoadjuvant chemotherapy is the pCR rate. pCR is a predictor for disease free-survival and overall survival [9]. In this study, 25.4% (32 of 126 patients) achieved pCR. Diéras et al. studied 200 patients who received neoadjuvant chemotherapy with an AP regimen or doxorubicin plus cyclophosphamide (AC) regimen. The pCR rates were 16% and 10% of patients in the AP and AC arms, respectively [8]. Malhotra et al. [15] reported a pCR rate of 15%, while other studies have reported rates in the range of 3–46% [9, 16]. The rate of pCR can vary depending on the definition of pCR as well as the clinicopathological characteristics. In our study, pCR was defined as the absence of invasive cancer in breast and axillary lymph nodes (ypT0/is ypN0).

Several studies have investigated the factors predicting pCR. Our study found significant associations between pCR and histological grade, clinical tumor stage, HER2 status, HR status, and clinical response. Our results are consistent with those of other studies. We found that higher cT-stages were associated with significantly lower pCR rates than lower cT-stages (cT3–4 vs. cT1-2; p < 0.05). Goorts et al. (n = 2366) reported that pCR rates for cT1, cT2, cT3, and cT4 were 31, 22, 18, and 17%, respectively. A significant finding from the study was that patients with a lower cT-stage (cT1-2) had a higher pCR rate than those with a higher cT-stage (cT3–4), and this was found to be an independent predictor (OR 3.15, p < 0.001) [17]. Furthermore, previous meta-analyses demonstrated a higher pCR rate in HR-negative or HER2-positive patients than in HR-positive or HER2-positive patients. Von Minkwitz et al. analyzed 6377 breast cancer patients receiving preoperative anthracycline-taxane chemotherapy in seven clinical trials. The results showed that the CR rate was 7.6% in the group of ER-positive patients, 26% in ER-negative patients, 7.4% in PgR-positive patients, and 22.9% in PgR-negative patients (p < 0.001) [18]. Yanli et al. studied 261 patients with operable primary breast cancer receiving neoadjuvant chemotherapy, with a pCR rate of 29.1%. The factors related to the pCR rates were as follows: ER (negative: 57.9% vs. positive: 42.1%), PgR (negative: 65.8% vs. positive: 34.2%), and HER2 status (positive: 54.7% vs. negative: 45.3%) [19]. Hong et al. reported that the pCR rate in the breast was higher in HER2-positive patients (HER2 positive: 33.3% vs. negative: 10.0%, p = 0.002) [20]. Cortazar et al. analyzed 12 studies on neoadjuvant therapy and found that the HER2-positive patients had higher pCR than those with HER2-negative disease [9].

In this retrospective study of 126 patients with stage III breast cancer treated with a neoadjuvant AP regimen, the mean follow-up was 75 months. The median DFS and OS were 33 months and 67 months, respectively. The 5-year and 10-year DFS were 38.0% and 29.7%, while the 5-year and 10-year OS rates were 52.9% and 36.7%, respectively. The study by Diéras et al. included 200 patients with stage II and III breast cancer who received doxorubicin and paclitaxel-based chemotherapy. The 5-year and 10-year event-free survival were 69.5% and 60.5%, while the 5-year and 10-year OS rates were 85.0% and 70.0%, respectively [8]. Another study involving 634 nonmetastatic cT4 breast cancer patients treated with neoadjuvant therapy had 10-year results of 52.3% for OS, 37.0% for invasive disease-free survival (IDFS), and 49.8% for distant disease-free survival [21]. Additionally, a retrospective cohort study of 1600 women treated with neoadjuvant therapy recorded 5-year OS and recurrence-free survival (RFS) rates of 79% and 67%, respectively; the 10-year OS and RFS rates were 64% and 58%, respectively [22]. Survival results in our study were lower than those in other studies, for several reasons. Firstly, the patients in our study were at a later stage, with more than half (54.0%) having stage IIIB or IIIC. Secondly, many patients were HER2-positive and did not have access to targeted therapy, especially trastuzumab. Finally, triple-negative breast cancer patients with residual disease after NAC did not receive capecitabine maintenance therapy after surgery.

In our study, the HR status was found to be a factor affecting DFS and OS. Patients with HR-positive breast cancer had longer DFS and OS than those with HR-negative breast cancer (p < 0.05). The 10-year OS rates were 45.6% and 25.5%, respectively (p = 0.004), and the 10-year DFS rates were 37.3% and 19.6%, respectively (p = 0.004). El-Sayed et al. studied 95 patients with locally advanced breast cancer who received neoadjuvant taxane-based treatment. The results showed that the DFS rates at 5 years were 82.3% and 26.5% for breast cancer patients with positive and negative HR, respectively (p < 0.0001, HR 21.48), and the OS rates were 84% and 35.7%, respectively (p = 0.0001, HR 11.59) [23]. Our results also confirmed that HER2 overexpression or amplification impacts the prognosis of stage III breast cancer patients. El-Sayed et al. reported that the 5-year DFS rates were 33.8% and 81.8% for patients with HER2-positive and HER2-negative breast cancer, respectively (p < 0.0001, HR 12.27), and the 5-year OS rates were 41.7% and 83.2%, respectively (p = 0.001, HR 7.14) [23].

In our study, we found that patients with pCR had better OS and DFS than patients with residual disease. Achievement of pCR in our cohort was significantly associated with survival outcomes. These findings are in concordance with a recently published large meta-analysis by Spring et al., which included more than 27,000 patients who were evaluated from 52 studies. The study found that patients who had pCR, as compared to the absence of pCR, had significantly better event-free survival and overall survival (HR 0.31, n = 26,378, and HR 0.22, n = 23,329, respectively) [24]. Diéras et al. studied patients with T2-3, N0-1, M0 disease who received preoperative chemotherapy with the AP regimen. At a median follow-up of 31 months, DFS was higher in patients who reached pCR than in those without pCR (91% vs. 70%) [8]. This result is similar to the findings of Cortazar et al. [9]. However, in our country, there are still many patients who come to the hospital when the disease is already in an advanced stage. Over the years, thanks to increased awareness campaigns, education, and screening, this rate has gradually decreased. In addition, FISH testing is now much more common than it was in the 2010s. Now, many patients have the opportunity to be treated with anti-HER2, CDK4/6 inhibitors, and immunotherapy, which improves the survival time of breast cancer patients.

The limitations of our study should be acknowledged. Firstly, the retrospective nature of the study may have limited our ability to control for all possible confounding variables, and therefore our findings should be interpreted with caution. Additionally, the small sample size and missing data, particularly regarding HR and HER2 status, may have impacted the accuracy of our results. FISH/chromogenic in situ hybridization (CISH) testing for HER2 is also beyond affordability for the reported population, so HER2 IHC (2+) patients were not evaluated by CISH or FISH. Furthermore, we did not have specific data on the use of endocrine therapy in our patients. This was due to the conditions at our hospital between 2009 and 2012, which prevented many patients from receiving consistent hormone therapy. Some patients started on aromatase inhibitors and then switched to tamoxifen, while others did the opposite. Finally, the primary aim of our study was to evaluate the response to treatment and survival outcomes. We did not focus on analyzing the toxicity or dose reductions related to the treatment. Future studies with larger sample sizes and more complete data collection would be necessary to confirm our findings and address these limitations.