This cross-sectional descriptive study is part of a larger investigation involving 250 stage III breast cancer patients. The sample size was calculated using a descriptive sample size estimation formula based on the expected pathological complete response (pCR) rate of 16.8%, according to the study by Le Thanh Duc et al. (2023). From this cohort, a convenient sample of 108 patients who received the dose-dense NAC regimen (2-week interval cycles) consisting of 8 chemotherapy cycles (4AC-4T: four cycles of Doxorubicin and Cyclophosphamide, followed by four cycles of Paclitaxel) was selected for analysis.

Eligible participants included women aged 18 years or older who were diagnosed with stage III breast cancer based on the TNM of the AJCC's 8^th classification (2017)6. Exclusion criteria included incomplete medical records, failure to complete the treatment regimen, severe comorbidities, pregnancy, or a history of other cancers. The study was conducted at the Vietnam National Cancer Hospital from August 2021 to August 2022, with most patients undergoing total mastectomy following NAC treatment.

All data were analyzed using SPSS 26. Descriptive statistics were applied to summarize patient demographics and clinical characteristics. T-tests and analysis of variance (ANOVA) were used to compare means, with statistical significance set at p < 0.05.

This study is part of the research project titled "Evaluation of Neoadjuvant Chemotherapy and Surgical Treatment of Stage III Breast Cancer," which was reviewed and approved by the Biomedical Research Ethics Council at K Hospital (certification number 1951/BVK-HĐĐ, dated August 1, 2022). Patients were fully informed and consented to participate in the study. The research was conducted according to strict ethical standards, and the authors declare no conflicts of interest in conducting or interpreting the study results.

The study included 108 patients with an average age of 45.16 ± 9.98 years. Most patients (34.26%) were aged 30 - 40, and 33.33% were over 50. Over half (56.48%) were diagnosed within the past 3 months, and 78.70% were still menstruating.

TNM Classification: Tumor staging revealed that 53.70% of patients had T4 tumors, with 70.37% showing cN2 nodal involvement. Stages IIIA and IIIB represented 37.96% and 38.89% of the cases, respectively.

Most tumors were of the non-special type (NST) (90.74%), and Grade II tumors were the most common (48.15%). Luminal B was the dominant molecular subtype (29.63%), followed by HER2-positive (24.07%) and triple-negative breast cancer (TNBC) (18.52%).

Table 1

Characteristics	n =108	Ratio (%)
Age Distribution
Under 30	5	4.63
30-40	37	34.26
40-50	30	27.78
Over 50	36	33.33
Duration Since Diagnosis
Under 3 months	61	56.48
3-6 months	21	19.44
More than 6 months	26	24.07
Menstrual Status
Menstruating	85	78.70
Menopausal	26	24.08

Table 3

Histological Subtype	n =108	Ratio (%)
NST	98	90.74
Invasive Lobular	1	0.93
Invasive Ductal	7	6.48
Metastatic Carcinoma	2	1.85
Tumor Grade
Unknown	32	29.63
Grade I	2	1.85
Grade II	52	48.15
Grade III	22	20.37
Molecular Subtypes
Luminal A	10	9.26
Luminal B/HER2(-)	32	29.63
Luminal B/HER2(+)	26	24.07
HER2(+)	20	18.52
TNBC	20	18.52

Table 4

Changes before and after treatment of	Mean	SD	95% CI		p
Tumor Size (at 4- Cycles)	28.29	22.69	23.92	32.66	0.00
Node Size (at 4- Cycles)	10.78	9.18	9.03	12.53	0.00
Tumor Size (at 8-Cycles)	38.21	24.51	33.47	42.95	0.00
Node Size (at 8-Cycles)	13.94	9.23	12.17	15.70	0.00

After four chemotherapy cycles, the tumor size was reduced by 28.29 mm, and lymph node size by 10.78 mm. After eight cycles, the tumor size was further reduced by 38.21 mm, and lymph nodes by 13.94 mm (p < 0.05). The complete clinical response (CR) increased from 6.48% to 19.44% between four and eight cycles. The pathological complete response (pCR) rate was 28.70%, with a residual disease (RD) rate of 71.29%.

At the 4-cycle evaluation, 7 out of 108 patients (6.48%) achieved a complete clinical response, which increased to 21 out of 108 patients (19.44%) by the 8-cycle evaluation. The number of patients with stable or progressive disease decreased from 3 out of 108 (2.78%) to 1 out of 108 (0.93%) cases and 2 out of 108 (1.85%), respectively. The overall response rate improved from 102 out of 108 patients (94.44%) after four cycles to 105 out of 108 patients (97.22%) after eight cycles.

Classification by Chevallier: the rate of pathological complete response (pCR) was 29.63% (32/108), and 6.48% showed a near-complete response. Partial responses were observed in 52.77% of patients, and 11.11% showed no response. Each bar shows the distribution of grades (CR, near CR, PR, No Response) across different cancer subtypes (Luminal A, Luminal B/HER2(-), Luminal B/HER2(+), HER2(+), and TNBC). Both the percentage and actual counts are displayed on the bars.

ypTNM Staging: This chart shows the distribution of TNM stages (0, IA, IIA, IIB, IIIA, IIIB, IIIC) for the same cancer subtypes, with both percentages and counts provided.

Figure 1

Figure 2

Most adverse effects were mild to moderate, including fatigue (81.48%) and hair loss (88.89%). Hematologic toxicity included mild anemia (16.67%) and neutropenia (38.89%). Mild liver function abnormalities were observed in 33.33-38.89% of patients, and 1.85% experienced Grade II cardiac toxicity.

Table 5

Adverse Effect	n = 108	Ratio (%)
Haematological
Mild Anemia (Hb 100-80g/dL)	18	16.67
Severe Anemia (Hb <80g/dL)	2	1.85
Leukopenia	28	25.93
Neutropenia	42	38.89
Liver Function
Mild GOT Elevation	36	33.33
Mild GPT Elevation	42	38.89
Renal Function
Increased Creatinine	2	1.85
Increased Ure	2	1.85
Other Adverse Effect
Nausea and Vomiting	49	45.37
Fatigue	88	81.48
Hair Loss	96	88.89
Cardiac Toxicity	2	1.85

The average age of our study population was 45.16 ± 9.98 years (median 45 years, range 29 – 66), with only 33.3% over the age of 50. This is consistent with the findings of Le T.D. et al. (2023)5, but the average age in our study is lower than that reported in more recent studies by Nguyen T.P.T. (2021) and Nguyen T.M.P. (2022), which involved high-dose 4AC-4T regimens11, 12. Despite these differences, the age distribution in our study aligns with global data, showing peak breast cancer incidence in women aged 40–50 in Southeast Asia1.

In terms of tumor staging, the majority of our patients had T4 tumors (53.70%) and significant nodal involvement, particularly N2 (70.37%). This high rate of advanced tumors reflects the trend in Viet Nam13, where patients are often diagnosed at later stages. This trend is also observed in Southeast Asia, with studies from Thailand and Malaysia similarly reporting high rates of T3 and T4 tumors at diagnosis. Additionally, 15% of patients had N3 nodal metastasis, consistent with global patterns of advanced breast cancer where nodal involvement is common14, 15.

In terms of histopathological characteristics, the majority of tumors in our study (90.74%) were invasive ductal carcinoma of no special type (NST), with Grade II accounting for 48.15%. This result is higher than the 70–80% typically reported by the World Health Organization (WHO)16. It also exceeds the findings of Le T. Duc et al. (2023), where NST accounted for 76.1% of 126 stage III breast cancer patients treated at a hospital between 2009 - 20125. However, it is lower than more recent reports, such as those by Nguyen T.P.T. (2021) and Nguyen T.M.P. (2022), where NST accounted for 96.7% and 95.4%, respectively11, 12. Phung T.H. (2021) even reported a rate of 100% (17). These findings suggest that NST is the predominant subtype in most stage III breast cancers.

The effectiveness of NAC in tumor downstaging is well-established (Figure 1), and our study reinforces these findings. The overall clinical response rate was 94.44% after four cycles and 97.22% after eight. These rates are consistent with other regional studies, such as one conducted at the 108 Military Central Hospital in Viet Nam, which reported a similar clinical response rate of 97.7%12. The slight increase in response after eight cycles suggests that extending chemotherapy regimens may further benefit tumor reduction. The reduction in tumor size and lymph node size, measuring 38.1 mm and 13.94 mm, respectively, after eight treatment cycles, demonstrates the response efficacy of the 4AC-4T regimen. These findings align with those from studies in China, which reported similar reductions in tumor size following dose-dense NAC17, 18.

The pathological complete response (pCR) rate in our study was 29.63%, consistent with other studies of dose-dense NAC regimens. For example, Nguyen T.M.P. (2022) reported a pCR rate of 31.8% at the same institution. Globally, pCR rates typically range from 20% to 30% for patients treated with anthracycline- and taxane-based NAC regimens. In our study, 71.29% of patients had residual disease (RD), including both local and regional RD, which aligns with similar studies in the region reporting RD rates of 65–70% after NAC. Although achieving pCR is considered a favorable prognostic factor, the presence of RD does not necessarily indicate poor outcomes, as some patients with RD can still achieve long-term disease control with appropriate adjuvant therapies19.

Using the St. Gallen consensus for molecular classification, Luminal B was the most common subtype (53.70%), followed by HER2-positive (42.59%) and triple-negative breast cancer (TNBC) (18.52%). The pCR rate for HER2-positive tumors (42.59%) aligns with previous studies showing high pCR rates in HER2-positive breast cancer treated with trastuzumab-based regimens. In contrast, the lower pCR rate in the TNBC group (18.52%) highlights the aggressive nature of these tumors and their relatively poor response to conventional chemotherapy compared to HER2-positive and Luminal B subtypes. These findings underscore the need for tailored treatment strategies, particularly for TNBC, which remains a significant clinical challenge. Our findings are consistent with other studies in the Asia-Pacific region. For instance, a study in Malaysia reported a similar pCR rate of 25% for patients treated with NAC for stage III breast cancer20. In comparison, a multicenter study in Japan found a slightly higher pCR rate of 35%, potentially reflecting differences in infrastructure, earlier access to treatment, and genetic variations in tumor biology21. The clinical response rates observed in our study are also comparable to those reported in China, where a large follow-up study found high response rates with dose-dense NAC regimens. However, variations in treatment protocols, such as the addition of targeted therapies like pertuzumab for HER2-positive cases, may explain the differences in pCR rates between countries in the region22.

The side effects observed during treatment were mostly mild to moderate (Grade I-II), with the most common being fatigue (88/108 patients), hair loss (96/108), and digestive disturbances (24/108). Notably, two patients (1.85%) experienced Grade II cardiac toxicity, but this did not necessitate changes in treatment. The overall side effect profile is consistent with other studies of dose-dense NAC regimens, emphasizing the manageable nature of these side effects when properly monitored.

Our study provides important insights into the response of stage III breast cancer to NAC in Vietnamese patients, but several limitations remain. First, the sample size of 108 patients, while sufficient for analysis, may not be representative of the broader population. A multicenter study with a larger sample size would yield more comprehensive results. Second, as a cross-sectional study, we were unable to assess long-term survival data and recurrence rates. Future research should focus on these outcomes to better understand the long-term efficacy of NAC.