INTRODUCTION

Breast cancer (BC) is a public health problem and is the current leading cause of cancer-related death among women worldwide ¹. Triple-negative breast cancer (TNBC) is frequently associated with early relapse, which leads to an increased risk of developing distant metastases and death compared to other subtypes ^2,3,4.

TNBC is defined by its lack of expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 receptor (HER2) and accounts for approximately 15%-20% of all BC cases ⁵. However, Latin American studies usually report higher percentages of new TNBC cases. In Peru and Colombia, TNBC prevalence rates are 21.3% and 20.6%, respectively ^6,7.

Despite pathologic tumor features (large tumor size, lymph node involvement, and advanced stages) having a clear association with worse survival outcomes ^8,9, early detection of TNBC remains a challenge in developing countries. A Peruvian study stated that only 7.2% of TNBC cases diagnosed between 2000 and 2014 were classified as stage I ¹⁰.

Adjuvant chemotherapy is currently the only systemic treatment available for early-stage TNBC patients ¹¹. However, there is uncertainty around selecting TNBC T1N0M0 patients who would benefit from it to avoid overtreatment. Studies have shown contradictory results regarding this topic. For example, Yi Xing Ren et al. suggested that adjuvant chemotherapy improves recurrence-free survival (RFS) in T1cN0M0 TNBC patients but not in T1b ¹². On the other hand, a meta-analysis demonstrated the survival benefit of adjuvant chemotherapy for patients with pT1bN0 and pT1cN0 TNBC ¹³. Therefore, there is a need to investigate the role of adjuvant chemotherapy in that population profile to provide clarity and improve the quality of life during treatment.

Thus, this study aims to evaluate the effect of adjuvant chemotherapy on overall survival (OS) and progression-free survival (PFS) among pT1N0M0 TNBC subgroups (pT1a/b vs. pT1c)

MATERIALS AND METHODS

RESULTS

DISCUSSION

Our study aimed to determine the benefits of adjuvant chemotherapy among TNBC patients with early-stage tumors from residual disease (pT1N0M0).

It is well-known adjuvant chemotherapy is the only approved treatment for early-stage TNBC patients and is recommended even for those with small and lymph node-negative tumors according to the 2023 European Society for Medical Oncology (ESMO) Clinical Practice Guideline (CPG) ¹⁶. It explains why more than half of our population received chemotherapy as a systematic treatment. This trend is also evident among pT1N0M0 TNBC patients from China, reaching 88.0% ¹³.

However, evidence suggests an unclear benefit of adjuvant chemotherapy in T1N0M0 subgroups. Our analysis indicated an improvement in PFS because of treatment only among pT1cN0M0. pT1a/bN0M0 TNBC patients with adjuvant chemotherapy did not experience a better outcome, neither OS nor PFS, compared to those who did not were treated. Similarly, Yi Xing Ren et al. demonstrated a significant RFS benefit in T1cN0M0 TNBC patients receiving adjuvant chemotherapy (HR: 0.24,95% CI:0.08-0.76, p=0.014). However, this effect was not observed in the T1b subgroup (HR=0.32, 95% CI: 0.03-3.18, p=0.330) ¹⁷. Moreover, differences were not found between patients with T1mic/T1a TNBC tumors and patients with T1b tumors in the distant recurrence rate in the receipt of chemotherapy (95.9% vs 94.5%, respectively, p=0.63)¹⁸.

On the contrary, the impact of chemotherapy on OS and breast cancer-specific survival (BCSS) was illustrated by Carbajal-Ochoa et al., who showed that adjuvant chemotherapy improved OS in T1b TNBC (HR:0.52, 95% CI:0.41-0.68, p<0.001) but did not significantly affect BCSS (HR:0.70, 95% CI: 0.45-1.07, p=0.10). In T1c, TNBC patients also reported an improvement in both OS (HR: 0.54, 95% CI: 0.47-0.62, p<0.001) and BCSS (HR: 0.79, 95% CI: 0.63-0.99, p=0.043) ¹⁹. Despite these benefits, the application of chemotherapy in T1a tumors was questioned by Bravo-Solarte et al., who observed no improvement in OS or BCSS post-chemotherapy in this subgroup ²⁰.

Our study is limited by its retrospective nature that led us to grouped T1a/b due to the few cases available. An et al., in their meta-analysis, demonstrated that adjuvant chemotherapy significantly reduced the rate of disease recurrence for patients with T1a/b disease as a group. Still, the population driving that was only patients with T1b disease, not those with T1a disease ¹³.

Another limitation was the lack of information on tumor-infiltrating lymphocytes (TILs) in clinical records of patients, which is the main reason this variable was not considered in our study. TILs have been identified as a prognostic biomarker in TNBC patients treated with adjuvant chemotherapy ²¹. A retrospective study that included 182 systemically untreated TNBC patients found a subgroup of patients with ≥ 50% TILs had a decrease in invasive disease-free survival (iDFS) rates ²². Park et al. also showed early TNBC patients with ≥ 30% TILs had excellent survival outcomes in the absence of adjuvant chemotherapy. Each 10% increment in TILs reduced the risk of iDFS, distant disease-free survival (D-DFS) and OS in 10% (95% CI, 0.82 to 0.97), 14% (95% CI, 0.77 to 0.95) and 12% (95% CI, 0.79 to 0.98), respectively ²³. In this sense, omitting TILs data could has limited our study since TILs play a promising role in predicting patient outcomes and guiding treatment decisions in early TNBC.

Figure 1: Overall survival analysis according to the use of adjuvant chemotherapy (A) Overall (B) Stratified by pT1a/b and pT1c. 

Figure 2: Progression- Free survival analysis according to the use of adjuvant chemotherapy (A) Overall (B) Stratified by pT1a/b and pT1c. 

CONCLUSION

In conclusion, while adjuvant chemotherapy evidently improves outcomes in certain subgroups of TNBC patients, particularly those with T1cN0M0 disease, its application in smaller T1a/b tumors requires careful consideration. Current consensus guidelines recommend chemotherapy in T1b TNBC patients, reflecting a cautious approach towards a subgroup where the evidence of benefit is mixed. Effectiveness of chemotherapy across different tumor sizes within the T1N0M0 category highlights the need for personalized treatment strategies and the identification of biomarkers that could predict response to therapy. Future research should aim to refine these strategies, such as including TILs data, ensuring patients receive the most appropriate and effective care tailored to their risk profile.