Breast cancer is the most commonly diagnosed cancer worldwide, and human epidermal growth factor receptor 2 (HER2)-positive breast cancer constitutes about 15–20% of all breast cancers and is typically associated with aggressive behavior and poor prognosis, making targeted therapy a cornerstone of its treatment [1–3]. Trastuzumab, a HER2 monoclonal antibody used in HER2-targeted therapy, improves outcomes for patients with HER2-positive breast cancer and is administered either after chemotherapy or in combination with chemotherapy following surgery [4–7].

However, the role of adjuvant chemotherapy and anti-HER2 targeted therapy in early HER2-positive breast cancer with T1a or T1b N0 tumors remains unclear. The National Comprehensive Cancer Network guidelines recommend considering adjuvant chemotherapy and trastuzumab for T1a/b N0 HER2-positive breast cancer [8]. However, these recommendations are primarily based on non-randomized retrospective studies, and randomized clinical trials or level 1 evidence supporting this approach is lacking. The adjuvant paclitaxel and trastuzumab (APT) regimen has demonstrated excellent disease-free survival (DFS) outcomes and has become the standard adjuvant treatment for patients with small node-negative HER2-positive breast cancer [9]. However, the evidence comes from a single-arm trial without randomized controlled data, and information on patients who did not receive anti-HER2 therapy remains scarce and outdated. Several retrospective studies have investigated the impact of adjuvant chemotherapy and anti-HER2 therapy in patients with T1a/T1b N0 HER2-positive breast cancer; however, the results remain controversial [7,10–12], highlighting the lack of clear evidence regarding the necessity and efficacy of adjuvant chemotherapy and anti-HER2 targeted therapy in T1a/T1b N0 HER2-positive early breast cancer. Therefore, further studies are needed to reevaluate the role of adjuvant therapy and establish optimal treatment strategies. In Korea, trastuzumab is not reimbursed for tumors smaller than 1 cm, providing a unique real-world setting to evaluate the impact of anti-HER2 therapy for this patient population.

The efficacy of adjuvant chemotherapy and anti-HER2 therapy in patients with T1a or T1b N0 HER2-positive early breast cancer remains a subject of ongoing debate [7,10–12,19–21]. Several retrospective studies have reported poorer outcomes in patients with T1a/T1b N0 HER2-positive breast cancer who did not receive adjuvant therapy compared with other subtypes, with one study reporting a 5-year recurrence-free survival rate of 77.1% (95% CI, 67–85%) [22]. In contrast, recent studies have shown a lower risk of distant recurrence in untreated patients (2–7%), highlighting the controversy surrounding prognosis and the role of adjuvant therapy in this population [19,20]. Kolben et al. [21] reported favorable outcomes for node-negative tumors smaller than 1 cm, particularly for those under 0.5 cm, where adjuvant chemotherapy showed no benefit. Similarly, an Italian observational study involving 303 patients found no significant difference in 5-year survival rates between patients who received adjuvant chemotherapy alone and those who received adjuvant chemotherapy with trastuzumab (95% with trastuzumab vs. 94.3% without trastuzumab, adjusted p = 0.621) [10]. The majority of patients who received chemotherapy alone were hormone receptor-positive and received adjuvant endocrine therapy, suggesting that trastuzumab may be less essential in hormone receptor-positive breast cancer. Conversely, a prospective single-center cohort study by Yang and Qu [12] analyzed data from January 2017 to December 2019 and included 168 patients with T1a/T1b N0 HER2-positive breast cancer. Approximately 60.7% of patients received both chemotherapy and targeted therapy, 28% received chemotherapy alone, and 11.3% received no adjuvant treatment. The 3-year IDFS rates were significantly higher in patients who received chemotherapy or combined chemotherapy and targeted therapy compared with untreated patients (100% vs. 97.9% vs. 89.5%, p < 0.001), with low rates of cardiac complications reported [12]. Another retrospective study also demonstrated significantly improved DFS in patients treated with adjuvant chemotherapy and trastuzumab [7]. A Canadian prospective registry study involving 583 patients with T1ab N0 HER2-positive breast cancer reported a 3-year survival rate of 99.1% compared with 96.9% in an untreated control group of 13,296 patients (adjusted HR 0.59, 95% CI 0.29–1.20) [11]. However, adjuvant chemotherapy and trastuzumab were associated with increased risks of coronary artery disease and febrile neutropenia. A 2023 systematic review and meta-analysis that included these heterogeneous retrospective data suggested that adjuvant trastuzumab-containing therapy was associated with improved prognosis in patients with HER2-positive T1a/bN0 breast cancer, although the available evidence was limited by the non-randomized nature of the included studies and between-study heterogeneity [23].

Despite this uncertainty, adjuvant chemotherapy and anti-HER2 therapy are frequently used in clinical practice. In particular, the single-arm phase 2 APT trial established weekly paclitaxel plus 1 year of trastuzumab as a widely adopted de-escalated regimen for small, node-negative HER2-positive breast cancer. In the final 10-year analysis, the APT regimen showed durable long-term outcomes, with a 10-year IDFS of 91.3%, a 10-year recurrence-free interval of 96.3%, and a 10-year OS of 94.3%, supporting this regimen as a reasonable treatment standard in this setting. However, because APT was a single-arm study, it did not address whether less toxic or chemotherapy-sparing HER2-directed strategies could provide comparable efficacy [9,24].

In this context, the randomized phase 2 ATEMPT trial further expanded the de-escalation landscape by evaluating adjuvant T-DM1 versus paclitaxel plus trastuzumab in patients with stage I HER2-positive breast cancer. In the recently reported 5-year analysis, 1 year of adjuvant T-DM1 was associated with excellent outcomes, with a 5-year IDFS of 97.0%, a recurrence-free interval of 98.3%, and an OS of 97.8% [25]. Although ATEMPT was not powered for a formal efficacy comparison between the regimens, and the 5-year IDFS in the TH arm was also favorable at 91.1%, these data suggest that multiple de-escalated anti-HER2-containing approaches can achieve excellent long-term disease control in selected patients with stage I disease. Nevertheless, treatment selection in this population remains challenging because efficacy must be balanced against tolerability and overtreatment in a group with an overall low event rate. The ongoing ATEMPT 2.0 trial was designed to further refine the treatment strategy by comparing TH with a shorter course of T-DM1 followed by trastuzumab, with the aim of maintaining efficacy while reducing toxicity [26]. Taken together, these studies indicate that the future direction of adjuvant treatment for small, node-negative HER2-positive breast cancer lies not only in determining the population of patients to receive anti-HER2-containing therapy but also in identifying those who may benefit from less intensive, biologically tailored regimens.

This retrospective, single-center study evaluated the efficacy and safety of adjuvant chemotherapy and anti-HER2 therapy in patients with T1a or T1b N0 HER2-positive early breast cancer. Overall, patients who received chemotherapy plus anti-HER2 therapy showed the most favorable long-term IBCFS, although the differences among the treatment groups were not statistically significant. When stratified by tumor size, the apparent numerical benefit of anti-HER2-containing treatment was more evident in patients with T1a tumors. In this subgroup, the 15-year IBCFS rate was 79.8% in the no-treatment group, 57.5% in the chemotherapy-only group, and 100% in the chemotherapy plus anti-HER2 group. By contrast, patients with T1b tumors showed similarly favorable IBCFS outcomes across the treatment groups, suggesting that treatment effect may differ according to tumor size and underlying recurrence risk. The seemingly better prognosis of untreated T1b tumors compared with that of untreated T1a tumors should, however, be interpreted with caution. Because patients with T1b tumors were more likely to receive chemotherapy and anti-HER2 therapy, this paradoxical finding may reflect treatment-selection imbalance and the small number of events rather than a true biologic advantage of T1b disease. In this regard, our data may indirectly suggest that, in real-world practice, clinicians tended to select more intensive adjuvant treatment for T1b tumors perceived to be at higher risk.

Regarding IDFS, a similar numerical advantage of anti-HER2-containing treatment was observed overall; however, the subgroup patterns were less consistent than those for IBCFS and differed according to tumor size. Taken together, these findings suggest that anti-HER2-containing adjuvant treatment may be associated with favorable long-term outcomes in selected patients, but these observations should be interpreted cautiously given the small sample size and limited number of events.

From the perspective of OS, chemotherapy-containing treatment was associated with numerically favorable long-term outcomes compared with no adjuvant treatment, and patients who received chemotherapy showed significantly better OS than those who did not. However, anti-HER2 therapy was not associated with a statistically significant OS difference in this cohort. Given the small number of deaths and the non-randomized nature of treatment selection in this retrospective cohort, these OS findings should be interpreted cautiously.

With respect to safety, no significant differences in any-grade adverse events were observed between the chemotherapy-only and chemotherapy plus anti-HER2 groups. Likewise, no significant between-group differences were observed in any-grade anemia or febrile neutropenia, and no clinically documented heart failure or decline in left ventricular ejection fraction was identified among patients who received anti-HER2 therapy. Because trastuzumab-related cardiotoxicity is a well-recognized adverse effect, cardiac monitoring remains an important component of treatment in clinical practice [27]. However, the retrospective collection of adverse event data and the absence of grade-specific toxicity information limit definitive safety comparisons.

This study has some limitations. First, it was a retrospective study conducted at a single institution, which introduces the possibility of selection bias and limits the generalizability of the findings. Second, the sample size was relatively small, and the numbers of recurrence and death events were limited, reducing the statistical power to detect differences between treatment groups. Third, baseline clinicopathologic characteristics were not fully balanced across treatment groups, and treatment allocation was not randomized, which might have influenced both treatment selection and long-term outcomes. Fourth, adverse event data were retrospectively collected from medical records and were available primarily in the form of presence or absence of events rather than grade-specific toxicity, limiting detailed safety comparisons. Finally, biomarker information for recurrent lesions was available only in a limited number of cases, restricting a more comprehensive assessment of subtype changes at recurrence.

In conclusion, anti-HER2-containing adjuvant treatment was associated with numerically favorable long-term outcomes in this cohort of patients with HER2-positive T1a/bN0 breast cancer, particularly among those with T1a tumors. Because of the retrospective design, baseline imbalances between the treatment groups, and the limited number of events, these findings should be interpreted with caution. Further large-scale prospective studies are warranted to refine risk stratification and optimize adjuvant treatment strategies for patients with small, node-negative HER2-positive breast cancer.