In the 17th International Consensus Conference on the Treatment of Patients with Early Breast Cancer in St. Gallen (SG-BCC) in 2021, some experts recommended that adjuvant chemotherapy is required for ≥ 5 mm lymph node negative TNBC [5]. 2022 NCCN guidelines, adjuvant chemotherapy is not recommended for patients with < 5 mm lymph node negative TNBC, but may be considered for patients with high-risk features (e.g., young, high-grade grade, etc.) [7]. chemotherapy [7]. Interestingly, however, one study found that cT1a/b lymph node negative TNBC is also potentially aggressive, with a significantly increased risk of local recurrence and breast cancer-related events compared to luminal A subtypes [13].2021 A study that included 6953 TNBC patients to assess the prognosis of T1a TNBC and the impact of tumor size on T1 TNBC survival T1a TNBC was found to have the worst prognosis among all small tumors (< 1 cm) of TNBC compared to other molecularly typed small tumors [14]. In addition, several studies have reported the aggressiveness of small TNBC tumors [13, 15] and the need for enhanced disease control through chemotherapy [16, 17]. This raises concerns as to whether omitting adjuvant chemotherapy may lead to undertreatment of T1a TNBC. Given the exclusion of small tumors from most clinical trials, T1a TNBC provides limited data and knowledge of its biological behavior remains inadequate. Therefore, in our study, 6482 female patients with T1N0M0 TNBC were included, with the primary aim of assessing whether chemotherapy is beneficial stratified by tumor size and age.
3.1 Benefit of chemotherapy in patients with T1micN0 TNBC
In this study, adjuvant chemotherapy was found to improve survival in the overall population of T1N0M0 TNBC patients, but chemotherapy in T1mic patients did not improve OS (p = 0.95), but decreased BCSS (p = 0.026). Of the 16 patients receiving chemotherapy in this study T1mic, 13 were WHOIII/IV,2 were WHOII.In breast cancer, histologic grade is considered an important risk factor for clinical prognostic outcome in breast cancer.Regardless of tumor size, hormone receptor status or lymph node metastasis status, higher histologic grade is associated with shorter survival and early recurrence [18]. The results of a 2015 study found that histologic grade was an independent risk factor predicting the use of chemotherapy in < 1 cm lymph node negative breast cancer [19].NCCN guidelines do not recommend chemotherapy for patients with < 5 mm lymph node negative TNBC, but adjuvant chemotherapy may be considered for those with higher histologic grade [7]. In a prospective study that included 375 patients with ≤ 1 cm (including T1mic) lymph node-negative early breast cancer, a good prognosis was found for T1mic lymph node-negative breast cancer with a 5-year recurrence-free survival rate of 94.7%, including 22 (18.6%) cases of triple-negative breast cancer, with only one patient (who did not receive chemotherapy) experiencing recurrence [20]. Previous studies have found a lower risk of recurrence and death for patients with breast cancer < 1 mm [21]. The T1mic patients in the present findings did not benefit from chemotherapy, again demonstrating that even T1mic TNBC with high histological grading do not benefit from chemotherapy.
3.2 Benefit of chemotherapy in T1aN0 TNBC patients
Recent guidelines have shown inconsistent opinions on whether to treat T1aN0 TNBC with chemotherapy. The American Society of Clinical Oncology guidelines (ASCO) [4], the St. Gallen International Expert Consensus [5] and the ESMO guidelines [6] recommend that chemotherapy is not recommended, and the 2022 NCCN guidelines do not recommend adjuvant chemotherapy, although it may be considered for those with high-risk features. For < 1 cm lymph node negative TNBC with good prognosis, chemotherapy may be considered to be omitted. Fewer randomized clinical trials have been conducted comparing adjuvant chemotherapy to unadjuvant chemotherapy for T1aN0 TNBC. In a prospective cohort study, 5-year distant recurrence-free survival rates were found to be 100% and 93% (95% CI, 84–97%) for patients with T1aN0 TNBC treated with versus without chemotherapy, respectively [8]. In another study, the benefit of adjuvant chemotherapy was not observed in pT1a patients, with 5-year RFS rates of 92.3% and 100% in pT1a TNBC patients receiving and not receiving chemotherapy, respectively (HR = 3.99, 95% CI, 0.005–317.5, p = 0.535) [9]. steenbruggen et al. examined 4366 patients with pT1N0M0 TNBC breast cancer patients in a retrospective study with a median follow-up of more than 8 years, adjuvant chemotherapy improved BCSS and OS in T1c patients and did not improve BCSS and OS in T1a and T1b patients [3]. a 2015 multicenter retrospective cohort study of 325 T1a patients with 27 T1aTNBC, which found that the T1aN0 subgroup receiving adjuvant systemic therapy significantly improved relapse-free survival and overall survival [17].Whether chemotherapy is required for T1aN0TNBC is controversial in current studies. The results of this study found that receiving chemotherapy significantly improved OS in T1aTNBC patients who received adjuvant chemotherapy compared to those who did not, which was not significant in BCSS.
3.3 Whether chemotherapy is beneficial in patients with T1bN0 TNBC
The 2022 NCCN guidelines and the St. Gallen expert consensus recommend adjuvant chemotherapy for T1b TNBC. According to a prospective cohort study in the NCCN database, women with pT1b TNBC who did not receive chemotherapy had a good prognosis, and among patients with pT1bN0 TNBC, the 5-year DRFS was 96% (95% CI, 90–98%) and 90% (95% CI, 81–95%) for those who received chemotherapy and those who did not receive chemotherapy, respectively[8]. In a retrospective study of 354 T1N0 TNBC patients by Ren et al. no survival benefit was found in T1b patients receiving adjuvant chemotherapy (HR = 0.32, 95% CI, 0.03–3.18, p = 0.330) [22]. In another study, the benefit of adjuvant chemotherapy was not observed in pT1b patients, with 5-year RFS of 91.4% and 90%, respectively (HR = 0.64, 95% CI, 0.05–7.74, p = 0.724) [9]. A recent retrospective study of 1849 patients based on the SEER database showed that BCSS was similar in T1bN0 TNBC patients receiving chemotherapy and those not receiving chemotherapy (96.1% vs 96.0%, p = 0.820) [23]. A meta-analysis was recently published in which adjuvant chemotherapy reduced the recurrence rate of T1mi/a/bN0 TNBC, especially T1bN0 [24]. Studies from the United States and the Netherlands have shown that adjuvant chemotherapy improves the prognosis of T1bN0 TNBC patients [3, 25]. The results of this study found that T1bN0 patients receiving chemotherapy were similar to BCSS without chemotherapy, but receiving chemotherapy improved OS. according to several recent guidelines and consensus recommendations for adjuvant chemotherapy in T1b TNBC, some patients may benefit from chemotherapy. Whether there are patients with T1b for whom chemotherapy is not recommended when age is taken into account will be described below.
3.4 Benefit of chemotherapy versus no chemotherapy in patients with T1N0 TNBC of different ages
According to previous reports, the proportion of older patients receiving chemotherapy is much lower than younger patients, which may affect the prognosis of older people, especially in triple-negative breast cancer [26, 27]. Compared to younger patients, older TNBC are thought to have more inert tumor behavior but a higher risk of disease-specific mortality [12]. Not all elderly breast cancer patients are eligible for surgery, chemotherapy and radiotherapy. To date, chemotherapy is the only systemic treatment with long-term efficacy in patients with TNBC [28]. There are relatively few clinical trial data on chemotherapy in the elderly population. Because chemotherapy is considered a double-edged sword in elderly TNBC due to its unique antitumor effects and high incidence of side effects, it has become increasingly important to understand how to best administer chemotherapy in elderly TNBC. Although most of the literature confirms that chemotherapy improves survival in elderly TNBC, it mainly lies in individuals with a high risk of recurrence [29, 30]. There is no clear-cut certain age threshold for TNBC that does not require chemotherapy. Previously published studies suggest that older breast cancer patients have a disproportionate mortality rate and that chemotherapy is less commonly used compared to younger individuals [28]. A recently published retrospective study that included 4696 elderly TNBC patients found that receiving chemotherapy in patients with stage I TNBC did not improve BCSS and OS [31].Syed et al. evaluated the use and survival benefit of chemotherapy for stage I-II breast cancer between 1973 and 2010 in ≥ 70 and < 70 years of age, with the proportion of < 70 and ≥ 70 years receiving chemotherapy The proportion of < 70 and ≥ 70 year olds receiving chemotherapy was 47% and 0%, respectively. Overall outcomes were found to be poor in both groups, with 5-year BCSS of 73% and 79% for patients < 70 and ≥ 70 years of age, respectively (p = 0.39) [32].2021 A systematic evaluation that included 2037 TNBC patients treated between 1973 and 2014 found that women ≥ 70 years of age were less likely to undergo surgical resection compared to women < 70 years of age ( 92.8% vs 94.6%, p = 0.002). Women older than 70 years were also less likely to use adjuvant therapy, including radiotherapy and chemotherapy [33]. For some older adults receiving chemotherapy did not improve survival, but rather increased drug toxicity and decreased quality of life. Most studies do not recommend chemotherapy for T1a patients, and chemotherapy for T1a patients ≥ 65 years of age in this study did not improve survival. It was also found that the proportion of patients receiving chemotherapy decreased with increasing age. Patients ≥ 75 years of age T1b who received chemotherapy did not improve survival. This study found a significant survival benefit for patients with T1c breast cancer who received chemotherapy, with the highest proportion of patients with T1c breast cancer receiving chemotherapy (77%), but patients > 80 years of age with T1c did not benefit from receiving chemotherapy. For older TNBC patients, a more conservative and prudent treatment plan should be adopted when choosing postoperative adjuvant therapy (radiotherapy, chemotherapy, or a combination of both), taking into account the patient's physical condition and comorbidities. Further research on the potential biological heterogeneity of older TNBC is needed to develop individualized chemotherapy regimens for older TNBC that are not limited by complications and to improve the prognosis and quality of life of older TNBC patients.
The present study has some advantages and limitations. One advantage is that we enrolled only T1N0M0 TNBC patients, whereas most previous studies evaluated the treatment of overall breast cancer patients, and T1N0M0 TNBC was only analyzed as a subgroup. Another advantage is that this study investigated the prognosis of patients with different cancer stages and ages according to consensus guidelines. Third, despite the low incidence of early TNBC, the study had an increased amount of data compared with other studies. However, this study also has some limitations, although we adjusted for multiple confounders, we were unable to assess whether Ki67 has an impact on chemotherapy in the elderly because the required data were not available in the SEER database.