To the best of our knowledge, this extensive retrospective cohort study of patients with HER-2-positive breast cancer after trastuzumab treatment is the first to demonstrate a significant association between PTV and a 3% decrease in OS. Consistent patterns of association between PTV and OS were also observed in subsequent subgroup analyses.
Breast cancer comprises three primary tumor subtypes that are categorized based on ER or PR expression and ERBB2 gene amplification. These subtypes exhibit distinct risk profiles and require various therapeutic approaches. Tailoring the optimal treatment for individual patients involves consideration of the tumor subtype, cancer anatomical stage, and patient preferences [6]. Indeed, the prognostic landscape of breast cancer has transitioned into an era of molecular prediction, particularly notable in HER-2-positive breast cancer, where targeted therapy offers promising survival outcomes. However, the trajectory of tumor management is evolving towards personalized treatment, emphasizing the necessity of investigating pertinent risk factors within the respective populations. Particularly in the era of targeted therapy, emphasis should be placed on both pathological features and patients' baseline conditions, encompassing psychological well-being, nutritional status, social support, and intrinsic tumor characteristics, such as tumor volume, ER/PR status, degree of pathological differentiation, and Ki-67 expression. In the present study, we conducted a survival analysis of patients with HER-2-positive breast cancer following adjuvant trastuzumab therapy, which revealed a correlation between PTV and OS.
To the best of our knowledge, few studies have reported an association between PTV and survival outcomes in patients with cancer, and only sporadic reports have shown that PTV is significantly associated with patient survival in certain head and neck tumor cohorts [7]. Flukes et al. noted that quantifying the tumor volume could help predict the risk of distant metastasis and mortality in sinonasal mucosal melanoma [8]. Lin et al. found that in patients treated with definitive radiotherapy for esophageal squamous cell carcinoma, a larger PTV was associated with poorer local control and OS [9]. Wald et al. observed that relative increases in tumor volume during treatment were associated with improved disease control and OS rates in patients with locally advanced non-small cell lung cancer [10]. Malik et al. reported that increased tumor size in cT3 acoustic neuroma was associated with poorer OS and disease-free survival [11]. However, the relationship between PTV and survival outcomes has not been extensively explored in studies on breast cancer.
These previous studies have consistently demonstrated an association between PTV and survival outcomes in selected tumor cohorts, suggesting that PTV may correlate with certain biological tumor characteristics, thereby contributing to differences in survival across specific patient populations. In the current study, we performed survival analysis investigating the relationship between PTV and OS as well as RFS. Our results, across both the dichotomized (two subgroups based on the optimal cutoff value of PTV, 17 mm) and quartile-based (four subgroups) PTV analyses, showed a significant inverse correlation - larger PTV was associated with poorer OS and RFS in patients with HER-2-positive breast cancer after treatment with trastuzumab. Olfatbakhsh et al. reported that tumor size and lymph node involvement, as indicators of delayed diagnosis, may affect the survival of patients with breast cancer; however, there is insufficient evidence for these being independent risk factors [12].
In addition, in the multifactorial analysis, corrected PTV and age had a significant effect on OS, whereas in the analysis of RFS, only PTV had an independent effect, which seems to be in line with the phenomenon observed in clinical practice and with the logic of its relevance, as age may affect OS but not RFS. The results of the subgroup analysis also supported these findings.
These findings suggest that PTV may serve as a risk factor for OS in patients with HER-2-positive breast cancer after trastuzumab treatment and could be a relevant biomarker. Further studies are warranted to elucidate the relationship between the PTV and OS in patients with HER-2-positive breast cancer after trastuzumab treatment.
The current study has some limitations. The database used in this study was not sufficiently variable, although it included several variables that have a greater impact on survival. Further, the specific treatment regimen was not detailed enough, and the personal history of the patients was not included as a variable. In addition, the missing data on covariates may have had an impact. Owing to the longer survival time associated with HER-2-positive breast cancer, fewer deaths occurred in the patient population. Although sufficient follow-up was conducted, longer observation is needed. Finally, future prospective studies are needed and more reliable variables should be evaluated to further substantiate the results of the current study.