The characteristics of BC in the older patients have been often reported. For example, large tumor size [13, 28–30], frequent skin infiltration [29, 31], infrequent lymph node metastasis [28, 30], high rate of HR positivity [13, 28], and fewer HER2-positive tumors [28–30] have been reported in older patients. The clinicopathological characteristics of older BC patients in our study shows strong correlation to the decision of administering POC or not, though some features similar to those reported by others were identified.
While age-related differences in pCR rates have not been reported in several clinical trials, a pooled analysis observed high pCR rate in younger BC patients . Moreover, reports suggest that the pCR rate decreased with age [10, 13]. Analysis of BC based on subtype in these studies suggested a strong correlation between HR+HER2- and TNBC, whereas no significant difference with age in HER2-positive BC, which differed in our study, and the exact reason remains to be identified. Further, there are various molecular subtypes of TNBC, and their age at onset and pCR rates have been observed to differ across studies [32–34]. We anticipate that our analysis may have been affected by differences in molecular subtypes of TNBC, or due to differences in the chemotherapy regimen. Furthermore, reports suggest that the expression of androgen receptor (AR) increases with age in BC patients [35–37], and that the AR-positive cases show low pCR rate than the AR-negative cases . Additionally, newer biomarkers may also affect these outcomes.
Moreover, von Waldenfels et al. have reported that prognosis worsens with age in BC patients . However, their study observed significant differences in prognoses between patients aged ≥65 years and those aged 40-50 or 51-65 years, but no significant difference between patients aged ≥65 years and those aged <40 years. Furthermore, studies reporting higher pCR rate in younger patients did not observe a significant difference in prognosis in TNBC . In contrast, studies reported more than 10 years back suggest poor prognosis [39–41], and aggressive cellular properties in the younger BC patients [39, 42–44]. AR expression also affects prognosis and may contribute . Additionally, with advent of newer biological treatments, the number of clinical trials claiming prognosis to differ with age have decreased.
Here, when we studied TILs at all ages, we observed correlation between TILs and clinicopathological factors, treatment effects, and prognosis similar to those reported previously. Moreover, our analysis suggests that younger BC patients had significantly higher TILs density than older BC patients. Additionally, age-related ORR and pCR rates differed in HER2-positive BC. Moreover, a pooled analysis for TNBC alone reported that the older patients had significantly lower TILs than in younger patients . This result can be attributed to the decrease in host immunity due to aging, and to the inherent cellular characteristics of BC that vary with age.
However, this study has a limitation that the criteria for dividing patients into younger and older patients was not well-defined, and that the clinicopathological factors, other than TILs density, differed with age. However, the change in TME with age suggests that it may have influenced the therapeutic effect due to the characteristics of the host's immune system, and the differences in cancer itself depending on the age. Additionally, in lung cancer, it has been reported that the therapeutic effect of the immune checkpoint inhibitors (ICIs) decreases in the older patients [46–48]. Therefore, age may also serve as an important clinical factor in deciding the course of treatment of BC patients with ICIs.