TNBC remains a challenge in breast cancer care for clinical oncologists. Although evidence-based guidelines are known to be beneficial in the TNBC subtype , to our knowledge, very few investigations have studied the influence of age on the prognosis of TNBC . Furthermore, the efficacy of breast cancer guidelines in elderly TNBC patients has explicitly been investigated to date and has only been investigated in non-TNBC patients [16, 17].
In the present study, we observed significantly inferior survival parameters in the TNBC cohort and in the different age groups of this cohort. The TNBC ≥65 subgroup demonstrated the worst survival. Guideline violations occurred significantly more often in the TNBC subgroups, particularly in the TNBC ≥65 subgroup. However, when comparing only those TNBC patients who were treated according to the guidelines, we found no significant differences in OAS or DFS between the age groups, indicating that guideline adherence is associated with improved survival parameters in primary TNBC patients overall different age groups. Conversely, the patients who did not undergo strict guideline-adherent treatment had a significant impairment in survival parameters, except for the 50–64 TNBC age group. Significantly higher rates of guideline violations concerning adjuvant chemotherapy could be observed in TNBC and it is, therefore, likely that these are the most important reasons for the inferior survival. Hence, it is most likely that the higher rates of chemotherapy guideline violations in the ≥65 TNBC patients contributed to their inferior survival [14, 15].
There are several other factors, such as higher rates of comorbidities, that could explain the inferior survival in the ≥65 age group. Indeed, there is a clear association between comorbidities and guideline adherence. Our study is an observational study, and confounding factors may have influenced both the treatment options (or guideline conformity) and survival. We observed a high percentage of non-guideline-adherent adjuvant treatment (51.1%) in the 50–64 TNBC subgroup, which was between the percentages of guideline-non-adherent therapy for the other age groups (42.0% for the <50 and 74.6% for ≥65 subgroups). In addition to the higher rates of comorbidities, the factors that might explain this result are the relatively low rates of G3 tumors (68.6%) in the 50–64 TNBC subgroup, the fact that 86.5% of the 50–64 TNBC subgroup received some type of chemotherapy (not all guideline-adherent, see Table 2), and the fact that 61.7% of the 50–64 TNBC subgroup were node negative. In summary, the 50–64 TNBC subgroup demonstrated a relatively low risk profile (a low rate of G3 and a high rate of node-negative patients) compared to the other TNBC subgroups, and 86.5% of these patients received any type of adjuvant chemotherapy; however, those chemotherapies were not all guideline-conforming therapies. Clearly, these circumstances lower the effects of guideline-adherent adjuvant treatment, leading to non-significant improvement in survival parameters.
Only a few clinical research studies have investigated the impact of guideline-adherent therapeutic regimens on clinical outcomes [17–19]. These studies have confirmed that there appears to be a strong association between guideline-adherent treatment and improved survival, particularly for several subtypes of breast cancer [20–23]. Although both patient-related and physician-related factors can preclude guideline-adherent treatment, comorbidities are probably among the most important of these factors [24, 25]. Indeed, comorbidities are one of the most important reasons why elderly breast cancer patients are not able to follow strict guideline-adherent therapy pathways, which is one of the reasons explaining their unfavorable outcome. Unfortunately, the present study cannot completely corroborate the significance of comorbidities for guideline adherence, as only NYHA and ASA scores were recorded. It is therefore necessary to address this issue in a prospective trial, which reduces confounding factors and allows measurement of comorbidities in a validated scoring system. Another point to consider is that some patients are not willing to follow strict adjuvant treatment pathways, and this factor was not recorded in this study either. In this specific cohort, all of the patients are treated in specialized and certified interdisciplinary breast cancer centers for which an interdisciplinary tumor board, for example, is a requirement for certification by the German Cancer Society. Several other factors influence guideline adherence in breast cancer, such as education, access to medical resources, health care services themselves, and an urban vs. rural location . Hence, in the current retrospective study, there are confounding factors affecting both the treatment and outcome parameters. To reduce the effects of these potentially confounding factors, we controlled our analyses for the most important prognostic factors (i.e., age, affected lymph nodes, grading, hormone receptor status, menopause status, year of diagnosis, treatment in a university hospital, tumor size, and comorbidity) and included a shared frailty term in our survival regressions.
An important methodological difficulty of the present study is the retrospective nature of data collection. It is, therefore, only possible to draw associations between guideline-adherent treatment and favorable outcome parameters. Drawing valid causal conclusions concerning survival parameters would only be appropriate if treatment allocations were randomized and prospective. However, randomization concerning guideline-adherent treatment is not viable because we cannot assign guideline-adherent and non-guideline-adherent therapeutic regimens at random to patients.