Staging examinations are crucial for patients with newly diagnosed breast cancer to assess prognosis and plan therapy accordingly. However, the incidence of metastasis at the initial diagnosis of EBC with a low-risk profile is low [14–16]. A systematic review of around 15,000 BC patients saw a median prevalence for distant metastases in stage I of 0.2% and stage II of 1.1% [16]. In the present study, we showed a similar result, with only 0.5% of asymptomatic, low-risk EBC (T1-2/N0) suffering distant metastases. Therefore, we can conclude that metastases are generally very rare in asymptomatic EBC. This aligns with previous studies and current guidelines, which suggest that staging diagnostics can be omitted in early stages of breast cancer [11, 12]. In 2012, it has already been recommended by the American Society of Clinical Oncology to avoid staging diagnostics for EBC in order to improve care while reducing costs in healthcare [17]. However, this does not appear to be adopted in clinical practice everywhere [18]. Reasons might be that patients frequently request staging scans and view them as part of "standard care" [19]. Furthermore, there is uncertainty as there might be higher detection rates with new imaging modalities and benefits of staging in more aggressive phenotypes [19]. In the present study, we wanted therefore to investigate whether Ki67 is a suitable marker for the necessity of staging diagnostics in EBC.
In the present study, we were able to demonstrate that 0% of low-risk EBC patients with Ki67 < 25% and only 1.1% of low-risk EBC patients with Ki67 ≥ 25% suffered distant metastases at initial diagnosis. However, 324 different staging diagnostics were performed in total, leading to 29 additional imaging (in 15.3% of patients) due to suspicious findings. This is in line with an Australian study, also detecting a false positive rate of 15% after initial staging [20]. A Canadian study showed even higher rates of additional staging diagnostics (42%) due to suspicious findings in initial imaging with CT and bone scan in patients with T1-2 and N0-1 breast cancer [21].
Regarding staging diagnostics, previous studies already demonstrated certain limitations. A systematic review of 22 studies found relatively high sensitivity in conventional imaging, while specificity varied (sensitivity/specificity: bone scintigraphy 98.0%/93.5%; chest X-ray 100%/97.9%; liver ultrasound 100%/96.7%; and CT chest/abdomen 100%/93.1%) [16]. However, in a recently published prospective trial involving 410 breast cancer patients, bone scintigraphy showed a lower sensitivity (81.48%), while specificity was 99.09% [22]. In the present study, we observed a false positive rate of 4.2% in bone scintigraphy, which is similar to the results of Schneider et al. (false positive rate 4.3%) [23]. In our study, chest x-rays revealed only 0.5% suspicious finding, and 1.1% of patients required additional imaging due to suspicious upper abdominal sonography. Previously, both chest x-rays [24, 25], and upper abdominal sonography [26] showed diagnostic limitations. Therefore, they have increasingly been replaced by CT scans of the chest and abdomen in recent years. However, CT scans have also shown a 15% false positive rate [27], with no demonstrated change in disease-free survival (DFS) using this staging method [28]. In the present study, 8 patients (7.8%) with Ki67 < 25% and 9 patients (10.3%) with Ki67 ≥ 25% needed additional imaging or follow-up. Regarding other imaging modalities, benefits of PET-CTs in the context of staging diagnostics for breast cancer were demonstrated in recent years [29–31]. Yet, the routine use of PET-CT is currently not recommended in national and international guidelines, as false negative results can occur, especially with slowly growing metastases or those smaller than 1cm [11, 12]. In the present study, only 3 patients performed PET-CT as initial staging diagnostics and all results were normal.
In conclusion we demonstrated that distant metastases are very rare in asymptomatic, low-risk EBC (T1/2, N0). This is in line with previously published studies [14–16]. In the present study, we revealed that with a Ki67 level below 25%, the likelihood of metastases in low-risk early breast cancer (EBC) is 0%. Consequently, staging tests are unnecessary in these cases. If staging diagnostics are still carried out, this may only lead to unnecessary radiation exposure for the patient during the initial staging diagnostics [32]. Furthermore, it may require additional follow-up diagnostics or histological clarifications due to the high incidence of false positive findings [7]. The psychological stress on patients with a new diagnosis of breast cancer is also significant. Anxiety, depression, uncertainty, and confusion often arise, particularly during the waiting period for test results [33]. Moreover, costs of nonindicated staging (depending on the performed diagnostics) are around $6000 per patient [34]. Additionally, it should be noted that staging tests can delay the initiation of treatment as they require more appointments [35]. The excessive number of unnecessary tests wastes resources that could be better utilized for patients who truly need them.
Limitations of this study are mainly due to the retrospective character. The need for further check-ups and follow-up diagnostics may depend on the respective diagnostician or institutional guidelines. Since this is an analysis of a single institution, no comparison was possible. However, the need for additional staging diagnostics due to false positive results was comparable to the data available in the literature [23, 27].