Adjuvant Therapy‐Related Shortening of Survival (ATRESS): An Underrated Phenomenon

Shortening of survival after dissemination following adjuvant treatment is not understood well enough and is difficult to search for in public databases because of the lack of specific search terms. We suggest using the acronym ATRESS, for “adjuvant therapy-related shortening of survival,” in future literature concerning this issue.In their analysis of docetaxel-containing regimens in metastatic breast cancer, Seidman et al. [1] reported progression-free and overall survival that was one-third better in patients without prior adjuvant taxane treatment than in patients after adjuvant taxane therapy, and they cautiously discussed therapy-induced resistance against these agents. However, they described an important phenomenon: shortening of survival after dissemination following adjuvant treatment. The relevant literature unanimously describes a reduction in survival of ∼30% after dissemination in spite of adjuvant therapy and was recently reviewed by us [2]. In the largest study on this issue, Pierga et al. compared the findings from 446 breast cancer patients with and 984 patients without adjuvant chemotherapy [3]. The disease-free interval from initial therapy to dissemination was identical (42 vs. 44 months). However, with adjuvant pretreatment, the subsequent remission rate (56%) and survival after dissemination (19 months) was lower than without adjuvant therapy (66% and 26 months; p < .0001 for both).Three factors inducing this effect have to be considered. First, adjuvant therapy is given in tumors with higher risk of relapse (e.g., initial N+ stage). Not only is the rate of dissemination in these tumors higher but also metastases are more aggressive, with shorter survival after dissemination [4]. This is the same in colorectal cancer, for which adjuvant chemotherapy remained an independent negative prognostic parameter in multivariate analysis [5]. Second, with adjuvant therapy, the most sensitive tumors are eliminated. Consequently, the recurring tumors are the more aggressive ones. Third, prior adjuvant therapy induced resistance in the relapsing tumors. This was shown in colorectal cancer, using mutation analysis in liver metastases that revealed different potential for inducing resistance among different cytostatics [6].Adjuvant taxanes in breast cancer may induce resistance predominantly against their own class of agents. Miller et al. found that when administering palliative paclitaxel after adjuvant taxane-free treatment, progression-free survival was 7.7 months versus only 3.0 months after adjuvant taxanes [7]. In our study, in agreement with the findings of Seidman et al. [1], overall survival after dissemination was shortened by one-third when patients received adjuvant taxanes compared with a non-taxane-containing adjuvant therapy [2].These mechanisms, which are also relevant for adjuvant hormonal and immunological treatments [2], are not understood well enough and are difficult to search for in public databases because of the lack of specific search terms. We suggest using the acronym ATRESS, for “adjuvant therapy-related shortening of survival,” in future literature concerning this issue.