Pathology: is it still necessary?

One may wonder what may be the reasons to ask this apparently odd question. Undoubtedly, the main concern is that we are still far away from being able to precisely identify the target population of patients for tailored interventions. It has been repeatedly shown by the results of large clinical trials that the benefit of new therapeutic approaches is relatively small, and that it is most likely confined to defined subgroups of patients, which should be properly identified for the adoption of the new treatment to be truly rewarding in clinical practice [1–4]. What is needed is an accurate assessment of the likelihood of individual patients to benefit from the different therapeutic options that are currently available. Traditionally, we have relied on the morphological and biological features of the tumor to identify patients at different risk of disease progression and for predicting the efficacy of different therapeutic approaches [5]. It is undisputable that this approach is not entirely satisfactory, because it only allows identification of a very limited number of subgroups of patients, characterized by a different risk of tumor progression (low, intermediate and high) and a different responsiveness to endocrine treatments (highly responsive, non-responsive and incompletely responsive) or to targeted interventions (HER2 positive and negative) [6]. Accordingly, we are still very far from a truly individualized therapeutic approach, most likely due to the relative paucity of the available prognostic and predictive parameters, which do not allow a more specific portrait of the individual patient to be drafted. Furthermore, we must admit that the pathological evaluation of breast cancer has shown additional drawbacks, mainly related to the lack of consistency and reproducibility in the assessment of at least some of the prognostic/predictive parameters. This is particularly true for the evaluation of hormone receptor status [4] and of the overexpression/amplification of the HER2 gene [7], where the rate of false-negative and false-positive results is exceedingly high. As a result, a growing sense of distrust towards the role of the traditional pathological characterization of breast cancer has emerged, and pathology is now viewed as a finite and possibly exhausted source of clinically important pieces of information.