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Stratified medicine is the management of a group of patients with shared biological characteristics by using molecular diagnostic testing to select the most optimal therapy in order to achieve the best possible medicinal outcome for that group.

Personalized Medicine is the Goal
In 1999 Robert Langreth and Michael Waldholz announced the “New Era of Personalized Medicine” in the Wall Street Journal, which promised targeting drugs for each unique genetic profile – but in fact, the first step towards a more individualized pharmacotherapy was already taken several decades before this manifesto . With the discovery of the estrogen receptor in the 1960’s and the introduction of the anti-estrogen tamoxifen in the 1970’s the road was prepared for a more individualized treatment of patients within breast cancer. The test for hormone receptor status became an important stratification factor for anti-estrogen treatment. In the 1990’s another targeted drug was introduced which was aimed at a selected group of cancer patients: women whose breast cancer tumors overexpressed the human epidermal growth factor receptor 2 (HER2). The drug was the monoclonal antibody trastuzumab (Herceptin®, Genentech, CA, USA) which was specifically targeted toward the HER2 protein of the tumor cells. Also for trastuzumab a pharmacodiagnostic test/ companion diagnostic test (see definition below) played an important role in relation to treatment stratification. This was the immunohistochemical assay for the HER2 protein (HercepTest™, Dako, Glostrup, Denmark).

The article by Robert Langreth and Michael Waldholz was the first to describe personalized medicine in the way it is perceived today – a combination of an identifiable target in the individual and a drug directed towards this target. In spite of the general perception of the term being “personalized medicine”, it might so far be more correct to use the term “stratified medicine”, as suggested by several authors. Personalized medicine is the situation where the treatment is completely tailored to meet the requirements of the unique individual patient based on a “complete” molecular diagnostic profile, whereas stratified medicine use molecular testing to stratify the patients with shared biological characteristics to the most optimal treatment, often using only a single or few molecular markers.



Stratified Medicine as the First Step
The philosophy behind personalized medicine is that every patient has a unique biology and pathophysiology that should be reflected in the choice of pharmacotherapy, thus resulting in an improved treatment outcome. As we see it right now, the implementation of personalized medicine will be a stepwise process where stratification of patients into biological subgroups will be the first important step. Here drug and pharmacodiagnostic/ companion diagnostic testing are very closely linked together, and the test result is used to stratify the patient to the most optimal treatment. Clear examples of stratified medicine are patients with breast cancer who can be grouped according to their biological characteristics, such as estrogen receptor positivity or HER2 overexpression, and be treated according to these characteristics with an anti estrogens or a HER2 inhibitor. The move from blockbuster medicine towards personalized medicine will be a stepwise process, where stratified medicine will be the first goal to be reached, as illustrated in the figure below.

Leaving the Blockbuster Era
We are slowly approaching the post blockbuster era, but it may take some time before we arrive there, and the promise about “targeting drugs for each unique genetic profile”, as announced by Robert Langreth and Michael Waldholz in Wall Street Journal in 1999, will be a scenario still awaiting further progress within molecular diagnostic testing and drug development. However, stratifications of patients with shared biological characteristics by using pharmacodiagnostic/ companion diagnostic testing will be an important step forward in realization of a more safe and effective pharmacotherapy.