Predictive markers in breast and other cancers: A review

Background: Unpredictable efficacy and toxicity are hallmarks of most anticancer therapies. Predictive markers are factors that are associated with response or resistance to a particular therapy. Methods: The English literature relating to predictive markers in oncology was reviewed. Particular attention was paid to metaanalyses, systematic reviews, prospective trials, and guidelines issued by expert panels. Results: The prototype predictive tests in oncology are the estrogen receptor (ER) and progesterone receptor (PR), which are used to select patients with breast cancer likely to respond to hormone therapy. A more recently introduced predictive marker is HER-2 for selecting patients with advanced breast cancer for treatment with the therapeutic antibody trastuzumab (Herceptin). In adjuvant breast cancer, overproduction of HER-2 may also indicate an enhanced sensitivity to high-dose anthracycline-based regimens. On the other hand, in both early and advanced breast cancer, high concentrations of HER-2 appear to correlate with a lower probability of response to hormone therapy. Although many different anticancer drugs appear to mediate tumor regression by inducing apoptosis, there is currently no consistent evidence that any of the molecules implicated in this process can be used as predictive markers. Conclusions: Currently, the only recommended predictive markers in oncology are ER and PR for selecting endocrine-sensitive breast cancers and HER-2 for identifying breast cancer patients with metastatic disease who may benefit from trastuzumab. For malignancies other than breast cancers, validated predictive markers do not exist at present. (C) 2005 American Association for Clinical Chemistry.