Abstract
Following the seminal introduction of CMF (cyclophos-phamide, methotrexate, and fluorouracil) for adjuvant breast cancer treatment more than three decades ago [1], the efficacy of adjuvant chemotherapy has gradually improved by the introduction of the anthracyclines [2] and, more recently, the taxanes [3]. However, while anthracycline-containing regimens have become standard treatment for oestrogen receptor (ER)-positive as well as ER-negative tumours, conflicting evidence has linked the use of adjuvant taxanes to improved outcome in patients with ER-positive tumours. This uncertainty has now, to a large extent, been resolved with the results from a recent study [4] revealing a benefit for ER-positive tumours with a high growth rate as evaluated by KI67 status, but no benefit for ER-positive tumours with a low KI67 score. These results indicate a way forward; while studies three decades ago centred on identifying prognostic factors in breast cancer, we are now starting to learn predictive factors identifying which tumours may achieve optimal benefit from defined therapeutic regimens [5]. This relates to established drug regimens and also to new experimental therapies in particular. While this is conventional wisdom with respect to targeted therapies, such as endocrine agents and anti-human epidermal growth factor receptor 2 (anti-HER-2) strategies, current data illustrate the need for predictive factors to enable optimal use of chemotherapy as well. Realizing the need to identify predictive factors and, ideally, to understand the mechanisms causing drug resistance [6], translational research aiming at identifying such biological parameters should be part of most phase I to III trials [7]. Before discussing future perspectives and the implementation of novel drugs, a brief summary of the state of the art for predictive factors in breast cancer therapy is provided.
Highlights
Following the seminal introduction of CMF for adjuvant breast cancer treatment more than three decades ago [1], the efficacy of adjuvant chemotherapy has gradually improved by the introduction of the anthracyclines [2] and, more recently, the taxanes [3]
Do scientific aims need to be redefined? The findings summarized above reveal an emerging understanding of the mechanisms controlling tumour response to therapy
While some of these parameters are used clinically, we are still far from the goal of ‘individualized medicine’ - the selection of optimal therapy at an individual level based on predictive factors
Summary
Following the seminal introduction of CMF (cyclophosphamide, methotrexate, and fluorouracil) for adjuvant breast cancer treatment more than three decades ago [1], the efficacy of adjuvant chemotherapy has gradually improved by the introduction of the anthracyclines [2] and, more recently, the taxanes [3]. While some of these parameters are used clinically (such as HER-2 amplifications for anthracycline dose selection), we are still far from the goal of ‘individualized medicine’ - the selection of optimal therapy at an individual level based on predictive factors To fully achieve such a goal will most probably require extension of our ambitions beyond identification of correlative predictive factors toward identification of the mechanisms causing drug resistance. The second approach - the design of therapeutic strategies from knowledge about particular gene defects in individual tumours - is illustrated by the development of poly ADP ribose polymerase (PARP) inhibitors for breast and ovarian cancers in patients harbouring BRCA1 or BRCA2 mutations. Competing interests The author declares that they have no competing interests
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