Over the last years, significant progress has been made in the management of breast cancer. The most impressive data come from the United Kingdom, where more than a 1/3 relative decrease in breast cancer mortality was noted over the last twenty years (fig. 1) (2). A similar trend can also be observed in many other countries but, unfortunately, not in Poland (1). This phenomenon is mostly related to the wide application of screening programs allowing for early diagnosis of malignancy and to improvements in the treatment of breast cancer, in particular of early disease.
Fig. 1. Decrease in breast cancer mortality in United Kingdom and USA (based on) (2).
A tendency to decrease the extent of surgery also applies to axillary lymph nodes. This is exemplified by the increasing use of sentinel lymph node technology, which in node negative patients allows for the omission of axillary lymph node dissection (5). As a consequence, the risk of arm lymphedema (which is a frequent complication of axillary lymphadenectomy, in particular when followed by postoperative radiotherapy) is markedly decreased.
The progress in systemic treatment of breast cancer is mostly related to the developments in molecular biology and a better understanding of breast cancer pathomechanisms. One of the most remarkable steps was the identification of molecular subtypes of breast cancer, based on multigene assays (6). These studies showed a number of distinct molecular breast cancer subtypes (luminal A, luminal B, basal, HER2+, normal breast-like) with various clinical behavior, prognosis and response to therapy. In consequence, these subtypes are currently considered separate clinical entities. Some of the multigene assays based on gene microarray technology have become commercially available and are accepted as ancillary tools in treatment decision-making in early breast cancer (7, 8). Better understanding of tumor biology has led to a profound modification of treatment strategies in early breast cancer. In particular, failure risk (which is directly related to tumor bulk and extent) has been substituted as the main factor driving treatment decision-making by biology of tumor and probability of benefit from a particular treatment modality (9).
As a result of studies on molecular pathomechanisms, a number of new “targeted” compounds have been developed and become available for breast cancer patients. Of these, a particularly important one is trastuzumab – a humanized monoclonal antibody against HER2. HER2 is a molecule belonging to the family of epidermal growth factor receptors and its overexpression or gene amplification in breast cancer cells (assessed by immunohistochemistry or in situ hybridization, respectively) is associated with shorter disease-free and overall survival (10).
Unlike most of the targeted agents, trastuzumab, when added to standard chemotherapy, was found to provide overall survival benefit in HER2 positive metastatic breast cancer patients. In the pivotal study, the median overall survival in patients treated with chemotherapy and trastuzumab was almost five months longer than with chemotherapy alone (11). In the subsequent randomized phase II study, the difference in median overall survival between chemotherapy + trastuzumab vs chemotherapy alone arms was even greater (over eight months, p = 0.0325) (12). Trastuzumab is generally well tolerated, with the main clinically relevant toxicity being cardiac dysfunction. This side-effect was observed mostly when trastuzumab was combined with anthracyclines and, in contrast to anthracycline-related damage, it is usually reversible and probably does not lead to long term sequelae. Moreover, with proper cardiac medication, this toxicity does not preclude further treatment with trastuzumab (13).
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