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Breast Cancer Panel: A Case-Based Discussion on the Use of Targeted Therapies for Primary and Metastatic Disease
Breast cancer (BC) is the most common cancer in
women, and the American Cancer Society
estimated that 212, 930 new cases of BC would
be diagnosed in 2005 in the United States, with
40,840 deaths attributable to this disease. At this
time the treatment paradigms are changing due to the
introduction of targeted therapies. This has led to an
improvement in treatment outcomes in both the metastatic and
adjuvant settings. Targeted therapies have been defined by the
National Cancer Institute (www.nci.gov) as a type of treatment that
uses drugs or other substances to identify and attack specific cancer cells
without harming normal cells, and include agents such as trastuzumab, a
monoclonal antibody directed against the Her-2 oncogene, and
bevacizumab, a monoclonal antibody aimed at the vascular endothelial
growth factor (VEGF) receptor. Although chemotherapy is still the mainstay of
treatment for both early stage and recurrent/metastatic breast cancer, targeted
therapies are increasingly being employed in conjunction with chemotherapy.
Perhaps the most striking example is the addition of trastuzumab to
chemotherapy as standard adjuvant therapy for women with early stage breast
cancers that overexpress the Her-2 oncogene, an approach that has been
shown to reduce the risk of recurrence by greater than 50% in such women
(Romond et al., 2005). Consistent with their novel mechanisms of action,
however, targeted therapies present unique challenges to oncology nurses in
terms of their side effect and toxicity profiles and administration concerns. Some,
such as cardiotoxicity, have the potential to be life-threatening.
This educational
activity will address the rationale and indications for use of these targeted
therapies in clinical breast cancer care, as well as their unique side effects,
toxicity profiles, and administration concerns. These objectives will be
accomplished not only by reviewing relevant clinical trials, but predominantly
through the use of an interactive case-based format with real patient scenarios discussed by a multidisciplinary panel of breast cancer clinical experts.
ADJUVANT TRASTUZUMAB WITH CHEMOTHERAPY:
FROM THE LABORATORY TO CLINICAL TRIALS TO
CLINICAL PRACTICE
HER2 overexpression is recognized as a high risk
factor and occurs in 50,000 women each year with
newly diagnosed breast cancer in the United
States. With carefully controlled studies, initially in
the metastatic setting and now in the adjuvant setting,
it has been demonstrated that women with this tumor
marker can expect marked improvement in clinical
outcomes, including overall survival, with the addition of
trastuzumab to their treatment regimens.
The importance of reliable HER2 testing cannot be overemphasized and
should be performed on all new cases of primary breast cancer. Joint
analysis of the B-31 and N9831 studies clearly showed the benefit of
adding targeted monoclonal therapy (trastuzumab) to adjuvant chemotherapy
in HER2 positive patients. Although there have been some differences between
the American studies and some of the foreign studies in design and patient
selection, they all showed favorable results with the addition of trastuzumab.
The importance of cardiac monitoring with trastuzumab is well recognized. In
contrast to doxorubicin cardiotoxicity, biopsy changes are not seen and seem
to be of a cellular dysfunction nature and almost always reversible.
The development of targeted therapy is a major breakthrough in the treatment
of breast cancer and the results of ongoing studies are eagerly awaited. Many
questions remain unanswered and include the optimal duration and sequencing
of trastuzumab therapy as well as its role in combination with other modalities of
treatment such as antiestrogen agents. Other new agents, which appear to act
on multiple pathways such as lapatinib, are appearing on the horizon.
