The immune system is active in breast cancer, playing a dual role in tumor progression and in immune surveillance. Infiltrating immune cells are both prognostic and predictive of response to standard breast cancer therapies.
Trastuzumab (Herceptin) is a therapeutic monoclonal antibody specific
for the human epidermal growth factor receptor type 2 (HER2), a
cell-surface tyrosine kinase receptor overexpressed by 25% to 30% of
breast cancers. The drug is now regarded as one option for standard
therapy in HER2-overexpressing metastatic breast cancers. It is associated
with a moderate response rate as a single agent, and in combination
with standard chemotherapy, can produce greater response rates
and prolong the survival of women with advanced breast cancer. Its
activity in metastatic breast cancer has led to active clinical trials examining
its potential role in the neoadjuvant and adjuvant settings.
The successful clinical development of trastuzumab provides further
proof of principle that biologically targeted therapies can have a profound
impact on the management of breast cancer. Here we review the
clinical development of this novel agent, emphasizing the potential for
therapeutic synergy when trastuzumab is combined with both standard
chemotherapy and innovative molecularly targeted and biologic agents.
Advances in biotechnology and basic immunology have converged
to create an unprecedented opportunity to use vaccines to harness the
power of the immune system in the fight against breast cancer. Cancer
vaccines have several therapeutic advantages over more traditional
breast cancer treatment modalities. First, targeting the antitumor
immune response to critical tumor-specific antigens defines a therapy
with exquisite specificity and minimal toxicity. Second, immune-mediated
tumor destruction occurs by mechanisms distinct from those underlying
the efficacy of chemotherapy and hormone therapy. Thus, immunotherapy
offers an approach to circumventing the intrinsic drug
resistance that currently underlies therapeutic failure. Third, the
phenomenon of immunologic memory endows immunotherapy with
the potential for creating a durable therapeutic effect that is reactivated
at the onset of disease relapse. Moreover, immunologic memory also
underlies the potential future use of vaccines for the prevention of
breast cancer. Early clinical trials have highlighted the promise of
breast cancer vaccines, and have further defined the challenges facing
translational scientists and clinical investigators. The judicious application
of laboratory advances to clinical trial design should facilitate
the development of immunotherapy as an additional major therapeutic
modality for breast cancer, with the potential for breast cancer prevention
as well as treatment.
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