My name is Sara Tolaney,
I'm a breast medical oncologist at the Dana-Farber Cancer Institute.
Today, I'm going to be reviewing immunotherapy for the treatment of
breast cancer with insights from the advanced disease setting.
Immunotherapy has really been
a paradigm shift in the way that we approach treatment for cancer.
It allows us to utilize the patient's own immune system to target
their malignancy and allows for the potential for a long duration responses.
It's been generally associated with
lower rates of toxicity than we've previously seen with
chemotherapy and it allows us to utilize
a smart strategy to overcome the molecular complexity of cancer.
Immunotherapy has been successful in the treatment of
both hematologic and solid tumors and very recently,
we've achieved the first FDA approval for immunotherapy in
metastatic triple-negative breast cancer with
the combination of nab-Paclitaxel and atezolizumab.
Development of immunotherapy in breast cancer has been
more challenging than it has been in some other solid tumors.
One reason for this may be that breast cancer is
associated with a lower tumor mutational burden than we've
seen in cancers where immunotherapy has been quite
successful such as melanoma and lung cancer.
If you can see here on this chart,
that both melanoma and lung cancer is associated with very high tumor mutational burdens,
whereas breast cancer has been associated with
much lower rates of tumor mutational burden.
This may be why we see
less neoantigen production and less stimulation of the immune system.
Most of the work focusing on immunotherapy in
breast cancer has initially been in the triple-negative setting.
The reasons for this are that triple-negative breast cancer has been
associated with relatively higher mutational load compared to
hormone receptor positive and HER2-positive disease
is associated with higher levels of tumor
infiltrating lymphocytes and has higher rates of
PD-L1 positivity compared to the other two sub-types.
The initial approach had been focused on checkpoint use
as monotherapy in triple-negative disease.