There is great interest in using tumor sequencing data to guide
therapy. It is increasingly used to select treatment for
patients with cancer, but its role in women with newly diagnosed breast
cancer is unknown.
Mayo Clinic researchers reported today in the Journal of the National Cancer Institute
the results of a prospective tumor sequencing study in women receiving
chemotherapy prior to breast surgery.
‘Mayo clinic researchers studied whether tumor genomic alterations could differentiate patients with chemotherapy sensitive and chemotherapy resistant disease.’
The goal was to determine whether
tumor genomic alterations could differentiate patients with chemotherapy
sensitive and chemotherapy resistant disease and to generate
patient-derived xenografts (mouse avatars) to validate their findings.
Matthew Goetz, medical oncologist and co-chair of
the Breast Cancer Genome-Guided Therapy (BEAUTY) study, said, "However, there
are limited data as to whether this approach is useful in women with
newly diagnosed breast cancer who are recommended chemotherapy prior to
breast surgery," he added.
The main findings of the BEAUTY study, published today in the online issue of Journal of the National Cancer Institute
demonstrated that the most common genetic changes were not more
commonly observed in chemotherapy resistant compared to chemotherapy
sensitive tumors. However, Mayo investigators identified that an
uncommon type of an aggressive breast cancer, the luminal androgen
receptor subtype of triple negative breast cancer (TNBC), was less
likely to respond to chemotherapy, and was more likely to contain a
unique type of mutation in p53, a tumor suppressor gene commonly mutated
"The long-term goal of the BEAUTY study is to enable individualized
treatment for each woman with breast cancer by using the genetic
information found in blood samples and tumor biopsies to select the most
effective therapies," says Judy Boughey, breast surgeon and
co-chair of the BEAUTY study.
According to Dr. Boughey this study was an important step in that
direction. A major goal towards more personalized therapies is the
development of new cancer models to test the efficacy of new treatments
before they are tested in patients. In the BEAUTY study, Mayo
researchers used core needle biopsies of the original tumor and
successfully "immortalized" breast cancer cells into mouse avatars in
more than 50% of patients with TNBC.
"The simultaneous generation of avatars and tumor sequence data from
patients that did not respond to chemotherapy has allowed our research
team to prioritize the selection of the new agents to study in the
laboratory," say Dr. Goetz.
"Using the data generated from this study, the Mayo BEAUTY team will
launch a successor study bringing forward new drugs to women with
chemotherapy resistant tumors", added Dr. Boughey.
The research team's goal is to bring forward the most promising
drugs to patients who have tumors resistant to current therapies.
As a result of the study researchers now know that:
- The most common and recurrent genomic alterations
observed in the BEAUTY study were equally as likely to be observed in
patients that responded to chemotherapy as those that did not respond.
- Many uncommon genomic alterations were observed, and
much larger studies will be needed to determine whether these unique
alterations identify groups of women more or less likely to respond to
- The development of patient derived xenografts using
needle biopsies from the primary breast tumor prior to surgery is
feasible, and the "avatars" that were developed in both patients that
did and did not respond to chemotherapy are a powerful tool for studying
new therapeutic strategies.
According to Keith Stewart, Carlson and Nelson Endowed
Director, Mayo Clinic Center for Individualized Medicine, cancer
patients have benefitted from Mayo Clinic research, integration and
application of new therapies targeted to their individual genetic
"Our research in precision medicine allows us to develop
personalized solutions to diagnose patients sooner, provide safer drug
therapies and customize treatment plans based on a patient's individual
genetic code" says Dr. Stewart, the Vasek and Anna Maria Polak Professor
of Cancer Research.