By Sharon Rosen and Susan Buckles
Approximately one out of eight American women will develop breast cancer during their lifetime. In the U.S., it is estimated that more than 315,000 women will be diagnosed this year with breast cancer. While statistics show fewer women are dying from the disease, breast cancer still remains the second leading cause of cancer deaths in women.
The need for earlier diagnosis and more precise treatment to address unmet patient needs continues to drive the research goals at the Center for Individualized Medicine. Physicians and scientists at Mayo Clinic are applying the latest genomic research both to improve early detection of breast cancer when it is most treatable and also to develop new, individualized therapies based on the unique genetic characteristics of each patient’s cancer.
Mayo Clinic research seeks to improve breast cancer care and treatment in three key ways.
Mammography and other screening tools have made great strides in finding breast cancer early, when it is most likely to be successfully treated. However, some early stage cancers are missed by conventional screening and are only detected after symptoms appear. In some cases, cancer is not detected until it has spread to other areas of the body.
Are there ways to improve early breast cancer detection?
Research suggests that blood tests may be able to find breast cancer early, by identifying small pieces of genetic material shed by tumors. Investigators at Mayo Clinic are working to validate use of a blood test to complement current screening methods for the earliest detection of breast cancer and other cancers in healthy individuals before they have any signs or symptoms of disease. This is known as liquid biopsy. Similar approaches are being applied to treatment and disease monitoring through a collaborative effort between the Division of Medical Oncology, Department of Laboratory Medicine and Pathology and Center for Individualized Medicine.
“Our clinical and research efforts in the liquid biopsy space are all focused on building a complete understanding of the complex biological and genetic processes underlying cancer. This will enable us to deliver personalized care to patients at the earliest possible stage,” says Minetta Liu, M.D., a medical oncologist in the Division of Medical Oncology.
Therapeutic treatments can shrink or slow the growth of cancer cells for women with advanced, stage IV breast cancer that has spread to other parts of the body. Many times, tumors become resistant to therapy, so it is not uncommon to change treatments often. By gaining a deeper understanding of cancer’s progression on a molecular level, researchers hope to match therapeutic options to a patient’s individual genetic makeup with the hope of selecting the treatment that is most likely to succeed.
A clinical trial at Mayo Clinic will use sophisticated genetic tests and research in mice to advance care for women with estrogen receptor-positive (ER-positive) breast cancer that has progressed to stage IV cancer.
The standard treatment for ER-positive breast cancer for the past 40 years has been therapies that target estrogen. Adding a new class of drugs called CDK 4/6 inhibitors to the treatment plan has been shown to slow the growth of cancer and extend life for patients with stage IV ER-positive breast cancer. However, it doesn’t stop tumor progression altogether.
Researchers will use advanced DNA and RNA sequencing to analyze genetic characteristics of the tumor and look for pathways of drug resistance. Those tests will be done before treatment begins and after two months. Investigators will attempt to grow the patient’s cancer in mice from a piece of the patient’s cancer tissue – this is known as mouse avatars or PDX models. Cancer-fighting drugs will be tested against cancers that grew in mice, to confirm the genetic pathways of resistance.
“This is the first study to prospectively evaluate advanced DNA sequencing technologies combined with tumor models grown in mice – mouse avatar, PDX models in women taking standard of care CDK 4/6 inhibitors for ER-positive breast cancer. The goal is to identify new genetic biomarkers of resistance and develop drugs that target resistance to the treatment of ER-positive metastatic breast cancer,” says Matthew Goetz, M.D., medical oncologist.
Dr. Goetz and Ciara O’Sullivan, M.B., Ch.B., also a Mayo oncologist, are co-principal investigators for the study.
Chemotherapy before surgery is prescribed for patients with aggressive forms of breast cancer. While this treatment helps shrink the tumor, chemotherapy does not shrink tumors in all patients.
In the Breast Cancer Genome-Guided Therapy (BEAUTY) study, Mayo researchers used genomic sequencing to identify unique genetic characteristics of tumors from patients whose disease was or was not eradicated by chemotherapy. They then used that information to develop alternative therapies for those who did not respond to chemotherapy.
“For patients with cancer remaining at the time of surgery, there is a great need to bring forward additional treatments that address chemotherapy resistance. The BEAUTY study was designed to develop tools and provide insights into the genetic and molecular underpinnings of chemotherapy resistance,” says Judy Boughey, M.D., breast surgeon and co-chair of the BEAUTY Study.
In the study, investigators successfully grew models of the patient’s cancer in mice – PDX models – to test effectiveness of alternative therapies on the tumors in mice.
“These PDX have already proved to be a powerful tool for us to test new drug therapies, especially those PDX models that were generated from women whose tumor was resistant to standard therapy," says Matthew Goetz, M.D., medical oncologist and co-chair of the BEAUTY study.
The next phase of the study will build on this research and will provide new drug therapies for patients with aggressive breast cancer who are resistant to standard chemotherapy given prior to surgery.
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See highlights from our recent Individualizing Medicine Conference 2017: Advancing Care Through Genomics:
Save the date for next year’s Individualizing Medicine Conference. It will be held Sept. 12-13, 2018.
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