Our knowledge of the makeup and behavior of tumors continually grows. As part of our research, our scientists are searching for more-precise markers in patients’ tumors that can help predict how they will respond to a specific treatment. We’re evaluating hormone receptors, cancer-related genes (called oncogenes), and certain enzymes produced by cancer cells that help the cells to spread. We’re particularly focused on the role of inherited genetic mutations in the development and progression of breast cancer as well as how it responds to treatment.
Our goal is to integrate these laboratory research findings into the care we offer you, so that we can customize your treatment based on the specific molecular signals that are driving the growth of your cancer. Our current research focus is on a selected number of cancer-specific genes that may identify vulnerable targets within some people’s cancers. We can treat tumors that carry these genes using new drugs in clinical trials. This is most applicable to advanced cancers but may also be used in some earlier stage tumors in the coming years.
We’ll also want to learn about other aspects of your cancer that can affect your treatment plan, including:
Breast cancer cells that have receptors for the hormone estrogen are called estrogen receptor–positive. Those with receptors for the hormone progesterone are called progesterone receptor–positive. If these receptors are not present, the cell is called hormone receptor–negative. Tumors that are hormone receptor–positive are more likely to respond to therapy with medications that lower the level of estrogen in your body, which take advantage of the cancer cell’s dependence on hormones for growth. They can also grow more slowly and in different patterns, although this varies quite a bit.
The drug tamoxifen (Soltamox®) acts by blocking the estrogen receptors of a breast cancer. Another class of drugs called aromatase inhibitors, used in postmenopausal women, interferes with the production of estrogen. This means there is less of this hormone to stimulate the receptors.
HER2/neu is a gene that, when activated, helps tumors grow. Tumors that have higher-than-normal amounts of this protein are called HER2 positive. They may respond to targeted therapies such as trastuzumab (Herceptin®), pertuzumab (Perjeta®), trastuzumab-DM1 (Kadcyla®), and lapatinib (Tykerb®), which block or interact with the HER2 receptor. Other drugs that work against this receptor and its signaling components are in development.
About 10 to 15 percent of breast cancers don’t contain receptors for estrogen, progesterone, or HER2/neu. They are called triple-negative breast cancers. Because these cancers don’t respond to standard drugs that target the hormones or HER2 receptors, they are primarily treated with chemotherapy. Triple-negative breast cancers also tend to be more aggressive, occur earlier in life, and pose a greater risk of returning sooner than other types of breast cancer.
Women with triple-negative breast cancer may be more likely to carry a BRCA mutation, especially if they are diagnosed at a young age. Our researchers and others around the world are studying the biology of triple-negative breast cancer to learn more about the disease and hopefully identify new therapeutic targets.
Oncotype DX® is an example of one test that is used to help guide decisions on whether chemotherapy should be given after surgery. It analyzes 21 genes in patients with breast tumors that are estrogen receptor–positive. Test results are translated into a recurrence score, which enables doctors to predict which women will benefit most from chemotherapy.
In special cases, we may also look for mutations using a test we developed called MSK-IMPACT™. It assesses more than 400 genes known to be associated with malignant tumors. Please note that not all patients are eligible, and only invasive carcinoma is suitable for testing. If you do qualify and we identify a specific mutation in a breast cancer or in one of its metastases, you may be able to enroll in a clinical trial that tests the effectiveness of new therapies targeting those specific genetic alterations. The MSK-IMPACT test is available only to patients who are treated at MSK and who are eligible for a formal clinical trial.