Abnormal genes can cause breast cells to grow out of control and become cancerous. By identifying specific gene mutations in tumors, doctors can provide improved targeted treatment for these breast cancers.
The ability to distinguish specific breast cancer gene faults or mistakes has given scientists the means to define types of breast cancer and choose treatments that will most effectively fight the cancer. The latest research shows that breast cancer therapies can be targeted based on an individual’s gene mutations, and new genetic tests are helping to stop cancer culprits. Researchers have also discovered new biomarkers (molecules in the body that signal the presence of the disease) that can help block cancer before it spreads.
Gregory Tsongalis, PhD, director of Molecular Pathology at Dartmouth University’s Norris Cotton Cancer Center (NCCC) in Lebanon, New Hampshire, and his colleagues recently wrote an article presenting an overview of the emergence of personalized therapy for breast cancer.
Breast cancer may be caused by inherited defective genes or by acquired mutated genes. Radiation or cancer-causing chemicals may be factors that lead to acquired mutated genes, but causes of these mutations are still largely unknown.
BRCA1 and BRCA2 are examples of genes that can have an inherited mutation. (BRCA stands for breast cancer). Normally, these genes help suppress proteins that can cause cancer. With mutated versions of these genes, a woman has an increased risk for developing breast cancer.
The National Cancer Institute reports that 12 percent of women overall will develop breast cancer at some point in their lives. For women who inherit BRCA1, an estimated 55 to 65 percent will develop breast cancer by age 70. Around 45 percent with BRCA2 will experience the same.
Genetic Vs Genomic Testing
Some use the terms “genetic” and “genomic” interchangeably, but genetic testing is most often used to describe the gene screening used to determine a patient’s risk of developing cancer (as with BRCA).
Subhakar Mutyala, MD, associate professor in the Department of Radiation Oncology at Texas A&M College of Medicine and associate director of the Scott & White Cancer Institute in Waco, told dailyRx News, "After Angelina Jolie announced her bilateral mastectomies, we have seen a rise in the number of women requesting [genetic testing]. Women with a strong family history of breast cancer should be tested."
Genomic testing is a genetic analysis of the tumor itself and provides a doctor with details on what is driving a cancer’s growth and what treatments the tumor may best respond to.
The information from genomic tests can also predict the risk of a cancer recurring after a patient receives the recommended therapy.
Currently available gene profiling tests for breast cancer (called diagnostic assays) are MammaPrint (Agendia, Amsterdam, The Netherlands), Oncotype DX (Genomic Health, Inc. Redwood City, CA) and the Genomic Grade Index (GGI).
The Oncotype DX breast cancer test, for example, looks at genes in a patient’s breast tumor to understand how these genes interact and influence the tumor’s behavior, but it does not provide information about a person’s inherited genetic make-up.
The test, which can cost $3,500 or more, requires that a small piece of tumor tissue be taken from the patient.
Three Major Cancer Categories
Dr. Tsongalis's paper focuses on genomic testing. This testing of breast tumor cells has helped scientists understand the biology of tumors and to pinpoint three major categories of breast cancer.
- ER-positive (estrogen receptor-positive). According to the American Cancer Society, about two thirds of breast cancers are hormone receptor-positive. These cancers have receptors for the hormones estrogen (ER-positive cancers) and/or progesterone (PR-positive cancers). These cancers need hormones to grow. Known to be less aggressive than other types of breast cancer, ER-positive cancers are often treated with selective estrogen receptor modulators (SERMs). These medications interfere with the effects of estrogen on these tumors. SERMs include tamoxifen (generic available, branded product no longer on the market), raloxifene (brand name Evista), toremifene (brand name Fareston) and aromatase inhibitors (AIs) such as letrozole (brand name Femara), anastrozole (brand name Arimidex) and exemestane (brand name Aromasin). These medications can work in different ways. AIs reduce the amount of estrogen in the body to slow or stop the growth of estrogen-sensitive tumors, for example, while tamoxifen blocks the cancer cells’ ability to use estrogen.
- HER2–positive. This type of breast cancer contains large amounts cells with a protein called human epidermal growth factor receptor 2 (HER2), which helps cancer cells grow and multiply. This gene mutation is not inherited from a parent and it tends to be more aggressive than other types of breast cancer. Medications the target HER2, killing cancer cells and stopping tumor spread, include trastuzumab (brand name Herceptin), lapatinib (brand name Tykerb), pertuzumab (brand name Perjeta) and trastuzumab emtansine (brand name Kadcyla).
- Triple negative (ER-negative/PR-negative/HER2-negative). This is a particularly aggressive form of breast cancer and has the poorest outcome for patients. These cancer cells lack estrogen receptors and progesterone receptors, and do not have an excess of the HER2 protein on their surfaces. According to the American Cancer Society, younger women and African American women tend to get this type of cancer compared to other populations. Chemotherapy can inhibit tumor growth, but no personalized therapy has been approved for triple negative cancer. Personalized treatment may be on the horizon as scientists have identified six subtypes of tumors, which is a first step in identifying biomarkers and developing therapies.
“A personalized approach [through genomic testing] increases the precision and success of breast cancer treatment,” said Dr. Tsongalis in a press release. “Molecular profiling exposes a tumor’s Achilles’ heel. We can see what messages the tumor cells are receiving and sending. It is a biological intelligence gathering mission in an attempt to interrupt the disease.”
By identifying the makeup of tumors through genomic testing, patients may also avoid unnecessary and potentially harmful treatments. Women with certain types of breast cancer may not need chemotherapy or radiation.
While NCCC runs genomic testing of breast cancer as part of routine care, it is not a regular part of most clinical care services as it is with lung and colon cancers, according to Dr. Tsongalis
Dr. Tsongalis told dailyRX News, “At NCCC all of our newly diagnosed breast cancer patients are tested for abnormality of the HER2 gene. In breast cancer, up to 35 percent of cancers have a gene defect that consists of abnormal copies of the HER2 gene. These patients are eligible for treatment with anti-HER2 therapies such as trastuzumab [Herceptin]."
Scientists are continuing to find new biomarkers, which is leading to the reclassification of cancers and the development of new, effective treatments that can be personalized to an individual breast cancer patient.
Dr. Tsongalis’s paper, titled "Personalized Therapy for Breast Cancer” was accepted in March for publication in Clinical Genetics.