December 05, 2019
6 Advances in Breast Cancer Diagnosis and Treatment
BY CYNTHIA DEMARCO
Breast cancer remains one of the two most-common types of cancer in the world, according to the World Health Organization. It’s the fifth-leading cause of cancer-related deaths annually. And more than 265,000 people will be diagnosed with it in the United States alone, during any given year.
But there is reason for hope. Research has yielded a number of exciting developments in breast cancer diagnosis and treatment that will improve the lives of breast cancer patients for years to come. We spoke with our Senthil Damodaran, M.D., Ph.D., Jennifer Litton, M.D., and Anthony Lucci, M.D., to learn more.
1. Node preservation reduces lymphedema cases
Axillary lymph nodes used to be removed from the armpit routinely during breast cancer surgery to test for metastasis. This caused chronic pain, numbness and lymphedema in about 1 in 5 patients. But studies have shown that many of those nodes can be preserved — without compromising long-term survival rates.
Sentinel node mapping lets surgeons identify which lymph nodes are most likely to be affected by a tumor. Targeted axillary dissection allows surgeons to potentially preserve nodes that once tested positive for cancer, but reverted to negative status after chemotherapy or another treatment. In both cases, if tests come back negative for cancer on the first few nodes taken out, the remaining nodes can be left alone. That means fewer complications, and fewer side effects for our breast cancer patients.
“About 15-20% of patients developed lymphedema when we were still routinely taking all the nodes out,” says Lucci, a surgical oncologist who specializes in breast cancer. “But when sentinel node mapping is done, and the rest of the nodes are left in place, that figure drops to 5%. And the chance of a recurrence in the axilla is quite small using this strategy. So, this is a huge deal. We’ve really been able to improve patients’ quality of life by dialing back our aggressiveness on routine lymph node removal.”
2. Genomic testing minimizes chemotherapy exposure
For years, many patients also got chemotherapy as a part of their breast cancer treatment. But a July 2018 study in the New England Journal of Medicine showed that chemotherapy wouldn’t benefit up to 85% of patients over age 50 whose breast cancer was HR+, HER- and had not spread to any lymph nodes.
The study involved a genomic assay (or OncotypeDX test) that looked at the expression of 21 different genes in a patient’s primary tumor. A tumor’s gene expression pattern shows whether or not it will be responsive to chemotherapy, or whether endocrine therapy alone (such as tamoxifen) would be a better choice. The study showed that patients scoring in the low-to-mid-risk range could safely skip chemotherapy, avoiding the hair loss, neuropathy, weight loss and other side effects that often come with it.
“Before that study, we didn’t know if it was safe to omit chemotherapy,” says Lucci. “Now, we know we can get the same overall outcome by doing less. So, we’re minimizing overtreatment. And it has totally changed how we practice medicine.”
3. Better identification of hereditary cancer syndromes
A number of genetic mutations — such as BRCA1 and BRCA2 — are already known to increase a person’s risk of developing certain cancers, including breast cancer. But now, next-generation gene sequencing techniques are helping researchers identify other hereditary cancer syndromes that can put people at risk.
“We always knew there were certain families with strong histories of cancer,” says Litton, a medical oncologist who specializes in breast cancer genetics. “But by analyzing blood and saliva, we can reach out to other family members earlier – both to provide preventive care through enhanced screenings and to identify existing cancers.”
4. An oral option for targeted therapy
Until recently, PARP inhibitors were used primarily to treat ovarian cancer. They work by preventing damaged cancer cells with specific genetic mutations from repairing themselves. Today, this targeted therapy is being used to treat breast cancer successfully, too.
“DNA has multiple ways to repair itself,” explains Litton. “So, when someone has a genetic mutation that closes one pathway, their DNA uses another one instead. PARP inhibitors block those escape routes, so cancer cells can’t grow and divide.”
Breast cancer is linked to fewer mutations than ovarian cancers, Litton notes, but PARP inhibitors can still exploit them. Two Phase III clinical trials are currently underway comparing PARP inhibitors to standard-of-care chemotherapy. The OlympiAD trial evaluated olaparib and the EMBRACA trial, led by Litton, evaluated talazoparib. Both trials showed improvements in progression-free survival for patients with an inherited BRCA gene mutation and metastatic breast cancer. Both studies also showed overall improvements in quality of life in patients who received these oral drugs, as opposed to those patients who received chemotherapy.
“It’s fantastic that patients now have an oral option in this class of drugs,” says Litton. “We’re exploring some very promising combinations in clinical trials that try to create a BRCA-like environment for PARP inhibitors to work, even in women who don’t have the targeted mutations. Early results indicate that some patients will still have a complete response: meaning no cancer can be found in their breasts at the time of surgery.”
5. New drug combination makes estrogen-blocking agents more effective
Patients with HR+ — or hormone receptor-positive — breast cancers are often prescribed estrogen-reducing agents such as letrozole and anastrozole to starve the tumors. Now, studies show that those patients do even better when hormone therapy is combined with CDK4/6 inhibitors, which prevent cancer cells from dividing.
“Three different CDK4/6 inhibitors have been approved by the U.S. Food & Drug Administration: abemaciclib, palbociclib and ribociclib,” says Damodaran, a medical oncologist who specializes in breast cancer. “When combined with hormone therapy, all three CDK4/6 inhibitors have shown immense improvement in progression-free survival in patients with stage IV breast cancer. So, this has become the standard of care in nearly all metastatic HR+ breast cancer patients for first-line treatment. It’s a big change in how we treat breast cancer.”
6. The next generation of monoclonal antibodies
Trastuzimab (Herceptin) is a monoclonal antibody that has been used to treat HER2+ breast cancer patients since the 1990s. It works by targeting the HER2 receptor, preventing cancer growth. Some breast cancers express too much HER2 protein, triggering the cells to multiply very rapidly.
Other monoclonal antibodies (such as pertruzimab/Perjeta) have since been developed. Today, this targeted therapy has gotten even more advanced. T-DM1 (Kadycla), an antibody-drug combination, has been approved for use in the treatment of HER2+ breast cancers. Antibody-drug combinations work like a “smart bomb,” delivering chemotherapy directly to cancer cells by attaching to their HER2+ receptors.
“Targeted therapies have transformed our approach to HER2+ breast cancers, and offer an opportunity to cure stage IV breast cancer in certain patients,” says Damodaran. “So, monoclonal antibodies have been a big game-changer.”