HonorHealth researches drugs that target differences in breast cancer subtypes

HonorHealth researches drugs that target differences in breast cancer subtypes

By Christina Fuoco-Karasinski

Not all breast cancers are the same. The team at HonorHealth Research and Innovation Institute leverage their knowledge of biologic differences in the different types of breast cancer to develop new drugs that precisely target the subtypes of this disease.

“My focus at the institute is developing new medications for women with advanced cancers in order to allow my patients access to these novel cutting-edge treatments here in their community,” says Dr. Jasgit Sachdev, director of Breast and Gynecological Early Phase Trials Program.

“Oftentimes, we are the first ones in the world evaluating a potentially promising new cancer medication.”
At the institute, Sachdev and her team study the safety of these medications, and the best doses and schedules with which to move forward. The hope is that someday these drugs may be approved by the Food and Drug Administration as a new cancer medication and help thousands of patients.

“The last few months, we have been looking at several different aspects of the body’s immune response to cancer and how we can leverage that to improve the effectiveness of our standard chemotherapies and radiation treatments,” she says.

“We’re looking for new targets on the immune cells of an individual and how those targets can be utilized for providing long-lasting responses for our patients with breast cancer.”
Sachdev and her team and are actively engaged in clinical trials for estrogen positive, triple negative and HER2+ breast cancers.

“In the last few years, the prognosis for all of these subtypes of cancers has continued to improve with new medications getting approved almost every year,” she says.

“This year, for example, we’ve had three different cancer medications that were approved for advanced HER2+ breast cancer, including for those patients in whom the cancer has spread to the brain. If you look at average survival for patients with stage IV HER2+ breast cancer 20 years ago, it was six months or less. Now, women with stage IV HER2+ breast cancer are living five years or longer. That’s a game changer. These kind of advances in treatment are only made possible through the courage and altruism of hundreds of patients who participate in these early clinical trials offering hope to many others who come after them.”
The survival rates and the quality of life of patients with all stages of breast cancer are continuing to improve, thanks to new medications researched at HonorHealth Research and Innovation Institute.
Recently, Sachdev’s team incorporated immunotherapy medications into the treatment of triple negative breast cancer.

“Immunotherapy refers to medicines that help your body’s immune system recognize where the cancer cells are lurking within the body and reeducate the immune system to go and eliminate them,” she says.
“For triple negative breast cancer, the only standard treatment options used to be chemotherapy, but chemotherapy does not always work very well for this subtype of breast cancer, especially if it recurs after treatment. The survival for women with advanced, stage IV triple negative breast cancer is typically a year to a year and a half at most. We now know that there is a proportion of triple negative breast cancers that tend to respond well to these immunotherapy drugs. Researchers are now combining chemotherapy and immunotherapy together to hit aggressive cancers with a one-two punch.

“The goal is to allow patients with stage IV cancers to live longer,” Sachdev adds. “Eventually, someday, they won’t have to remain on chemotherapy forever. Maybe we can start off by damaging the cancer cells with chemotherapy and then the immune cells of the body can have that memory of what bad cancer cells look like and can fight them off every time they try to resurge.”
In the next few months, Sachdev and her team will look at other forms of new immunotherapy drugs, including trials where they can inject immune stimulants directly into the cancer mass. That will cause local inflammation in that tumor, and that trigger will bring the immune cells toward the inflamed area to get rid of the tumor.

“That’s an innovative approach we’re excited about. Stimulating a local immune response in the injected tumor, we hope, in turn will stimulate an overall immune attack on the tumors all over the body, even the ones that are far away from the injected tumor,” Sachdev says.

About 80% of breast cancers are estrogen positive or hormone receptor positive. Approximately 30% to 40% of patients who are diagnosed with early stage breast cancer can have a relapse despite surgery and other treatment including chemotherapy, radiation and estrogen-blocking treatments.
“Our goal is to continue to improve our treatment strategies to reduce the proportion of patients who suffer a recurrence despite the best standard treatment. For patients who do have recurrence of their cancer, our goal is to make our treatments more tolerable in order to allow them to live long despite their disease and have a good quality of life.”

Her goal is to move away from chemotherapy that can be life altering for patients. So, she’s looking at new medications that can help to continue to delay the need for chemotherapy for these patients.
“We want them to stay on effective yet more tolerable treatments, like oral medications that target protein signaling in patients whose tumors have become resistant to estrogen-blocking pills. These medications are different than chemotherapy because patients can take them at home without the need for infusions, without losing their hair and without having nausea and other side effects of chemotherapy,” Sachdev says.
“In doing so, we’re effectively treating their breast cancer. Patients are living longer and feel like they’re living a very normal life by not having to go through harsh side effects of chemotherapy. We have ongoing trials that are continuing to explore new targeted oral medication options for these patients.”

Her mission
Sachdev focused on breast cancer, inspired by her mentor, who was a breast cancer specialist.
“I really liked his approach of treating each patient individually and tailoring a treatment decision with the patient’s active participation, carefully weighing the benefit and risks of each treatment option,” she says.
“Being a woman, myself, I find myself relating a lot more to my patients. When I was in training to be an oncologist, I had my first child. I would see young women having to make difficult decisions about the impact of chemotherapy on their future likelihood of being able to carry a pregnancy and have children. I would help them navigate through these tough decisions. I could see firsthand the tremendous emotional side effect of our treatments on these young women with breast cancer. That spurred an interest in trying to understand why some women were more susceptible to developing breast cancer at a young age. In the last five to 10 years, genetic risk for breast cancer has been studied more extensively.
“I think we’re still at the tip of the iceberg, but we’re recognizing that clusters of breast cancers and other cancers in certain families could be related to genes that patients inherit. We used to think of those as just being related to those with mutations in the BRCA1 and BRCA2 genes, which are the most-common genes that cause hereditary breast cancer. Now we know there are many more genes that could be responsible in combination with lifestyle and environmental risk factors.”

Sachdev says there are now treatment options that are geared specifically toward women with hereditary breast cancer. These targeted medications, called PARP inhibitors, have been approved in the last three to four years and work very well in those who have inherited a BRCA mutation. They exploit the vulnerability of these mutated cancer cells and take away their survival strategy, causing damage to the cancer cell DNA.
“PARP inhibitors have made a huge impact in improving longevity for these patients,” Sachdev says. “They’re not chemotherapy. These drugs are pills that patients can take at home with very manageable side effects—no hair loss, no nausea, no vomiting. So, a lot of times, patients come in and comment, ‘If I didn’t tell anybody, nobody would know I have breast cancer.’ That’s extraordinary, in my opinion.
“The important message here is patients still have a good quality of life. They can spend quality time doing things that they like. At the same time, these medicines are prolonging their life. That’s because we continue to learn about the biology of all these different subtypes of breast cancers that historically were thought of as one disease with one treatment approach. We’re learning to differentiate them through our biologic experiments that provide a platform to develop new treatment options.

“An important new protocol at HonorHealth Research and Innovation Institute involves collecting tumor cells from the patient by a biopsy and then growing them in the laboratory to mimic how they grow inside the body (called an organoid system). This approach allows us to directly visualize the growth of cancer cells and use different treatment approaches to block this growth and disrupt their support system. We are hopeful this will lead to identification of new targets and ways to intercept those targets and cancer pathways.”

Dr. Jasgit Sachdev at HonorHealth Research and Innovation Institute can be reached by contacting the Oncology Research Nurse Navigation Team at 480-323-1364 or email clinicaltrials@honorhealth.com.