Addressing Long-term Effects of Breast Cancer Treatment

October 25, 2022

People diagnosed with breast cancer have a better chance of surviving the disease today than just five years ago, thanks to early detection, awareness, and improved therapies. But many of the estimated 3.8 million breast cancer survivors in the U.S. face new challenges associated with survivorship.

An upcoming clinical trial at Columbia University’s Irving Medical Center provides a vivid example of how breast cancer treatment has evolved in recent years. Instead of evaluating a new chemotherapy or diagnostic test, the trial will test strategies for limiting the side-effects of existing treatment regimens. The work is part of an ongoing expansion in the field’s focus—breast cancer survivorship care—as powerful new therapies are not only driving many patients’ cancers into short-term remission, but allowing them to survive for years or decades after their diagnoses.

“It’s definitely good news that we’ve made a lot of advances, and people are living longer with this disease,” says Melissa Accordino, MD, a member of the Herbert Irving Comprehensive Cancer Center and director of quality and patient safety in the Division of Hematology/Oncology at Columbia’s Vagelos College of Physicians and Surgeons. She adds that “when people are living longer, which is great, there’s more opportunity for side effects to happen and for side effects to remain, and that can definitely impact quality of life.”

The side effects of breast cancer diagnosis and treatment vary between patients, but can range from depression to early menopause and other physiological problems.

Dr. Accordino and her colleagues study peripheral neuropathy, which can cause neurological symptoms such as numbness, tingling, or chronic pain in patients’ hands or feet after chemotherapy.

“Peripheral neuropathy could present very differently in different individuals, and it could be long lasting and never go away and never improve, and that could certainly be very debilitating,” she says.

While some studies have reported that up to 80% of breast cancer patients treated with standard taxane therapy experience neuropathy after treatment, many of those patients see their symptoms diminish over time. The prevalence of longer-term persistent neuropathy has been harder to quantify, as studying it requires years of follow-up. The underlying mechanisms by which taxane treatment causes neuropathy also remain obscure. Anecdotally, Dr. Accordino says that only a small percentage of patients with post-treatment neuropathy fail to improve, but regardless of how widespread and long-lasting the condition is, there is no question it interferes with many patients’ daily lives.

Investigating new strategies to combat long-term side effects

“What we do know is that there are potentially strategies to prevent peripheral neuropathy from happening,” says Dr. Accordino.

One way to do that could be vasoconstriction, or restricting blood flow to patients’ hands and feet while they’re receiving their chemotherapy doses. Because the drugs are delivered through the bloodstream, peripheral vasoconstriction reduces the exposure of peripheral nerves to the compounds, while still allowing the drugs to reach cancer cells in the breasts. It’s not a new idea; special cooling caps, which constrict blood vessels in the scalp during chemotherapy, already help prevent treatment-induced hair loss.

Dr. Accordino’s initial tests and work by others have proved that cooling or compressing patients’ extremities decreased their rates of peripheral neuropathy after treatment. Unfortunately, patients had difficulty tolerating the cooling intervention; sitting through an entire chemotherapy session with cold hands and feet is uncomfortable. As a result, patients were less likely to comply with it. Now, Dr. Accordino’s team is designing a much larger clinical trial to try to address that issue, while also comparing three different vasoconstriction strategies to determine which works best. Patients will receive either constant compression, intermittent compression, or a combined compression and cooling intervention.

“The point of the compression [in the third group] is not really to offer increased vasoconstriction, it’s to make the cold therapy more tolerable,” she says.

The trial is expected to open in early 2023. “I’m hoping we can finish this upcoming study relatively quickly,” says Dr. Accordino, adding that “if one of these strategies works on a device that could be easily commercially available, we could prevent a large number of patients from developing neuropathy … in a relatively easy fashion that is certainly scalable.”