In breast cancer treatment, when is less actually more?
That question is the crux of a the COMET trial: a study designed to understand the risks and benefits of people with low-risk, non-invasive breast cancers, or ductal carcinoma in situ (DCIS), opting for active monitoring instead of surgery.
The results of the two-year follow-up, presented at the 2024 San Antonio Breast Cancer Symposium and published in JAMA Oncology, are promising. They showed that both arms of the study—one that underwent surgery, following the current standard-of-care, and another that opted for active monitoring with breast imaging and a physical exam every six months—had similar outcomes: neither group were more likely to develop invasive cancer than the other.
The study, however, didn’t stop there. Dr. Ann Partridge, a breast medical oncologist at the Dana-Farber Cancer Institute, was a lead author on the study’s patient reported outcomes: how did patients feel when following a lower intervention path?
To Treat or Not to Treat
DCIS, which accounts for about one-quarter of all breast cancer diagnoses in the U.S., presents a unique challenge for physicians, Partridge said.
“Non-invasive breast cancer is something that might turn into invasive breast cancer and harm a woman, but it might not.”
She explained that DCIS is currently treated similarly to invasive breast cancers—often with a combination of surgery, radiation, and endocrine therapy—in the absence of knowledge about the natural history of the cancer, or how the disease would progress without intervention.
However, each treatment comes with side effects, which is what prompted the question: "Could we do less and still have good outcomes for these women?"
What are Patient Reported Outcomes?
“They're just what they sound like,” said Partridge.
She explained that patient reported outcomes allow researchers to hear and understand a patient’s lived experience throughout a study by using “validated survey measures,” or instruments, to make sure they measure what they intend to measure.
In the case of the COMET trial, researchers intended to observe how active monitoring, rather than surgery, impacted a person’s quality of life and psychosocial health, including the prevalence of depression and anxiety.
“We use these validated instruments to look at the patient experience going on the study at baseline and then overtime to see how the patient experiences things over time,” said Partridge. “We often compare these patient reported outcomes between study groups to see if a given treatment or management strategy impacts patients differently.”
What they found after the two-year follow-up was not what they thought, she explained. Those who left their cancer and were followed with active monitoring experienced similar rates of anxiety or depression as those who followed standard-of-care treatment.
However, Partridge said, these results do not come without a caveat: “This isn't for everyone.”
She explained that anecdotally, patients may have been offered to participate in the trial but were uncomfortable with potentially being randomized into the active monitoring arm. This could mean that the psycho-emotional state of someone who agreed to participate may be different.
Growing Our Understanding of DCIS
While the initial outcomes of the COMET trial are exciting, “we have only presented and looked at two year outcomes.” Partridge explained they intend to continue following the patients in the trial to see five-, seven-, and hopefully ten-year outcomes, complemented by additional patient reported outcomes.
The researchers also want to to take a deeper dive into the cancer itself.
“We also want to look at biomarkers, which means looking at the actual tumor cells and the cells around it, and other features of the biomedical situation of the patients to understand what might predict a person going on to getting invasive breast cancer and what might predict safety.”
She explained that doing so will also allow them to better understand the cases of DCIS that do turn into invasive disease, what kind of invasive breast cancer, and whether “active monitoring worked better in any particular group than another.”
“We'll see these things over time as the study matures.”
Unique Challenges for Younger Populations
To note, the COMET trial excluded patients under 40-years-old. Why?
“The COMET trial was designed with safety at the foremost of our thoughts,” said Partridge, who explained that those who are diagnosed under the age of 40 often present with higher-risk cancers.
For example, she said, people under 40 typically are not being routinely screened with mammograms and often present with bigger tumors. “You [also] tend to see more aggressive subtypes of breast cancer, including DCIS, in younger patients,” said Partridge.
Those who are being screened below the age of 40 likely have a known risk factor, like a genetic variant, “and we didn't want to expose that woman to any undue risk before we could determine whether it's safer in a lower risk population in general.”
However, as a principal investigator on the Young Women’s Breast Cancer Study (YWS), supporting younger populations is a cause Partridge is passionate about.
“Early onset breast cancer is unfortunately increasing in the United States,” she said. “I think it's critical that we put our feet on the gas even more than we have to understand why that's happening, to try and prevent that from happening from a population basis.
“Then when women do indeed get breast cancer at a young age—defined as 40 and under in most studies—how can we better treat them and better support them in their survivorship?”
A call-to-action Partridge has for young people impacted by breast cancer? “When you're offered a study, participate in it if it makes sense for you.”
“We want to learn from every young patient who gets diagnosed with breast cancer so that we can use your experience to inform how we care for women in the future.”
