Clinical Challenge: Overdiagnosis of DCIS and High-Risk Breast Lesions

Before breast screening with mammography became routine, ductal carcinoma in situ (DCIS) and high-risk breast lesions were rarely found. Now with the widespread use of mammography, those breast abnormalities are more frequently found; but whether, and what kind of, treatment is warranted remains controversial.

Evidence of this problem is the fact that DCIS was estimated to comprise 16% of breast cancer diagnoses between 2012 and 2016, but more recent estimates place the incidence between 20% and 25%.

Also, a study of more than 375,000 mammography screenings found that the frequency of detecting a high-risk breast lesion after core needle biopsy tripled during the 6-year study period, increasing from 3.2% in 2011 to 9.5% in 2016. An increase in surgeries was also seen.

But detecting more DCIS and high-risk breast lesions has not led to improved outcomes, particularly for DCIS.

“While we’re diagnosing more DCIS and we’re treating more DCIS, you would think that it would translate to a decrease in invasive cancer, but that’s not the case,” said Susie X. Sun, MD, breast surgeon and assistant professor at The University of Texas MD Anderson Cancer Center in Houston. She explained that the incidence of invasive cancer has been stable despite finding more DCIS and treating more DCIS, according to the latest Breast Cancer Facts and Figures.

Working Together

Sun said there is “a lot of variability” around treatment of high-risk breast lesions, such as atypical ductal hyperplasia (ADH) and atypical lobular hyperplasia (ALH). She works with a multidisciplinary team to more accurately determine how high risk a lesion is to avoid overtreating these patients.

She explained that while not all high-risk lesions require excision, they do get excised at a lot of institutions. At her center, a conference every week is dedicated to discussing patients’ high-risk lesions, with surgeons, pathologists, radiologists, and other relevant experts present, Sun said.

Together, the team reviews the patient cases and details, from their imaging studies to biopsy slides, and comes up with a multidisciplinary consensus regarding the risk of finding a breast cancer at the time of excision, also known as the upgrade rate. Based on that risk, the team recommends whether excision is warranted or if the patient’s lesion can be safely monitored with imaging.

Shift in Conventional Thought

“Historically speaking, the thought was, if you have DCIS, eventually you’re going to get invasive cancer,” said Sun. “But we really don’t know if that is true or not.”

Although DCIS is considered a precursor to invasive breast cancer, long-term evidence suggests that, while a proportion of patients do develop invasive breast cancer, many don’t. For instance, a 2006 review of the literature indicated that between 14% and 53% patients with DCIS develop invasive breast cancer during a time period of 10 or more years.

A 2015 retrospective study with long-term follow-up for 45 women with low-grade DCIS who did not receive treatment beyond tissue biopsy found that 16 women, or 36%, were later diagnosed with invasive breast cancer.

The presence of previously unknown DCIS has even been found during autopsies of women. “Who knows how long these women have had this DCIS that they just lived with their entire lives,” Sun said.

“Now there is this concern with overtreatment of DCIS,” said Sun. Most women are treated with surgical excision, usually followed by radiation, and mastectomy is not uncommon.

Sun explained that some people think that if DCIS doesn’t have a propensity to spread anywhere else in the body, treatment won’t impact overall survival.

“So why are we doing all of this? Why are we treating it the way we treat invasive cancer?” she posited.

An observational study in JAMA Oncology with 20 years of follow-up found that while patients with DCIS who underwent more aggressive treatment generally had a lower risk of ipsilateral recurrence, their risk of dying from breast cancer was the same as those with less treatment.

For example, among patients who underwent lumpectomy, those who also had radiation had a lower risk of invasive recurrence in the ipsilateral breast compared with those who did not have radiation but did not have a lower risk of dying from breast cancer at 10 years.

“We know we are overtreating DCIS that, when diagnosed, will never harm the women,” said Charles Shapiro, MD, a hematologist-oncologist at the Icahn School of Medicine at Mount Sinai in New York City, echoing a similar view. “We are just not smart [enough] to pick those out, but I am confident we will get there in the next 5 to 10 years.”

De-escalating Treatment

Sun and Shapiro noted that there are several ongoing studies aiming to de-escalate treatment for DCIS: the COMET, LORIS, LORD, and LORETTA trials.

The LORIS trial, conducted in Europe, and the LORD trial, conducted in the U.K., were both initially comparing active monitoring for low-risk DCIS to surgery (LORIS) or standard treatment (LORD) but had to convert to registry trials given slow patient accrual. LORETTA is a single-arm trial in Japan evaluating active surveillance and endocrine therapy in patients with low-risk DCIS.

The COMET trial, conducted in the U.S., is currently the only prospective randomized clinical trial evaluating active monitoring compared with surgery for patients with low-risk DCIS. It is projected to finish in 2023.

“These trials will provide information on the natural history of DCIS and help identify situations where DCIS can be monitored without surgical excision,” said Sun.