BARCELONA-A multicenter nationwide Italian study of patients with ductal carcinoma in situ (DCIS) treated with breast conservative surgery (BCS) and whole breast radiotherapy has updated risk criteria to help women opt for gentler treatments and avoid toxicities from overtreatment.

"A diagnosis of DCIS can be frightening, but also confusing. Although we know that very few patients will go on to develop invasive cancer, we don't know which ones they will be and so we offer treatments such as surgery and radiotherapy and sometimes hormone therapy," said Icro Meattini, MD, Consultant Clinical Oncologist in the Radiation Oncology Department at Azienda Ospedaliero-Universitaria Careggi, University of Florence, Italy, at the 2018 European Breast Cancer Conference (Abstract 215).

As a result of the new study, Meattini was able to list leading factors that could prompt less-aggressive therapy. "Clear margins, advanced age, positive hormonal status-these [indicate] low-grade tumors most suitable for de-escalation," he said.

With more than 20 percent of patients diagnosed with breast cancer and a lack of agreement about the role of adjuvant treatments after surgery for DCIS, Meattini said DCIS was challenging. "We were looking for prognostic factors and a low-risk group of patients for whom de-escalation of treatment is a suitable option-because overtreatment is a concern."

Multicenter Study

In a retrospective analysis from nine centers in Italy, 1,072 patients with DCIS were treated with BCS and adjuvant radiotherapy. Among 557 patients who were ER-positive, just over half received adjuvant endocrine therapy (ET). The study reported 5- and 10-year local recurrence (LR) rates (in situ or invasive recurrence), overall survival (OS), and breast cancer-specific survival (BCSS).

The researchers confirmed factors for low risk that included ER-positivity and post-menopausal status, which were both protective. "Final surgical margin status is the most important [poor prognostic] factor. Less than 1 mm final surgical margin is related to worse outcome and higher risk of local relapse," Meattini said.

After a mean follow-up of 8.4 years, there were 67 relapses and 47 deaths. Twenty-five patients had in situ LR and 42 had invasive relapse. Eleven of the deaths were related to breast cancer.

The mean time to LR was 7 years; 3.4 percent of patients had LRs within 5 years and by 10 years the rate had risen to 7.6 percent. OS rates at 5 years and 10 years were 98.5 percent and 97 percent, respectively. The BCSS rates at 5 years and 10 years were 99.7 percent and 99.1 percent, respectively.

Univariate analysis found postmenopausal status to be protective with a hazard ratio (HR) of 0.5. Progesterone receptor-positive patients had a similar degree of protection from recurrence (HR=0.46). Even more protective were ER positivity (HR=0.32) and the use of ET (HR-0.39).

Having final surgical margins (FSM) below 1 mm significantly increased LR rates (HR=3.25).

At multivariate analysis, post-menopausal status (HR=0.40) and positive hormone receptors (HR=0.35) remained significant favorable factors, while FSM below 1 mm (HR=3.3) was confirmed to increase LR.

Analysis of the impact of adjuvant ET for the ER-positive group of patients revealed no significant effect in terms of all LR, invasive LR, or OS. The researchers stated that no clinical variable statistically affected OS and BCSS rates.

De-Escalation Trials Needed

"I think these data should be integrated with existing data from controlled trials and help in a multidisciplinary approach to select patients for de-escalation. For example, post-menopausal patients, ER-positive patients, and clear margin patients are candidates [for] de-escalation of treatment," Meattini said.

"We observed quite low risk of local recurrence at 5 and 10 years-in line with the literature-even in patients who did not receive adjuvant endocrine therapy," he said, noting that ET did not make much difference, even in patients who were ER-positive. "Half of the patients with positive hormonal status received endocrine treatments, [but it] did not seem to influence local recurrence." He suggested that de-escalation of adjuvant hormonal treatment could be an option for these patients.

The study found very low rates of death for patients treated with BCS for in situ disease. "We found less than 1 percent of breast cancer-specific survival, so this is a really good prognosis disease."

Clear Surgical Margin

Meattini said the lack of a clear surgical margin was the most important factor. "Extra radiation boost in cases of positive margins seems not to be able to overcome this adverse prognostic factor. Even systemic therapy is not able to [do so]."

He urged clinicians to make multidisciplinary evaluations of patients. "Consider not only the local recurrence rate. Consider the performance status, comorbidity, and the age [and] frailty of patients because many patients could be more suitable for less-intensive treatment."

Meattini heralded the results of this study as offering all patients with DCIS reassurance that the risk of their cancer returning was very low when treated with breast-conserving surgery followed by radiotherapy. "For patients who are post-menopausal or whose cancer is ER-positive, the likelihood of recurrence is even lower. [And] where the results of surgery reveal very small cancer-free margins, the risk of recurrence is higher."

He made a call for individualization of therapy and research on treatment de-escalation. "Now we need to do more research to find out if lower-risk patients can safely be given less treatment-or even no treatment-as well as studies on how best to treat higher-risk patients. It's vital that each patient receives treatment that is best suited to their individual cancer and their particular circumstances."

"Thousands of women are diagnosed with DCIS every year," noted Isabel T. Rubio, MD, PhD, Surgical Oncologist and Director of the Breast Surgical Unit at Clinica Universidad de Navarra in Madrid, Spain, and co-chair of the 2018 European Breast Cancer Conference, who was not involved in the research. "Although it is non-invasive, a proportion of patients will go on to develop invasive breast cancer. So, surgery and radiotherapy are usually recommended. This study provides more reassurance to patients that their risk of recurrence is low. It also provides doctors with more information on which patients have a higher chance of a recurrence, and points the way to further research on how to tailor treatments to individual patients."

Peter M. Goodwin is a contributing writer.