'Encouraging' Results With Pre-Op Therapy for DCIS

First-of-Its-Kind Trial

Nick Mulcahy

April 17, 2020

First-of-its-kind findings suggest that hormonal therapy could be the primary treatment instead of surgery for women who are diagnosed with a precursor of breast cancer, ductal carcinoma in situ (DCIS).

New results show that pre-operative endocrine therapy produced measurable radiographic changes in a cohort of postmenopausal women with estrogen receptor (ER)–positive disease. Additionally, 15% had pathologic complete responses, which were assessed after surgery as part of the study design.

The study was published on March 3 in the Journal of Clinical Oncology.

Before the current results, the benefit of endocrine therapy in the absence of surgery for DCIS has been "largely unknown," say the authors, led by Shelley Hwang, MD, of Duke University, Durham, North Carolina.

The data "represent an important step forward" in developing nonsurgical regimens for breast cancer risk reduction, say Matteo Lazzeroni, MD, and Andrea De Censi, MD, of the European Institute of Oncology, Milan, Italy, in an accompanying editorial.

They explain that primary endocrine treatment and/or active surveillance are not generally offered in DCIS because it's hard to tell which lesions are indolent and which are likely to progress to invasive disease.

However, the editorialists point out that two phase 3 studies, including the Comparison of Operative versus Monitoring and Endocrine Therapy (COMET) trial in the United States, are examining endocrine therapy as a long-term alternative to surgery for low-risk DCIS.

In the meantime, clinicians can look at the data from Hwang and colleagues and find "encouraging" results, the Italian duo say.

Complete Response in 15%

The new study is a phase 2, single-arm, multicenter US cooperative-group trial, known as Cancer and Leukemia Group B (CALGB) 40903, now part of the Alliance for Clinical Trials in Oncology. The trial involved 79 postmenopausal patients diagnosed with ER-positive DCIS without invasion. Patients were treated with letrozole 2.5 mg per day for 6 months before surgery.

The primary end point was the change in 6-month tumor volume from baseline (as assessed by magnetic resonance imaging [MRI]).

A total of 67 patients completed the 6 months of drug therapy and had all of the necessary imaging; most had intermediate- or high-grade disease (90.6%).

Median reduction from baseline MRI volume (1.4 cm3) was 0.8 cm3 (71.7%) at 6 months (P < .001).

Of the 59 patients who underwent surgery per study protocol, DCIS remained in 50 patients (85%), invasive cancer was detected in six patients (10%), and no residual DCIS or invasive cancer was seen in nine patients (15%), report the authors.

That only 10% of patients were upgraded after surgery was a surprise, say the editorialists.

That suggests "a possible down staging effect of letrozole for concurrent invasive cancer at baseline," they speculate, adding that such an effect would be an important potential benefit of this nonsurgical treatment of DCIS.

The authors highlighted the fact that nine patients (15%) had no disease present at surgery. These pathologic complete responses included three of the five patients in the cohort with low-grade DCIS. These outcomes occurred despite calcifications that ranged from 15 mm to 59 mm among the nine patients, they comment.

"Although this [complete response] finding is not definitive because of the small sample size and short duration of treatment, it nevertheless is provocative and suggests some women with DCIS may in the future be candidates for primary endocrine therapy alone," write Hwang and team.

The authors also acknowledge that MRI has known limitations for assessing DCIS, "including variable concordance with pathologic size." Notably, about 25% of the baseline MRIs in the study did not meet study criteria.

Nevertheless, the authors observe that two other histologies with a high risk of subsequent breast cancer, lobular carcinoma in situ and atypical hyperplasia, are treated preventively with primary endocrine therapy.

So this treatment approach exists and "should be studied more in DCIS as a long-term to surgery for low-risk DCIS," the authors conclude.

Change is needed, suggest the editorialists.

DCIS of the breast accounts for up to 25% of all breast cancers in the era of screening mammography, they point out.

However, while DCIS incidence has increased by more than seven times from 1980 to 2007, its treatment has not translated into a decreased incidence of invasive breast cancer during this period.

The study was supported the National Cancer Institute. Hwang has disclosed no relevant financial relationships, but multiple study authors have ties to pharmaceutical companies. The editorial was supported by grants from the Italian Ministry of Health, Italian Association for Cancer Research, and the Italian League Against Cancer; and partially supported by the Italian Ministry of Health. Lazzeroni reported no relevant financial relationships, but De Censi disclosed research funding from Ente Ospedaliero Ospedali Galliera and non-financial ties to Novartis.

J Clin Oncol. 2020;38:1284-92, 1252-54. Abstract, Editorial

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