Gene Signature May Be Similarly Prognostic in ILC and IDC

Susan London

October 20, 2020

The MammaPrint 70-gene signature has similar prognostic performance in women with early-stage invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) and may help guide chemotherapy decisions, according to an exploratory analysis of the MINDACT trial reported at the 12th European Breast Cancer Conference.

ILC is enriched with features indicating low proliferative activity, noted investigator Otto Metzger, MD, of the Dana Farber Cancer Institute in Boston.

"Data from retrospective series have indicated no benefit with adjuvant chemotherapy for patients diagnosed with early-stage ILC," he said. "It's fair to say that chemotherapy decisions for patients with ILC remain controversial."

With this in mind, Metzger and colleagues analyzed data for 5,313 women who underwent surgery for early-stage breast cancer (node-negative or up to three positive lymph nodes) and were risk-stratified to receive or skip adjuvant chemotherapy based on both clinical risk and the MammaPrint score for genomic risk. Fully 44% of women with ILC had discordant clinical and genomic risks.

With a median follow-up of 8.7 years, the 5-year rate of distant metastasis–free survival among all patients classified as genomic high risk was 92.1% in women with IDC and 88.1% in women with ILC, with overlapping 95% confidence intervals. Rates of distant metastasis–free survival for patients with genomic low risk were 96.4% in women with IDC and 96.6% in women with ILC, again with confidence intervals that overlapped.

The pattern was essentially the same for overall survival, and results carried over into 8-year outcomes as well.

"We believe that MammaPrint is a clinically useful test for patients diagnosed with ILC," Metzger said. "There are similar survival outcomes for ILC and IDC when matched by genomic risk. This is an important message."

It should be standard to omit chemotherapy for patients who have ILC classified as high clinical risk but low genomic risk by MammaPrint, Metzger recommended. "By contrast, MammaPrint should facilitate chemotherapy treatment decisions for patients diagnosed with ILC and high-risk MammaPrint," he said.

Prognostic, but Predictive?

"This is a well-designed prospective multicenter trial and provides the best evidence to date that MammaPrint is an important prognostic tool for ILC," Todd Tuttle, MD, of University of Minnesota in Minneapolis, said in an interview.

Tuttle said he mainly uses the MammaPrint test and the OncoType 21-gene recurrence score to estimate prognosis for his patients with ILC.

These new data establish that MammaPrint is prognostic in ILC, but the value of MammaPrint's genomic high risk result for making the decision about chemotherapy is still unclear, according to Tuttle.

"I don't think we know whether MammaPrint can predict the benefit of chemotherapy for patients with stage I or II ILC," he elaborated. "We need further high-quality studies such as this one to determine the best treatment strategies for ILC, which is a difficult breast cancer."

Study Details

Of the 5,313 patients studied, 487 had ILC (255 classic and 232 variant) and 4,826 had IDC according to central pathology assessment, Metzger reported.

MammaPrint classified 39% of the IDC group and 16% of the ILC group (10% of those with classic disease and 23% of those with variant disease) as genomically high risk for recurrence. The Adjuvant! Online tool classified 48.3% of ILC and 51.5% of IDC patients as clinically high risk.

Among the 44% of women with ILC having discordant genomic and clinical risk, discordance was usually due to the combination of low genomic risk and high clinical risk, seen in 38%.

The curves for 5-year distant metastasis–free survival stratified by genomic risk essentially overlapped for the IDC and ILC groups. Furthermore, there was no significant interaction of histologic type and genomic risk on this outcome (P = .547).

The 5-year rate of overall survival among women with genomic high risk was 95.6% in the IDC group and 93.5% in the ILC group. Among women with genomic low risk, 5-year overall survival was 98.1% in the IDC group and 97.7% in the ILC group, again with overlapping confidence intervals within each risk category.

The study was funded with support from the Breast Cancer Research Foundation. Metzger disclosed consulting fees from AbbVie, Genentech, Roche, and Pfizer. Tuttle disclosed no conflicts of interest.

SOURCE: Metzger O et al. EBCC-12 Virtual Conference. Abstract 6.

This article originally appeared on, part of the Medscape Professional Network.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as: