Genetic test identifies patients with invasive lobular breast cancer at high risk of disease recurrence

A test that scans the activity of 70 genes in breast cancer tissue can help identify patients with invasive lobular carcinoma (ILC) who have a high risk of the cancer recurring or progressing after surgery, new research by Dana-Farber Cancer Institute investigators shows. The findings, based on an international clinical trial involving nearly 500 women with ILC, will be presented at the 12^th European Breast Cancer Conference (EBBC) today.

Although the vast majority of patients who undergo surgery for ILC respond well to hormone therapy and do not require further treatment, some patients face an increased risk of the cancer recurring and might benefit from follow-up treatment with chemotherapy, radiation therapy, or targeted therapies. In the new study, researchers found that the 70-gene test, known as MammaPrint, identified some of these high-risk patients in a phase III clinical trial.

ILC accounts for about 10% of cases of invasive breast cancer.  Determining which patients are likely to benefit from treatment after surgery and hormonal therapy has been a challenge.

“The decision about whether or not to treat patients diagnosed with invasive lobular carcinoma with chemotherapy is difficult,” says Dana-Farber’s Otto Metzger, MD, who will be presenting the research at the EBBC. “Results from earlier research that I carried out with Professor Christos Sotiriou at the Institut Jules Bordet, in Belgium, indicated that 10 to 15% of ILC cases were classified as high-risk at a genomic level. These had worse survival outcomes when compared to those classified as low-risk.”

The new study drew on data from the MINDACT study, a phase III trial comparing genetic testing and traditional clinical tests in their ability to determine which women with breast cancer that has spread to no more than three lymph nodes are likely to benefit from chemotherapy after surgery. Of the 5,313 participants evaluated in the trial, 487 had ILC, including 255 classic cases of the disease and 232 variants, and 4,826 had invasive ductal carcinoma (IDC),

The 70-gene signature test classified 16.2% of the patients with ILC, and 39.1% of those with IDC, as being at high genomic risk for cancer recurrence.

The researchers found that estimates for the proportion of patients surviving without the disease recurring (disease-free survival, DFS) or without the disease spreading to other parts of the body (distant metastases-free survival, DMFS) at five years were similar for both ILCs and IDCs that had been classified as high-risk by the 70-gene signature test. DFS was 87.1% for IDC and 84.6% for ILC. DMFS was 92.3% for IDC and 89.4% for ILC.

Estimates for IDCs and ILCs that the 70-gene signature test classified as low risk were also similar. DFS was 92.5% for IDC and 92% for ILC. DMFS was 96.5% for IDC and 96.6% for ILC.

Says Metzger, “We found that DMFS and DFS estimates were similar for ILC and IDC classified as either low or high-risk by the 70-gene signature test. This suggests that the test has prognostic value for ILC. The incorporation of biological features defined by the 70-gene signature test in the treatment decisions for patients diagnosed with ILC should facilitate a complex decision-making process, that includes the extent of disease, other health conditions and patients’ preferences.”

In a statement before the conference, the principal investigator of the MINDACT trial, Fatima Cardoso, MD, director of the Breast Unit of the Champalimaud Clinical Centre, in Lisbon, Portugal, said, “Here we report for the first time the utility of the 70-gene signature test in a large group of patients with ILC in the MINDACT randomised phase III clinical trial. These results are important for clinicians to help them choose a precise treatment approach tailored to the individual patient.”