Genetic Test Spots High-Risk Invasive Lobular Carcinoma

By Megan Brooks

October 06, 2020

NEW YORK (Reuters Health) - A test that looks at the activity of 70 genes in breast tumors can help identify women with invasive lobular carcinoma (ILC) at high-risk of cancer recurrence or progression after surgery who may benefit from additional therapy, according to new research.

ILC accounts for 10% of invasive breast cancers. Although most women who have surgery respond well to hormone therapy and need no further treatment, some face an increased risk of the recurrence and might benefit from chemotherapy, radiation or targeted therapies.

Pinpointing this high-risk group has been "challenging," Dr. Otto Metzger of Dana-Farber Cancer Institute and Harvard Medical School in Boston, who presented the data October 2 at the virtual European Breast Cancer Conference, told Reuters Health by phone.

Dr. Metzger and colleagues assessed the utility of the MammaPrint 70-gene signature test to spot high-risk women with ILC who might benefit from additional therapy. Participants included more than 5,000 women from the MINDACT trial, including 487 with ILC (255 classic cases of the disease and 232 variants) and 4,826 with invasive ductal carcinoma (IDC).

"This is a very pristine data set in the sense that we have central pathology review and MammaPrint for all cases," Dr. Metzger told Reuters Health. Also, the women were followed for an average of five years, "which is a good follow-up for this type of breast cancer."

MammaPrint classified 16.2% of all ILC and 39.1% of IDC as high-genomic-risk. When comparing classic to variant ILC, the test classified 10.2% of classic ILC and 22.8% of ILC variants as high-risk.

"This tells us that we have a significant proportion of lobular patients classified as high-risk, and we should try to identify them in our clinical practice, given the implications for treatment decision," Dr. Metzger said.

At five years, disease-free survival (DFS) and distant-metastases-free survival (DMFS) were similar for both ILC and IDC classified as high-risk. DFS was 84.6% for ILC and 87.1% for IDC. DMFS was 89.4% and 92.3%, respectively.

DFS and DMFS for ILC and IDC classified as low-risk were also similar. DFS was 92.0% and 92.5% and DMFS was 96.6% and 96.5%, respectively.

The finding that DFS and DMFS estimates were similar for ILC and IDC classified as either low- or high-risk by the 70-gene signature test "suggests that the test has prognostic value for ILC," Dr. Metzger said in a conference statement.

"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," Dr. Metzger stated.

"ILC in general is thought to be a subtype where the great majority of patients would not benefit from adjunct chemotherapy after an early diagnosis," Dr. Metzger told Reuters Health. "The data from MINDACT say in a very elegant way that this is not necessarily true, because when you take MammaPrint results, you can see that a significant proportion of lobular carcinoma is classified as high-risk. This type of analysis does not give us a clear answer to say that the high-risk lobular should be treated with chemotherapy but indirectly points to that direction."

Commenting on the results in a statement, conference chair Dr. Nadia Harbeck said,"The results of this study show that the 70-gene signature test may play a useful role in the clinic when doctors are considering whether their patients with invasive lobular carcinoma might benefit from treatments such as chemotherapy in addition to surgery."

"This analysis of over 5,000 women with early breast cancer in the MINDACT trial is an important contribution to our knowledge of the best way of treating these women," said Dr. Harbeck of the University of Munich in Germany.

The research was funded with support from the Breast Cancer Research Foundation. Dr. Metzger has disclosed financial relationships with AbbVie, Genentech, Roche and Pfizer.

SOURCE: https://bit.ly/36pumFU 12th European Breast Cancer Conference, presented October 2, 2020.

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