Extracting Clues from a Rare Type of Breast Cancer

A detailed tumor profile of molecular and protein alterations in a rare breast cancer subtype called metaplastic breast cancer, was one of the top studies presented at the Miami Breast Cancer Conference this year.

A detailed tumor profile of molecular and protein alterations in a rare breast cancer subtype called metaplastic breast cancer, was one of the top studies presented at the Miami Breast Cancer Conference this year.

Researchers used technology from Caris Life Sciences to conduct an analysis of tumor samples from 126 patients with metaplastic breast cancer, a rare subtype typically classified as triple negative. They found mutations or proteomic characteristics that could potentially match patients with approved targeted therapies in 16 areas, or with immunotherapies now under study.

Metaplastic breast cancer represents less than 1 percent of all breast cancers and is often combined with triple-negative cancers, although the tumors have a very different profile, says Sherri Z. Millis, a scientist at Caris, the lead author on the top medical oncology abstract.

Investigators culled the tissue specimens from 2,000 triple-negative breast cancer tumor samples that Caris has amassed in its database since 2009. The tumors were sequenced using either Sanger or next-generation technologies, analyzed for protein expression with immunohistochemistry, and for gene amplification with in situ hybridization assays.

Those that were the most prevalent mutations or biomarkers that could potentially correlate with already approved therapies were:

· mTOR pathway inhibitors: PI3K pathway alterations, either through PTEN loss or PIK3CA mutations (52 percent of cases)

· Gemcitabine: low RRM1 expression (68 percent)

· Imatinib or antiandrogen therapies: cKIT (9 percent) or androgen receptor protein overexpression (8 percent)

· MEK inhibitors: HRAS (21 percent) or BRAF mutations (2 percent)

In addition, high expression levels of PD-1 and its ligand, PD-L1, would make patients with those characteristics potential candidates for clinical trials of immunotherapy agents under study, the researchers said.

Millis said the study illustrates the value of tumor analysis. “Every person’s cancer is unique and the only way to get at the uniqueness of that cancer is to do the genetic and the proteomic testing,” she says.

“We were able to identify that the majority of the metaplastic triple-negative population has something that has a targetability in an FDA-approved medication,” added Millis.

Going forward, Millis said, “One of the future goals is to look at metaplastic breast cancers and identify potentially a different standard of treatment compared to the triple-negative breast cancers. They’re both very aggressive diseases. There are not a lot of good treatment options, so anything we can do to identify treatment options is going to be helpful to these women.”