Top MBCC Abstracts Focus on Tumor Profiling and Radiotherapy Paradigms

Patrick I. Borgen, MD

A detailed tumor profile of molecular and protein alterations in a rare breast cancer subtype and a retrospective analysis about the impact of radiation after breast conserving surgery took home top honors at the Miami Breast Cancer Conference this year.

The two abstracts, one in the medical oncology category and one in the surgical oncology track, were chosen from a field of 80 abstracts submitted for consideration, with entrants divided almost evenly between the divisions. Faculty members evaluated the abstracts and chose the winners.

Program Chair Patrick I. Borgen, MD, said he was pleased both with the number of submissions—which represent an increase over last year—and the quality of the research. He said he is contemplating ways to enhance this aspect of the conference to give the submitted abstracts greater visibility, in order to attract “bright young investigators” to the annual gathering.

“We want to involve them early in their careers so that Miami becomes home,” he said. “We want to establish Miami as a place where they’ve presented, they’ve learned, and they want to come back to year after year.”

In the winning medical abstract, researchers used technology from Caris Life Sciences to conduct a multiplatform 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 FDA-approved targeted therapies in 16 areas, or with immunotherapies now under study.

In the top surgical abstract, a team from Upstate Cancer Center in Syracuse, New York, examined data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) registry to determine whether older women with estrogen receptor (ER)—negative breast cancer derive benefit from adjuvant radiation following breast conserving surgery.

Extracting Clues From Tumors

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

The other members of the research team were Joyce A. O’Shaughnessy, MD, co-director of Breast Cancer Research at Texas Oncology/US Oncology at Baylor Charles A. Sammons Cancer Center in Dallas, and Rebecca Feldman, PhD, also of Baylor.

Investigators culled the tissue specimens from 2000 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.

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

• mTOR pathway inhibitors: PI3K pathway alterations, either through PTEN loss or PIK3CA mutations (52% of cases)
• Gemcitabine: low RRM1 expression (68%)
• Imatinib or antiandrogen therapies: cKIT (9%) or androgen receptor protein overexpression (8%)
• MEK inhibitors: HRAS (21%) or BRAF mutations (2%)

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 said.

“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.”

Examining Radiotherapy Assumptions

In the top surgical oncology abstract, researchers sought to evaluate whether radiotherapy would benefit patients aged 70 years or older with ER-negative, T1 invasive ductal breast cancer who had undergone breast conserving surgery.

The randomized CALGB 9343 study found that radiotherapy did not improve overall survival (OS) for patients of similar age and tumor size with ER-positive disease, said lead author Emily C. Daugherty, MD, of the Department of Radiation Oncology at Upstate Cancer Center. She and her colleagues, Michael R. Daugherty, MD, and Anna Shapiro, MD, wondered whether the same findings would hold true for patients with ER-negative disease, who have fewer treatment options.

To explore the question, the researchers queried SEER registries for patients surgically treated for breast cancer between 1998 and 2011, and created two cohorts: one for the 3685 patients treated with radiation and another for the 1493 individuals who did not receive radiation.

The outcomes between the two groups differed sharply. The 5-year median OS for patients who received radiotherapy was 139 months, or 81.0%, versus 88 months, or 61.7%, for those who did not (P <.0001). Additionally, the 5-year cancer-specific survival rates were 93.1% with radiotherapy versus 85.0% without radiotherapy (P <.0001).

The differences are “pretty large and significant,” said Emily Daugherty. She said a limitation of the study was that the data are retrospective and were drawn from registries.

However, she said, the differences in survival rates—particularly cancer-specific survival&mdash;are large enough that physicians should consider the potential benefit in this setting. “It warrants a good discussion with the patient and seeing what their goals of care are,” Daugherty said.

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