Adam M. Brufsky, MD, PhD
Although new targeted therapies have been introduced in recent years for patients with advanced hormone receptor (HR)-positive breast cancer, questions remain on the most effective ways to use these treatments throughout the continuum of disease, according to experts who participated in an OncLive
Several multiparametric genomic assays have been developed to predict recurrence in patients with early-stage disease, but the panelists agreed that more research is needed to clarify how these assays predict the need for and response to chemotherapy. The panelists also discussed prospective strategies for individualizing treatment for locally advanced and metastatic HR-positive breast cancer based on recent clinical trial data for extended adjuvant endocrine therapy and combinations, including aromatase inhibitors (AIs), cyclin-dependent kinase (CDK) 4/6 inhibitors, selective estrogen receptor (ER) degraders, mTOR inhibitors, and PI3K inhibitors.
Multiparametric Genomic Assays
Panelists agreed that several multiparametric genomic assays that predict risk for recurrence can guide oncologists and patients when making clinical decisions for early-stage breast cancer. However, Mark E. Robson, MD
, stated that the inability to predict benefit from chemotherapy is a key shortcoming with many of the assays. “When it comes down to conversations with the patients, you want to know are they or are they not going to benefit from incremental therapy,” said Robson.
The MINDACT trial1
investigated whether a 70-gene signature test (MammaPrint) accurately predicted response to adjuvant chemotherapy in patients with breast cancer (≤3 positive lymph nodes). Use of the test led to a 14% reduction in administration of adjuvant chemotherapy for patients classified as low genomic/high clinical risk or high genomic/low clinical risk. The low genomic/high clinical risk patients who did not receive chemotherapy had a 5-year distant metastases-free survival of 94.7%, surpassing the null hypothesis of 92%. However, Robson cautioned that MINDACT was designed as a noninferiority trial, and was thus underpowered to determine conclusively the lack of chemotherapy benefit. Furthermore, he indicated that some patients and their oncologists may wish to pursue chemo- therapy, even if the predicted benefit is small. “Some people think that a 1 or 2 percentage point benefit in terms of chemotherapy benefit in that genomically low, clinically high-risk group is worthwhile,” Robson said.
The panelists also stated that results from the TransATAC trial2
suggested that the predictive power of these genomic assays may depend on the presence of node-positive disease. The study, which compared the prognostic performance of 6 signatures over a 10-year follow-up in postmenopausal patients with HR-positive breast cancer, showed that the Clinical Treatment Score and EndoPredict were most prognostic for node-positive cancer, whereas the PAM50-based Prosigna was most prognostic for node-negative cancer.
Additionally, only EndoPredict accurately predicted relapse in the 5- to 10-year range (after cessation of treatment) for patients with node-positive cancer, which led Adam M
. Brufsky, MD, PhD
, the moderator of the panel, to question the utility of genomic assays for predicting long-term relapse and chemotherapy benefit in this group of patients. However, Kimberly L. Blackwell, MD,
was less concerned about genomic assays for node-positive tests; she stated that she typically recommends extended adjuvant chemotherapy for all patients with node-positive, HR-positive cancer who can tolerate it regardless of the results on a genomic assay. Blackwell also noted that previous data validating the 21-Gene Recurrence Score in node-positive patients and the MINDACT trial provide “a consistent signal that these genomic predictors actually do work in node-positive [disease],” although she indicated that the ability of the assays to predict need for chemotherapy in this group remains to be determined.
Nevertheless, Blackwell emphasized that providing information on the biology of the tumor with a genomic assay is often more relevant for assessing clinical risk than tumor size and lymph node status, because they can guide treatment for a case, such as a grade 1, ER-negative tumor, that “doesn’t make any sense.”