Including Tumor Biological Factors Improves Breast Cancer Staging

Refining the American Joint Committee on Cancer (AJCC) breast cancer staging system to include molecular tumor markers will improve patient risk stratification and determination of prognosis, according to research discussed at the 34th Annual Miami Breast Cancer Conference, held March 9–12 in Miami Beach, Florida.

“Incorporating biologic factors into breast cancer staging refines the stratification of patients by prognosis,” said Kelly K. Hunt, MD, FACS, Breast Surgical Oncology, University of Texas MD Anderson Cancer Center in Houston. “Biological factors have been incorporated into the 8th edition of the AJCC breast cancer staging system. […]It’s encouraged that we continue to use anatomic staging, particularly because in parts of the world we do not have biomarker information. But now we’re going to include prognostic staging as well.”

Breast cancer has traditionally been staged using the tumor-node-metastasis (TNM) system from earlier editions of the AJCC guidelines. The system was first developed in 1959 and is updated periodically to incorporate new information about tumor anatomy and extent, and prognosis. Individual tumor, lymph node, and metastatic status are classified into stages based on anatomic criteria, and associations with patient outcomes have been assessed with large cohorts, Hunt noted.

Every patient should have anatomic stage recorded in their medical record, Hunt said. But patients with disease of a particular anatomic stage can face “very different” risks depending on tumors’ estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) status, as well as “clinically relevant gene expression profiles,” she noted.

Hierarchal clustering analysis has revealed clinically relevant gene expression profiles revealing that basal (ER-negative), HER2-positive, and luminal (ER-positive) can all have different outcomes regardless of L (lymph node) stage.

The AJCC 8th edition therefore includes anatomic TNM staging and prognostic stage group that incorporates TNM, grade, and ER, progesterone receptor (PR), and HER2 status.

“It also includes multigene panels as stage modifiers when available,” Hunt noted.

This inclusion of biologic tumor markers should allow more precise prognostication, Hunt said.

With colleagues at MD Anderson Cancer Center, she developed a novel staging system based on analyses of 3,728 patients with breast cancer treated there between 1997 and 2006, who had not undergone neoadjuvant chemotherapy. ER and PR status were assessed using immunohistochemistry (IHC) and HER2 status was determined by IHC or fluorescent in situ hybridization (FISH). In univariate analyses, each of these factors was strongly associated with disease-specific survival (DSS), she noted.

The team assessed the best staging system of six different candidate models and then used the National Cancer Institute’s Surveillance, Epidemiology, and End Results data to externally validate their analysis. The resulting clinical, pathological stage, ER status, and tumor grade (CPS+EG) staging system outperformed the AJCC clinical stage at baseline (before treatment) and AJCC pathologic staging after chemotherapy, Hunt said.

“Of course we know that pathologic information after chemotherapy does give us certain information about prognosis and certainly those with pCR [pathologic complete response] have the best prognosis,” she noted. “But we also know that the biology of tumor and presenting clinical stage are important information.”

The CPS+EG staging system “stratifies patients into subgroups with different outcomes and has been validated with both internal and external patient cohorts,” Hunt said.

Hunt and colleagues recently updated their CPS+EG staging system using the revised ER-positivity definition (≥ 1%) and HER2 status. They named the resulting CPS+EG+HER2 staging system the “Neo-Bioscore.”

The AJCC 8th edition staging system similarly incorporates a Prognostic Stage Group that considers anatomic TNM staging, tumor grade, and ER, PR, and HER2 biomarkers, Hunt noted.

“Cancer registries in the US will now use the Prognostic Stage Group for breast cancer case reporting,” she said.