THE RECENTLY issued 8th revision to the American Joint Committee on Cancer (AJCC) Breast Cancer Staging System incorporates tumor biology and prognostic stage groups and thus has become more accurate and clinically relevant, according to two speakers at the 2018 Miami Breast Cancer Conference.1,2
“Breast tumor biology is critically important. The different subtypes of biology impact survival—both overall and relapse-free,” said Elizabeth Mittendorf, MD, PhD, Director of the Breast Immuno-Oncology Program at Dana-Farber/Brigham and Women’s Cancer Center in Boston.
The new prognostic stage groups incorporate grade, estrogen receptor status, progesterone receptor status, and HER2 status, combining these biologic factors with tumor-nodal-metastasis (TNM) categories.
Elizabeth Mittendorf, MD, PhD
Sara A. Hurvitz, MD
The result, said Sara A. Hurvitz, MD, Director of the Breast Cancer Clinical Research Program and Co-Director of the Santa Monica–UCLA Outpatient Hematology/Oncology Practice at the David Geffen School of Medicine, is that 30% to 40% of patients are now reassigned to a different stage group than the one assigned on the basis of anatomic staging.
According to Dr. Mittendorf, about one-third of patients are downstaged from their original classification, whereas 7% are upstaged. “It better groups patients with similar prognoses…. This becomes important in the staging system and allows us to downstage a lot of our patients,” Dr. Hurvitz said. “It’s important to integrate this into our practices.”
TNM Alone No Longer Acceptable
FOR EXAMPLE, 5-year breast cancer–specific survival, as determined from the California Cancer Registry, varies among women with the same TNM stage but differs by different subtype. For a woman who has stage T2N0 disease, the 5-year breast cancer–specific survival is 96% if she is hormone receptor–positive/HER2-negative, 94% if she is hormone receptor–positive/ HER2-positive, 92% if she is HER2-positive/hormone receptor– negative, and 88% if she has triple-negative breast cancer.
“The difference based on subtype actually becomes greater the higher the stage of disease,” said Dr. Mittendorf. For stage IV breast cancer, the 5-year breast cancer–specific survival rate is 47% for women with hormone receptor–positive/HER2-negative disease, but it is 17% for those with triple-negative breast cancer.
This example points to the need to make the staging system more relevant to current practice, she revealed. To do so, the expert panel incorporated biologic tumor markers to give a more precise determination of prognosis.
Dr. Hurvitz indicated that all patients, prior to treatment, will have a clinical prognostic stage calculated, including those undergoing neoadjuvant therapy. If patients have surgery as their initial treatment, they will have pathologic prognostic staging performed. The incorporation of molecular profiling was done based on data from arm A of the TAILORx study. Patients with an Oncotype DX Breast Recurrence Score of < 11 are classified as pathologic prognostic stage group 1A.
Who’s Upstaged, Who’s Downstaged?
DR. HURVITZ noted that under the 8th AJCC system, most triple-negative breast cancer is upstaged and more hormone receptor–positive disease is downstaged (especially if patients are HER2-positive). “In HER2-negative, hormone receptor–positive disease, many are downstaged as well, and now we’re able to use genomic profiling to further downstage some patients who have a low Recurrence Score,” she added. “Many HER2-positive tumors are downstaged with this current system, because the prognosis of these patients in the HER2-targeted era is better.”
Dr. Hurvitz encouraged clinicians to consult the AJCC Cancer Staging Posters on the AJCC website or download an app that calculates the stage based on TNM and hormone receptor status (itunes.apple.com/us/app/tnm8-breast-cancer-calculator/ id1294700966); the latter allows for inclusion of the 21-Gene Recurrence Score for hormone receptor–positive, node-negative patients. “Just get this app!” she said. “It’s totally easy.” ■
DISCLOSURE: Dr. Mittendorf reported financial relationships with Galena Biopharma, Antigen Express, Genentech, AstraZeneca, and EMD Serono. Dr. Hurvitz reported relationships with Amgen, Bayer, Boehringer Ingelheim, Genentech, GlaxoSmithKline, Pfizer, Roche, Biomarin, Merrimack, OBI Pharma, Puma Biotechnology, Dignitana, Medivation, Lilly, and Novartis.
1. Mittendorf E: Introduction to the 8th edition of the AJCC staging system for breast cancer. 2018 Miami Breast Cancer Conference. Presented March 9, 2018.
2. Hurvitz SA: Clinical implications of the 8th edition of the AJCC staging system. 2018 Miami Breast Cancer Conference. Presented March 9, 2018.