The issue of whether adjuvant chemotherapy provides benefit in early breast cancer was settled back in the 1980s, he noted when introducing the study. “Since that time, it’s been unethical to randomize women in those settings to no chemotherapy. Most of the studies have been different types of chemotherapies as choices.”
In contrast, participants in the 77B trial were randomized to two adjuvant chemotherapy arms (cyclophosphamide alone or cyclophosphamide, methotrexate, and fluorouracil) and two nonchemotherapy arms (levamisole or no agent). Main findings showed that chemotherapy improved 10-year invasive disease–free survival (Cancer. 2010;116:2081-9).
According to results of the subtyping, which Dr. Nielsen and colleagues performed in a central lab, 26% of the tumors were of luminal A subtype, meaning they were estrogen receptor positive and HER2 negative, had a low proliferation index (13% or fewer cells staining for Ki67), and had high progesterone receptor expression (more than 20% of cells staining) (J Clin Oncol. 2013;31:203-9).
These patients did not derive significant benefit from chemotherapy. In contrast, patients with other subtypes (luminal B, HER2E, or triple negative) had a marked benefit (hazard ratio, 0.50; 95% CI, 0.38-0.66; P less than .001).
The heterogeneity in treatment impact between luminal A and non–luminal A subtypes was statistically significant (interaction test P = .048). Analyses also showed a similar trend for the endpoint of 25-year overall survival.
Discussing study caveats, Dr. Nielsen acknowledged that immunohistochemistry scoring can be subjective. “Currently, we are trying to get the original [tissue] blocks. Isolating RNA for gene profile analysis is another way to identify the subtypes,” he explained.