As recently as 20 years ago, the entity of triple-negative breast cancer (TNBC) was not even considered a unique subset of breast cancer, but rather the absence of hormonal responsiveness. Today, we clearly recognize it as a distinct clinical subtype with specific biological characteristics. In this issue, an analysis of an institutional cohort of early-stage TNBC is presented, with the aim of determining prognostic factors for local and distant recurrence and mortality. This study showed that lymphovascular invasion (LVI) was an independent adverse prognostic for all outcomes. This is important as we refine decision branch points for the treatment of TNBC, which include what is the minimum size for node-negative disease for which omission of chemo- therapy may be appropriate (a very small fraction in general), when should postmastectomy and regional node irradiation be included, and where might additional treatments such as platinum agents, or additional postoperative chemotherapy following standard neoadjuvant chemotherapy be used? The optimal factors remained undefined, and this article may add LVI to the list needed to construct decision-making nomograms

One of the aspects pointed out in the article by Dr Thomas and colleagues is the high prevalence in African American women, an important observation made initially over 10 years ago in the North Carolina Breast Cancer Study by Lisa Carey and colleagues.¹ The current article found that a greater delay from diagnosis to treatment was evident in this group. Molecular profiling shows that TNBC is further broken down into several subsets defined by basal-like, immune, mesenchymal, and luminal/ androgen receptor gene signature and biological characteristics.2 While these classifications are still fuzzy, they seem to correlate with the fact that TNBC does appear more intrinsically immunogenic, and early studies show more responsiveness to checkpoint inhibitor immunotherapy compared with other receptor subtypes. We are also learning that these subtypes may not be fully discerned by conventional receptor subtyping of TNBC. In fact, low ER/PR (<10%) cases appear to be more like TNBC by gene expression pattern.³

Even though newer commercial assays exist to discern these subtypes, we are not using these for routine treatment decisions. However, they are being increasingly used for targeted therapy clinical trial assignments and will, in some form or another, represent a new paradigm for clinical care using the next generation of drugs.

References

• Carey LA, Perou CM, Livasy CA, et al. Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. JAMA. 2006;295(21):2492-2502.
• Lehmann BD, Jovanović B, Chen X, et al. Refinement of triple-negative breast cancer molecular subtypes: implications for neoadjuvant chemotherapy selection. PLoS One. 2016;11(6):e0157368. doi: 10.1371/journal.pone.0157368.
• Iwamoto T, Booser D, Valero V, et al. Estrogen receptor (ER) mRNA and ER-related gene expression in breast cancers that are 1% to 10% ER-positive by immunohistochemistry. J Clin Oncol. 2012;30(7):729-734.