Use of immunohistochemical markers can refine prognosis in triple negative breast cancer

Abstract

Background: Basal-like breast cancer has been extensively characterized on the basis of gene expression profiles, but it is becoming increasingly common for these tumors to be defined on the basis of immunohistochemical (IHC) staining patterns, particularly in retrospective studies where material for expression profiling may not be available. The IHC pattern that best defines basal-like tumors is under investigation and various combinations of ER, PR, HER2-, CK5/6+ and EGFR+ have been tested.

Methods: Using datasets from two different hospitals we describe how using different combinations of immunohistochemical patterns has different effects on estimating prognosis at different time intervals after diagnosis. As our baseline, we used two IHC patterns ER-/PR-/HER2-("triple negative phenotype", TNP) and ER-/HER2-/CK5/6+ and/or EGFR+ ("core basal phenotype", CBP).

Results: There was no overall difference in survival between the two hospital-based series, but there was a difference between the TNP and non-TNP groups which was most marked at 3 years (76.8% vs 93.5%, p < .0001). This difference reduced with time, suggesting that long term survivors (beyond 10 years) in the TNP group may have comparable survival to non-TNP cases. A similar difference was seen if CBP was used instead of TNP. However when CK5/6 and/or EGFR expressing tumors were analyzed without consideration of ER/PR status, the reduction in survival increased with time, becoming more pronounced at 10 years than at 3 years.

Conclusion: Our findings suggests that CK5/6 and/or EGFR expressing tumor types have a persistently poorer prognosis over the longer term, an observation that may have important therapeutic implications as drugs that target the EGFR are currently being evaluated in breast cancer.

Figure 1

Poisson regression curve examining the relationship between tumor size, lymph node status and TNP group. The number of positive lymph nodes showed a closer correlation with tumor size in the non-TNP group compared to the TNP group.

Figure 2

Survival until breast cancer death by TNP status. Survival at 3 years time was 76.8% in the TNP cases versus 93.5% among non-TNP cases (p < .0001); Survival at 10 years time were, respectively 65.0% and 74.2% (p = .03).

Figure 3

Survival until breast cancer death by Ck5/6 and EGFR status. Survival at 3 years time was 85.6% among CK5/6 and/or EGFR positive cases versus 93.4% among cases that were negative for both CK5/6 and EGFR (p = .02); Survival at 10 years time was 61.4% and 78.5% (p = .0007) respectively.

Figure 4

Relationship between TNP, survival and lymph node status – lymph node positive subgroup. In TNP cases, the magnitude of the decrease in survival was approximately 1.5-fold greater at 3 years in the lymph node positive subgroup (Figure 4) compared to the lymph node negative subgroup (Figure 5).

Figure 5

Relationship between TNP, survival and lymph node status – lymph node negative subgroup. In TNP cases, the magnitude of the decrease in survival was approximately 1.5-fold greater at 3 years in the lymph node positive subgroup (Figure 4) compared to the lymph node negative subgroup (Figure 5).