Background: Invasive breast cancer (IBC) is a heterogeneous disease. Gene expression profiling has identified several biologically distinct subtypes of IBCs. As proposed by Cheang et al, immunohistochemical (IHC) markers can be used as a surrogate for the molecular classification of IBC. Purpose: To evaluate different clinical behavior, relationship with other clinical-pathological features and survival outcomes of patients (pts) with different subtypes of IBC as classified using IHC markers. Methods: We evaluated 3461 IBC pts treated from 1995 to 2008 classified as: luminal A (ER and PR + , HER2- and Ki67< 14%), luminal B (ER and/or PR + , HER2- and Ki67 ≥ 14%), luminal C (ER and/or PR + , HER2 + , any Ki67), HER2+ (ER and PR, HER2 + , any Ki67), triple negative-TN (ER and PR-, HER2-, any Ki67). Log-rank test and Cox regression model were performed to evaluate the impact of IHC subtypes on overall survival (OS), Event Free Survival (EFS) and their correlation with other known prognostic factors. Results: We identified 909 (26.4%) luminal A, 1722 (49.9%) luminal B, 325 luminal C (9.4%), 209 (5.7%) HER2+ and 296 (8.6%) TN. Median age was 61 years. Luminal A was more frequently associated with older age, smaller size, negative axilla involvement, low grade ( p < 0.001). There were 644 (18,6%) events (local and distant relapses, contralateral and second tumors): 100 in luminal A (11%), 334 in luminal B (19.4%), 62 in luminal C (19%), 66 in HER2+ (31%) and 84 in TN (28%). Different subtypes showed preferential sites of first local or distant relapses: luminal A had more bone and loco-regional and less visceral relapses than other subtypes. Median disease free interval (DFI) was longer in luminal A (60.3 months) than in luminal B (39.1 m), C (27.8 m), HER2 (30.8 m) and TN (23.3 m). At median follow up of 77 months, EFS and OS were 94.0 and 92.1% in luminal A, 86.2 and 82.7% in luminal B, 86.2 and 86.8% in luminal C, 72.7 and 72.7% in HER2 + , 78.0% and 73.9% in TN ( p < 0.001). Luminal A presented the best prognosis among other luminal subtypes. IHC-based subtypes prognosis (EFS and OS) was independent of nodal status, grading, tumor size and age. Conclusions: In our experience IHC-based classification appared to be useful to divide IBCs in different biological entities. Its application could help the tailoring of adjuvant therapies improving patient outcomes.

CLINICAL BEHAVIOR AND PROGNOSIS OF DIFFERENT IMMUNOHISTOCHEMISTRY-DETECTED SUBTYPES OF INVASIVE BREAST CANCER: A MONOINSTITUTIONAL SERIES.

Eccher, Claudio;
2012-01-01

Abstract

Background: Invasive breast cancer (IBC) is a heterogeneous disease. Gene expression profiling has identified several biologically distinct subtypes of IBCs. As proposed by Cheang et al, immunohistochemical (IHC) markers can be used as a surrogate for the molecular classification of IBC. Purpose: To evaluate different clinical behavior, relationship with other clinical-pathological features and survival outcomes of patients (pts) with different subtypes of IBC as classified using IHC markers. Methods: We evaluated 3461 IBC pts treated from 1995 to 2008 classified as: luminal A (ER and PR + , HER2- and Ki67< 14%), luminal B (ER and/or PR + , HER2- and Ki67 ≥ 14%), luminal C (ER and/or PR + , HER2 + , any Ki67), HER2+ (ER and PR, HER2 + , any Ki67), triple negative-TN (ER and PR-, HER2-, any Ki67). Log-rank test and Cox regression model were performed to evaluate the impact of IHC subtypes on overall survival (OS), Event Free Survival (EFS) and their correlation with other known prognostic factors. Results: We identified 909 (26.4%) luminal A, 1722 (49.9%) luminal B, 325 luminal C (9.4%), 209 (5.7%) HER2+ and 296 (8.6%) TN. Median age was 61 years. Luminal A was more frequently associated with older age, smaller size, negative axilla involvement, low grade ( p < 0.001). There were 644 (18,6%) events (local and distant relapses, contralateral and second tumors): 100 in luminal A (11%), 334 in luminal B (19.4%), 62 in luminal C (19%), 66 in HER2+ (31%) and 84 in TN (28%). Different subtypes showed preferential sites of first local or distant relapses: luminal A had more bone and loco-regional and less visceral relapses than other subtypes. Median disease free interval (DFI) was longer in luminal A (60.3 months) than in luminal B (39.1 m), C (27.8 m), HER2 (30.8 m) and TN (23.3 m). At median follow up of 77 months, EFS and OS were 94.0 and 92.1% in luminal A, 86.2 and 82.7% in luminal B, 86.2 and 86.8% in luminal C, 72.7 and 72.7% in HER2 + , 78.0% and 73.9% in TN ( p < 0.001). Luminal A presented the best prognosis among other luminal subtypes. IHC-based subtypes prognosis (EFS and OS) was independent of nodal status, grading, tumor size and age. Conclusions: In our experience IHC-based classification appared to be useful to divide IBCs in different biological entities. Its application could help the tailoring of adjuvant therapies improving patient outcomes.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11582/272219
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