Impact of hormone receptor status on patterns of recurrence and clinical outcomes among patients with human epidermal growth factor-2-positive breast cancer in the National Comprehensive Cancer Network: a prospective cohort study

Ines Vaz-Luis, Rebecca A Ottesen, Melissa E Hughes, P Kelly Marcom, Beverly Moy, Hope S Rugo, Richard L Theriault, John Wilson, Joyce C Niland, Jane C Weeks, Nancy U Lin, Ines Vaz-Luis, Rebecca A Ottesen, Melissa E Hughes, P Kelly Marcom, Beverly Moy, Hope S Rugo, Richard L Theriault, John Wilson, Joyce C Niland, Jane C Weeks, Nancy U Lin

Abstract

Introduction: In gene expression experiments, hormone receptor (HR)-positive/human epidermal growth factor-2 (HER2)-positive tumors generally cluster within the luminal B subset; whereas HR-negative/HER2-positive tumors reside in the HER2-enriched subset. We investigated whether the clinical behavior of HER2-positive tumors differs by HR status.

Methods: We evaluated 3,394 patients who presented to National Comprehensive Cancer Network (NCCN) centers with stage I to III HER2-positive breast cancer between 2000 and 2007. Tumors were grouped as HR-positive/HER2-positive (HR+/HER2+) or HR-negative/HER2-positive (HR-/HER2+). Chi-square, logistic regression and Cox hazard proportional regression were used to compare groups.

Results: Median follow-up was four years. Patients with HR-/HER2+ tumors (n = 1,379, 41% of total) were more likely than those with HR+/HER-2+ disease (n = 2,015, 59% of total) to present with high histologic grade and higher stages (P <0.001). Recurrences were recorded for 458 patients. HR-/HER2+ patients were less likely to experience first recurrence in bone (univariate Odds Ratio (OR) = 0.53, 95% Confidence Interval (CI): 0.34 to 0.82, P = 0.005) and more likely to recur in brain (univariate OR = 1.75, 95% CI: 1.05 to 2.93, P = 0.033). A lower risk of recurrence in bone persisted after adjusting for age, stage and adjuvant trastuzumab therapy (OR = 0.53, 95% CI: 0.34 to 0.83, P = 0.005) and when first and subsequent sites of recurrence were both considered (multivariable OR = 0.55, 95% CI: 0.37 to 0.80, P = 0.002).

Conclusions: Presenting features, patterns of recurrence and survival of HER2-positive breast cancer differed by HR status. These differences should be further explored and integrated in the design of clinical trials.

Figures

Figure 1
Figure 1
Overall survival since time of diagnosis by HR status. Note: HR, Hormone receptor. Adjusted by age, race/ethnicity, stage at diagnosis, grade and year of diagnosis.
Figure 2
Figure 2
Overall survival since time of diagnosis by HR status and receipt adjuvant trastuzumab. Note: Reference group are those who are HR positive and received Trastuzumab. HR, Hormone receptor; TRZ, Trastuzumab. Adjusted by age, race/ethnicity, stage at diagnosis, grade and year of diagnosis.

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