HR+HER2+ BREAST CANCER AND RECURRENCE RISK 

Breast Cancer ResearchImpact 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
Abstract and Introduction
Abstract

Breast Cancer Res. 2012;14(5) 

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=".001" 0.34="0.34" 0.53="0.53" 0.82="0.82" 458="458" 95="95" bone="bone" confidence="confidence" em="em" experience="experience" first="first" for="for" hr-="hr-" in="in" interval="interval" less="less" likely="likely" nbsp="nbsp" odds="odds" patients.="patients." patients="patients" ratio="ratio" recorded="recorded" recurrence="recurrence" recurrences="recurrences" to="to" univariate="univariate" were="were">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).

As compared with patients with HR+/HER2+ disease, those with HR-/HER2+ disease had significantly increased hazard of early, but not late, death (hazard ratio of death zero to two years after diagnosis = 1.92, 95% CI: 1.28 to 2.86, P = 0.002, hazard ratio of death two to five years after diagnosis = 1.55, 95% CI: 1.19 to 2.00, P = 0.001; hazard ratio of death more than five years after diagnosis = 0.81, 95% CI: 0.55 to 1.19, P = 0.285, adjusting for age, race/ethnicity, stage at diagnosis, grade and year of diagnosis).

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.

 Disclosures