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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-Luis12*, Rebecca A Ottesen3, Melissa E Hughes1, P Kelly Marcom4, Beverly Moy5, Hope S Rugo6, Richard L Theriault7, John Wilson8, Joyce C Niland3, Jane C Weeks1 and Nancy U Lin1

Author Affiliations

1 Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA

2 Clinical and Translational Oncology Research Unit, Instituto de Medicina Molecular, Lisbon, Portugal

3 Department of Information Sciences, City of Hope Comprehensive Cancer Center, Duarte, CA, USA

4 Department of Medical Oncology, Duke University Medical Center, Durham, NC, USA

5 Department of Medicine, Massachusetts General Hospital, Boston, MA, USA

6 Department of Medicine, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA

7 Department of Breast Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX, USA

8 Department of Internal Medicine, Arthur G. James Cancer Hospital, Ohio State University, Columbus, OH, US

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Breast Cancer Research 2012, 14:R129  doi:10.1186/bcr3324

See related editorial by Norton and Perez,

Published: 1 October 2012



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.


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.


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).

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).


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.