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

Abstract

IntroductionIn 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.MethodsWe 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.ResultsMedian 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).ConclusionsPresenting 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.

Hormone receptor status does not alter the effect of trastuzumab in breast cancer

“…HR positivity was associated with a favorable DFS and OS. The discrepancy with our data could be attributed to the unbalanced groups in the study by Vaz-Luis et al (2012). Similar to our collective, HR− tumors were more likely to present unfavorable prognostic factors such as a higher histological grade.…”

“…This is consistent with several prior studies describing different rates of recurrence and hazard of death depending on HR status (Dignam et al 2009, Early Breast Cancer Trialists' Collaborative Group et al 2011, Vaz-Luis et al 2012, Strasser-Weippl et al 2015 suggesting that HR− and HR+ HER2+ breast cancer represent two different entities (Burstein 2005). In this regard, our observations highlight the fact that HR status remains an important prognostic factor regardless of HER2 status and trastuzumab treatment.…”

“…To the best of our knowledge, the impact of HR status on the survival effect of trastuzumab in early breast cancer has only been investigated in one study (Vaz-Luis et al 2012). In this study of 3394 patients with HER2+ breast cancer, the trastuzumab survival effect was significantly affected by HR status.…”

“…Several studies have clearly demonstrated that HR expression is associated with a reduced rate of pathological complete response (pCR) (Guiu et al 2013). However, the impact of HR status on disease-free (DFS) and overall survival (OS) of patients treated with trastuzumab is controversial (Brufsky et al 2005, Kim et al 2012, Vaz-Luis et al 2012, Perez et al 2014, Zhang et al 2015. This controversy could be due to the heterogeneity of studies regarding adjuvant and metastatic trastuzumab treatment.…”

Impact of Age, Tumor Size, Lymph Node Metastasis, Stage, Receptor Status and Menopausal Status on Overall Survival of Breast Cancer Patients in Pakistan

“…Also ER positivity was greater in patients 50 years of age or older (Goyanes et al, 2010). In contrast patients with Her 2 neu positivity are younger, present with higher T stage, nodal involvement and higher grade (Vaz-Luis et al, 2012). Studies have also shown that patients who are ER, PR positive and Her 2 neu negative have decreased incidence of both local and distant recurrence as compared to those who are ER, PR negative and Her 2 neu positive (Shim et al, 2014).…”