Background: Breast cancer (BC) subtypes have different survival and response to therapy. We studied predictors of central nervous system metastases (CNS-M) and outcome after CNS-M diagnosis according to tumor subtype.
This article examines how discouraging the use of anthracyclines in combination with trastuzumab in patients with human epidermal growth factor receptor 2 positive metastatic breast cancer because of fears of cardiotoxicity has influenced the use of these agents in this patient setting.
Background: Hormone receptors (HR) and the human epidermal growth factor receptor 2 (HER2) are key biological factors in breast cancer. Gene expression profile studies indicate that HER2-positive/HR-positive and HER2-positive/HR-negative tumors fall into two distinct subtypes. These two subtypes carry a different prognosis in the absence of HER2-targeting. Furthermore, a relationship has been documented between increasing HR expression and reduced chemoresponsiveness. Despite these differences, HER2-positive abvanced breast cancer patients are usually treated with a unified approach of combining chemotherapy with an HER2-targeting agent, regardless of HR status. We studied the association between hormone receptor (HR) expression and the clinical outcome of women with HER2-positive advanced breast cancer receiving chemotherapy plus trastuzumab.
Methods: The effect of HR expression on overall response rate (ORR) and progression-free survival (PFS) to trastuzumab-based treatment was studied by univariate and multivariate analysis. HR positivity was defined as 1% or more tumor cells positive for the estrogen (ER) and/or for the progesterone (PgR) receptor by immunohistochemistry. For both ER and PgR, we studied different thresholds to identify levels of expression associated with the clinical outcomes of interest.
Results: 227 consecutive advanced breast cancer patients receiving trastuzumab plus chemotherapy between June 1999 and November 2008 at two Institutions were retrospectively analyzed. One hundred eleven patients (49%) had HR-positive tumors. Compared with low or no expression, high expression of ER (30% or more) predicted reduced probability of tumor response to trastuzumab plus chemotherapy (multivariate odds ratio 0.422, 95% confidence interval-C.I. 0.222-0.803, p = 0.009). In patients with HR-positive tumors the addition of maintenance endocrine therapy to trastuzumab after the completion of chemotherapy was associated with a significant increase in progression-free survival (hazard ratio-HR 0.521, 95% C.I. 0.3325-0.836, p = 0.007). Patients with HR-positive tumors not receiving maintenance endocrine therapy had similar PFS than patients with HR-negative tumors (HR 0.914, 95% C.I. 0.654-1.279, p = 0.601). In patients not receiving maintenance endocrine therapy, high ER expression (30% or more cells) was associated with non-significant trend towards reduced risk of progression, compared with patients with low or absent ER expression (HR 0.747, 95% C.I. 0.516-1.081, p = 0.122). Conclusions: Our results suggest a predictive role of HR expression in HER2-positive tumors. Further investigation in this patient subset is warranted to optimize the use of HER2-targeting agents, chemotherapy and endocrine therapy.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD10-07.
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