Purpose: Gene expression analysis identifies several breast cancer subtypes. We examined the relationship of neoadjuvant chemotherapy response to outcome among these breast cancer subtypes. Experimental Design: We used immunohistochemical profiles [human epidermal growth factor receptor 2^positive (HER2+)/hormone receptor^negative for HER2+/estrogen receptorn egative (ERÀ), hormone receptor and HER2À for basal-like, hormone receptor^positive for luminal] to subtype a prospectively maintained data set of patients with breast cancer treated with neoadjuvant anthracycline-based (doxorubicin plus cyclophosphamide, AC) chemotherapy. We analyzed each subtype for clinical and pathologic response to neoadjuvant chemotherapy and examined the relationship of response to distant disease^free survival and overall survival. Results: Of the 107 patients tested, 34 (32%) were basal-like, 11 (10%) were HER2+/ERÀ, and 62 (58%) were luminal. After neoadjuvant AC, 75% received subsequent chemotherapy and all received endocrine therapy if hormone receptor^positive. The chemotherapy regimen and pretreatment stage did not differ by subtype. Clinical response to AC was higher among the HER2+/ERÀ (70 %) and basal-like (85 %) than the luminal subtypes (47 %; P < 0.0001).Pathologic complete response occurred in 36% of HER2+/ERÀ, 27% of basal-like, and 7% of luminal subtypes (P = 0.01). Despite initial chemosensitivity, patients with the basal-like and HER2+/ERÀ subtypes had worse distant disease^free survival (P = 0.04) and overall survival (P = 0.02) than those with the luminal subtypes. Regardless of subtype, only 2 of 17 patients with pathologic complete response relapsed. The worse outcome among basal-like and HER+/ ERÀ subtypes was due to higher relapse among those with residual disease (P = 0.003). Conclusions: Basal-like and HER2+/ERÀ subtypes are more sensitive to anthracycline-based neoadjuvant chemotherapy than luminal breast cancers. Patients that had pathologic complete response to chemotherapy had a good prognosis regardless of subtype. The poorer prognosis of basal-like and HER2+/ERÀ breast cancers could be explained by a higher likelihood of relapse in those patients in whom pathologic complete response was not achieved.Gene expression studies have identified three major subtypes of breast cancer (basal-like, HER2+/ERÀ, and luminal; ref. 1) that have differing prognoses (2). A particularly poor outcome is seen among the two hormone receptor -negative subtypes (i.e., basal-like and HER2+/ERÀ), compared with the hormone receptor -high luminal group (2, 3). Evidence suggests that the effect of improved adjuvant chemotherapy is greater among hormone receptor -negative breast cancer (4). A recent report revealed significantly higher pathologic complete response to neoadjuvant chemotherapy among basal-like and HER2+/ERÀ subtypes compared with luminal subtypes (5). If so, this raises the question of whether the traditional perspective of pathologic complete response as a proxy for relapse and survival holds true across e...
Background: Validation of a novel gene expression signature in independent data sets is a critical step in the development of a clinically useful test for cancer patient risk-stratification. However, validation is often unconvincing because the size of the test set is typically small. To overcome this problem we used publicly available breast cancer gene expression data sets and a novel approach
Background: The epidermal growth factor receptor (EGFR/HER1) and its downstream signaling events are important for regulating cell growth and behavior in many epithelial tumors types. In breast cancer, the role of EGFR is complex and appears to vary relative to important clinical features including estrogen receptor (ER) status. To investigate EGFR-signaling using a genomics approach, several breast basal-like and luminal epithelial cell lines were examined for sensitivity to EGFR inhibitors. An EGFR-associated gene expression signature was identified in the basal-like SUM102 cell line and was used to classify a diverse set of sporadic breast tumors.
Classification of residual tumor in the breast and axillary surgical specimens after neoadjuvant chemotherapy using the revised AJCC TNM system is useful for predicting distant relapse and survival.
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