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...

Microarray profiling of invasive breast carcinomas has identified five distinct subtypes of tumors (luminal A, luminal B, normal breast-like, HER2 overexpressing, and basal-like) that are associated with different clinical outcomes. The basal-like subtype is associated with poor clinical outcomes and is the subtype observed in BRCA1-related breast cancers. The aim of this study was to characterize the histologic and immunophenotypic properties of breast basal-like carcinomas that were first positively identified using DNA microarray analysis. Detailed histologic review was performed on 56 tumors with known microarray profiles (23 basal-like, 23 luminal, and 12 HER2 þ ). Immunohistochemistry for estrogen receptor (ER), HER2, EGFR, smooth muscle actin (SMA), p63, CD10, cytokeratin 5/6, cytokeratin 8/18, and vimentin was performed on 18 basal-like, 16 luminal, and 12 HER2 þ tumors. The basal-like tumors were grade 3 ductal/NOS (21/23) or metaplastic (2/23) carcinomas that frequently showed geographic necrosis (17/23), a pushing border of invasion (14/23), and a stromal lymphocytic response (13/23). Most basal-like tumors showed immunoreactivity for vimentin (17/18), luminal cytokeratin 8/18 (15/18), EGFR (13/18), and cytokeratin 5/6 (11/18), while positivity for the myoepithelial markers SMA (4/18), p63 (4/18) and CD10 (2/18) was infrequent. All basal-like tumors tested were ERÀ and HER2À. Morphologic features significantly associated with the basal-like subtype included markedly elevated mitotic count (Po0.0001), geographic tumor necrosis (P ¼ 0.0003), pushing margin of invasion (P ¼ 0.0001), and stromal lymphocytic response (P ¼ 0.01). The most consistent immunophenotype seen in the basal-like tumors was negativity for ER and HER2, and positivity for vimentin, EGFR, cytokeratin 8/18, and cytokeratin 5/6. The infrequent expression of myoepithelial markers in basal-like carcinomas does not support a direct myoepithelial cell derivation of these tumors. These findings should further assist in the identification of basal-like carcinomas in clinical specimens, facilitating treatment and epidemiologic studies of this tumor subtype.

The prognostication of head and neck squamous cell carcinoma (HNSCC) is largely based upon the tumor size and location and the presence of lymph node metastases. Here we show that gene expression patterns from 60 HNSCC samples assayed on cDNA microarrays allowed categorization of these tumors into four distinct subtypes. These subtypes showed statistically significant differences in recurrence-free survival and included a subtype with a possible EGFR-pathway signature, a mesenchymal-enriched subtype, a normal epithelium-like subtype, and a subtype with high levels of antioxidant enzymes. Supervised analyses to predict lymph node metastasis status were approximately 80% accurate when tumor subsite and pathological node status were considered simultaneously. This work represents an important step toward the identification of clinically significant biomarkers for HNSCC.