Purpose: Molecular classification of breast cancer has been proposed based on gene expression profiles of human tumors. Luminal, basal-like, normal-like, and erbB2+ subgroups were identified and were shown to have different prognoses. The goal of this research was to determine if these different molecular subtypes of breast cancer also respond differently to preoperative chemotherapy. Experimental Design: Fine needle aspirations of 82 breast cancers were obtained before starting preoperative paclitaxel followed by 5-fluorouracil, doxorubicin, and cyclophosphamide chemotherapy. Gene expression profiling was done with Affymetrix U133A microarrays and the previously reported ''breast intrinsic''gene set was used for hierarchical clustering and multidimensional scaling to assign molecular class. Results: The basal-like and erbB2+ subgroups were associated with the highest rates of pathologic complete response (CR), 45% [95% confidence interval (95% CI), 24-68] and 45% (95% CI, 23-68), respectively, whereas the luminal tumors had a pathologic CR rate of 6% (95% CI, 1-21). No pathologic CR was observed among the normal-like cancers (95% CI, 0-31). Molecular class was not independent of conventional cliniocopathologic predictors of response such as estrogen receptor status and nuclear grade. None of the 61genes associated with pathologic CR in the basal-like group were associated with pathologic CR in the erbB2+ group, suggesting that the molecular mechanisms of chemotherapy sensitivity may vary between these two estrogen receptor^negative subtypes. Conclusions: The basal-like and erbB2+ subtypes of breast cancer are more sensitive to paclitaxel-and doxorubicin-containing preoperative chemotherapy than the luminal and normallike cancers.Breast cancer is a clinically heterogeneous disease. Histologically similar tumors may have different prognoses and may respond to therapy differently. It is believed that these differences in clinical behavior are due to molecular differences between histologically similar tumors. DNA microarray technology is ideally suited to reveal such molecular differences. A novel molecular classification of breast cancer based on gene expression profiles was recently proposed (1). The investigators identified a set of stably expressed genes (''intrinsic gene set''; n = 534) that accounted for much of the molecular differences between 42 breast cancers and did hierarchical cluster analysis to identify subgroups of cancers with separate gene expression profiles. Luminal, basal-like, normal-like, and erbB2+ subgroups were identified and were shown to have different prognoses (1 -4). These results were confirmed in follow-up experiments by the same group and others using larger numbers of cases. The basal-like (mostly estrogen receptor negative) and erbB2+ (mostly HER-2 amplified and estrogen receptor negative) subgroups had the shortest relapse-free and overall survival, whereas the luminal-type (estrogen receptorpositive) tumors had a more favorable clinical outcome (2 -4).

In our cohort of patients with breast cancer and CNS metastases, patients with HER2-positive disease treated with trastuzumab had longer times to development of and better survival from CNS metastases compared with patients with HER2-positive disease who had never received trastuzumab and patients with HER2-negative breast cancer.

BACKGROUND. Inflammatory breast cancer (IBC) is the most aggressive manifestation of primary breast cancer. The authors compared the prognostic features of IBC and non‐IBC locally advanced breast cancer (LABC) to gain insight into the biology of this disease entity. METHODS. This retrospective analysis consisted of 1071 patients, comprising 240 patients with IBC and 831 patients with non‐IBC LABC who were enrolled in 10 consecutive clinical trials (5 from each disease group). All patients received similar multidisciplinary treatment. The authors measured time to disease recurrence for each individual site from the start of treatment to the date of disease recurrence or last follow‐up (recurrence‐free survival) and overall survival rates to the date of last follow‐up or death. RESULTS. The median follow‐up period was 69 months (range, 1–367 months). Pathologically complete response rates were 13.9% and 11.7% in the IBC and non‐IBC LABC groups, respectively (P = .42). The 5‐year estimates of cumulative incidence of recurrence were 64.8 % and 43.4% (P < .0001), respectively, for IBC and non‐IBC LABC. IBC had significantly higher cumulative incidence of locoregional recurrence and distant soft‐tissue and bone disease. The 5‐year overall survival (OS) rate was 40.5% for the IBC group (95% CI, 34.5%–47.4%) and 63.2% for the non‐IBC LABC group (95% CI, 60.0%–66.6%; P < .0001). CONCLUSIONS. IBC was associated with a worse prognosis and a distinctive pattern of early recurrence compared with LABC. These data suggested that investigating factors affecting “homing” of cancer cells may provide novel treatment strategies for IBC. Cancer 2007. © 2007 American Cancer Society.

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These data demonstrate the expression of growth factor and chemokine receptors in IBC. The expression of these receptors is associated with increased risk of recurrence and death, and thus, they may represent potential therapeutic targets in IBC.