Abstract P1-11-13: Triple Negative or HER2 Positive Subtypes of Breast Cancer Groups Are Chemo-Sensitive, but Higher Rate of Brain Metastasis Contributes Poorer Prognosis
Authors: N Tokudome, Y Ito, S Takahashi, S Taira, C Tsutsumi, K Kobayashi, M Oto, M Ito, K Inoue, A Kuwayama, Y Nakayama, Y Miyagi, T Osako, R Horii, F Akiyama, T Iwase, K. Hatake
Journal: Cancer Research (2010)

Abstract Background: The purpose of this study was to determine the primary chemosensitivity and prognosis among women with four common breast subtypes, Luminal A, Luminal B, HER2 and Triple negative (TN). In this study, we evaluated the response to primary chemotherapy of each subtype, reported the outcome of each subgroup after primary chemotherapy. Method: We analyzed the outcome and characteristics of patients treated with primary chemotherapy using anthracycline and/or taxanes. Before initiation of chemotherapy, invasive carcinoma was confirmed on initial biopsy specimen obtained and hormone receptor status and HER2/neu status was also determined on this specimen. ER and PgR positivity was recognized at a cut-off of &amp;gt; 10% positive nuclei by immunohistochemistory (IHC). HER2/neu-positive status was defined as either 3+ by IHC or presence of gene amplification by fluorescence in situ hybridization testing. Breast cancer subtypes were defied as follow, TN (ER-, PgR-, HER2-), Luminal A (ER+ and/or PgR+, HER2-), Luminal B (ER+ and/or PgR+, HER2+), HER2 (ER-, PgR-, HER2+). Result: Between 2000 and 2007, 639 breast cancer patients were treated with primary chemotherapy at Cancer Institute Hospital. Clinical and immunohistochemical data was available on 503 patients. Median observation period was 49.9 months (2.8-122.4). In these cases, 105 cases (20.9%) were defined as TN, 276 cases (54.9%) were defined as Luminal A, 49 cases (9.7%) were defined as Luminal B, 73 cases (14.5%) were defined as HER2, respectively. 138 patients (27.4%) received anthracycline-based regimen, 139 patients (27.6%) received taxane, 227 patients (45.1%) received taxane-anthracycline combination regimen. The pathologic complete response (pCR) rate of each group was 15.2%, 2.0%, 8.2%, 16.4%, in TN, Luminal A, Luminal B, HER2, respectively (P&amp;lt;0.001). The 5-yr disease free survival estimated 69.1%, 74.4%, 62.8%, 70.6% (p=0.140), and the 5-yr overall survival estimated 69.1%, 75.6%, 88.6%, 69.4% in TN, Luminal A, Luminal B, HER2, respectively (p=0.007). Mean survival time from the first recurrence was 21.1 months (95%CI 11.5-30.7), 40.6 months (95%CI 31.6-49.6), 81.8 months (95%CI 59.1-104.5), 30.0 months (95%CI 21.1-38.9), respectively (P&amp;lt;0.001). According to the first recurrence, most frequent visceral metastatic site of TN and HER2 patients was brain (P&amp;lt;0.001), and median time to brain metastasis was 13.2 months (95%CI 8.5-17.9). Surprisingly, three (21.4%) of the patients who had brain metastasis resulted in pCR by primary chemotherapy. Of note, Luminal A patients were more likely to have bone metastasis than other groups at first (p=0.003), and median time to bone metastasis was 16.3 months (95%CI 14.1-18.6). Conclusions: With primary chemotherapy, pCR rate of TN and HER2 were higher than Luminal groups, but they developed brain metastasis early irrespective of pCR, this might contribute to their worse prognosis. In contrast, Luminal A developed bone metastasis at first, this might result in good prognosis instead of their low pCR rate. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-11-13.