Clinicopathological analyses of triple negative breast cancer using surveillance data from the Registration Committee of the Japanese Breast Cancer Society.
ABSTRACT Triple negative (TN) breast cancer is defined as a subtype that is negative for estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2). To clarify the characteristics of TN breast cancer, surveillance data of the Registration Committee of the Japanese Breast Cancer Society were analyzed.
Of 14,748 cases registered in 2004, 11,705 (79.4%) were examined for ER, PgR, and HER2. Of these, the most prevalent (53.8%) was a hormone-responsive subtype with ER positive/PgR positive/HER2 negative, followed by TN subtype (15.5%).
The proportion of postmenopausal patients was relatively high in the TN subtype. This cancer was diagnosed at a slightly advanced stage and with more cases positive for lymph node metastases than other subtypes. Morphologically, the TN subtype was more frequently classified as solid-tubular carcinoma. Mucinous, tubular, or secretary carcinomas were frequently found in the hormone receptor positive/HER2 negative subtype, while squamous cell carcinoma, spindle cell carcinoma, and metaplastic carcinoma with bone/cartilage metaplasia were very frequently found in the TN group. Apocrine carcinoma was also found very frequently in the TN group. Selection of chemotherapy was not based on receptor subtypes, but was determined by the degree of tumor progression.
Although TN types are similar to basal-like breast tumor, as determined by gene profiling, their diagnosis needs verification by determination of the level of epidermal growth factor receptor or cytokeratin 5/6 expression. TN type should be examined further for immunohistochemical features and analyzed for prognostic details in this cohort.
[Show abstract] [Hide abstract]
ABSTRACT: Genetic variants are reported to play an important role in the susceptibility of breast cancer. Ribonucleotide reductase 1 (RRM1) is suggested to play an essential role in the regulation of cancer development. The purpose of this study was to identify novel gene polymorphisms of RRM1 -756T>C and RRM1 -269 C>A specific to patients with breast cancer and healthy controls. A total of 833 subjects, including 321 healthy controls and 512 patients with breast cancer, were recruited in this study. Allelic discrimination of RRM1 -756T>C (rs11030919) and RRM1 -269C>A (rs12806698) polymorphisms of the RRM1 gene was assessed with the real-time polymerase chain reaction. The adjusted odds ratios and 95% confidence intervals were 1.20 (0.71-2.04) and 1.10 (0.65-1.86) to have breast cancer among individuals with CC alleles of RRM1 -756T>C and individuals with AA alleles of RRM1 -269C>A gene polymorphism, respectively, compared to individuals having wild type of RRM1 gene polymorphisms. Also, there was no significant genetic interaction effect on the susceptibility of breast cancer and nonassociation between genetic polymorphisms and clinical statuses of breast cancer. Gene polymorphisms of RRM1 -756T>C and RRM1 -269C>A may be not an important factor for the susceptibility of breast cancer.Journal of Clinical Laboratory Analysis 07/2014; 28(4). DOI:10.1002/jcla.21682 · 1.14 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Better treatments for triple-negative breast cancer (TNBC) are needed. To address this need, we studied the effects of preoperative metronomic paclitaxel/cyclophosphamide/capecitabine (mPCX) followed by 5-fluorouracil (FU)/epirubicin/cyclophosphamide (FEC) as preoperative chemotherapy in TNBC patients. Forty primary TNBC patients received four cycles of metronomic paclitaxel (80 mg/m(2) on Days 1, 8, and 15), cyclophosphamide (50 mg/body daily), and capecitabine (1,200 mg/m(2) daily), followed by four cycles of 5-FU (500 mg/m(2)), epirubicin (100 mg/m(2)), and cyclophosphamide (500 mg/m(2)) every 3 weeks. The primary end point was the pathological complete response (pCR) rate. Forty patients formed the intent-to-treat population. The median dose intensities of paclitaxel, cyclophosphamide, and capecitabine were 89.7, 92.1, and 89.8 %, respectively. Five patients discontinued mPCX and two discontinued FEC, primarily because of adverse events, resulting in a per-protocol population (PPS) of 33 patients. The pCR (ypT0/Tis ypN0) rate was 47.5 % (19/40) in the intent-to-treat population and 54.5 % (18/33) in the PPS. The clinical response rates were 36/40 (90.0 %) and 31/33 (93.9 %) in the intent-to-treat and PPS, respectively. The breast conservation rate was 72.7 % (24/33), and 5/13 patients underwent partial resection instead of pre-planned total mastectomy. Grade 3-4 adverse events included neutropenia (35 %), leukopenia (25 %), and hand-foot syndrome (8 %). Metronomic PCX followed by FEC chemotherapy was associated with a high pCR rate and low toxicity in TNBC patients. Further studies of this regimen in larger numbers of patients are warranted.Cancer Chemotherapy and Pharmacology 05/2014; 74(2). DOI:10.1007/s00280-014-2492-y · 2.57 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Triple negative breast cancer (TNBC) is currently the only major breast tumor subtype without effective targeted therapy and as a consequence in general has poor outcome. To identify new therapeutic targets in TNBC we performed an shRNA screen for protein kinases commonly amplified and overexpressed in breast cancer. Using this approach, we identified AKT3 as a gene preferentially required for the growth of TNBCs. Downregulation of Akt3 significantly inhibits the growth of TNBC lines in 3D spheroid cultures and in mouse xenograft models whereas loss of Akt1 or Akt2 have more modest effects. Akt3 silencing markedly upregulates the p27 cell cycle inhibitor and this is critical for the ability of Akt3 to inhibit spheroid growth. In contrast to Akt1, Akt3 silencing results in only a minor enhancement of migration and does not promote invasion. Depletion of Akt3 in TNBC sensitizes cells to the pan-Akt inhibitor GSK690693. These results imply that Akt3 has a specific function in TNBCs, thus, its therapeutic targeting may provide a new treatment option for this tumor subtype.Cancer Research 12/2013; 74(3). DOI:10.1158/0008-5472.CAN-13-2175 · 9.28 Impact Factor