Texas Oncology U.S. Oncology
Texas Oncology U.S. Oncology
Robert N.,U.S. OncologyVirginia Cancer Specialists |
Krekow L.,U.S. Oncology Texas Oncology |
Stokoe C.,Texas Oncology U.S. Oncology |
Clawson A.,Abraxis BioScience |
And 3 more authors.
Breast Cancer Research and Treatment | Year: 2011
Every-2-week (dose-dense) adjuvant doxorubicin (A) plus cyclophosphamide (C) followed by paclitaxel is a safe and effective adjuvant chemotherapy regimen. Every-3-week nab-paclitaxel is safe and more effective at 50% higher dose than every-3-week paclitaxel in metastatic breast cancer (BC). This study evaluated the safety of adjuvant dose-dense AC followed by dose-dense nab-paclitaxel for early-stage BC. Women with operable, histologically confirmed BC received four cycles of dose-dense A 60 mg/m 2 plus C 600 mg/m 2 with pegfilgrastim, followed by dose-dense 260 mg/m 2 nab-paclitaxel (with pegfilgrastim given as needed). Endpoints were adverse events (AEs), including myelosuppression. Patients with neuropathy were followed until symptom improvement to grade ≤1. Thirty women received four cycles of dose-dense AC with no unanticipated AEs, one withdrew after AC therapy. Of 29 women who began nab-paclitaxel therapy, 27 received all the four doses (mean cumulative dose, 959 mg/m 2); one discontinued nab-paclitaxel after two doses due to unacceptable AEs. Four patients had a grade 3 nab-paclitaxel-related neuropathy (no grade 4 event). Of 29 patients, 34% received pegfilgrastim during nab-paclitaxel therapy and 31% had a nab-paclitaxel treatment delay, mainly due to hematologic toxicity. Based on the Kaplan-Meier probability estimates, the percentage of patients having ≤1 grade neuropathy at the end of treatment, 2, and 8 months after treatment were 59, 79, and 97%. Administering adjuvant dose-dense AC followed by 260 mg/m 2 dose-dense nab-paclitaxel was feasible in women with early-stage BC, with manageable AEs. Most patients had ≤1 grade neuropathy 2 months after treatment completion. © 2010 Springer Science+Business Media, LLC.
Santarpia L.,Hospital of Prato |
Santarpia L.,University of Houston |
Qi Y.,University of Houston |
Stemke-Hale K.,University of Houston |
And 18 more authors.
Breast Cancer Research and Treatment | Year: 2012
The mutation pattern of breast cancer molecular subtypes is incompletely understood. The purpose of this study was to identify mutations in genes that may be targeted with currently available investigational drugs in the three major breast cancer subtypes (ER+/HER2-, HER2+, and Triple Negative). We extracted DNA from fine needle aspirations of 267 stage I-III breast cancers. These tumor specimens typically consisted of >80 % neoplastic cells. We examined 28 genes for 163 known cancer-related nucleic acid variations by Sequenom technology. We observed at least one mutation in 38 alleles corresponding to 15 genes in 108 (40 %) samples, including PIK3CA (16.1 % of all samples), FBXW7 (8 %), BRAF (3.0 %), EGFR (2.6 %), AKT1 and CTNNB1 (1.9 % each), KIT and KRAS (1.5 % each), and PDGFR-α (1.1 %). We also checked for the polymorphism in PHLPP2 that is known to activate AKT and it was found at 13.5 % of the patient samples. PIK3CA mutations were more frequent in estrogen receptor-positive cancers compared to triple negative breast cancer (TNBC) (19 vs. 8 %, p = 0.001). High frequency of PIK3CA mutations (28 %) were also found in HER2+ breast tumors. In TNBC, FBXW7 mutations were significantly more frequent compared to ER+ tumors (13 vs. 5 %, p = 0.037). We performed validation for all mutated alleles with allele-specific PCR or direct sequencing; alleles analyzed by two different sequencing techniques showed 95-100 % concordance for mutation status. In conclusion, different breast cancer subtypes harbor different type of mutations and approximately 40 % of tumors contained individually rare mutations in signaling pathways that can be potentially targeted with drugs. Simultaneous testing of many different mutations in a single needle biopsy is feasible and allows the design of prospective clinical trials that could test the functional importance of these mutations in the future. © 2012 Springer Science+Business Media, LLC.