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1.  Biomarker Modulation Following Short Term Vorinostat in Women with Newly-Diagnosed Primary Breast Cancer 
Purpose
Agents that target the epigenome demonstrate activity in breast cancer models. In preclinical studies, the histone deacetylase inhibitor vorinostat induces cell cycle arrest, apoptosis and differentiation. We evaluated biomarker modulation in breast cancer tissues obtained from women with newly-diagnosed invasive disease who received vorinostat and those who did not.
Experimental Design
Tumor specimens were collected from 25 women who received up to 6 doses of oral vorinostat 300 mg twice daily and from 25 untreated controls in a non-randomized study. Candidate gene expression was analyzed by RT-PCR using the Oncotype DX® 21-gene assay, and by immunohistochemistry for Ki-67 and cleaved caspase-3. Matched samples from treated women were analyzed for gene methylation by QM-MSP. Wilcoxon non-parametric tests were used to compare changes in quantitative gene expression levels pre- and post-vorinostat with changes in expression in untreated controls, and changes in gene methylation between pre- and post-vorinostat samples.
Results
Vorinostat was well-tolerated and there were no study-related delays in treatment. Compared to untreated controls, there were statistically significant decreases in the expression of proliferation-associated genes Ki-67 (p=0.003), STK15 (p=0.005), and Cyclin B1 (p=0.03) following vorinostat, but not in other genes by the Oncotype DX® assay, or in expression of Ki-67 or cleaved caspase-3 by immunohistochemistry. Changes in methylation were not observed.
Conclusions
Short term vorinostat administration is associated with a significant decrease in expression of proliferation-associated genes in untreated breast cancers. This demonstration of biological activity supports investigation of vorinostat in combination with other agents for the management of breast cancer.
doi:10.1158/1078-0432.CCR-13-0033
PMCID: PMC3718062  PMID: 23719261
Breast cancer; epigenetics; histone deacetylase inhibitors; vorinostat; predictive biomarkers
2.  Physician Survey of the Effect of the 21-Gene Recurrence Score Assay Results on Treatment Recommendations for Patients With Lymph Node–Positive, Estrogen Receptor–Positive Breast Cancer 
Journal of Oncology Practice  2011;7(2):94-99.
This physician survey looks at the effect of the 21-gene recurrence score assay results on adjuvant treatment recommendations for patients with lymph node–positive, estrogen receptor–positive breast cancer.
Purpose:
To survey the effect of the 21-gene recurrence score (RS) assay results on adjuvant treatment recommendations for patients with lymph node–positive (N+), estrogen receptor–positive (ER+) breast cancer.
Methods:
Medical oncologists who ordered the 21-gene RS assay were invited to complete a survey regarding their most recent patient with N+/ER+ breast cancer. We obtained responses from 160 (16%) of the 1,017 medical oncologists.
Results:
Most of the respondents were in community (71%) versus academic (25%) settings and had practiced for a median of 11 years. T1, T2, or T3 disease was reported in 62%, 35%, and 3% of patients, respectively. One, two, three, or ≥ 4 nodes were reported in 69%, 18%, 6%, and 3% of patients, respectively. Eighty-six percent of the oncologists made treatment recommendations before obtaining the RS; 51% changed their recommendations after receiving the RS. In 33%, treatment intensity decreased from chemotherapy plus hormonal therapy to hormonal therapy alone. In 9%, treatment intensity increased from hormonal therapy alone to chemotherapy plus hormonal therapy. In 8%, treatment recommendations changed in a way that did not fit the definition of either increased or decreased intensity.
Conclusion:
In this survey of physician practice, the RS result was used to guide adjuvant treatment decision making in N+/ER+ breast cancer more often in patients with tumors less than 5 cm in size and one to three positive lymph nodes than in patients with larger tumors and four or more positive nodes and yielded an overall reduction in recommendations for chemotherapy.
doi:10.1200/JOP.2010.000046
PMCID: PMC3051869  PMID: 21731516

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