Our Clinical Trials Continually updated listing of our clinical trials for breast cancer 
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Clinical research in breast cancer encompasses the areas of surgery, radiation therapy, chemotherapy, imaging techniques -- such as magnetic resonance imaging (MRI) and digital mammography -- and genetics.
Almost every effective systemic therapy developed in the past decade has been studied by members of our clinical staff. In addition, members of the breast team have led many clinical trials, including those developing novel surgical approaches, imaging techniques, and radiation modalities.
Among our recent research accomplishments:
Detection, Diagnosis, and Prognosis
- A number of investigators from several programs are involved in basic and translational research related to breast cancer. We are designing preclinical and clinical studies utilizing targeted agents specific for genes that predict metastasis to the lungs. To better predict the risk of distant metastases, we are building on our vast experience with sentinel-node mapping and determining the clinical impact of axillary metastases through prospective studies and a retrospective review of our large database of untreated node-negative patients with long-term follow-up. Nature 2005;436:518-524. [PubMed Abstract]
- In women with a high risk of developing breast cancer, screening breast MRI can identify cancer that is not detected by mammography or physical examination in 4 percent of women. We have quantified the frequency of cancer as a function of specific MRI features, including lesion size. In collaboration with the Department of Surgery, we have developed and refined biopsy methods for lesions identified only by MRI, using preoperative localization for surgical biopsy and vacuum-assisted needle biopsy. AJR 2005; 185:183-193. [PubMed Abstract]; AJR 2006; 186: 426-430. [PubMed Abstract]
- As an adjunct to breast MRI, magnetic resonance spectroscopy (MRS) of the breast has the potential to decrease the number of benign biopsies performed for MRI-detected lesions, while missing virtually none of the cancers. We now plan to identify subpopulations of patients who are most likely to benefit from breast MRI, to prospectively study the sensitivity and specificity of spectroscopy in a variety of settings, and to refine MRI-guided intervention methods. We will study MRS to monitor the response to chemotherapy and will evaluate MRI-guided high-focused ultrasound for the percutaneous ablation of breast lesions -- a technique that holds promise for nonsurgical treatment. Radiology 2006; 239:686-692. [PubMed Abstract]
Targeted Chemotherapeutic Approaches
Our team explores treatments on a continuum from newly diagnosed breast cancer to late-stage disease.
- For women requiring adjuvant therapy, we have shown that weekly paclitaxel combined with trastuzumab for patients with HER2-positive disease improved outcomes when administered as part of a sequential regimen. NEJM 2005;353:1673-1684. [PubMed Abstract]
- Interest in the link between estrogen and angiogenesis has led to studies combining letrozole and bevacizumab. We are also developing sequential dose-dense strategies for the administration of cytotoxic agents (taxanes and epothilones) in combination with a number of targeted therapeutics. For example, we have shown that dose-dense adjuvant therapy may be safely combined with trastuzumab. Current projects include clinical trials assessing lapatinib and bevacizumab, each in combination with dose-dense chemotherapy. The latter trial incorporates correlative studies exploring the pathophysiology of hypertension in these otherwise healthy patients in preparation for planned national randomized trials. Proc ASCO 2006;582.
- Our work exploring HSP90 as an exploitable target has given rise to applications in several areas. Investigators are using the ansamycin 17-AAG or other inhibitors to interdict HSP90 function clinically. For breast cancer, we are studying 17-AAG alone and in combination with specific, rationally selected therapeutics including trastuzumab and taxanes, based on preclinical experiments predicting efficacy. These efforts have yielded the first evidence of conventional antitumor activity for 17-AAG in a cohort of women with HER2-positive, trastuzumab-refractory metastatic breast cancer. Proc ASCO 2006. We are broadening our translational studies focusing on HER2. One project will provide sequential tissue from HER2-overexpressing breast cancer so we can conduct laboratory studies examining the mechanisms of resistance. A related project seeks to identify cross-talk and signal-transduction dependencies between the HER2 and COX2 systems. This work has led us to analyze COX2 inhibition in metastatic breast cancer and in the preoperative setting. Cancer Res 2006;66:5504-5511. [PubMed Abstract]; Cancer Res 2005;65:10113-10119, 2005. [PubMed Abstract]
Radiation Therapy
- We are continuing efforts to improve target homogeneity in the breast and to decrease exposure to surrounding normal tissues, using intensity-modulated radiation therapy and a prone treatment board designed at MSKCC. Long-term local control in the prone position matches data in the conventional supine position with a more favorable toxicity profile for lung, heart, and skin tissue. Given the cardiotoxicity of commonly used adjuvant systemic agents, this approach may lead to a decreased risk of late effects.
- Based on both the decreased risk of local failure in older women and the feasibility of single-dose partial breast irradiation demonstrated by investigators in Milan, Italy,[JG1] we developed a technique called intraoperative partial breast radiation using a high-dose rate remote afterloader for use during breast conserving surgery, a procedure that is performed in a shielded operating room. A specially designed HAM applicator was produced for this study, and the feasibility of the approach was demonstrated in our first patient cohort (limited to women 60 years or older). Both the surgery and the single-dose radiation are delivered together on an outpatient basis. Int J Radiat Oncol Biol Phys. 2007;68(1):73-81. [PubMed Abstract]; Int J Radiat Oncol Biol Phys. 2007;69(1):19-24. [PubMed Abstract]
