Breast Cancer -- Clinical Research Program

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 for breast cancer 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 aimed at developing novel surgical approaches, imaging techniques, and radiation modalities.

Among our recent research accomplishments:

Molecular Pathology

  • We are engaged in projects defining the prevalence of germline genetic alterations in BRCA1, BRCA2, and other genes (such as ATM) in women with, or at risk for, breast cancer; determining the clinical phenotype and outcome of hereditary breast cancer; and developing new strategies for the management of women at risk.
  • Investigators have found new clues about how metastatic cancer can form long after a primary tumor has been removed. Researchers introduced into the systemic circulation of mice untransformed mouse mammary cells engineered to express the inducible oncogenic transgenes NYC and KRAS (D12). They showed that such cells can bypass transformation at the primary site and develop into metastatic pulmonary lesions upon immediate or delayed oncogene activation. Mammary cells lacking oncogenic transgenes displayed a similar capacity for long-term residence in the lungs but did not form ectopic tumors. Science. 2008 Sep 26;321(5897):1841-4. [PubMed Abstract]
  • Research led by Memorial Sloan Kettering investigators identifies three genes that specifically mediate the metastasis of breast cancer to the brain and illuminates the mechanisms by which this spread occurs. The study showed that COX2 and HB-EGF — genes that induce cancer cell mobility and invasiveness — were found to be genetic mediators in the spread of breast cancer to the brain. A third gene, ST6GALBAC5, was shown to provide cancer cells with the capability of exiting the circulation and passing through the blood-brain barrier to enter brain tissue. Nature. 2009 Jun 18;459(7249):1005-9. [PubMed Abstract]

Imaging

  • We are evaluating breast MRI and positron emission tomography scanning for the detection and staging of early-stage disease, and are exploring MRI as an interval screening modality for women at high risk of developing breast cancer. We are also studying the costs of these more intensive surveillance strategies. One advance was our description of the utility of spectroscopy as a means of improving the specificity of biopsy recommendations. Radiology. 2007 Oct; 245(1):80-7. [PubMed Abstract]

Local and Regional Treatment

  • Our group has defined the feasibility of delivering postoperative radiation with standard-of-care treatment plans to women who choose immediate reconstruction after mastectomy. Intl J Radiat Oncol Biol Phys. 2008 Jan 1;70(1):43-50. [PubMed Abstract]
  • We have retrospectively analyzed our experience with inflammatory breast cancer and have documented favorable long-term results with both local control and survival using combined modality therapy that includes a lower and better-tolerated radiation dose following neoadjuvant chemotherapy and mastectomy.
  • Building on our large sentinel node experience, we are determining the impact of immunohistochemically detected axillary metastases through prospective studies and a retrospective review of our database of untreated lymph-node-negative patients with long-term follow-up. The study demonstrates that in a cohort of patients who did not receive systemic therapy and who were followed long-term, micrometastases in axillary nodes are associated with decreased survival. The data supports the use of pathologic techniques to detect these small metastases to allow the appropriate tailoring of systemic therapy. J Clin Oncol. 2008 Apr 10; 26(11):1803-09. [PubMed Abstract]

New Agents

  • We are engaged in a variety of clinical research projects across a spectrum that includes exploring systemic treatments from prevention, adjuvant therapy, and palliative care. Our work has led to the establishment of a new standard of adjuvant chemotherapy regimen called dose-dense therapy and proof of the safety of this regimen combined with trastuzumab. J Clin Oncol. 2008 Apr 10;26(8):1216-22. [PubMed Abstract]

Targeted Therapies

  • One effort focuses on the development of 17-AAG, an ansamycin shown preclinically to act as a broad receptor inhibitor, alone and in combination with specific rational targeted therapeutics and/or chemotherapy agents as predicted to be effective in preclinical experiments. This project has yielded the first evidence of antitumor activity for 17-AAG in a cohort of women with HER2-positive, trastuzumab-refractory metastatic breast cancer. J Clin Oncol. 2007 Dec 1;25(34):5410-5417.[PubMed Abstract]