Monica Bertagnolli, MD
Chief, Division of Surgical Oncology
Professor of Surgery
President, Alliance for Clinical Trials in Oncology
Dana-Farber Cancer Institute
Brigham and Women's Hospital
Harvard Medical School
2013-2014 BCRF Project:
(The ANN INC. Award)
On behalf of Alliance for Clinical Trials in Oncology
Co-Investigators: Wendy L. Frankel, MD, Ohio State University; and Jennifer Ligibel, MD, Dana-Farber Cancer Institute, Brigham & Women's Hospital, Harvard Medical School, Boston, MA
A major goal of the Alliance for Clinical Trials in Oncology, a National Cancer Institute-designated clinical trials cooperative group formerly known as Cancer and Leukemia Group B, is to develop and use tissue-based biomarkers to individually tailor treatment to achieve the best possible breast cancer outcome at least cost to the patient in terms of side effects and quality of life. BCRF support will enable this research group to continue to conduct innovative clinical and genetic studies to address these critical issues. Recent clinical trials have shown that the preoperative administration of systemic therapy (e.g. chemotherapy, hormonal therapy, targeted therapy) is safe and effective. In addition, from a research standpoint, it has two major benefits: 1) researchers can quickly see whether drugs shrink the cancer and 2) they can study the tumors before and after treatment to assess the impact of the therapies. With BCRF support, the Alliance has tested two new targeted therapies using this approach. In patients with tumors that are dependent on HER2 (CALGB 40601), they have compared trastuzumab (Herceptin®) versus lapatinib (Tykerb®) versus both, with the results suggesting that in most breast cancer subtypes, both agents is best. In patients with HER2 normal tumors (""HER2 negative""), they are testing the addition of an antibody that shuts off new blood vessel formation (Avastin® or bevacizumab), and whether adding in another chemotherapeutic agent helps (CALGB 40603); these results have been submitted to the San Antonio annual meeting for presentation in December. As the Alliance consortia hascollected tumor samples from all patients enrolled in these studies, they have the unique opportunity to examine the effects of the treatments on tumors before surgery. This knowledge will inform future treatment trials in breast cancer.
Now that the clinical trials have reached their accrual goal and the primary endpoint has been analyzed, the Alliance study team is able to focus on the correlative science analyses. They will utilize prior BCRF funding for whole genome sequencing of specimens collected from patients on the CALGB 40601 trial; we will use funds from the 2013 grant to fund completion of the RNA sequencing for these two studies.
Update on correlative Science for CALGB 40601 and CALGB 40603 (Neo-adjuvant breast trials): In patients with tumors that are dependent on HER2, the researchers have compared trastuzumab (Herceptin®) versus lapatinib (Tykerb®) versus both, with the results suggesting that in most subtypes, both agents is best. In patients with hormone receptor-poor, HER2 normal tumors ("HER2 negative") (often referred to as triple-negative cancers), they are testing the addition of an antibody that shuts off new blood vessel formation (Avastin® or bevacizumab), and whether adding in another chemotherapeutic agent helps. Results for the primary endpoints for these studies – comparing the ability of the control and experimental treatments to completely eliminate cancer from the breast and lymph nodes before surgery – were presented at national cancer conferences in 2013; going forward, the researchers will focus on identifying which of these patients are more (or less) likely to respond to these treatments.
Update on CALGB 40903, “Phase II study of preoperative letrozole for postmenopausal ER-positive ductal carcinoma in situ”: Because physicians do not have tools to predict which patient with DCIS is at high risk for future development of invasive breast cancer, the only treatment options for patients with DCIS are surgery in combination with radiation, and endocrine therapy. Presently, no other less aggressive treatment option exists, even if the perceived risk of cancer progression is small. In this proposed study, researchers will obtain breast MRIs several times before surgery to monitor response to therapy, as well as collect breast tissue at diagnosis and following 6 months of hormonal therapy. Importantly, quality of life correlates will also be studied for the effect of letrozole in the neoadjuvant setting. This study represents one of the first opportunities to see the effect of endocrine therapy and imaging diagnostics on DCIS before surgery. Results should improve understanding of endocrine therapies and breast imaging with MRI in pre-invasive breast disease. The study opened to accrual in February 2012. To date, 35 patients have been accrued. The study team has focused efforts to enhance accrual, and the study team and Alliance Accrual Task Force are collaborating to enact an accrual enhancement plan that will engage local investigators, participating sites, patient advocacy groups and the study team.
Update on Expanded Biostatistical Support for the CALGB Breast Committee : As a result of the BCRF support, the Alliance has hired a master’s level statistician who has assisted in the analysis of clinical and correlative endpoints, as well as preparation for manuscripts and presentations. This has aided in the analyses of clinical and correlative endpoints for 3 high profile studies for the Alliance breast committee. Two of these studies, CALGB 40601 and 40603, have been presented at national meetings in 2013. Presently, these results are being finalized for manuscript submission as well as ongoing correlative analyses.
Dr. Bertagnolli is a Professor of Surgery at Harvard University Medical School and the Chief of the Division of Surgical Oncology at Brigham and Women's Hospital and Dana-Farber Cancer Institute. Dr. Bertagnolli is a member of the Gastrointestinal Cancer and Sarcoma Disease Centers at the Brigham and Women's/Dana Farber Cancer Center, where she collaborates with colleagues in medical oncology, radiation oncology, and pathology to treat cancer patients in a tertiary care setting.
Dr. Bertagnolli maintains an active research laboratory whose work focuses upon understanding the role of the adenomatous polyposis coli (APC) gene in epithelial tumor formation. She was also one of the organizing members of gastrointestinal correlative science initiatives within the NCI-funded Cancer Cooperative Groups, where she facilitated integration of tumor-specific molecular markers of treatment outcome into nation-wide clinical cancer treatment protocols. Dr. Bertagnolli has had numerous leadership roles in multi-institutional cancer clinical research consortia, and currently serves as President of the Alliance for Clinical Trials in Oncology (ACTION), a group combining the Cancer and Leukemia Group B (CALGB), the North Central Cancer Treatment Group (NCCTG), and the American College of Surgeons Oncology Group (ACOSOG).