Dana-Farber / Brigham and Women's Cancer Center

Dedicated, Specialized Treatment for Triple-negative Breast Cancer

Dedicated, Specialized Treatment for Triple-negative Breast Cancer

The Breast Oncology Center at Dana-Farber/Brigham and Women’s Cancer Center has a team of five dedicated breast pathologists who provide expert consultation for breast cancer cases that are difficult to manage.

“It’s important for any triple-negative diagnosis to be unequivocal because there is no current targeted therapy for that subgroup. We want to make sure that these patients aren’t really ER or HER2 positive,” said Brigham and Women’s and Dana-Farber/Brigham and Women’s Cancer Center pathologist Andrea Richardson, MD, PhD.

To better characterize triple-negative breast cancer (TNBC), research programs at the Breast Oncology Center include efforts to identify biomarkers and develop targeted drugs.

Characterizing Triple-negative Breast Cancer

Directed by Dr. Richardson, the Breast Tissue Bank, part of the Dana-Farber/Harvard Cancer Center Specialized Program of Research Excellence (SPORE), was established in 2000. It contains approximately 2,500 frozen breast tumor specimens. This tissue bank has contributed to the early and ongoing genetic characterization of breast cancer subtypes, such as work identifying the chromosomal changes involved in triple-negative breast cancer (Cancer Research. Jan 2004;64:64-71), and work showing that BRCA1-mutant tumors and triple-negative tumors show similar phenotypes and gene expression signatures possibly related to defects in DNA repair mechanisms (Breast Cancer Res Treat. 2005 May;91(2):179-86).

triple-negative tumor
An MRI scan showing a large triple-negative tumor (first image) and resolution of the cancer after completing cisplatin trial.
 
molecular detail of triple-negative breast cancer.
The molecular detail of triple-negative breast cancer.
(A= H&E, B= ER, C= PR, D= HER2, E= Ki67, F= p53, G=CK14, H= p63).

Triple-negative Breast Cancer Biomarker Discovery

Dr. Garber and colleagues recently completed two clinical trials testing the use of cisplatin for patients with triple-negative breast cancer. Dr. Garber collaborated with Dr. Richardson in the analysis of tumor tissue collected before and after cisplatin treatment. The results of the first trial, reported in the Journal of Clinical Oncology (J Clin Oncol. 2010 Mar 1;28(7):1145-53), showed that 22 percent of patients had a complete pathologic response (no detectable residual tumor at surgery), suggesting that a certain subtype of triple-negative breast cancers may be very responsive to cisplatin. These results were confirmed in the second trial testing the use of cisplatin and the anti-angiogenesis drug, bevacizumab. 

Dr. Richardson and colleagues have examined breast tissue banked from participants in the two cisplatin trials to find biomarkers that may help identify patients who will respond to cisplatin.

“We have found that certain levels of chromosomal changes, measured in tumor DNA, will predict who will be most sensitive to cisplatin,” said Dr. Richardson, who led the team recently publishing these results in the new AACR journal Cancer Discovery (Cancer Discov. OnlineFirst Mar 22, 2012).

The Search for a Targeted Drug for Triple-negative Breast Cancer

Because there is no current targeted drug therapy for triple-negative breast cancer, Drs. Richardson and Garber are pursuing translational research into promising targets, including PARP-inhibiting drugs. A PARP-inhibitor is currently in trial for tumors with BRCA mutations. “Since PARP inhibitors have shown a lot of promise in the BRCA-mutant tumors, we hope they will be effective in sporadic (non-inherited) triple-negative tumors, too,” said Dr. Richardson. A trial using a PARP-inhibitor combined with cisplatin for triple-negative breast cancer, led by Dr. Garber, was recently completed and will be presented at the ASCO meeting in June 2012.

Other promising trials for TNBC, including trials combining PARP inhibitors with other agents, are in development at the Dana-Farber/Brigham and Women’s Cancer Center, including several in collaboration with the Early Drug Development Center.  For more information, contact Principal Investigator Sara Tolaney, MD, MPH (617)632-2335 at stolaney@partners.org.

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Dana-Farber President Comments on National Cancer Report

Benz, Jr., MD comments on the Annual Report to the Nation

Dana-Farber president Edward J. Benz, Jr., MD, comments on the
Annual Report to the Nation on the Status of Cancer,
citing encouraging news as well as areas where improvement is needed.

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