Frontiers in Preoperative Chemotherapy
Preoperative chemotherapy for breast cancer first emerged as a method to shrink advanced, inoperable tumors enough to allow for successful mastectomy. The effectiveness of this technique led researchers to test preoperative chemotherapy in women whose tumors could be removed by surgery.
Today, after several large-scale clinical trials have demonstrated the safety and efficacy of preoperative chemotherapy for breast cancer, "anyone who will require [a] therapy in question" is a candidate to receive that therapy before surgery, stated Drs. Julie Gralow, from Fred Hutchinson Cancer Center, and Eric Winer, from the Dana-Farber Cancer Institute, at the NCI-sponsored conference "Preoperative Therapy in Invasive Breast Cancer: Reviewing the State of the Science and Exploring New Research Directions," held March 26 and 27 on the NIH campus.
Now, as discussed at the conference, clinical trials hold the promise of personalizing breast cancer treatment in the future. "When a drug is given preoperatively, you have access to the tumor as it's being perturbed," explained Dr. Jo Anne Zujewski, a breast cancer specialist with NCI's Division of Cancer Treatment and Diagnosis. In the preoperative setting, researchers can measure the immediate response of individual tumors to new therapies, and correlate that response with the molecular characteristics and genetic mutations found in those tumors. The ultimate goal is to improve outcomes for patients by targeting the therapy to the specific tumor type. In addition, because smaller tumors often require less extensive surgery, cosmetic outcome may be improved with a potential for decreased surgical morbidity.
The understanding that breast cancer is not a single entity, but a diverse set of diseases driven by different mutations that respond differently to therapy, revolutionized both the treatment of breast cancer and the research into new, targeted drugs. Doctors routinely administer estrogen-blocking drugs such as tamoxifen or aromatase inhibitors to women whose tumors overexpress receptors for estrogen, and the drug trastuzumab to women whose tumors overexpress the tumor marker HER2. By testing new drugs before surgery, where there is an opportunity to correlate response to treatment with common tumor characteristics, "we may be able to individualize the care of future patients off trials to an even greater extent. The hope is that we can subdivide tumors and patients to maximize effectiveness and minimize toxicity from therapy," said Dr. Winer.
In addition to using preoperative therapy to better define subgroups of breast cancer that might respond to new treatments, researchers hope that a new generation of trials can better define how to treat patients whose tumors do not respond to traditional chemotherapy. Currently, when chemotherapy is given preoperatively, investigators can see whether the drugs have an effect on the tumor. However, if a tumor does not respond, switching to another chemotherapy regimen mid-treatment hasn't been shown to make a difference.
"It seems that with chemotherapy, tumors either respond or not. You either have a chemosensitive tumor or a chemoresistant tumor," said Dr. Gralow. New trials will look at whether targeted biological drugs such as antiangiogenesis agents can help women whose tumors are resistant to preoperative chemotherapy.
One caveat stressed by participants at the conference was that "there is an incredible need for multidisciplinary care of patients and multidisciplinary involvement in research," due to the complexities that arise from using therapy that can cause a tumor to shrink or disappear even before surgery, explained Dr. Winer. "You can't provide optimal clinical care unless you have medical oncologists, surgeons, pathologists, radiation oncologists, breast imagers, and oncology nurses all working very closely together. And you can't pull off the research unless you have all of these clinicians plus a dedicated group of basic and translational scientists, and we should never forget the critical role played by our colleagues in biostatistics."
The conference videocast, including the statement of the science, is available at http://videocast.nih.gov. To download podcasts from the conference or PDFs of the slide presentations, visit the conference Web site at http://ctep.cancer.gov/bcmeeting.
— Sharon Reynolds