Radiation Therapy for Breast Cancer
Progress in clinical practice and personalizing treatment requires clinical trials
BY JULIA WHITE, MD, director of Breast Radiation Oncology and vice chair for Clinical Research, Department of Radiation Oncology, The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute; chair of the Radiation Therapy Oncology Group (RTOG) Breast Cancer Committee
By 2003, gene expression and profile studies were showing that breast cancer – previously regarded as a single disease – had four or five subtypes. In April 2012, the journal Nature published a study based on genome and transcriptome profiles from nearly 2,000 women that identified 10 breast-cancer subtypes.
As our understanding of breast cancer evolves, it’s critical that the practice of radiation oncology, a principal treatment modality for breast cancer, keep pace. We accomplish this, of course, through research. Our ultimate goal is to improve clinical practice so that we can better provide the right treatment for each woman’s particular form of the disease. Changing the practice of medicine requires sufficient evidence, which is generally defined as the outcomes from at least two phase III randomized clinical trials.
But how do we determine which clinical trials to initiate? In radiation oncology, that typically happens in two ways. They can develop from intriguing preclinical and early-phase clinical studies that bubble up from single institutions, or they can arise when we bring together the best thinkers in radiation oncology to identify problems emerging from daily practice, and then design early-phase trials that begin to address them. I’m involved in two Radiation Therapy for ongoing trials that exemplify both approaches.
NSABP 239/RTOG 0413 is a 4,300-woman phase III trial that compares a six-week course of radiation following lumpectomy to a one-week course of radiation (10 treatments given twice daily over one week versus one treatment per day given for six to seven weeks). The trial includes correlative studies to discover what types of breast cancer are most amenable to a one-week partial-breast regimen. I am co-principal investigator on this study, which is accruing patients now.
This trial grew from evidence coming from Europe and within the United States indicating that therapy could be delivered over a shorter time by radiating just the lumpectomy site rather than the entire breast. That initial evidence led to early-phase trials such as RTOG 9517 in 2000, a phase I/II trial evaluating brachytherapy as partial breast irradiation for stage I and II breast cancer, and RTOG 0319, a phase I/II trial evaluating three-dimensional conformal radiation therapy of the region of the lumpectomy cavity for early-stage breast cancer in 2003.
RTOG 1014 is an example of a study initiated in response to a clinical question. The current standard of care for women with recurrent cancer following lumpectomy and radiation prescribes a mastectomy. The question was whether the entire breast should be removed in these women, or would a second lumpectomy and a partial breast reirradiation be less traumatic and equally effective?
In 2011, we organized RTOG investigators and initiated a phase I safety and feasibility study evaluating breast preservation therapy for recurrent disease as a first step toward replacing the current standard of care.
RTOG is developing other studies that are likewise based either on early data that might influence practice and require phase III clinical testing, or on a clinical need that requires early data to help answer the question and suggest different treatment models.
The breast-cancer program here at Ohio State has the same objectives. With a strong team of scientists, and as one of only seven centers funded by the National Cancer Institute to conduct both phase I and phase II clinical trials, Ohio State is a leader in early-phase work. In addition, the OSUCCC – James Stefanie Spielman Comprehensive Breast Center brings together a range of clinical specialists and breast services under one roof, and the Ohio State breast cancer program bridges that comprehensive clinical-care component with its robust scientific program.
Our growing understanding of breast cancer will lead to improvements in radiation therapy for women with breast cancer that will increasingly individualize therapy over the next five to 10 years. These advances will require good patient participation in current and future clinical trials that will help us offer the right radiation therapy for the right woman and the right disease in the framework of breast cancer.