Experts from ACR's Clinical Research Center discuss their efforts to improve the outcomes and quality of life of women diagnosed with breast cancer.
ACR's clinical research efforts bring together physicians throughout the medical community in search of new tools in the fight against breast cancer. In recognition of National Breast Cancer Awareness Month, the Bulletin spoke with ACRIN and Radiation Therapy Oncology Group (RTOG®) breast cancer leadership about trials, results, and the future of breast cancer research.
Christopher E. Comstock, MD
Comstock is an attending Radiologist and director of breast imaging postgraduate training and education at Memorial Sloan-Kettering Cancer Center. He became chair of ACRIN's Breast Committee in 2012 and now serves as diagnostic vice chair of the ECOG-ACRIN Cancer Research Group's Breast Committee.
Q: What are some of the significant trends in breast cancer imaging research?
A: The question of how we can use imaging to improve breast cancer treatment underlies the recently opened Alliance A011104/ACRIN 6694 trial (which looks at the effect of preoperative breast MRI on surgical outcomes, costs, and quality of life of women with breast cancer). The trial includes 536 patients with stage I-II triple negative or HER2-amplified breast cancer who are eligible for breast-conserving therapy. Patients will be randomized to conventional imaging or conventional evaluation plus preoperative breast MRI, toward the goal of identifying patients with extended disease and reducing the rates of reoperation and breast cancer recurrence.
Reflecting a "less is more" perspective, a developing trial of patients with ductal carcinoma in situ, or DCIS, will combine MRI with a genetic DCIS score to identify those at low risk of invasive disease who can forgo radiation treatment. Additional research focuses on identifying whether multiple lumpectomies can be completed when imaging indicates absence of bridging disease. Currently, all such instances are treated with mastectomy.
Q: What breast cancer imaging trial results are expected in the near future?
A: Soon to be published are the three-year results of the ACRIN 6657 trial that, at one year study participant follow up, found change in tumor volume measurement derived from dynamic contrast-enhanced, or DCE, MRI to be effective in predicting breast tumor response to neoadjuvant treatment. Positive three-year data regarding use of this imaging biomarker will provide radiologists with a valuable tool for multidisciplinary treatment planning.
Q: What are examples of breast cancer research in the pipeline?
A: A developing study evaluating the utility of MR diffusion-weighted imaging (DWI) for detection and diagnosis of breast cancer (ACRIN 6702). The trial will collect multicenter data to provide definitive answers about an imaging method that measures the mobility of water molecules in vivo. DWI is sensitive to such tissue characteristics as cell density, membrane permeability, and microstructure. Researchers hope that DWI and DCE techniques are shown to improve MRI specificity, which could influence clinical patient management by reducing the number of unnecessary biopsies of MRI-detected breast lesions.
Q: What are some of the research challenges of conducting multicenter trials in breast cancer?
A: Because funding is no longer readily available for the larger-type trials that evaluate new imaging technologies for breast cancer screening and diagnosis, it will be necessary to identify novel and more economical methods of conducting breast imaging research.
A long-range challenge is to determine which imaging technology best meets the needs of women with average to moderate breast cancer risk associated with dense breasts. The need is exacerbated by the increase in states requiring breast screening facilities to notify such women of their need for additional screening, despite the lack of data establishing the most appropriate type of adjuvant imaging. This is a prime example of the type of mainstream clinical imaging questions that the ACRIN Breast Committee has tackled in the past.
Radiation Therapy Research
Julia R. White, MD, FACR
White is a professor in the Department of Radiation Oncology at the Ohio State Comprehensive Cancer Center. She has chaired the RTOG Breast Cancer Working Group since 2006 and is the co-chair of the NRG Oncology Breast Cancer Committee.
Q: What recent research results have emerged from the RTOG Breast Cancer Working Group?
A: A major accomplishment has been the reporting of results of RTOG 9804 (a phase III trial of observation versus radiotherapy for good risk DCIS of the female breast) at the American Society for Radiation Oncology 2012 Annual Meeting. Analysis of diligent seven-year study participant follow-up showed that standard clinical and pathological criteria could be used to identify women with DCIS who are at low risk for breast cancer recurrence. Of the group thus identified, those not receiving radiotherapy had a recurrence rate of 6.4 percent and those electing radiotherapy had a rate of 1 percent. This is important information for clinicians to consider when counseling patients diagnosed with DCIS about treatment options.
RTOG has also played an important role in developing accelerated partial breast irradiation (APBI) for breast-conservation treatment. Long-term outcomes at 12 years of RTOG 9517 (a phase I/II trial to evaluate brachytherapy as the sole method of radiation therapy for stage I and II breast carcinoma) were reported at the American Society of Clinical Oncology 2012 Breast Cancer Symposium. The trial showed an ipsilateral breast recurrence risk of 6 percent. At ASTRO this year, we reported an update at eight years of RTOG 0319, a phase I/II trial to evaluate 3-D conformal radiation therapy (3D-CRT) confined to the region of the lumpectomy cavity for stage I and II breast carcinoma. The results show good durable outcomes — a 5.9 percent ipsilateral breast recurrence rate — in terms of cancer control for APBI.
Q: What research results might the ACR Bulletin readership anticipate?
A: The encouraging results of the single-arm APBI trials provided key evidence that led to the conduct of the collaborative National Surgical Adjuvant Bowel and Breast Project (NASBP) B-39/RTOG 0413 trial, a randomized phase III study of conventional whole-breast irradiation versus partial-breast irradiation for women with stage 0, I, or II breast cancer. Although surveillance, epidemiology, and end results data indicate that partial-breast irradiation techniques are gaining momentum in clinical practice, we lack mature data comparing the strategy of irradiating only the highest-risk breast quadrant over an accelerated course of several days with irradiating the whole breast over several weeks. The NASBP B-39/RTOG 0413 trial results will provide crucial data about whether APBI yields equivalent local control for select low-risk patients. More than 2,000 of the accrued 4,200+ study participants were enrolled by RTOG.
Q: What about women who aren't candidates for APBI?
A: More than half of them women who undergo lumpectomy would never have the opportunity to undergo APBI. That's why I'm really excited about RTOG 1005, a phase III trial of accelerated whole-breast irradiation with hypofractionation plus concurrent boost versus standard whole-breast irradiation plus sequential boost for early-stage breast cancer. The rapidly accruing trial for women at higher-than-average risk for local recurrence is investigating whether using very modern technology, such as 3D-CRT and intensity modulated radiotherapy, enables physicians to treat the high-risk portion of the breast with a higher radiation dose and the remainder of the breast with a slightly lower dose, all within three weeks.
RTOG's contribution to breast cancer care may result in an accelerated course of treatment lasting less than three weeks, which would help with sequencing chemotherapy, reduce fatigue, lessen the overall treatment burden, and potentially provide some biologic advantages.
Q: Are research efforts underway for women with later-stage cancer?
A: With the Alliance for Clinical Trials in Oncology, we are developing very exciting phase II and phase III protocols of stereotactic body radiotherapy (SBRT) for women with oligometastatic breast cancer. The trial will investigate whether ablation of discrete metastatic lesions in combination with systemic therapy improves both progression-free and overall survival. This is the first metastatic breast cancer trial investigating if survival is extended with the use of SBRT, a technology in which RTOG has played a key role.
By Nancy Fredericks, MBA, and Julie Catagnus, MSW, ELS