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From OncoLog, June 2013, Vol. 58, No. 6

Prediction Tool Helps Determine Whether Older Breast Cancer Patients Will Benefit from Radiation

By Amelia Scholtz

A statistical tool is now available to predict the likely individual benefit of radiation therapy for older women who have undergone breast-conserving surgery for breast cancer. 

The prediction tool is based on a nomogram that uses patient-specific factors to calculate a patient’s risk of requiring subsequent mastectomy—the most common treatment for local breast cancer recurrence—within 5 and 10 years after breast-conserving surgery alone and after breast-conserving surgery plus adjuvant radiation therapy.

“The question of when it is okay to treat older women with breast cancer using lumpectomy without radiation has been an ongoing source of controversy,” said Benjamin Smith, M.D., an assistant professor in the Department of Radiation Oncology at The University of Texas MD Anderson Cancer Center. He and colleagues from MD Anderson and the University of Chicago conducted the study that produced the nomogram. “Our concern was that the National Comprehensive Cancer Network guideline statement was not sufficiently nuanced to truly capture the breadth of types of patients for whom radiation therapy can be omitted,” Dr. Smith said.

The decision-making tool

The decision-making tool, which is available on MD Anderson’s Web site, first asks the user to designate the patient’s age and race, the tumor’s size and estrogen receptor status, and the lymph node status. The tool then provides the described patient’s risks of needing a mastectomy by 5 and 10 years after surgery with and without radiation. For example, a physician might select an age of 66–69 years, white race, tumor size of 2.0 cm or less, negative or borderline-positive estrogen receptor status, and negative nodal status that was assessed clinically but not pathologically. For a patient with those characteristics, the nomogram calculates the risks of needing mastectomy by 5 and 10 years to be 9% and 21%, respectively, if the patient does not receive radiation therapy; however, if the patient does receive radiation therapy, the risks of needing mastectomy by 5 and 10 years are 2% and 5%, respectively.

The online tool offers advantages for both clinicians and patients. “For physicians, risk prediction tools that allow you to take the experience from the literature and then apply it to your patient can really improve decision making,” Dr. Smith said. The tool also facilitates patient autonomy in decision-making by showing the likely benefit of radiation therapy in easily understood terms.

Graphic: Nonogram for calculating survival probability

The research behind the tool

The process of creating the nomogram began with Dr. Smith and his colleagues using the Surveillance, Epidemiology, and End Results–Medicare database to identify women who were diagnosed with breast cancer at ages 66–79 years between 1992 and 2002 and who had no cancer history. Women 80 years and older were excluded because the team’s earlier research suggested that those patients were unlikely to benefit significantly from radiation therapy. Also excluded were patients diagnosed with ductal carcinoma in situ and those with missing data. The final cohort included approximately 16,000 patients, 89% of whom received radiation therapy after their initial surgery.

The next step was to identify risk factors for subsequent mastectomy. Younger age, larger tumor size, and black race were found to be independent risk factors for mastectomy in the patient cohort. The researchers also studied which patients received the greatest benefit from adjuvant radiation therapy. Estrogen receptor positivity was associated with lower tumor grade, which itself was associated with a smaller benefit from radiation. Patients who had pathologically confirmed disease in one or more lymph nodes or who had node-negative disease that had been diagnosed only clinically were the most likely to benefit from radiation therapy.

Yu Shen, Ph.D., a professor in the Department of Biostatistics, and Diane Liu, M.S., a statistical analyst in that department, used these data to generate the nomogram in consultation with physician-scientists. They then internally validated the nomogram, and after some refinement, its accuracy was similar to that of predictive tools used for other purposes in clinical practice.

The observational data used to produce the nomogram had several limitations worth noting. The cohort included relatively few black women, making it difficult for researchers to determine why black race appeared to be a risk factor for subsequent mastectomy. Additionally, the use of mastectomy as a proxy for local disease recurrence does not account for the minority of recurrences that are treated with lumpectomy. Therefore, the absolute risk of recurrence is almost certainly higher than the risk of mastectomy recorded in the study. Finally, data for additional possible risk factors such as surgical margin status and lymphovascular space invasion were not available.

Despite these limitations, the results produced by the nomogram are consistent with the findings of a 10-year, prospective, randomized trial reported by Hughes and colleagues at the annual American Society of Clinical Oncology meeting in 2010. Moreover, Dr. Smith is hopeful that his team will ultimately be able to externally validate the data on which the nomogram is based, possibly using data from other population-based tumor registries.

Physicians and patients can access the prediction tool and other clinical calculators at http://www.mdanderson.org/education-and-research/resources-for-professionals/clinical-tools-and-resources/clinical-calculators/index.html.

For more information, call Dr. Benjamin Smith at 713-563-2380.

Other articles in OncoLog, June 2013 issue:

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