CERTAIN LUMINAL A BREAST CANCERS MIGHT NOT NEED RT

NEW YORK (Reuters Health) - Some women with low-risk luminal A breast cancer may not benefit from breast radiotherapy, new research suggests.

"This study allowed us to assess the breast relapse rate after endocrine therapy without radiotherapy in women with lower-risk disease, which previous studies have not been able to do. Low-risk Luminal A tumors were likely to have the best outcome," Dr. Anthony W. Fyles, of Princess Margaret Cancer Centre in Toronto, Ontario, Canada, told Reuters Health by email.

"We anticipated that women with luminal A tumors would have a small benefit from breast radiation but it was not clear whether it would be low enough to consider omitting radiation and using endocrine therapy alone after lumpectomy and endocrine therapy," said Dr. Fyles. "We anticipate that these women will not require breast radiation, once confirmatory trials are completed."

As reported online May 11 in the Journal of Clinical Oncology, Dr. Fyles and colleagues conducted a subset analysis of participants in the Toronto-British Columbia (TBC) trial.

In this study, 769 women age 50 and older (median age, 68) with node-negative invasive adenocarcinoma no larger than 5 cm (pT1/T2) were randomly assigned after breast-conserving surgery to either tamoxifen alone (20 mg daily for five years) or tamoxifen and radiotherapy (40 Gy in 16 daily fractions over three to four weeks, followed by a 12.5 Gy boost in five daily fractions).

Using archival formalin-fixed paraffin-embedded blocks obtained from 501 (65%) of the original participants, the researchers performed immunohistochemical analyses of estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 (HER2), cytokeratin 5/6, epidermal growth factor receptor, and Ki-67.

From this, they classified patients as luminal A (n=265), luminal B (n=165), or high-risk subtype (luminal HER2, n=22; HER2 enriched, n=13; basal like, n=30; or triple-negative nonbasal, n=6).

During the 10-year-median follow up, there were 69 breast cancer relapses and 137 deaths. The 10-year overall survival came to 84% in both groups.

Subtype was prognostic for ipsilateral breast recurrence (IBR), and luminal subtypes seemed to benefit less from radiation than high-risk subtypes, but not significantly so (luminal A hazard ratio, 0.40; luminal B HR, 0.51; high-risk subtype HR, 0.13).

In an exploratory analysis of women with low-risk tumors (over age 60, T1, grade 1 or 2), the 10-year risk of IBR was 3.1% for luminal A subtype (n=151) vs 11.8% for high-risk subtypes (n=341, P=0.0063). Low-risk luminal A patients had a 10-year IBR rate of 1.3% with tamoxifen compared with 5.0% with tamoxifen plus radiation (P=0.42).

In multivariable analysis, IBR was significantly associated with radiotherapy (HR 0.31; P<0 .001="" 0.20="" 2.2="" a="" and="" clinical="" group="" luminal="" p="" risk="" subtype="">

Dr. Jennifer R. Bellon of the Dana-Farber Cancer Institute and Brigham and Women's Hospital in Boston, who wrote an accompanying editorial, told Reuters Health by email, "Radiation is costly, and can have serious side effects. Figuring out which patients can safely avoid radiation would be a huge step forward."

Dr. Bellon called for more research in this area. "Medical oncologists have for several years been more aware of the varying biologic behaviors of breast cancers, and have tailored their treatments accordingly. Traditionally, radiation oncologists have been more anatomic in their thinking (how big is the tumor, and where has it spread). Understanding how the biology impacts the risk of local and regional recurrence is a next logical step," she said.

Dr. Fyles added in an email, "To change practice we require a second confirmatory trial, and that study is ongoing. Further questions remain about the best and most clinically applicable biomarker to select patients and further trials are planned to evaluate these."

SOURCE: http://bit.ly/1L4qUx4 and http://bit.ly/1HgbDYx

J Clin Oncol 2015.