Luminal A Subtype Breast Cancer: Forgo Radiation?

Aspecific subgroup of women with early-stage breast cancer may be able to avoid adjuvant radiation, according to a presentation at the 2012 Annual Meeting of the American Association for Cancer Research (AACR) held in Chicago, Illinois. Women with the luminal A subtype of breast cancer, particularly those older than age 60, had fewer local recurrences at 10 years when treated with tamoxifen alone versus tamoxifen plus radiation therapy in a post hoc analysis of a randomized trial that compared these 2 forms of treatment.

Senior author of this paper, Fei-Fei Liu, MD, radiologist at Princess Margaret Hospital, senior scientist at the Ontario Cancer Institute, and professor at the University of Toronto, Canada, cautioned that local radiation therapy is still the standard of care for all other breast cancer subtypes.

Liu commented that avoiding radiation therapy in these patients, who account for about 25% of all newly diagnosed breast cancer cases in North America, could achieve an estimated $400 million in savings for the healthcare system in the United States.

The luminal A subtype of breast cancer is defined as estrogen receptor–positive, progesterone receptor–positive, HER2-negative, and low Ki-67 (<14%), a proliferation marker. The study was based on molecular subtyping analysis of 304 tumor blocks from 769 women with early T1 or T2, node-negative breast cancer who participated in a randomized controlled trial comparing tamoxifen plus whole-breast radiation therapy versus tamoxifen alone. Using immunohistochemistry, the researchers classified tumors into 6 categories: luminal A, luminal B, luminal-HER2, HER2-enriched, basal-like, or triple-negative phenotype nonbasal.

Overall, breast cancer recurrence at 10 years was 13.8% with tamoxifen alone compared with 5% for tamoxifen plus breast radiation. The luminal A subtype had the best outcome of any subgroup, with a 10-year risk of local relapse of 8% with tamoxifen alone versus 4.6% with tamoxifen and radiation. Luminal A patients older than age 60 had a 10-year local recurrence rate of 4.3% on tamoxifen alone versus 6% for combined modality therapy. Grade 1/2 luminal A tumors had a similar rate of recurrence regardless of treatment; 4.9% with tamoxifen versus 5.5% with tamoxifen plus radiation. The researchers said that these findings suggest that local breast radiation therapy did not affect the outcome of older patients with the luminal A subtype.

By contrast, radiation therapy had a positive impact on other breast cancer subtypes. For example, women with luminal B tumors had a 10-year recurrence rate of 16.1% with tamoxifen alone versus 3.9% with tamoxifen plus radiation therapy. A similar trend was seen for HER2, HER2-enriched, and basal-like tumors, but the numbers in each group were small.

These findings have implications for personalized cancer medicine, suggesting that Ki-67 be added to the current standard testing for hormone receptor and HER2 status in newly diagnosed patients with breast cancer. If these data on the luminal subtype A tumors are validated, that would pave the way for discussions with patients with this subtype about the need to undergo radiation therapy in addition to tamoxifen or other adjuvant therapy.

In a news release from AACR, Liu was quoted as saying: “This is yet another powerful example of ‘personalized cancer medicine.’ When this information is combined with well-conducted randomized clinical trials, significant advances can be made whereby we can truly start to tailor therapies, based on new molecular markers, which can be introduced into routine clinical practice.”