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Node-Negative Breast Cancer: Indications that Post-Op Radiation Therapy Not Needed in Women with Luminal A Subtype Receiving Tamoxifen

Carlson, Robert H.

doi: 10.1097/01.COT.0000419652.44095.43

CHICAGO—Women over age 60 with the luminal A subtype of node-negative breast cancer may not need post-lumpectomy radiation therapy if they are receiving tamoxifen, according to preliminary results from a long-term, randomized Canadian study reported here at the American Association for Cancer Research Annual Meeting (Abstract 1032).

At 10 years, women over age 60 with luminal A tumors had relapse rates of 4.3% with tamoxifen alone vs. 6% with tamoxifen plus radiation.

Principal investigator Fei-Fei Liu, MD, Senior Scientist and Head of the Division of Applied Molecular Oncology at Ontario Cancer Institute and Professor at the University of Toronto, explained that the study was begun 20 years ago to determine whether breast radiation was necessary for everyone, and whether patients were being overtreated.

“Not being able to break down into molecular subtypes, the overall conclusion was that we still had to proceed with radiation therapy,” she said. The original randomized study, by researchers in Toronto and Vancouver, followed 769 women over age 50 with T-1/2 node-negative breast cancer randomly selected to receive five years of tamoxifen alone or tamoxifen plus whole breast radiation therapy (NEJM 2004; 351:963–970)

At 10 years, the ipsilateral breast tumor recurrence rate was 13.8% with tamoxifen alone and 5.3% for tamoxifen plus radiation.

Subtype analysis is a feature of the latest part of the study, she said, adding that subtypes were identified in 253 tumors by immunohistochemical (IHC) analysis. In 133 women with tumors identified by IHC microarray to have luminal A tumors (ER or PR positive, HER2 negative, Ki-67<14%), the relapse rates were 8% with tamoxifen alone vs. 4.6% with tamoxifen plus radiation.

A total of 103 women over age 60 with luminal A tumors had relapse rates of 4.3% with tamoxifen alone vs. 6% for those with tamoxifen and radiation.

And in terms of tumor grade, the 114 women with Grade I/II luminal A tumors had very similar rates of ipsilateral breast tumor recurrence regardless of their treatment: 4.9% with tamoxifen alone vs. 5.5% with tamoxifen and radiation.

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RT Definitely Helpful in Other Breast Cancer Subtypes

Liu stressed, though, that radiation is of definite benefit in patients with other subtypes—for example, the 82 women in the study with luminal B tumors (Ki-67>14%) had a relapse rate of 16.1% with tamoxifen alone vs. 3.9% with tamoxifen and radiation. “And women with luminal B, luminal HER-2, HER-2 positive, and basal subtypes had a 10-year local relapse rate of 22.6% for the 59 women treated with tamoxifen alone vs. 6.3% for the 61 women receiving tamoxifen plus breast radiation,” she said.

It is important to note that these data apply only to lymph-node negative disease, she added.

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Avoid Unnecessary Radiation

The potential impact of the new data is considerable, since luminal A node-negative breast cancer is estimated to account for about 25% of all newly diagnosed breast cancer patients in North America every year, she said.

“If we are able to corroborate and validate these data, the proportion of patients who could potentially avoid unnecessary radiation therapy would save about $20 million in Ontario alone.” That is based on 9,000 new breast cancer patients diagnosed there every year, and on a course of radiation therapy costing about $8,000. “Extrapolating the numbers to the US, the estimated savings would be about $400 million per year,” she said.

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Ki-67 Recommended

Liu and colleagues recommended adding Ki-67 to the current standard IHC panel for breast cancer, and “discussing the possibility of avoiding radiation with lymph-node negative patients in whom the luminal A subtype is identified, if they are taking tamoxifen or an equivalent medication, especially patients who are 60 years old or older.”

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Aromatase Inhibitors?

At a news conference at the meeting that highlighted the study among several breast cancer abstracts considered newsworthy, the moderator, Worta McCaskill-Stevens, MD, asked how aromatase inhibitors, now commonly prescribed after lumpectomy, would affect these findings.

Liu said that there have been no randomized breast cancer trials comparing aromatase inhibitors with or without breast radiation. Nevertheless, she said that since aromatase inhibitors could be considered equivalent to tamoxifen, the implication would be that the results would still apply.

McCaskill-Stevens commented that U.S. oncologists would need to see data showing that aromatase inhibitors have the same effect in the luminal A patients.

The question of aromatase inhibitors was also brought up from the audience at Liu's oral presentation, with a comment from Rowan T. Chlebowski, MD, PhD, Professor and Chief of the Department of Internal Medicine and Medical Oncology/Hematology at Harbor-UCLA Medical Center Department of Internal Medicine. “With aromatase inhibitors reducing local recurrence rates even more, the impact would be even greater,” he said. “But on the opposite side, we now have short-course radiation therapy which would cut down on the savings you're talking about.

“And there are some places that wouldn't want to use an expensive Ki-67 proliferative index to signal luminal A status—there is controversy about using that. So how are you moving this complex protocol forward?”

Liu replied that there are no randomized trials of aromatase inhibitors with/without radiation, but that she thinks the story would be relatively similar that for tamoxifen vs. tamoxifen/radiation.

“And we have just completed a study randomizing between a short-course of five days of radiation therapy vs. a standard of three to five weeks of therapy. We are now collecting the data, but early data suggest that toxicity, particularly bone fractures, might be a little bit higher with the short courses.”

© 2012 Lippincott Williams & Wilkins, Inc.
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