Some Older Breast Cancer Patients Could Skip Radiation (CME/CE)

By?Charles Bankhead, Staff Writer, MedPage Today

Published: April 01, 2012

Reviewed?by?Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco.

CHICAGO -- Many older women with newly diagnosed breast cancer might safely avoid adjuvant radiation therapy, according to a study reported here.

Radiation therapy did not reduce the risk of local recurrence beyond the benefit afforded by tamoxifen alone in women older than 60 with luminal A breast cancer or in women with grade I-II luminal A breast cancer.

Avoiding radiation therapy in those subgroups could lead to a $400 million savings in healthcare costs, Fei-Fei Liu, MD, reported at the American Association for Cancer Research (AACR) meeting.

"Luminal A lymph node-negative breast cancer is estimated to account for about 25% of all newly diagnosed breast cancer in North America every year," Liu, of the University of Toronto, said during an AACR press briefing. "These patients can avoid unnecessary treatments."

"We estimated a savings of $20 million annually in Ontario if radiation therapy were avoided in early luminal A breast cancer. Extrapolating the figures to the United States resulted in a savings of about $400 million per year," Liu added.

The preferred approach to treating early breast cancer consists of surgery followed by systemic therapy and radiation therapy. Most women can tolerate this approach to treatment, but the therapies can cause side effects, which can be severe in some cases, Liu noted.

Additionally, most radiation therapy schedules are inconvenient and require daily travel, or travel on most days of the week until the treatment is completed. Younger patients also face a risk of secondary malignancies following radiation therapy.

As previously reported, the standard of care for early breast cancer (tamoxifen plus radiation therapy) was compared with tamoxifen alone in prospective clinical trial involving patients with T1 or T2, node-negative breast cancer (N Engl J Med 2004;351:963).

The primary endpoint was ipsilateral recurrence at 10 years. When the study ended, women who did not receive radiation therapy had almost a three-fold higher incidence of recurrence (13.8% versus 5.3%, P<0.0001).

Since the trial ended, breast cancer researchers have learned that invasive breast cancer is not a single disease but comprises at least five or six subtypes, said Liu.

To assess the impact of radiation on breast cancer subtypes, investigators returned to the database and tissue bank for the randomized trial. Molecular subtype was determined for 304 tumors by means of immunohistochemistry and tissue microarrays.

Subtyping included analysis of estrogen receptor, progesterone receptor, the Ki-67 proliferation marker, HER2, epidermal growth factor receptor, and cytokeratin (CK) 5/6.

On the basis of the IHC results and microarray analysis, tumors were assigned to six categories:

• luminal A
• luminal B
• luminal-HER2
• HER2 enriched
• basal-like
• triple-negative phenotype-nonbasal

The patients included in the tissue analysis included 145 participants from the tamoxifen arm and 159 from the tamoxifen-radiotherapy arm.

The lowest rate of recurrence in both treatment arms was observed in patients with luminal A tumors (ER- or PR-positive, HER2-negative, and Ki-67<14%). In those 133 patients, the recurrence rate was 8% with tamoxifen alone and 4.6% with tamoxifen and radiotherapy, a nonsignificant difference (P=0.3).

Liu and colleagues then looked at combinations of characteristics among patients with luminal A tumors.

Among 103 women who were 60 or older, the recurrence rate was 4.3% with tamoxifen alone and 6% with multimodality adjuvant therapy (P=0.9). The 114 women with grade I-II luminal A tumors had a recurrence rate of 4.9% with tamoxifen and 5.5% with tamoxifen plus radiotherapy (P=0.9).

In contrast, the 82 patients with luminal B tumors (Ki-67>14%) had a recurrence rate of 16.1% with tamoxifen, declining to 3.9% when radiation therapy was administered (P=0.05). Tumors in the three remaining categories had even higher rates of recurrence with tamoxifen alone, although each category comprised a small number of women.

Though preliminary, an analysis based on six tumor markers showed that "older luminal A patients with grade I/II tumors demonstrated the lowest risk of breast relapse, for which RT had minimal impact, suggesting that such patients could be managed with tamoxifen alone," Liu and colleagues concluded in their presentation at the meeting.

"It is of note that this subgroup represents a significant proportion of women in this trial -- 133 of 304, or 43%," they said. "In contrast, breast radiation therapy remains beneficial for women with higher-risk subtypes."

Liu had no relevant disclosures.

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