CHICAGO – Older breast cancer patients with the luminal A tumor subtype may be able to forgo whole breast radiation therapy if they are taking tamoxifen or other breast cancer hormone therapy.
Preliminary results from a randomized clinical trial of tamoxifen with and without radiation therapy showed that radiation therapy had minimal impact on the risk of developing ipsilateral breast tumor recurrence in patients aged 50 years and older with T1 and T2 node-negative breast cancer identified with luminal A disease based on 6-marker immunohistochemistry testing.
In contrast, radiation therapy appeared to decrease the risk of breast cancer relapse in patients with luminal B, human epidermal growth factor receptor 2 (HER2)–enriched, and basal tumor subtypes, according to radiation oncologist Dr. Fei-Fei Liu of Princess Margaret Hospital, the Ontario Cancer Institute, and the University of Toronto, all in Toronto. She discussed the findings in a press conference April 1 at the annual meeting of the American Association for Cancer Research.
Luminal A tumors – estrogen receptor (ER) or progesterone receptor (PR) positive, HER2-negative, and low Ki-67 (a nuclear marker for cell proliferation) – are associated with a relatively good prognosis compared with the other subtypes, she noted.
To determine the predictive value of tumor subtype for ipsilateral recurrence in this population, Dr. Liu and her colleagues performed molecular subtyping for ER, PR, Ki-67, HER2, EGFR, and cytokeratine 5/6 on 304 available tumor specimens from 769 women in a clinical trial. All had been randomized to treatment with tamoxifen and whole breast radiation or tamoxifen alone between December 1992 and June 2000.
Based on the subtyping results, the patients were classified as luminal A, luminal B, luminal HER2, HER2-enriched, basal-like, or triple-negative phenotype–non-basal and followed for a median of 10 years, she said.
In the overall group of 769 women, the recurrence rate at a median of 10 years was 13.8% in the tamoxifen-only group and 5.0% in the combination group, Dr. Liu reported, noting that, in a multivariate analysis, "patient age, tumor size, estrogen-receptor positive status, and combination tamoxifen/whole breast radiation therapy were all significant factors."
Of the 304 tissue microarrays, 145 came from patients treated with tamoxifen only and 159 from patients treated with tamoxifen plus radiotherapy. In this population, the best outcomes were observed in 133 patients with luminal A tumors; their rate of ipsilateral recurrence was statistically similar at 8% among those in the tamoxifen-only group and 4.6% in the tamoxifen plus radiation group, Dr. Liu reported.
The 103 women older than 60 years with luminal A tumors fared particularly well, with rates of 4.3% with tamoxifen alone and 6.0% with tamoxifen and radiotherapy. The respective rates for the 114 women with grade I-II luminal A tumors also were similar at 4.9% and 5.5%, she said.
In contrast, the ipsilateral recurrence rates for the tamoxifen only and tamoxifen plus radiation groups were, respectively, 16.1% and 3.9% in 82 patients with luminal B tumors (differentiated from luminal A tumors by Ki-67 expression greater than 14%), said Dr. Liu.
Further, although the number of HER2 (11), HER2-enriched (11), and basal-like tumors (16) were small, "we saw higher relapse rates in patients who did not undergo radiation therapy," she said.
Luminal A lymph-node negative breast cancer represents approximately 25% of all cases of newly diagnosed breast cancer in North America, according to Dr. Liu. In addition to sparing a large number of women unnecessary radiation exposures, unwanted side effects, and inconvenience, bypassing radiation therapy in early cases would save millions of health care dollars each year.
"We estimated a savings of $20 million annually in Ontario if radiation therapy were avoided in early luminal A [breast cancer]," she said. "Extrapolating the figures to the [United States] resulted in a savings of about $400 million per year."
Dr. Liu stressed that the data presented at the meeting are preliminary but noted that, if the findings are validated through the analysis of a larger number of tumor samples, "we would recommend adding Ki-67 to the current standard immunohistochemistry panel, 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."
Dr. Liu disclosed no conflicts of interest.