SAN ANTONIO — Lumpectomy and tamoxifen without radiotherapy is a reasonable choice for women aged 70 years or older with early-stage estrogen receptor-positive breast cancer, Dr. Kevin S. Hughes said at a breast cancer symposium sponsored by the Cancer Therapy and Research Center.
The supporting evidence comes from a new 8.2-year update of a large randomized, multicenter, prospective trial. The resultant conclusion—that radiotherapy adds only limited benefit—is identical to the lesson drawn from an earlier 5-year follow-up of the same women (N. Engl. J. Med. 2004;351:971–7). At the time of the earlier analysis, critics insisted that 5 years wasn't long enough to show the benefits of radiation. But at 8.2 years, the case for radiotherapy hasn't grown any stronger, said Dr. Hughes, a surgical oncologist at Massachusetts General Hospital, Boston.
The study, known as Cancer and Leukemia Group B (CALGB) 9343, involved 631 women aged 70 or older who had clinical stage I, node-negative, estrogen receptor-positive breast cancer measuring 2 cm or smaller in size. All underwent lumpectomy and were randomized to receive tamoxifen and radiotherapy, or tamoxifen alone.
By 8.2 years, 20 patients in the tamoxifen-only arm had an ipsilateral breast recurrence, compared with 4 patients in the radiotherapy arm. This translates into an absolute 5% reduction in in-breast recurrence. There was also an absolute 0.9% lower incidence of axillary recurrence, for an overall absolute 5.9% decrease in locoregional recurrence in the radiotherapy group.
But this modest benefit didn't confer any clinically meaningful advantages for radiation in this aged population. Radiotherapy had no benefit over tamoxifen alone in terms of rates of ultimate breast preservation, distant metastases, death from breast cancer, or all-cause mortality.
Of the study participants, 29% were dead by 8.2 years, but only six in the radiotherapy arm and five in the no-radiotherapy arm actually died of breast cancer.
“In this population, breast cancer is not the major issue these people are facing,” Dr. Hughes noted.
Audience member Dr. Laura J. Esserman hailed CALGB 9493 as “a great study.” “I hope everyone heard the results and is offering these choices to their patients,” added Dr. Esserman, professor of surgery and director of the breast care center at the University of California, San Francisco.
Another surgeon observed that if the more generous lumpectomies that are now standard had been the norm in the 1990s when study participants had their surgery, their locoregional recurrence rate with tamoxifen alone would likely be even lower than it was in the study.
But other audience members noted that the overview analysis presented by the Oxford, England-based Early Breast Cancer Trialists' Collaborative Group at the San Antonio meeting 2 years ago concluded that a survival advantage for radiotherapy becomes significant at 15 years. What good are 8.2-year follow-up data, they asked, when a physician is faced with an otherwise healthy 70-year-old who might well live for another 15–20 years?
“We have to look at physiologic age as well as chronologic age,” Dr. Hughes replied. “As patients are physiologically older, I think we'd all agree that radiation becomes unnecessary. What we argue about is, [at what point do] patients become physiologically older.”
He added that he's not convinced the overview analysis findings apply to the type of patients in CALBG 9493. “What critics have brought up before is the idea that, as we [do more] follow-up, we'll see more and more in-breast recurrences in the group that didn't have radiotherapy. I think it's just as likely we'll see more in-breast recurrences in the arm that had radiation. I don't think we can predict what will happen beyond this point.”
'In this population [of women aged 70 years and older], breast cancer is not the major issue these people are facing.' DR. HUGHES