Partial Breast Irradiation Shows Promise in Breast Cancer

• PHILADELPHIA—Accelerated partial breast irradiation (APBI) may be an effective and well-tolerated alternative to standard radiotherapy in early-stage breast cancer, and partial breast irradiation with interstitial brachytherapy also appears feasible in women who have had a recurrence after previous breast radiotherapy, according to two papers presented at the 48th Annual Meeting of the American Society for Therapeutic Radiation and Oncology.

In women with early-stage breast cancer treated with lumpectomy and axillary node dissection, APBI was associated with excellent in-breast control rates and survival after more than 6 years' median follow-up. Douglas W. Arthur, MD, of the Medical College of Virginia Hospitals of Virginia Commonwealth University, reported the results of this multi-institution phase II trial, conducted by the Radiation Therapy Oncology Group (abstract 51). "These results are directly comparable to the previous single-institution APBI studies with similar extended follow-up. This experience continues to support the concept of APBI," he said.

The study enrolled 99 patients from 11 institutions between 1997 and 2000. To be eligible, women were required to have stage I or II unifocal tumors less than 3 cm in size and showing invasive nonlobular histology, with negative surgical margins and no extensive intraductal component. At least six lymph nodes were removed at the time of lumpectomy, and women with up to three positive nodes without extracapsular extension were allowed to participate.

Brachytherapy was administered within 6 weeks of lumpectomy. At the discretion of the treating institution, brachytherapy could be delivered at a low dose rate (45 Gy in 3 to 5 days) or a high dose rate (34 Gy in 10 twice-daily fractions over 5 days). Chemotherapy and/or tamoxifen could be given at the treating physician's discretion. The study was not designed to compare high-dose-rate and low-dose-rate therapy, Dr. Arthur pointed out. Median follow-up was 6.5 years with high-dose-rate therapy and 7 years with low-dose-rate therapy.

Results of treatment were similar in the two groups. Of the 66 women who received high-dose-rate therapy, two had local failure, for an overall 5-year failure estimate of 3%. Three patients experienced regional failure, including one with locoregional failure. The two patients with local failure had mas-tectomies, as did a third patient for cosmetic reasons. Estimated 5-year disease-free survival was 86%, and overall survival was 92%.

Of the 33 women who received low-dose-rate therapy, four patients had local failure, for a 5-year estimate of 6%. One patient experienced regional failure. An additional two patients had mastectomies for cosmetic reasons. Estimated 5-year disease-free-survival in this group was 88%, and overall survival 94%. In the combined group of patients, the estimated 5-year local failure rate was 4%.

Local Recurrence

A second phase I/II study found preliminary evidence that lumpectomy with partial breast brachytherapy could be an effective treatment for local recurrence in patients who had previously received external-beam irradiation (abstract 53). Mastectomy is the standard of care for cancer diagnosed in a previously irradiated breast, said Manjeet Chadha, MD, of Beth Israel Medical Center, New York. "In women who do not undergo mastectomy, the local failure rate with surgery alone is in the range of 35%. Re-irradiation of the whole breast is not recommended due to the potential risk for unacceptable tissue toxicity," Dr. Chadha said.

Participants were 20 women, 15 who had received lumpectomy and radiation therapy for breast cancer and 5 who previously underwent mantle radiotherapy for lymphoma. The median time between the first and second cancer was nearly 10 years (about 8 years for breast cancer and 20 years for lymphoma). All patients had a localized, new or recurrent, in-situ or invasive breast cancer. All had a multidisciplinary evaluation and refused the recommended mastectomy. Patients underwent lumpectomy and had negative surgical margins. Any systemic therapy was postponed until after brachytherapy.

Interstitial low-dose-rate brachytherapy with iridium-192 was used in all cases. The six participants in phase I received a dose of 30 Gy, and when long-term toxicity proved low, the dose was increased to 45 Gy for phase II.

Brachytherapy was well tolerated, with no grade 3-4 toxicity. Grade 1-2 fibrosis occurred in 18 patients and skin hyperpigmentation in three. The women with previous breast cancer had some degree of breast asymmetry due to their first surgery. The second lumpectomy and brachytherapy did not worsen the cosmetic outcome in these patients, Dr. Chadha said.

With median follow-up approaching 3 years, all patients were free of breast cancer and all but one were alive. One patient experienced a local relapse at 27 months, which was salvaged with mastectomy. This patient had a previous breast cancer and had experienced her first recurrence within 4 years of the original cancer. She was in the group that received 30 Gy irradiation.