Single-Dose Partial Breast Irradiation Safe for Some Women with Invasive Breast Cancer
In a randomized phase III trial, women who received single-dose partial-breast irradiation during breast-conserving surgery had the same likelihood of having their cancer recur in the same breast after 4 years of follow-up as women who received standard whole-breast external beam radiation therapy after surgery.
Lancet, published online ahead of print, June 4, 2010 (see the journal abstract).
Women with early-stage breast cancer often undergo breast-conserving surgery (BCS) instead of mastectomy (removal of the entire breast). During BCS, only the portion of the breast containing the tumor and a few nearby lymph nodes are removed. To reduce the likelihood of cancer recurrence, standard treatment includes a course of external-beam radiation therapy (EBRT) to the whole breast after BCS. This type of radiation therapy is given in small doses given five times a week for about six weeks.
Because EBRT requires a large amount of time, as well as travel to and from a treatment center, researchers are developing ways to deliver radiation therapy in fewer treatment sessions to women receiving BCS. One such method is accelerated partial-breast irradiation, in which radiation is delivered specifically to the area of the breast that contained the tumor instead of to the whole breast. Partial-breast irradiation is given in fewer, higher doses than EBRT.
Many types of technology to deliver partial-breast irradiation are under development. In a randomized phase III clinical trial called TARGIT-A, researchers compared partial-breast irradiation given during surgery (i.e., intraoperatively) with standard whole-breast EBRT for women receiving BCS for invasive breast cancer.
Researchers from nine countries randomly assigned 1,113 women to receive a single dose of approximately 20 Gy of intraoperative partial breast irradiation using a device called the Intrabeam and 1,119 to receive whole-breast EBRT at a dose of 40 Gy to 56 Gy given in a total of 15 to 25 fractions (with an optional booster dose at the end of treatment). All participating doctors received special training in the use of the Intrabeam device.
All of the women were 45 years of age or older and eligible for BCS for a single invasive tumor. The trial was restricted to patients with ductal carcinoma; patients with lobular carcinoma, which has a higher risk of recurrence, were excluded. However, some patients in the intraoperative treatment group (about 15 percent) were found to have lobular carcinoma or other high-risk disease during surgery, and these patients later received additional EBRT. Women in both groups received hormone therapy and chemotherapy as needed.
The women returned for initial follow-up visits 3 and 6 months after treatment, after which they were scheduled for assessment every 6 months for up to 5 years and then annually for up to 10 years. The primary outcome was local cancer recurrence in the same breast. The trial was a non-inferiority trial, which means that it aimed to show that intraoperative partial breast irradiation did not result in worse outcomes than standard EBRT. The researchers also recorded side effects from both treatments.
The study was lead by Dr. Jayant S. Vaidya from the Research Department of Surgery, University College London, in the United Kingdom.
Most women participating in TARGIT-A had small tumors: 36 percent had tumors smaller than 1 cm in diameter (about the size of a pencil eraser) and 50 percent had tumors of between 1 cm and 2 cm in diameter. Only 14 percent of the women had tumors that were larger than 2 cm in diameter. The majority of tumors were of low grade, and in more than 80 percent of the women cancer had not spread to any lymph nodes.
After 4 years of follow-up, only five women in the EBRT group and six in the intraoperative partial-breast irradiation group had experienced a local recurrence of their cancer—a nearly identical rate. This result indicates that intraoperative partial breast irradiation was not inferior to standard EBRT in this trial.
The occurrence of side effects was also similar between the two groups. Women who underwent intraoperative partial-breast irradiation had more instances of wound seroma (development of fluid pockets at the site of surgery) requiring frequent drainage, but major complications related to radiation therapy were more common in the EBRT group.
Dr. Bhadrasain Vikram, Chief of NCI’s Clinical Radiation Oncology Branch, noted that these results cannot be generalized to other types of partial-breast irradiation. “If you want these results, you have to use this device and this treatment schedule,” he said. Other clinical trials, including one by the National Surgical Adjuvant Breast and Bowel Project, are currently comparing different methods of partial-breast irradiation with standard EBRT.
In addition, explained Dr. Vikram, partial-breast irradiation is not appropriate for every patient with invasive ductal breast carcinoma. The overwhelming majority of patients in this trial had small tumors that were estrogen-receptor positive and no cancer spread to the lymph nodes. Therefore, that’s the group of patients that this technique would be most applicable to. Giving this regimen to patients who don’t meet that profile would be somewhat risky, because we don’t know if partial-breast irradiation would be adequate for preventing recurrence.
The risk of local recurrence in patients receiving BCS followed by EBRT is highest in the second and third years after treatment. Because the local recurrence rate was similar in the two groups in this trial and no local recurrences were seen in either group during the fourth year of follow-up, the authors conclude that their trial “provides robust and mature evidence that substantiates previous findings showing that targeted intraoperative radiotherapy is safe,” stated the authors. “These results challenge…that whole-breast radiotherapy is necessary in this group of patients,” they concluded.
This trial may be particularly relevant to women over the age of 70 with early-stage breast cancer, said Dr. Vikram. Another recent clinical trial suggested that the inconvenience of EBRT may outweigh its benefits for these women. However, “for those patients, intraoperative partial-breast irradiation would be almost ideal, because treatment would be over by the time they woke up from anesthesia, and they wouldn’t have to come back for weeks and weeks of radiation treatment,” he explained.
But younger patients would also benefit, he concluded. “This technique takes out the hassle factor from radiation therapy and allows a patient to preserve her breast and not have to worry about recurrence. Appropriate patients would definitely benefit from using this technique versus skipping radiation altogether.”