New Era for Radiation

Surgery combined with radiation is standard treatment for local control of early-stage breast cancer. Studies show that a lumpectomy followed by whole-breast radiation offers women just as low a risk of local recurrence as a mastectomy. The exception may be in women over age 70 who have small, estrogen-positive tumors, since studies show equivalent survival rates for these women using hormonal therapy alone.

Radiation also may improve survival in some cases of higher risk tumors, so some physicians are recommending radiation after mastectomy.

While the need to optimize radiation in local control is accepted, a number of trials are exploring new ways to deliver radiation in a shorter time as well as ways to help radiation pack more of a punch. For instance, boost radiation, an additional, focused course of treatment, has been shown in clinical trials to improve local control of breast cancer, says Terry Mamounas, MD, medical director of Aultman Cancer Center.

Boost radiation typically is administered in the area where the tumor was removed for an additional week after six weeks of whole-breast radiation.

Another innovation is radiosensitization, where a substance, such as a drug, is used to make the tumor more vulnerable to radiation therapy.

“Boost is something we now routinely use,” Mamounas says. The trade-off, he adds, may be a little more fibrosis, scarring and hardening of the breast tissue in a small percentage of patients.

Another innovation is radiosensitization, where a substance, such as a drug, is used to make the tumor more vulnerable to radiation therapy.

Preclinical research has indicated that use of the targeted breast cancer therapy Herceptin (trastuzumab) appears to make tumor cells that overproduce the HER2 oncogene more sensitive to radiation.

This theory is now being tested in a phase 3 clinical trial in patients with HER2-positive ductal carcinoma in situ.

Combining radiation and Herceptin has already been found to be safe in patients with invasive HER2-positive breast cancer, says Mamounas. Other drugs, such as Xeloda (capecitabine) and investigational biological drugs called PARP inhibitors, are being studied in this setting.

Other innovations in radiation therapy are aimed at improving convenience for the patient. One such approach is accelerated, whole-breast radiation, in which the course of treatment is streamlined from six weeks to three or four, with slightly higher doses administered. (Larger doses given in fewer appointments is known as hypofractionated radiation therapy.)

“There have been a number of studies that have proved for some patients that it’s as appropriate and effective, and shortens the course of therapy,” says Bruce Haffty, MD, medical director of The Cancer Institute of New Jersey. Research continues in this area, but guidelines for treating patients in this manner are being established.

Scientists are also evaluating partial-breast radiation that focuses on the area where the patient’s lumpectomy occurred.

While clinical trials are still enrolling women to look at the effectiveness of partial-breast radiation, a study released in a 2010 issue of The Breast Journal offered the results of a meta-analysis (a pooled analysis of numerous smaller clinical trials) comparing partial-breast radiation with whole-breast radiation that found no statistically significant difference between partial- and whole-breast radiation associated with death or distant recurrence. However, there was a stastically significant association between partial-breast radiation and increaed risk of local and axillary recurrence.

The study’s authors concluded that, while partial-breast radiation does not seem to jeopardize survival and may be used as an alternative to hole-breast radiation, the issue of locoregional recurrence needs to be further addressed.

Women considering possible radiation delivery options should talk with their surgeon and radiation oncologist about what’s known, what kind of factors are used to select appropriate candidates and whether any of the trial approaches result in long-term or late effects.

The study also examined the effectiveness of another partial-breast radiation technique that involves implanting radioactive seeds in the lumpectomy cavity known as brachytherapy, or internal radiation. Strict guidelines as to who might be a candidate for partial-breast radiation outside of clinical trials have been established by the American Society for Radiation Oncology (ASTRO, see "Guiding the Use of Partial-Breast Radiation").

Women considering possible radiation delivery options should talk with their surgeon and radiation oncologist about what’s known, what kind of factors are used to select appropriate candidates and whether any of the trial approaches result in long-term or late effects.

In the latest delivery option now being researched, women would wake up from surgery having completed their radiation treatment. A clinical trial presented at the 2010 meeting of the American Society of Clinical Oncology offered results for TARGIT, short for Targeted Intraoperative Radiation Therapy. In TARGIT, physicians give a single dose of radiation to the cavity where the tumor was removed from women undergoing lumpectomy for early-stage breast cancer while they are still in the operating room with the incision open.

The results of the 10-year clinical trial found that the single-dose intraoperative radiation treatment was both safe and effective and would save time and money for patients, who would wake from surgery having finished radiation, according to a press release from the University of California, San Francisco, the lead U.S. cancer center in the study.

While a number of breast cancer experts expressed excitement about TARGIT, an equal number cited issues with the study, including the cost and availability of the specialized radiation equipment in the operating room, the reduced radiation received by the women undergoing TARGIT and the lack of long-tem follow-up.

Anthony Zietman, MD, professor of radiation oncology at Harvard Medical School and chair of ASTRO calls it “intriguing but still unproven.”

“Intraoperative only radiates the lining of the cavity where the cancer was,” he says. “What if there is cancer elsewhere in the breast?”

What everyone agrees on is that TARGIT will remain experimental until these questions are answered. As with other forms of partial-breast radiation, some centers are beginning to offer TARGIT for select patients based on age, tumor size, location, negative nodes and other factors. Apart from this, the standard of care in radiation remains whole-breast radiation except for women over aged 70 who have very favorable, early-stage disease.