Impact of local control on survival

In the era before systemic therapy, the impact of local therapy on survival was not dramatic. In fact, it was hard to demonstrate. For example, one could prevent local recurrence through the use of postmastectomy radiation; however, the correlation between local recurrence and distant metastatic spread was so great that although local recurrence was prevented, the fate of the patient had already been determined. Now that we have effective systemic therapies to address micrometastases, we have evidence that adding radiation therapy to systemic therapy in appropriate selected patients may improve survival. We are going through a period of time when, as systemic therapy improves, local treatment becomes more important. Eventually, when systemic therapy is better, the need for local therapy will hopefully drop out.

Lumpectomy without radiation therapy for invasive disease

Long-standing randomized trial data have clearly demonstrated the equivalence of mastectomy to lumpectomy and radiation. Trials evaluating lumpectomy with and without radiation are more recent and are not individually powered to demonstrate a survival benefit; however, a meta-analysis of the various trials suggests a small improvement in survival with the addition of radiation to lumpectomy (Vinh-Hung 2004).

The survival benefit does not appear to be quite as great as that seen in patients at high risk who receive radiation after mastectomy, probably because most of the patients undergoing lumpectomy are in a more favorable situation initially, so fewer events will occur later. In either situation — adding radiation to mastectomy or lumpectomy — local recurrence is reduced by 70 percent. Local recurrence after mastectomy or lumpectomy is the result of a mixture of tumor biology and inadequate treatment. If the meta-analyses indicate a reduction in the local recurrence with adjuvant radiation, without a corresponding improvement in survival, then that provides strong evidence for biology. However, if you are able to improve survival by prevention of local recurrence, then the idea that a proportion of local recurrences lead to metastases is plausible. One of the hallmarks of cancer is genomic instability. It is not difficult to hypothesize that the tumor is more disordered at recurrence than the primary tumor. As a result, the metastatic potential of a tumor may be very different at recurrence than at presentation.

Techniques for partial breast irradiation (PBI)

Of the techniques currently being used for partial breast irradiation, the approach with the longest-term data is interstitial implantation. With this technique, plastic tubing is inserted into the breast around the primary tumor area, and then loaded with radioactive material to irradiate the tumor bed area. We have fairly good results at five years with this approach. In my judgement, and that of my patients, the interstitial implantation is the least patient-friendly and it appears archaic. When we first began performing breast-conserving therapy, we didn’t have electron beam, so we applied boosts with the implants. I did at least 300 of these procedures, and it was somewhat traumatic for a patient to have needles sticking out from the breast.

The MammoSite was approved by the FDA approximately two years ago based on safety data. This seems to be fairly well tolerated, with just one catheter emerging from the breast. The balloon is inserted into the area of the breast where the tumor was removed and then filled with radioactive material to irradiate the area surrounding the cavity (Streeter 2003). A third approach of PBI currently used in the United States is a newly evolving method of external beam radiation that enables treatment of a tightly targeted area in the breast. In Europe, there is also great interest in the use of intraoperative radiation. Professor Veronesi in Milan has been giving single-fraction electron-beam treatment at the time of lumpectomy (Veronesi 2005). Mike Baum’s study uses the TARGIT — a tiny irradiator — at the time of lumpectomy to irradiate the cavity (Viadya 2002). Both of these randomized trials are nearing completion.

We have a scarcity of long-term data with PBI in a disease with a long natural history. The NSABP will soon open a nationwide trial of conventional whole breast irradiation versus partial breast irradiation of any type. In light of that large Phase III study, we will probably allow the nonprotocol use of PBI but patient selection will be critical. I believe it’s appropriate for women older than 50 who have adequate surgical margins and negative nodes. Concerns still exist about long-term skin toxicity, fibrosis and wound healing, and the patient electing PBI will need to be treated by experts at the procedure.

Select publications

Dr Harris is a Professor and Chair of the Department of Radiation Oncology at Dana-Farber Cancer Institute, Brigham and Women’s Hospital, Harvard Medical School in Boston, Massachusetts.