Radiation therapy is an integral part or the management of early stage breast cancer. At least 5 other randomized trials have firmly established the role of radiation in breast conserving therapy (BCT). Traditionally, BCT consist of limited surgery and whole breast radiation. Although this treatment provides excellent local control and equivalent survival to modified radical mastectomy (MRM) in appropriately selected patients, this achievement is not without physical and social costs. Specifically the physical cost of radiation includes but is not limited to skin damage, rib fracture, lung damage, heart damage, pain and poor cosmesis. There are also social costs. Radiation in BCT is typically given daily for 5-7 weeks. This results in lost time from loved ones and livelihood. Additional time is lost when patients often have to travel great distances to the nearest radiation oncology center. The fear of side effects of whole breast radiation and the inconvenience of a 7-week treatment schedule, force women who are candidates for BCT, to choose MRM and therefore suffer an unnecessary anatomical loss.
To allow greater freedom of choice in local therapy, much research has gone into developing altered breast-conserving therapies that would provide the same local control and survival but at much lower social and physical cost. This research has basically taken two paths: 1) shorten the course of therapy and 2) decrease the amount of breast treated.
Altered fractionation schedules have been developed with the goal of decreasing the course of whole breast radiation. The most common alternative schedule was evaluated in a randomized prospective trial by Whelan et al. In that trial the authors compared 50 Gy in 25 fractions to 42.5 Gy in 16 fractions. There was no statistically significant difference between the schedules with respect to local control, survival, toxicity, or cosmetic outcome. This trial was criticized for not having long enough follow-up even though the results reported were at median follow-up of 5 years. As a result, in part, American radiation oncologists have not embraced this accelerated regimen.
In addition to decreasing the duration, researchers are presently investigating decreasing the amount of breast tissue irradiated, partial breast irradiation (PBI). PBI also allows the use of larger fraction sizes, because the volume of breast at risk of radiation toxicity is relatively small. Traditionally, the most common form of PBI has been interstitial brachytherapy of the tumor bed. Vicini et al. and Kuske et al. have both reported series where women with early stage breast cancer were treated with conservative surgery followed by interstitial implants. , , In their expert hands, the authors reported local control rates equivalent to historic controls of women treated with the standard 6 weeks of external beam. These authors also reported acceptable toxicity profiles and cosmetic outcome. Although these techniques are not new, they have not been compared to standard therapy in randomized prospective fashion.
A new brachytherapy procedure is currently gaining popularity in the community setting, despite the lack of any long-term data on control and safety. This new procedure/device Mammosite, entails placing a balloon in the tumor bed immediately after resection. The balloon is expanded to fill the cavity, then a radioactive source is later placed in the center of the balloon to deliver a dose to a 1cm rim of surrounding tissue. The efficacy of this procedure is questionable as only a small amount of tissue surrounding the cavity will receive a therapeutic dose. Keisch et al., who did the work for FDA approval of this device, reported an 86% good cosmetic outcome at 1 month. Clearly the follow-up period is too short to determine true late toxicity of this procedure.
PBI research has been conducted with external beam therapy as well. Veronesi et al. are currently exploring delivering a single fraction of electrons to the tumor bed immediately after lumpectomy. In their paper with a median follow-up of 8 months there were no reported local failures. It will be interesting to see the late effects of such a large single dose. Baglan et al. have reported on the use of quadrant/tumor bed 3-D conformal radiation therapy. In their publication of 12 patients 7 of which were not actually treated, the authors claim that this treatment is feasible and well tolerated. The authors delivered a large dose twice a day for 5 days. This is an extremely aggressive dosing schedule in which one would expect severe late complications. The authors admit that it is too soon to evaluate local control, chronic toxicity and cosmetic results of this technique.
Breast cancer management often includes systemic therapy as well. Controversy exists on how to best sequence radiation and chemotherapy. There is evidence showing that delaying radiation until after chemotherapy is associated with increased local failure and delaying chemotherapy until after radiation is associated with increased distant failure. As systemic control is deemed the most important, it is common practice to delay the radiation until after chemotherapy. To maximize local control some have proposed moving radiation closer to surgery. This has been achieved by alternating chemo with radiation while others propose concurrent chemo-radiation. , , With the shortened course of radiation available with PBI, this timing may be less of an issue.
Nonetheless, PBI may represent a new treatment paradigm. Presently there is a trial open looking at the feasibility of doing partial breast radiation and there are several trials on the drawing board hoping to address this issue as well. Within 3-4 months we hope to have one such trial be open here at Johns Hopkins. Needles to say this is a topic in which many women with breast cancer and their physicians have great interest.
Many women are forced to choose mastectomy over breast conserving therapy because of fear of toxicity, poor cosmetic outcome, and duration of therapy. If any of these hurdles could be removed or lowered, women will have greater freedom to choose the local management of their breast cancer that best reflects their true desires. PBI has the potential to lower these hurdles and consequently allow free choice.
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