Five-year Analysis of Treatment Efficacy and Cosmesis by the American Society of Breast Surgeons MammoSite Breast Brachytherapy Registry Trial in Patients Treated with Accelerated Partial Breast Irradiation (APBI)
Reviewer: Charles B. Simone, II, MD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: November 9, 2009
Presenter: F.A. Vicini Presenter's Affiliation: William Beaumont Hospital, Royal Oak, MI Type of Session: Scientific
For patients undergoing breast conserving surgery with lumpectomy or quadrantectomy, adjuvant whole breast radiation therapy has consistently been demonstrated to significantly decrease ipsilateral breast tumor recurrences. This benefit with whole breast radiation therapy has been demonstrated for ductal carcinoma in situ (DCIS) and for invasive early-stage breast malignancies.
As most recurrences following breast conserving therapy develop in the same quadrant as the initial tumor, more recent investigation has examined radiation therapy only to the tumor bed and not the entire ipsilateral breast. Accelerated partial breast irradiation (APBI) can be delivered via intracavitary or interstitial brachytherapy or by external beam techniques.
The MammoSite® Breast Brachytherapy System is a method to deliver APBI that uses a single catheter with a balloon tip that is placed into the lumpectomy. A radioactive source is introduced into the balloon for a brief dwell time twice daily for five days.
Although local recurrence rates with APBI have been low and cosmesis has been acceptable, there is limited long-term follow-up data available for patients treated with this technique.
This study assessing the five-year data on treatment efficacy and cosmetic results among patients enrolled on the American Society of Breast Surgeons (ASBS) MammoSite® breast brachytherapy registry trial.
Materials and Methods
Upon study closure in July 2004, 1,440 patients with 1,449 cases of early-stage breast cancer undergoing breast conserving therapy were treated at 97 institutions with the MammoSite® device. APBI was delivered to 34 Gy in 3.4 Gy fractions.
Patients had invasive breast cancer (1,255 cases, 87%) with a median tumor size of 10 mm or DCIS (194 cases, 13%) with a median tumor size of 8 mm. When evaluating nodal status, 83% or patients had negative nodal disease, 3% had nodal metastasis, and 14% did not have assessment of the axillary lymph nodes. When evaluating margin status, 1% had positive surgical margins, 91% had negative margins, and 8% had close margins. Fifty-three percent of patients received hormonal therapy, 6% received chemotherapy, and 6% received both hormonal therapy and chemotherapy.
The median follow-up for all surviving patients was 60.5 months. Follow-up was complete through October 30, 2009.
After a median follow-up of 49 months, 2.6% of patients in this study developed an ipsilateral breast tumor recurrence. A subset analysis of the first 400 consecutive cases enrolled was performed, with 352 of these patients having invasive disease and 48 having DCIS. With a median follow-up of 58 months, the 5-year actuarial rate of ipsilateral breast tumor recurrence was 3.26% (3.69% for patients with invasive disease and 0.0% for those with DCIS).
With longer follow-up, the 5-year rate of ipsilateral breast tumor recurrence among patients with invasive disease was 3.80%, with 1.2% of patients failing at the site of the index lesion and 2.7% failing elsewhere within the ipsilateral breast. Less than one percent (0.84%) of patients with invasive disease failed in the axilla). The 5-year rate of ipsilateral breast tumor recurrence for patients with DCIS was 2.63%. No patient with DCIS failed in the axilla or at the site of the index lesion.
Among patients with higher risk features, including those with positive margins or positive axillary lymph nodes, or those aged <50 years, the 5-year ipsilateral breast tumor recurrence rate was 5.28%. This was no significantly higher than for patients with lower risk features (p = 0.02362).
Among the entire cohort, the only variable associated with ipsilateral breast tumor recurrence was estrogen receptor status (p = 0.0022). This association was even greater for patients with invasive disease (p = 0.0007). For the entire cohort, no other variables were associated with ipsilateral recurrence, including patient age <50 (p = 0.6305), margin status (p = 0.9997), tumor size (p = 0.9997), or positive nodes (p = 0.8251). When assessing only patients with invasive disease, in addition to estrogen receptor status, grade (p = 0.0512) and chemotherapy (p = 0.0157) were also found to influence ipsilateral breast tumor recurrence. Age and margin status were found to significantly influence ipsilateral breast tumor recurrence among patients with DCIS.
A seroma developed in 28% of patients in this trial, including occurring in 35.5% of patients with an open tumor bed cavity. The percentage of patients with good to excellent cosmetic ipsilateral breast results, as determined by physicians, was 94.6% at one year, 93.8% at two years, 93.3% at three years, 90.5% at four years, and 90.6% at five years. The development of an infection (p = 0.0104) and skin spacing (p = 0.0208) significantly influenced cosmetic results.
Treatment efficacy five years after treatment with APBI using the MammoSite® device are good with 5-year local control >95% for patients with DCIS and invasive early-stage breast cancer. These results are similar to those reported with other forms of APBI or whole-breast irradiation with similar follow-up and risk factors for ipsilateral breast tumor recurrence.
The cosmetic outcomes of patients in this study generally were good to excellent.
This represents the largest group of patients treated with contemporary APBI with 5-years of follow-up.
This study demonstrated low rates of local failure in the appropriately selected patients enrolled on this trial. These results are in line with recurrence rates demonstrated in other published series of patients treated with APBI or whole breast radiation therapy. However, previous reports by the National Surgical Adjuvant Breast and Bowel Project has demonstrated that a relatively high proportion of ipsilateral breast recurrences among patients with node-negative disease and a positive estrogen receptor status can occur after ten years from the time of breast conserving therapy with whole breast radiation therapy. Additional follow-up, therefore, is warranted to determine if the rate of recurrence remains similar to historical controls treated with whole breast radiation therapy.
It should be noted that this trial was developed by the manufacturer with clearance from the US Food and Drug Administration. The ASBS assumed management of this trial in 2003. It is also noteworthy that study data was initially managed by Synergis, Inc prior to 2006. However, the content of scientific publications will be at the discretion of the ASBS.
The American Brachytherapy Society (ABS) and the ASBS have released similar criteria for patient selection for APBI. Both societies recommend APBI for patients ≥45 years of age with invasive ductal adenocarcinoma tumors ≤3 cm with no axillary lymph node metastasis (by axillary lymph node dissection or sentinel lymph node biopsy) and negative resection margins (no tumor at the inked margin for the ABS, negative microscopic surgical margins for the ASBS). The ASBS also recommends APBI for patients with DCIS tumors ≤3 cm. At this time, it is strongly recommended that any patient not meeting these criteria, but wanted to be treated with APBI, should be enrolled on a clinical trial. Too few patients with high risk features were included in this study to make definitive recommendations regarding the efficacy of APBI in this cohort of patients.
The authors did not include any patient-reported cosmetic endpoints. However, the cosmetic results, as judged by physicians, were good to excellent in 90.6% at five years. This percentage is stable from the assessment at four years (90.5%) and may indicate that no significant decline in cosmesis with be identified with longer follow-up. However, as fibrosis and tissue remodeling can occur in the late setting, this group of patients should continue to be assessed for late cosmetic toxicity.
Confirmatory randomized studies will be needed before concluding that APBI is an acceptable substitute for whole breast external beam radiation therapy for patients undergoing breast conservation therapy. The National Surgical Adjuvant Breast and Bowel Project and the RTOG (NSABP B-39/RTOG 0413) phase III trial comparing whole breast radiation therapy to APBI should help to determine the role for APBI. However, the accrual of "low-risk" patients was completed in 2006 and higher risk patients (age <50, estrogen receptor-negative, axillary lymph node metastasis) are still being enrolled.
While we await the results of NSABP B-39/RTOG 0413, the current study likely will prove to be “practice affirming.” This ASBS study has demonstrated similar excellent rates of local control and similar patterns of failure as has been previously published, but it provides more extended follow-up in a larger group of patients than has previously been reported. While this study supports the continued usage of APBI in women with DCIS or early stage invasive breast cancer on a clinical trial, longer follow-up will be required to determine if this technique should be administered as a standard treatment option off of a clinical trial.
Dec 8, 2011 - Accelerated partial breast brachytherapy, in older women with invasive breast cancer treated with conservative surgery, is less effective and more toxic than whole breast irradiation, according to a study presented at the annual San Antonio Breast Cancer Symposium, held from Dec. 6 to 10.