Phase II Trial of Five-Fraction Accelerated Partial Breast Irradiation Using Noninvasive Image-Guided Breast Brachytherapy.

PURPOSE/OBJECTIVE(S): NIBB has potential advantages over other APBI techniques by delivering highly conformal radiation with minimal collateral dose to the heart and lung compared with external beam techniques, but unlike other brachytherapy techniques NIBB is non-invasive. Previous data has shown encouraging outcomes using a 10-fraction regimen. To improve efficiency, convenience, and cost, reduction in the fraction number is desirable. Final results of a prospective phase II trial are reported. MATERIALS/METHODS: NIBB APBI was delivered using 28.5Gy in 5 fractions daily over 1 week. Patient eligibility criteria required: invasive carcinoma ≤2.0 cm or DCIS ≤3.0 cm, ER positive (if invasive), lymph node negative, LVI absent, and lumpectomy with margins negative by 2mm. The primary endpoint was grade ≥ 2 subcutaneous fibrosis/induration <30%. Secondary endpoints included any late toxicity, cosmetic outcome, and local control. RESULTS: 40 patients were treated with a median follow-up of 59.7 months. The mean age was 67 years (50-89 years) and tumor size was 1.0cm (0.3-2.0cm). 80% had invasive carcinoma. The mean breast separation with compression was 6.7cm (3.5-8.9cm). The 5-year actuarial local control was 96.6% and overall survival was 96.9%. Grade 2 and 3 late toxicities were 15% and 0%, respectively. The rate of grade 2 subcutaneous fibrosis/induration was 2.5% (+/-2.5%) meeting the study's primary endpoint. The most common late toxicity of any grade was skin telangiectasia; 22.5% grade 1 and 15% grade 2. Only breast separation was associated with telangiectasia risk, p=0.002. Overall cosmetic outcome was excellent, good, and fair/poor in 75%, 25%, and 0%, respectively. CONCLUSIONS: NIBB APBI delivered in 5 fractions results in a low rate of late toxicity and a high rate of good/excellent cosmetic outcomes. Telangiectasia risk can be minimized by keeping breast separation ≤7.0cm. The local failure rate was appropriately low. Further investigation of this technique is warranted.

Microinvasive breast cancer and the role of sentinel lymph node biopsy.

Whether sentinel lymph node biopsy (SLNB) should be performed in patients with microinvasive breast cancer (MIBC) has been a matter of debate over the last decade. MIBC has a favorable prognosis and while metastasis to the axilla is rare, it can impact treatment recommendations. In this study we evaluated clinical and histological features in both MIBC and background DCIS including ER, PR, and HER-2, number of foci of MIBC, the extent of the DCIS, nuclear grade, presence of comedo necrosis, as well as surgical procedures, adjuvant treatment and follow up to identify variables which predict disease free survival (DFS), as well as the factors which influence clinical decision making. Our study included 72 MIBC patients with a mean patient follow-up time of 55 months. Three patients with MIBC had recurrence, and two deceased, leaving five patients in total with poor long-term outcomes and a DFS rate of 93.1%. Performing mastectomy, high nuclear grade, and negativity for ER and HER-2 were found to be associated with the use of SLNB, although none of these variables were found to be associated with DFS. One positive lymph node case was discovered following SLNB in our study. This suggests the use of SLNB may provide diagnostic information to some patients, although these are the anomalies. When comparing patients who had undergone SLNB to those which had not there was no difference in DFS. Certainly, the use of SLNB in MIBC is quite the conundrum. It is important to acknowledge that surgical complications have been reported, and traditional metrics used for risk assessment in invasive breast cancer may not hold true in the setting of microinvasion.

Phase 2 Trial of Accelerated Partial Breast Irradiation (APBI) Using Noninvasive Image Guided Breast Brachytherapy (NIBB).

PURPOSE: Noninvasive image guided breast brachytherapy (NIBB) is a novel approach to delivery of accelerated partial breast irradiation (APBI) that may hold advantages over established techniques. NIBB is not invasive but maintains a high level of precision by using breast immobilization via breast compression and image guidance; it therefore does not require large planning tumor volume margins. We present the primary outcomes of this prospective phase 2 study (BrUOG Br-251). METHODS AND MATERIALS: Eligible patients with early-stage breast cancer underwent NIBB APBI using a dose 34 Gy in 10 fractions delivered daily or twice a day. Treatment was delivered using an Ir-192 high-dose-rate source via specialized applicators. Two orthogonal treatment axes were used for each fraction. The primary endpoints were late toxicity and cosmesis assessed at 2 and 5 years. Toxicity was assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events v3.0. Cosmesis was assessed using the NRG/Radiation Therapy Oncology Group scale. Ipsilateral breast tumor recurrence was defined as any recurrence or new primary in the treated breast. RESULTS: Forty patients underwent protocol treatment. Median patient age was 68 years (50-92 years). Mean tumor size was 1.1 cm (0.3-3.0 cm). Among the cohort, 62.5% had invasive carcinoma and 37.5% had ductal carcinoma in situ. Thirty-nine percent elected to receive hormone therapy. No grade ≥3 late toxicities were observed at any time point. Grade 2 toxicity was 5% and 10% at 2 and 5 years, respectively. Telangiectasia grade 1 and 2 occurred in 27.5% and 5%, respectively. Breast separation of >7 cm was associated with telangiectasia (P < .01). The rate of good to excellent cosmetic outcome was 95% at 2 years and 100% at 5 years. With a median follow-up of 68 months, the actuarial 5-year freedom from ipsilateral breast tumor recurrence was 93.3% (±4.8%), and overall survival was 93.7% (±4.4%). CONCLUSIONS: NIBB to deliver APBI is well tolerated with a low incidence of significant late toxicity and has favorable cosmetic outcomes. Continued evaluation of the NIBB APBI technique in a larger cohort is warranted.

Stromal ColXα1 expression correlates with tumor-infiltrating lymphocytes and predicts adjuvant therapy outcome in ER-positive/HER2-positive breast cancer.

BACKGROUND: The breast cancer microenvironment contributes to tumor progression and response to chemotherapy. Previously, we reported that increased stromal Type X collagen α1 (ColXα1) and low TILs correlated with poor pathologic response to neoadjuvant therapy in estrogen receptor and HER2-positive (ER+/HER2+) breast cancer. Here, we investigate the relationship of ColXα1 and long-term outcome of ER+/HER2+ breast cancer patients in an adjuvant setting. METHODS: A total of 164 cases with at least 5-year follow-up were included. Immunohistochemistry for ColXα1 was performed on whole tumor sections. Associations between ColXα1expression, clinical pathological features, and outcomes were analyzed. RESULTS: ColXα1 expression was directly proportional to the amount of tumor associated stroma (p = 0.024) and inversely proportional to TILs. Increased ColXα1 was significantly associated with shorter disease free survival and overall survival by univariate analysis. In multivariate analysis, OS was lower in ColXα1 expressing (HR = 2.1; 95% CI = 1.2-3.9) tumors of older patients (> = 58 years) (HR = 5.3; 95% CI = 1.7-17) with higher stage (HR = 2.6; 95% CI = 1.3-5.2). Similarly, DFS was lower in ColXα1 expressing (HR = 1.8; 95% CI = 1.6-5.7) tumors of older patients (HR = 3.2; 95% CI = 1.3-7.8) with higher stage (HR = 2.7; 95% CI = 1.6-5.7) and low TILs. In low PR+ tumors, higher ColXα1 expression was associated with poorer prognosis. CONCLUSION: ColXα1 expression is associated with poor disease free survival and overall survival in ER+/HER2+ breast cancer. This study provides further support for the prognostic utility of ColXα1 as a breast cancer associated stromal factor that predicts response to chemotherapy.

Distress: Characterizing What Causes the Thermometer to Shift in Patients with Newly Diagnosed Breast Cancer Attending a Multidisciplinary Clinic.

BACKGROUND: A diagnosis of breast cancer (BC) can result in multifactorial stress. If not addressed, distress can have a negative impact on outcomes. The experience of patients with newly diagnosed BC has not been sufficiently investigated. This study characterizes distress among new patients in a multidisciplinary care (MDC) clinic. The study aimed to determine the degree of distress at presentation, to characterize the sources, and to evaluate the impact of an MDC visit. METHODS: A retrospective review was performed from January 2015 to November 2017. Charts were accessed for demographics, tumor characteristics, and treatment data. Distress scores (DS) and problems as captured using the National Comprehensive Cancer Network (NCCN) Distress Thermometer were completed before evaluation and in a subgroup after an MDC visit. Predictors of severe distress (DS ≥4) were investigated using multivariable logistic regression. The paired t test was used to determine the impact of an MDC visit. RESULTS: The mean initial DS (n = 474) was 4.98. The top four sources of distress were worry, anxiety, fears, and sadness. Age younger than 65 years was significantly associated with a higher DS at presentation (p < 0.003). Among the patients queried before and after MDC (n = 137), a significant reduction in distress was identified (5.58-2.94; p < 0.0005). CONCLUSIONS: Severe distress was found in 66 % of the patients with a recent diagnosis of BC, with younger age related to higher distress scores at presentation. Emotional stressors were the predominant factors accounting for distress. A same-day MDC visit was associated with a significant reduction in DS. These data indicate the importance and feasibility of proactively screening patients. Our research lends support to the value of multidisciplinary evaluation in this setting.

Three-Dimensional Bioabsorbable Tissue Marker Placement is Associated with Decreased Tumor Bed Volume Among Patients Receiving Radiation Therapy for Breast Cancer.

PURPOSE: BioZorb® (Focal Therapeutics, Aliso Viejo, CA) is an implantable 3-dimensional bioabsorbable marker used for tumor bed volume (TBV) identification during postoperative radiation therapy (RT) planning. We aimed to calculate and compare RT TBVs between two cohorts managed with and without the device. METHODS AND MATERIALS: Data from patients with breast cancer who were treated at Rhode Island Hosptial, Providence RI between May 1, 2015 and April 30, 2016 were retrospectively reviewed and grouped based on 3-dimensional bioabsorbable marker placement. Pathology reports were used to calculate tumor excision volume (TEV) after breast conservation. Specifically, the three dimensions provided were multiplied to generate a cubic volume, defined as TEV. TBV was calculated using treatment volumes generated with Philips Pinnacle3 treatment planning software (Andover, MA). Linear regression analyses assessed the relationship between excised TEV and TBV. T tests compared the slopes of the best fit lines for plots of TEV versus TBV. RESULTS: In this retrospective case-control study, 116 patients undergoing breast RT were identified; of whom 42 received a 3-dimensional bioabsorbable marker and 74 did not. The mean TEVs were 102.7 cm3 with the device and 103.2 cm3 without the device, and the mean TBVs for the same groups were 27.5 cm3 and 40.1 cm3, respectively. The TBV standard errors for patients who did and did not receive 3-dimensional bioabsorbable markers were 23.739 and 38.685, respectively. The t tests found the slopes of the lines of best fit for these cohorts to be statistically significantly different (P = .001), with smaller TBVs achieved with 3-dimensional bioabsorbable marker placement. CONCLUSIONS: When comparing TBVs between patients contemporaneously treated with or without a 3-dimensional bioabsorbable marker, device placement was associated with statistically significantly smaller TBVs in the setting of similar TEVs.

Five fraction accelerated partial breast irradiation using noninvasive image-guided breast brachytherapy: Feasibility and acute toxicity.

PURPOSE: To improve efficiency, convenience, and cost, a prospective phase II trial was initiated to evaluate accelerated partial breast irradiation delivered with noninvasive image-guided breast brachytherapy (NIBB) via five once-daily fractions. METHODS AND MATERIALS: Women ≥50 years old with early-stage breast cancer undergoing breast conserving surgery were enrolled. Eligibility criteria included invasive carcinoma ≤2.0 cm or ductal carcinoma in situ ≤3.0 cm, ER positive (if invasive), lymph node negative, LVI absent, and margins negative by 2 mm. Patients received a total dose of 28.5 Gy in five daily fractions. NIBB was delivered using two orthogonal axes for each fraction. Applicators were selected to encompass the lumpectomy cavity with a 1.0 cm clinical target volume margin and 0 to 0.5 cm planning target volume margin. Acute and late toxicity was assessed based on CTCAE v3.0. RESULTS: Forty patients with a mean age of 67 years underwent protocol treatment. Mean tumor size was 1.0 cm (0.3-2.0 cm). Eighty percent had invasive carcinoma and the remainder had ductal carcinoma in situ. Mean tumor bed volume was 21 cc (5-79 cc) and mean breast volume was 1319 cc (499-3044 cc). Mean breast separation with compression was 6.7 cm (3.5-8.9 cm). All patients tolerated well. Median discomfort with compression was 1 (range: 0-7) on a 10-point pain scale. Acute skin reaction was Grade 0-1 in 70%, Grade 2 in 28%, and Grade 3 in 3%. Acute skin toxicity was not associated with breast size but was associated with larger breast separation with compression (p < 0.01) and larger applicator size (p < 0.01). No Grade 3+ late toxicity or local recurrences have been observed at a median followup of 14 months. CONCLUSIONS: Accelerated partial breast irradiation delivered using NIBB over five daily fractions is a convenient treatment option that is feasible and well tolerated.

Can Sentinel Lymph Node Biopsy Be Spared in Papillary Carcinoma of the Breast?

BACKGROUND: Papillary carcinoma (PC) of the breast represents ∼0.5% of all newly diagnosed cases of breast cancer and usually has an indolent course. The current data suggest lack of a consensus in the surgical management of this disease. Because patients can occasionally develop metastatic disease, sentinel lymph node (SLN) biopsy is often performed during surgery. MATERIALS AND METHODS: In the present study, we retrospectively evaluated the histologic characteristics of 99 cases of PC with or without associated frank invasive carcinoma, including 43 encapsulated or intracystic PCs, 24 solid PCs, and 32 intraductal PCs, and correlated these with the incidence of nodal metastasis. RESULTS: Of the 99 cases, 64 were tumor stage Tis (noninvasive), 5 were T1 microinvasive, 17 T1a, 5 T1b, 5 T1c, and 3 were T2. A total of 37 patients (37%) underwent axillary staging, including 31 SLN biopsies and 6 axillary dissections. Only 1 patient (2.7%) with noninvasive solid PC had evidence of nodal metastasis. Follow-up information was available for 81 patients, with a mean follow-up period of 4.9 years (range, 1-13 years). Two local recurrences, no distant metastases, and no disease-related deaths were recorded. CONCLUSION: PC rarely involves the lymph nodes even in tumors with an associated frank invasive component, and the overall prognosis and long-term survival is excellent. We propose that evaluation of the SLN should not be routinely indicated for patients with PC treated by local control lumpectomy.

Identification of stromal ColXα1 and tumor-infiltrating lymphocytes as putative predictive markers of neoadjuvant therapy in estrogen receptor-positive/HER2-positive breast cancer.

BACKGROUND: The influence of the tumor microenvironment and tumor-stromal interactions on the heterogeneity of response within breast cancer subtypes have just begun to be explored. This study focuses on patients with estrogen receptor-positive/human epidermal growth factor receptor 2-positive (ER+/HER2+) breast cancer receiving neoadjuvant chemotherapy and HER2-targeted therapy (NAC+H), and was designed to identify novel predictive biomarkers by combining gene expression analysis and immunohistochemistry with pathologic response. METHODS: We performed gene expression profiling on pre-NAC+H tumor samples from responding (no or minimal residual disease at surgery) and non-responding patients. Gene set enrichment analysis identified potentially relevant pathways, and immunohistochemical staining of pre-treatment biopsies was used to measure protein levels of those pathways, which were correlated with pathologic response in both univariate and multivariate analysis. RESULTS: Increased expression of genes encoding for stromal collagens, including Col10A1, and reduced expression of immune-associated genes, reflecting lower levels of total tumor-infiltrating lymphocytes (TILs), were strongly associated with poor pathologic response. Lower TILs in tumor biopsies correlated with reduced likelihood of achieving an optimal pathologic response, but increased expression of the Col10A1 gene product, colXα1, had greater predictive value than stromal abundance for poor response (OR = 18.9, p = 0.003), and the combination of increased colXα1 expression and low TILs was significantly associated with poor response in multivariate analysis. ROC analysis suggests strong specificity and sensitivity for this combination in predicting treatment response. CONCLUSIONS: Increased expression of stromal colXα1 and low TILs correlate with poor pathologic response in ER+/HER2+ breast tumors. Further studies are needed to confirm their predictive value and impact on long-term outcomes, and to determine whether this collagen exerts a protective effect on the cancer cells or simply reflects other factors within the tumor microenvironment.

The rationale, technique, and feasibility of partial breast irradiation using noninvasive image-guided breast brachytherapy.

PURPOSE: Noninvasive image-guided breast brachytherapy (NIBB) is a novel approach to deliver accelerated partial breast irradiation (APBI). NIBB is noninvasive, yet maintains a high degree of precision by using breast immobilization and image guidance. This makes NIBB an attractive alternative to existing APBI techniques. METHODS AND MATERIALS: Forty patients were enrolled to an institutional review board-approved prospective clinical trial evaluating APBI using NIBB. The NIBB technique is described in detail. Briefly, patients were treated with the breast compressed and immobilized sequentially in two orthogonal axes for each fraction. Radiation was delivered using collimated emissions from a high-dose-rate iridium-192 source via specialized applicators. The prescribed dose was 34.0 Gy in 10 fractions. Feasibility and tolerability of treatment were assessed. RESULTS: All patients completed protocol treatment. The median age was 68 years. Sixty-three percent of patients had invasive carcinoma, and 37% had ductal carcinoma in situ. All were node negative. Ninety-three percent of patients were postmenopausal. Mean tumor size, tumor bed volume, and breast volume were 1.1 cm, 22.4 cc, and 1591 cc, respectively. NIBB treatment was well tolerated. Median patient-reported discomfort was 1 on a 10-point pain scale. Treatment delivery times were reasonable. The average treatment time per axis was 14 min (5-20 min), and the average time from start of first treatment axis to completion of orthogonal axis was 43 min (30-63 min). Acute skin toxicity was Grade 0, 1, and 2 in 20%, 53%, and 28% of patients, respectively. There were no Grade 3 or greater acute toxicities observed. CONCLUSIONS: NIBB holds promise as an alternative method to deliver APBI. NIBB is feasible and well tolerated by patients. Further investigation of NIBB to deliver APBI is warranted.

Axillary ultrasound and fine-needle aspiration in the preoperative evaluation of the breast cancer patient: an algorithm based on tumor size and lymph node appearance.

OBJECTIVE: The objective of our study was to evaluate the utility of ultrasound-guided fine-needle aspiration (FNA) of the axillary lymph nodes in breast cancer patients depending on the size of the primary tumor and the appearance of the lymph nodes. SUBJECTS AND METHODS: Data were collected about tumor size, lymph node appearance, and the results of ultrasound-guided FNA and axillary surgery of 224 patients with breast cancer undergoing 226 ultrasound-guided FNA. Lymph nodes were classified as benign if the cortex was even and measured < 3 mm, indeterminate if the cortex was even but measured ≥ 3 mm or measured < 3 mm but was focally thickened, and suspicious if the cortex was focally thickened and measured ≥ 3 mm or the fatty hilum was absent. The results of ultrasound-guided FNAs were analyzed by the sonographic appearance of the axillary lymph nodes and by the size of the primary tumor. The sensitivity and specificity of ultrasound-guided FNA were calculated with axillary surgery as the reference standard. The sensitivity and specificity of axillary ultrasound to predict the ultrasound-guided FNA result were calculated. RESULTS: Of the 224 patients, 51 patients (23%) had a positive ultrasound-guided FNA result, which yields an overall sensitivity of 59% and specificity of 100%. The sensitivity of ultrasound-guided FNA was 29% in patients with primary tumors ≤ 1 cm, 50% in patients with tumors > 1 to ≤ 2 cm, 69% in patients with tumors > 2 to ≤ 5 cm, and 100% in patients with tumors > 5 cm. The sensitivity of ultrasound-guided FNA in patients with normal-appearing lymph nodes was 11%; indeterminate lymph nodes, 44%; and suspicious lymph nodes, 93%. Sonographic characterization of lymph nodes as suspicious or indeterminate was 94% sensitive and 72% specific in predicting positive findings at ultrasound-guided FNA. CONCLUSION: Ultrasound-guided FNA of the axillary lymph nodes is most useful in the preoperative assessment of patients with large tumors (> 2 cm) or lymph nodes that appear abnormal.

Frequent pathologic complete responses in aggressive stages II to III breast cancers with every-4-week carboplatin and weekly paclitaxel with or without trastuzumab: a Brown University Oncology Group Study.

PURPOSE: To evaluate the efficacy and safety of neoadjuvant carboplatin and weekly paclitaxel +/- weekly trastuzumab in resectable and locally advanced breast cancer. PATIENTS AND METHODS: Women with stages IIA to IIIB disease received carboplatin dosed by six times the area under the curve every 4 weeks and paclitaxel 80 mg/m(2) weekly for 16 weeks, and weekly trastuzumab was added for human epidermal growth factor receptor 2 (HER2) -positive status. The primary end point was the pathologic complete response (pCR) rate, defined as the absence of invasive disease in the breast and axillary nodes. Postoperative therapies were at the discretion of the treating physicians. RESULTS: Fifty-five patients were enrolled, and of these 43 had resectable disease. The median age was 54 years (range, 31 to 74 years). Treatment was well tolerated; there were no episodes of febrile neutropenia or grade 4 thrombocytopenia, and there were only two instances of grade 3 peripheral neuropathy. Overall, the pCR rate was 45%. The pCR rate was 43% (95% CI, 28% to 58%) in patients with resectable disease. Higher pCR rates occurred in patients with HER2-positive tumors (76% v 31% for HER2-negative tumors; P = .003), with estrogen receptor (ER) -negative tumors (75% v 27% for ER-positive tumors; P = .001), or with triple-negative tumors (67% v 12% ER-positive and HER2-negative tumors; P = .002). At a median of 28 months postoperation, recurrence-free survival (RFS) was 88.7%. If patients with ER-positive and HER2-negative tumors are excluded from analysis, patients who achieved a pCR were less likely to experience disease recurrence (RFS, 86%) than those who did not achieve a pCR (RFS, 75%). CONCLUSION: Neoadjuvant carboplatin and weekly paclitaxel +/- trastuzumab achieve high pCR rates in patients with HER2-positive and triple-negative disease without exposure to an anthracycline. Preliminary RFS results are encouraging but are likely influenced by adjuvant therapy received. Additional study of this regimen in high-risk patients is warranted.

Preliminary results of a phase I/II study of HDR brachytherapy alone for T1/T2 breast cancer.

PURPOSE: To investigate the feasibility, toxicity, cosmetic outcome, and local control of high-dose-rate (HDR) brachytherapy alone without whole breast external beam irradiation for early-stage breast carcinoma. METHODS AND MATERIALS: Between June 1997 and August 1999, 32 women diagnosed with a total of 33 AJCC Stage I/II breast carcinomas underwent surgical breast excision and postoperative irradiation using HDR brachytherapy interstitial implantation as part of a multi-institutional clinical Phase I/II protocol. Eligible patients included those with T1, T2, N0, N1 (< or =3 nodes positive), and M0 tumors of nonlobular histologic features with negative surgical margins, no extracapsular lymph node extension, and a negative postexcision mammogram. Brachytherapy catheters were placed at the initial excision, reexcision, or either sentinel or full-axillary sampling. Direct visualization, surgical clips, and ultrasound and/or CT scan assisted in the delineation of the target volume, defined as the excision cavity plus a 2-cm margin. High-activity 192Ir (3-10 Ci) was used to deliver 340 cGy/fraction, 2 fractions/d, for 5 consecutive days, to a total dose of 34 Gy to the target volume. Source position and dwell times were calculated using standard volume optimization techniques. RESULTS: The median follow-up of all patients was 33 months, and the mean patient age was 63 years. The mean tumor size was 1.3 cm, and 55% had an extensive intraductal component. Three patients had positive axillary nodes. Two patients experienced moderate perioperative pain that required narcotic analgesics. No peri- or postoperative infections occurred. No wound healing problems and no significant skin reactions related to the implant developed. The Radiation Therapy Oncology Group late radiation morbidity scoring scheme was applied to the entire 33-case cohort. In the assessment of the skin, 30 cases were Grade 0-1 and 3 cases were Grade 2. Subcutaneous toxicity was scored as 11 patients with Grade 0, 3 with Grade 1, 8 with Grade 2, 3 with Grade 3, and 8 with Grade 4. Clinically evident fat necrosis occurred in 8 patients at a median of 7.5 months after HDR brachytherapy completion. The only variables significantly associated with Grade 3-4 toxicity were the number of source dwell positions and the volume of tissue encompassed by the prescription isodose shell. The global cosmetic scores after a minimum of 18 months' follow-up were 0 cases with poor, 4 with fair, 5 with good, and 24 with excellent scores. One case of ipsilateral breast tumor recurrence was diagnosed 23 months after HDR brachytherapy, for a 4-year actuarial recurrence rate of 3%. This failure appeared to be a new primary tumor, because it was histologically distinct from the initial tumor and was located 9 cm from the initial tumor bed and 3 cm from the edge of the implant volume. CONCLUSION: Radiotherapy of the tumor bed alone with HDR interstitial brachytherapy is associated with a 33% incidence of Grade 3-4 s.c. toxicity, but with generally favorable overall cosmetic results. The risk of toxicity appears to be primarily related to the implant volume. With limited follow-up, the incidence of ipsilateral breast tumor recurrence was low.