Targeted Intraoperative Radiotherapy (TARGIT-IORT) for Early-Stage Invasive Breast Cancer: A Single Institution Experience.

Purpose/Objective: We present our single-institution experience in the management of invasive breast cancer with targeted intraoperative radiotherapy (TARGIT-IORT), focusing on patient suitability for IORT determined by the American Society for Radiation Oncology (ASTRO) Accelerated Partial Breast Irradiation (APBI) consensus guidelines. Materials/Methods: We identified 237 patients treated for biopsy-proven early-stage invasive breast cancer using low energy x-ray TARGIT-IORT at the time of lumpectomy between September 2013 and April 2020 who were prospectively enrolled in an institutional review board (IRB) approved database. We retrospectively reviewed preoperative and postoperative clinicopathologic factors to determine each patient's ASTRO APBI suitability (suitable, cautionary or unsuitable) according to the 2017 consensus guidelines (CG). Change in suitability group was determined based on final pathology. Kaplan-Meier methods were used to estimate the survival probability and recurrence probability across time. Results: 237 patients were included in this analysis, based on preoperative clinicopathologic characteristics, 191 (80.6%) patients were suitable, 46 (19.4%) were cautionary and none were deemed unsuitable. Suitability classification changed in 95 (40%) patients based on final pathology from lumpectomy. Increasing preoperative lesion size or a body mass index (BMI) ≥ 30 kg/m2 were significant predictors for suitability group change. Forty-one (17.3%) patients received additional adjuvant whole breast radiotherapy after TARGIT-IORT. At a median follow up of 38.2 months (range 0.4 - 74.5), five (2.1%) patients had ipsilateral breast tumor recurrences (IBTR), including two (0.8%) true local recurrences defined as a recurrence in the same quadrant as the initial lumpectomy bed with the same histology as the initial tumor. IBTR occurred in 1/103 (0.09%) patient in the post-op suitable group, 4/98 (4.08%) patients in the post-op cautionary group, and no patients in the post-op unsuitable group. At 3-years, the overall survival rate was 98.4% and the local recurrence free survival rate was 97.1%. Conclusion: There is a low rate of IBTR after TARGIT-IORT when used in appropriately selected patients. Change in suitability classification pre to postoperatively is common, highlighting a need for further investigation to optimize preoperative patient risk stratification in this setting. Patients who become cautionary or unsuitable based on final pathology should be considered for additional adjuvant therapy.

A Single institution's randomized double-armed prospective study of lumpectomy margins with adjunctive use of the MarginProbe in nonpalpable breast cancers.

Breast conservation surgery (BCS) aims to excise all cancerous tissue while minimizing the amount of healthy breast tissue removed. Up to 30% of patients undergoing BCS require a second operation for re-excision to obtain negative margins. Previous studies reported a lower re-excision rate with intraoperative use of the MarginProbe device (Dune Medical Devices). This device utilizes radiofrequency spectroscopy to detect differences between cancerous and normal tissue. From July 2009 to January 2010, our institution enrolled 46 patients electing for BCS in a prospective double-arm randomized controlled trial and had a significantly lower re-excision rate than that reported in the multicenter trial. Intraoperatively, after performing conventional lumpectomy with excision of any additional shavings deemed necessary based on palpation and visual inspection alone, patients were then randomized. In the device arm, the surgeon used the MarginProbe to interrogate the lumpectomy specimen, taking additional shavings from the cavity surfaces corresponding to the parts of the specimen read as positive by the device. In the control arm, only standard intraoperative assessments were performed. All specimens were evaluated by pathologists who were blinded to the study arm. In this population, 72% had invasive ductal carcinoma (IDC), 20% had ductal carcinoma in situ (DCIS), and 8% had invasive lobular carcinoma (ILC). Average age was 64 years old. The average size of the specimen was 5.6 cm, the average volume was 37.8 cm3 , and the average weight was 32.7 g. The mean size of DCIS was 1.4 cm. For invasive specimens, 32 were T1 and 7 were T2. Prior to randomization, 43 patients were thought to have positive or close margins and therefore underwent additional shavings. Twenty-three patients were randomized to the device arm and 23 to the control arm. In the device arm, 14 (60%) patients had IDC, 7 (30%) had DCIS, and 2 (8%) had ILC, vs the control arm where 19 (82%) patients had IDC, 2 (8%) had DCIS, and 2 (8%) had ILC. Eight (35%) patients in the control group vs 1 (4%) in the device group underwent re-excision for margin involvement (P < .05). The use of the MarginProbe device at our institution significantly improved the ability of our surgeons to obtain clear margins during initial BCS. Our results show a lower re-excision rate (4%) than those published in the multicenter trial (19.8%). We postulate that in the face of more patients having DCIS in our device group (30%), our surgeons responded by taking thicker shavings when the MarginProbe device reported margin involvement during the initial lumpectomy, resulting in greater success achieving clear final margins on the shaved tissue and a significantly lower re-excision rate than previously reported with the MarginProbe device.

In the Setting of Negative Mammogram, Is Additional Breast Ultrasound Necessary for Evaluation of Breast Pain?

PURPOSE: To evaluate whether in the setting of negative diagnostic mammogram for breast pain additional ultrasound is necessary. METHODS: Retrospective IRB-approved review of our database identified 8085 women who underwent ultrasound evaluation for breast pain from 1/1/2013-12/31/2013. Of 8085 women, 559 women had mammogram evaluation preceding the ultrasound and these women comprise the basis of this study. The patient's age, type of mammogram examination (screening or diagnostic), Breast Imaging-Reporting and Data System (BI-RADS) breast density (BD), type of breast pain (focal, diffuse, cyclical, unilateral, bilateral), additional breast symptoms (palpable concern, nipple discharge, skin changes, others), mammogram or ultrasound findings and final BI-RADS assessment, follow-up imaging, and follow-up biopsy results were reviewed and recorded. RESULTS: The median age of patients was 46 years old (range: 27-97). Patients recalled from negative screening mammogram were 29.8% (167/559). Patients with preceding negative diagnostic mammogram were 70.2% (392/559). The BI-RADS BD distribution was BD1: 5.5%, BD2: 39.9%, BD3: 46.0%, BD4: 8.6%. Final BI-RADS assessments were BI-RADS 1/2 (79%), BI-RADS 3 (12.9%), BI-RADS 4 (8.1%), BI-RADS 5 (0%). Majority (66.9%, 374/559) of the patient had breast pain alone. Additional breast symptoms were also noted as follows: palpable concern (24%), nipple discharge (3.9%), skin changes or other (5.2%). On follow-up evaluation, 26 findings were recommended for tissue sampling yielding 2 malignancies (0.4%, 2/559) in 2 patients. In the setting of negative mammogram and clinical symptom of breast pain alone yielded no malignances (NPV, 100%, 374/374) and was not impacted by BD. In patients with additional symptoms accompanying pain, malignancies were present despite negative mammogram in 2 patients; nipple discharge (4.5%, 1/22), and palpable concern (0.7%, 1/134). CONCLUSION: In the setting of negative mammogram and breast pain alone, additional evaluation with ultrasound is likely low yield and may be unnecessary. However, with additional symptoms such as palpable concern or nipple discharge, ultrasound is likely an important adjunct modality for identifying mammographically occult tumors.

Predictors of breast cancer development in women with atypical ductal hyperplasia and atypical lobular hyperplasia.

BACKGROUND: Atypical ductal hyperplasia and atypical lobular neoplasia are common benign breast diseases that increase breast cancer risk. We performed a cohort analysis that compared atypia patients for additional risk factors to asses the effect on breast cancer risk by atypia status. METHODS: This longitudinal cohort study used data from the Women At Risk High-Risk Registry at Columbia University Medical Center, New York. Women with atypia were compared to women without atypia across known risk factors to determine the combined effect on breast cancer development. Odds ratios (ORs) stratified by atypia status were calculated for each risk factor of interest with 95% confidence intervals (95% CIs). P values were calculated to determine statistical significance. RESULTS: The study population included 1598 high-risk women, 921 (57.6%) of whom had a history of biopsy-proven atypia. The remaining 677 high-risk women (42.4%) did not have atypia. Fifty women (3.1%) developed breast cancer. Alcohol was significantly associated with the development of breast cancer (P = 0.02) and increased breast cancer risk among women with atypia (OR, 2.13; 95% CI, 0.95-4.81) compared to women without atypia (OR, 1.71). The odds of breast cancer were higher for atypia patients with first-degree relatives (OR, 1.48; 95% CI, 0.64-3.35) compared to women with a relative and no atypia diagnosis (OR, 0.98; 95% CI, 0.41-2.63). The other risk factors of interest did not differ significantly by atypia status. CONCLUSIONS: Atypia patients who drank alcohol and had a first-degree relative with breast cancer have an increased risk of breast cancer compared to those without atypia. Continued understanding of the high-risk population will lead to more individualized protocols for risk reduction and prevention.