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BACKGROUND The authors' purpose was to create a nomogram using machine learning models predicting risk of breast reconstruction complications with or without postmastectomy radiation therapy. METHODS Between 1997 and 2017, 1617 breast cancer patients undergoing mastectomy and breast reconstruction were analyzed. Those with autologous, tissue expander/implant, and single-stage direct-to-implant reconstruction were included. Postmastectomy radiation therapy was delivered either with three-dimensional conformal photon or proton therapy. Complication endpoints were defined based on surgical reintervention operative notes as infection/necrosis requiring debridement. For implant-based patients, the authors studied capsular contracture requiring capsulotomy and implant failure. For each complication endpoint, least absolute shrinkage and selection operator-penalized regression was used to select the subset of predictors associated with the smallest prediction error from 10-fold cross-validation. Nomograms were built using the least absolute shrinkage and selection operator-selected predictors, and internal validation using cross-validation was performed. RESULTS Median follow-up was 6.6 years. Among 1617 patients, 23 percent underwent autologous reconstruction, 39 percent underwent direct-to-implant reconstruction, and 37 percent underwent tissue expander/implant reconstruction. Among 759 patients who received postmastectomy radiation therapy, 8.3 percent received proton-therapy to the chest wall and nodes and 43 percent received chest wall boost. Internal validation for each model showed an area under the receiver operating characteristic curve of 73 percent for infection, 75 percent for capsular contracture, 76 percent for absolute implant failure, and 68 percent for overall implant failure. Periareolar incisions and complete implant muscle coverage were found to be important predictors for infection and capsular contracture, respectively. In a multivariable analysis, we found that protons compared to no postmastectomy radiation therapy significantly increased capsular contracture risk (OR, 15.3; p < 0.001). This was higher than the effect of photons with electron boost versus no postmastectomy radiation therapy (OR, 2.5; p = 0.01). CONCLUSION Using machine learning, these nomograms provided prediction of postmastectomy breast reconstruction complications with and without radiation therapy. CLINICAL QUESTION/LEVEL OF EVIDENCE Risk, III.

PURPOSE: Elective operations including surgeries for breast cancer were significantly reduced during the height of the surge of COVID-19 cases in Massachusetts. The safety of performing breast reconstruction during the pandemic was unknown. This study aims to review the safety of performing mastectomy with immediate breast reconstruction during the first COVID-19 surge in Massachusetts. METHODS: A retrospective chart review of patients who underwent mastectomy with immediate breast reconstruction by Massachusetts General Hospital breast and plastic surgeons immediately preceding and during the COVID-19 pandemic was performed. RESULTS: Thirty patients (34 breasts) underwent mastectomies with immediate breast reconstruction during the COVID-19 restriction period in Massachusetts. Most reconstructions were unilateral. All reconstructions were performed with implants or expanders, and no autologous reconstructions were performed. Two patients (2 breasts) had operative complications. The complication rate during the pandemic was similar to the complication rate pre-pandemic. No patients or surgeons experienced symptoms or positive COVID-19 tests. Over 90% of patients were discharged the same day. CONCLUSION: Prosthetic breast reconstruction was able to be performed safely during the height of the COVID-19 pandemic surge in Massachusetts. Strict screening protocols, proper use of personal protective equipment, and same-day discharge when possible are essential for patient and surgeon safety during the pandemic.

Nipple-sparing mastectomy (NSM) is now routinely offered to BRCA mutation carriers for risk reduction. We assessed the rates of ipsilateral cancer events after prophylactic and therapeutic NSM in BRCA1 and BRCA2 mutation carriers. BRCA1 and BRCA2 mutation carriers undergoing NSM from October 2007 to June 2019 were identified in a single-institution prospective database, with variants of unknown significance being excluded. Patient, tumor, and outcomes data were collected. Follow-up analysis was by cumulative breast-years (total years of follow-up of each breast) and woman-years (total years of follow-up of each woman). Overall, 307 BRCA1 and BRCA2 mutation carriers (160 BRCA1, mean age 41.4 years [range 21–65]; and 147 BRCA2, mean age 43.8 years [range 23–65]) underwent 607 NSMs, with a median follow-up of 42 months (range 1–143). 388 bilateral prophylactic NSMs had 744 cumulative woman-years of follow-up, with no new cancers seen (< 0.0013 new cancers per woman-years); 251 BRCA1 prophylactic NSMs had 1034 cumulative breast-years of follow-up, with no new ipsilateral cancers seen (< 0.0010 per breast-year); 66 BRCA1 therapeutic NSMs had 328 cumulative breast-years of follow-up, with one ipsilateral cancer recurrence not directly involving the nipple or areola (0.0030 per breast-year); 237 BRCA2 prophylactic NSMs had 926 cumulative breast-years of follow-up, with no new ipsilateral cancers seen (< 0.0011 per breast-year); and 53 BRCA2 therapeutic NSMs had 239 cumulative breast-years of follow-up, with two ipsilateral recurrent cancers, neither of which directly involved the nipple or areola (0.0084 per breast-year). The risk of new ipsilateral breast cancers is extremely low after NSM in BRCA1 and BRCA2 mutation carriers. NSM is an effective risk-reducing strategy for BRCA gene mutations.

Purpose Safe breast cancer lumpectomies require microscopically clear margins. Real-time margin assessment options are limited, and 20–40% of lumpectomies have positive margins requiring re-excision. The LUM Imaging System previously showed excellent sensitivity and specificity for tumor detection during lumpectomy surgery. We explored its impact on surgical workflow and performance across patient and tumor types. Methods We performed IRB-approved, prospective, non-randomized studies in breast cancer lumpectomy procedures. The LUM Imaging System uses LUM015, a protease-activated fluorescent imaging agent that identifies residual tumor in the surgical cavity walls. Fluorescent cavity images were collected in real-time and analyzed using system software. Results Cavity and specimen images were obtained in 55 patients injected with LUM015 at 0.5 or 1.0 mg/kg and in 5 patients who did not receive LUM015. All tumor types were distinguished from normal tissue, with mean tumor:normal (T:N) signal ratios of 3.81–5.69. T:N ratios were 4.45 in non-dense and 4.00 in dense breasts (p = 0.59) and 3.52 in premenopausal and 4.59 in postmenopausal women (p = 0.19). Histopathology and tumor receptor testing were not affected by LUM015. Falsely positive readings were more likely when tumor was present Conclusions Intraoperative use of the LUM Imaging System detected all breast cancer subtypes with robust performance independent of menopausal status and breast density. There was no significant impact on histopathology or receptor evaluation.

The 2014 Society of Surgical Oncology/American Society for Radiation Oncology (SSO/ASTRO) breast-conserving surgery (BCS) margin guidelines for invasive cancer recommended “no ink on tumor” as an adequate margin width. However, 2016 SSO/ASTRO margin guidelines for pure DCIS recommended a 2 mm margin. Thus, management of a margin with DCIS > 0 mm but

PURPOSE To independently evaluate the impact of axillary surgery type and regional lymph node radiation (RLNR) on breast cancer–related lymphedema (BCRL) rates in patients with breast cancer. PATIENTS AND METHODS From 2005 to 2018, 1,815 patients with invasive breast cancer were enrolled in a lymphedema screening trial. Patients were divided into the following 4 groups according to axillary surgery approach: sentinel lymph node biopsy (SLNB) alone, SLNB+RLNR, axillary lymph node dissection (ALND) alone, and ALND+RLNR. A perometer was used to objectively assess limb volume. All patients received baseline preoperative and follow-up measurements after treatment. Lymphedema was defined as a ≥ 10% relative increase in arm volume arising > 3 months postoperatively. The primary end point was the BCRL rate across the groups. Secondary end points were 5-year locoregional control and disease-free-survival. RESULTS The cohort included 1,340 patients with SLNB alone, 121 with SLNB+RLNR, 91 with ALND alone, and 263 with ALND+RLNR. The overall median follow-up time after diagnosis was 52.7 months for the entire cohort. The 5-year cumulative incidence rates of BCRL were 30.1%, 24.9%, 10.7%, and 8.0% for ALND+RLNR, ALND alone, SLNB+RLNR, and SLNB alone, respectively. Multivariable Cox models adjusted for age, body mass index, surgery, and reconstruction type showed that the ALND-alone group had a significantly higher BCRL risk (hazard ratio [HR], 2.66; P = .02) compared with the SLNB+RLNR group. There was no significant difference in BCRL risk between the ALND+RLNR and ALND-alone groups (HR, 1.20; P = .49) and between the SLNB-alone and SLNB+RLNR groups (HR, 1.33; P = .44). The 5-year locoregional control rates were similar for the ALND+RLNR, ALND-alone, SLNB+RLNR, and SLNB-alone groups (2.8%, 3.8%, 0%, and 2.3%, respectively). CONCLUSION Although RLNR adds to the risk of lymphedema, the main risk factor is the type of axillary surgery used.

Targeted axillary dissection (TAD) involves sentinel lymph node biopsy (SLNB) and excision of a biopsy-proven node marked by a clip. This study evaluates the feasibility of non-radioactive wireless localizers for targeted excision of clipped axillary lymph nodes. We identified biopsy-proven, node-positive breast cancer patients treated with neoadjuvant therapy (NAT) and TAD from 2016 to 2020, and included those with a clipped node localized using SAVI SCOUT, Magseed, or RFID Tag. Primary outcome measures were (1) successful localization (ultrasound or mammographic-guided placement

Purpose During the COVID-19 pandemic, most breast surgery for benign and malignant conditions has been postponed, creating a backlog of patients who will need surgery. A fair and transparent system for assessing the risk of further delaying surgery for individual patients to prioritize surgical scheduling is needed. Methods Factors related to risk of delaying surgery for breast patients were identified. Scores were assigned to each factor, with higher scores indicating a greater risk from delaying surgery. REDCap and Microsoft Excel tools were designed to track and score delayed patients. Results Published data and multidisciplinary clinical judgement were used to assign risk scores based on patient and tumor factors, length of delay, and tumor response to preoperative therapy. Patients completing neoadjuvant chemotherapy were assigned the highest scores as their options for delaying surgery are most limited. Among patients receiving neoadjuvant endocrine therapy or no medical therapy, higher scores were assigned for low-estrogen receptor or high-genomic risk scores, higher grade, larger tumors, younger age and longer delay. High priority scores were assigned for progression during preoperative therapy. Low scores were assigned for re-excisions, atypical lesions and other benign indications. There was good agreement of the tool’s ranking of sample patients with rankings by experienced clinicians. The tool generates risk-stratified patient lists by surgeon or institution to facilitate assignment of surgery dates. Conclusions This tool generates a clinically consistent, risk-stratified priority list of breast surgical procedures delayed by the COVID-19 pandemic. This systematic approach may facilitate surgical scheduling as conditions normalize.

To explore the optimal type of breast reconstruction and the time interval to postmastectomy radiotherapy (PMRT) associated with lower complications in breast cancer patients receiving neoadjuvant chemotherapy. We reviewed the medical records of 300 patients who received neoadjuvant chemotherapy, mastectomy with breast reconstruction and PMRT at our institution from 2000 to 2017. Reconstruction types included autologous flaps (AR), single-stage-direct-to-implant and two-stages expander/implant (TE/I). The primary endpoint was the rate of reconstruction complications including infection, skin and fat necrosis. Subgroup analysis compared rates of capsular contracture, implant rupture, implant exposure and overall implant failure in single-stage-direct-to-implant to TE/I. The secondary endpoint was identifying the time interval between surgery with immediate implant-based reconstruction and PMRT associated with lower probability of implant failure. Logistic regression models, Kaplan–Meier estimates and Polynomial regression were used to assess endpoints. The median follow-up was 43.5 months. 29.3%, 28.3% and 42.4% of the cohort had AR, TE/I and single-stage-direct-to-implant D, respectively. The 5-year cumulative incidence rate of complications was 14.0%, 29.7% and 19.4% for AR, TE/I and single-stage-direct-to-implant, respectively (Log rank p = 0.02). Multivariate analysis showed significant association between TE/I and higher risk of infection (OR 8.1, p = 0.009) compared to AR, while single-stage-direct-to-implant and AR were comparable (OR 3.2, p = 0.2). On subgroup analysis, TE/I was significantly associated with higher rates of implant failure. The mean wait time to deliver PMRT after immediate reconstruction with no adjuvant chemotherapy was 8.4 and 10.7 weeks in single-stage-direct-to-implant and TE/I, respectively (p

Background We previously reported that breast conservation was feasible for women with large or irregularly shaped breast cancers when tumor resection was guided by multiple localizing wires. We now report long-term outcomes of multiple-wire versus single-wire localized lumpectomies for breast cancer. Patients and Methods We retrospectively reviewed wire-localized lumpectomies at our institution from May 2000 to November 2006. Rates of ipsilateral in-breast tumor recurrence, metastasis, and subsequent unplanned diagnostic imaging and biopsy were compared between multiple-wire and single-wire cohorts. Results We identified 112 multiple-wire and 160 single-wire breast cancer lumpectomies that achieved clear margins. Median age was 64 years in the multiple-wire cohort and 57 years in the single-wire cohort. Mean lumpectomy volume was 75 mL in multiple-wire patients and 49 mL in single-wire patients (P = .003). Invasive tumor size, axillary node status, and use of radiation and systemic therapy were similar, but the multiple-wire group had more patients with ductal carcinoma-in-situ only (38% vs. 28%). At 108 months’ median follow-up, there was no significant difference in local or distant recurrence rates between multiple-wire and single-wire cohorts. Six (5%) multiple-wire patients and 6 (4%) single-wire patients had local recurrences and 3 (3%) multiple-wire and 5 (3%) single-wire patients developed metastatic disease. Unplanned diagnostic imaging was required for 53 (47%) multiple-wire and 65 (41%) single-wire patients. Subsequent ipsilateral biopsy occurred in 15 (13%) multiple-wire and 19 (12%) single-wire patients. Conclusion Breast-conserving surgery with multiple localizing wires is a safe alternative to mastectomy for breast cancer patients with large mammographic lesions.

Clinical trials are currently ongoing to determine the safety and efficacy of active surveillance (AS) versus usual care (surgical and radiation treatment) for women with ductal carcinoma in situ (DCIS). This study aimed to determine upgrade rates of DCIS at needle biopsy to invasive carcinoma at surgery among women who meet the eligibility criteria for AS trials. A retrospective review was performed of consecutive women at an academic medical center with a diagnosis of DCIS at needle biopsy from 2007 to 2016. Medical records were reviewed for mode of presentation, imaging findings, biopsy pathology results, and surgical outcomes. Each patient with DCIS was evaluated for AS trial eligibility based on published criteria for the COMET, LORD, and LORIS trials. During a 10-year period, DCIS was diagnosed in 858 women (mean age 58 years; range 28–89 years). Of the 858 women, 498 (58%) were eligible for the COMET trial, 101 (11.8%) for the LORD trial, and 343 (40%) for the LORIS trial. The rates of upgrade to invasive carcinoma were 12% (60/498) for the COMET trial, 5% (5/101) for the LORD trial, and 11.1% (38/343) for the LORIS trial. The invasive carcinomas ranged from 0.2 to 20 mm, and all were node-negative. Women who meet the eligibility criteria for DCIS AS trials remain at risk for occult invasive carcinoma at presentation, with upgrade rates ranging from 5 to 12%. These findings suggest that more precise criteria are needed to ensure that women with invasive carcinoma are excluded from AS trials.

Purpose To compare single-stage direct-to-implant (DTI) immediate reconstruction to the commonly used 2-stages expander and implant (TE/I) or autologous reconstruction with focus on postmastectomy radiation therapy (PMRT) setting. Methods and Materials We reviewed the charts of 1,286 patients who underwent 1,814 breast reconstructions at our institution with and without PMRT from 1997 to 2017. Patients were divided into 6 groups according to type of reconstruction and PMRT status. Primary objective was reconstruction complications defined solely on surgical reintervention operative notes such as infection, skin necrosis, and fat necrosis across all groups. Implant-related complications such as capsular contracture, implant rupture or exposure, or implant failure were compared between TE/I and DTI. Kaplan–Meier estimates were used to calculate 5-year cumulative incidence of complications. The secondary objective was to compare the 3 reconstruction types in settings of immediate reconstruction followed by PMRT on multivariable analysis. Results Median follow-up was 5.8 years. Among 1286 patients, 41.1% (N = 529/1286) received PMRT. Among 1814 reconstructed breasts, autologous, single-stage, and TE/I represented 18.7%, 34.8%, and 46.2%, respectively. With no PMRT, the 5-year cumulative incidence of any reconstruction complication was 11.1%, 12.6%, and 19.5% for autologous, DTI, and TE/I reconstructions, respectively. The addition of PMRT resulted in 5-year cumulative incidence of 15.1%, 18.2%, and 36.8%, respectively. The multivariable analysis showed that DTI was associated with lesser complications compared with TE/I, whereas no significant difference was noted between DTI and autologous. Conclusions Single-stage DTI reconstruction had significantly lower complication rates than TE/I with and without PMRT. Single-stage complication rates were not significantly different from autologous complication rates in PMRT settings. Single-stage reconstruction may offer a valuable option for patients receiving PMRT.

Background: Standard surgical techniques result in positive lumpectomy margins 20-40% of the time. These positive margins require surgical re-excision which places significant burden on the healthcare system and patients. The LUM Imaging System consists of a fluorescent drug, a hand-held wide-field detector (LUM Imaging Device) used to image the surgical cavity walls intraoperatively in real-time after the resection of the main lumpectomy specimen, and a proprietary tumor detection algorithm that highlights regions in the tumor bed suspected to contain residual cancer. Methods: The Intraoperative Detection of Residual Cancer in Breast Cancer trial (NCT03321929) is a non-randomized, open-label, multi-site trial. This is a prospective, interventional feasibility study and is a pilot arm to a pivotal study which will further evaluate the safety and efficacy of the LUM Imaging System. This study enrolls women, over the age of 18 and with histologically or cytologically confirmed primary invasive breast cancer (IBC), ductal carcinoma in situ (DCIS) or a combination of IBC/DCIS undergoing a lumpectomy for their breast malignancy. LUM015, a fluorescent drug, is injected prior to the subject’s lumpectomy procedure. Surgeons perform their standard of care lumpectomy followed by intraoperative imaging of the lumpectomy cavity with the LUM Imaging System. In real-time, the LUM Imaging System highlights areas within the tumor bed that may contain, residual abnormal tumor tissue. Surgeons remove additional tissue based on the guidance of the LUM Imaging System. A maximum of two additional tissue shaves may be obtained. All excised tissue specimens are evaluated by routine pathology and correlated to the output of the LUM Imaging System. Results and Discussion: Sixteen medical centers across the United States enrolled 234 subjects into this study. Preliminary data on 141 subjects has been evaluated. The median age of enrolled women undergoing surgery using the Lumicell system was 61 years old. The histology of tumor type in women evaluated in this analysis is representative of the general population, with 21% diagnosed with ductal carcinoma in-situ (DCIS), 11% diagnosed with invasive lobular carcinoma, and 64% diagnosed with invasive ductal carcinoma (with or without DCIS features present). Most women (71%) presented with a palpable mass on physical examination prior to their lumpectomy surgery. Radiological imaging prior to lumpectomy showed scattered areas of fibroglandular density in 49% of the enrolled subjects and heterogeneously dense breast tissue in 42% of the enrolled subjects. The use of the LUM Imaging System positively impacted enrolled subjects; approximately 10% of subjects (N=14) had residual tumor detected and removed from the tumor bed guided by the LUM Imaging System after the standard of care surgery was completed. Without the use of this guidance technology, tumor tissue would have been left behind in this cohort of subjects, potentially requiring additional surgical intervention or other therapy, or local recurrence. The mean absolute volume of tissue removed due to guidance by the Lumicell System was 15 cc corresponding to about 15% of the total tissue removed. The LUM Imaging System correctly identified all positive margins in 28% of subjects with a positive margin after standard of care, and directed excision of additional tissue to create a wider margin. 12% of the patients with positive margins were converted to a negative margin by removing additional tissue guided by this imaging system. Future studies are planned that will measure the sensitivity and specificity of the device. Citation Format: Jorge Ferrer, David Carr, Peter Blumencranz, Daleela Dodge, Nayana Dekhne, Irene Wapnir, Kelly Hunt, Linsey Gold, Stephanie Valente, Peter Beitsch, Donna Dyess, Shelly Hwang, Lynne Clark, Beth-Ann Lesnikoski, Anees Chagpar, Stephen Karp, Brian Schlossberg, Sean Madden, Manna Chang, Kate Smith, David Strasfeld, W David Lee, Barbara Smith. Results from the expansion into multiple institutions for training in the use of the LUM imaging system for intraoperative detection of residual cancer in the tumor bed of female subjects with breast cancer clinical trial [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-20-06.

Background Obtaining tumor-free margins is critical to prevent recurrence after lumpectomy for breast cancer. Unfortunately, current approaches leave positive margins that require second surgeries in 20–40% of patients. We assessed the LUM Imaging System for real-time, intraoperative detection of residual tumor. Methods Breast lumpectomy cavity walls and excised specimens were assessed with the LUM Imaging System after 1 mg/kg intravenous LUM015, a protease-activatable fluorescent agent. Fluorescence at potential sites of residual tumor in lumpectomy cavity walls was evaluated intraoperatively with a sterile hand-held probe, with real-time predictive results displayed on a monitor intraoperatively, and later correlated with histopathology. Results In vivo lumpectomy cavities and excised specimens were imaged after LUM015 injection in 45 women undergoing breast cancer surgery. Invasive ductal and lobular cancers and intraductal cancer (DCIS) were included. A total of 570 cavity margin surfaces in 40 patients were used for algorithm development. Image analysis and display took approximately 1 s per 2.6-cm-diameter circular margin surface. All breast cancer subtypes could be distinguished from adjacent normal tissue. For all imaged cavity surfaces, sensitivity for tumor detection was 84%. Among 8 patients with positive margins after standard surgery, sensitivity for residual tumor detection was 100%; 2 of 8 were spared second surgeries because additional tissue was excised at sites of LUM015 signal. Specificity was 73%, with some benign tissues showing elevated fluorescent signal. Conclusions The LUM015 agent and LUM Imaging System allow rapid identification of residual tumor in the lumpectomy cavity of breast cancer patients and may reduce rates of positive margins.

PURPOSE To evaluate the safety and efficacy of proton beam radiation therapy (RT) for patients with breast cancer who require regional nodal irradiation. METHODS Patients with nonmetastatic breast cancer who required postoperative RT to the breast/chest wall and regional lymphatics and who were considered suboptimal candidates for conventional RT were eligible. The primary end point was the incidence of grade 3 or higher radiation pneumonitis (RP) or any grade 4 toxicity within 3 months of RT. Secondary end points were 5-year locoregional failure, overall survival, and acute and late toxicities per Common Terminology Criteria for Adverse Events (version 4.0). Strain echocardiography and cardiac biomarkers were obtained before and after RT to assess early cardiac changes. RESULTS Seventy patients completed RT between 2011 and 2016. Median follow-up was 55 months (range, 17 to 82 months). Of 69 evaluable patients, median age was 45 years (range, 24 to 70 years). Sixty-three patients (91%) had left-sided breast cancer, two had bilateral breast cancer, and five had right-sided breast cancer. Sixty-five (94%) had stage II to III breast cancer. Sixty-eight (99%) received systemic chemotherapy. Fifty (72%) underwent immediate reconstruction. Median dose to the chest wall/breast was 49.7 Gy (relative biological effectiveness) and to the internal mammary nodes, 48.8 Gy (relative biological effectiveness), which indicates comprehensive coverage. Among 62 surviving patients, the 5-year rates for locoregional failure and overall survival were 1.5% and 91%, respectively. One patient developed grade 2 RP, and none developed grade 3 RP. No grade 4 toxicities occurred. The unplanned surgical re-intervention rate at 5 years was 33%. No significant changes in echocardiography or cardiac biomarkers after RT were found. CONCLUSION Proton beam RT for breast cancer has low toxicity rates and similar rates of disease control compared with historical data of conventional RT. No early cardiac changes were observed, which paves the way for randomized studies to compare proton beam RT with standard RT.

Bilateral reduction mammoplasty is one of the most common plastic surgery procedures performed in the U.S. This study examines the incidence, management, and prognosis of incidental breast cancer identified in reduction specimens from a large cohort of reduction mammoplasty patients. Breast pathology reports were retrospectively reviewed for evidence of incidental cancers in bilateral reduction mammoplasty specimens from five institutions between 1990 and 2017. A total of 4804 women met the inclusion criteria of this study; incidental cancer was identified in 45 breasts of 39 (0.8%) patients. Six patients (15%) had bilateral cancer. Overall, the maximum diagnosis by breast was 16 invasive cancers and 29 ductal carcinomas in situs. Thirty-three patients had unilateral cancer, 15 (45.5%) of which had high-risk lesions in the contralateral breast. Twenty-one patients underwent mastectomy (12 bilateral and nine unilateral), residual cancer was found in 10 in 25 (40%) therapeutic mastectomies. Seven patients did not undergo mastectomy received breast radiation. The median follow-up was 92 months. No local recurrences were observed in the patients undergoing mastectomy or radiation. Three of 11 (27%) patients who did not undergo mastectomy or radiation developed a local recurrence. The overall survival rate was 87.2% and disease-free survival was 82.1%. Patients undergoing reduction mammoplasty for macromastia have a small but definite risk of incidental breast cancer. The high rate of bilateral cancer, contralateral high-risk lesions, and residual disease at mastectomy mandates thorough pathologic evaluation and careful follow-up of these patients. Mastectomy or breast radiation is recommended for local control given the high likelihood of local recurrence without either.

Radiofrequency identification (RFID) tag localization (TL) is a technique of localizing non-palpable breast lesions that can be performed prior to surgery. We sought to evaluate whether TL is comparable to wire localization (WL) in regard to specimen size, operative time, and re-excision rate. A retrospective cohort analysis was performed on TL and WL excisional biopsies and lumpectomies performed by 5 surgeons at 2 institutions. Cases were stratified by surgery type and surgical indication. Associations between localization technique and specimen volume, operative time, and re-excision rate were assessed by univariate and multivariate analyses. A total of 503 procedures were included, 147 TL (29.2%) and 356 WL (70.8%). Nineteen (12.9%) RFID tags were placed before surgery, ranging 1–22 days. All intended targets were removed. TL and WL excisional biopsy and lumpectomy specimen volumes were similar (p = 0.560 and 0.494). TL and WL excisional biopsy and lumpectomy + SLNB operative times were similar (p = 0.152 and 0.158), but TL lumpectomies without SLNB took longer than WL (57 min vs 49 min; p = 0.027). Re-excision rates were similar by surgical procedure (p = 0.615), surgical indication (DCIS p = 0.145; invasive carcinoma p = 0.759), and confirmed by multivariable analysis (OR 0.754, 95% CI 0.392–1.450; p = 0.397). TL has similar surgical outcomes to WL with added benefit that TL can occur prior to the day of surgery. TL is an acceptable alternative to WL and should be considered for non-palpable breast lesions.

Objectives The study’s goals were to characterize decisional conflict and preparedness for making the decision about having CPM among breast cancer patients considering CPM who do not carry cancer-predisposing mutation and to evaluate correlates of decisional conflict and preparedness. Methods 93 women considering CPM completed a survey of decisional conflict and preparedness for the CPM decision, knowledge, perceived risk, self-efficacy, reasons for CPM, input from others and discussion with the doctor about CPM, and cancer worry. Results Between 8% and 27% of women endorsed elevated decisional conflict. Most women were satisfied with preparatory information that they were provided. Knowledge was low. Top reasons for choosing CPM were the desire for peace of mind, lowering the chance of another breast cancer, and improving survival. Conclusions Decisional conflict is elevated in a subset of patients considering CPM. A more well-informed decision may be fostered by a comprehensive discussion about CPM with the patient’s clinician, fostering self-efficacy in managing cancer worry, and helping patients understand their motivations for CPM. Practice implications Clinicians working with breast cancer patients considering CPM should discuss the CPM decision, foster self-efficacy in managing cancer worry, and help patients understand their motivations for the surgery.

Background: The addition of pertuzumab to trastuzumab and chemotherapy significantly improves the pathologic complete response (pCR) rate in HER2+ localized breast cancer in the preoperative setting. Although many patients are converted to breast conserving therapy (BCT) candidates by neoadjuvant HER2-directed therapy, a significant proportion opt for a mastectomy for various reasons. Among mastectomy procedures, nipple sparing mastectomy (NSM) is frequently chosen instead of non-nipple sparing mastectomy (NNSM). In this study, we evaluated the surgical and long-term outcomes of HER2+ patients receiving neoadjuvant pertuzumab-containing regimens. Methods: We performed a retrospective review of localized breast cancer patients treated with neoadjuvant pertuzumab-containing regimens from 2011 to 2016, who underwent BCT or mastectomy at an academic institution and two community-based practices. Disease characteristics, treatment regimens, surgical outcomes, and recurrence data were extracted from the electronic medical records. Results: Among 90 patients with stage II-III HER2+ breast cancer, 45 received AC-THP (50.0%), 26 received THP (with adjuvant AC) (29.0%), and 19 received TCHP (21.0%). The majority of patients had grade 3 tumors (61.1%), clinical stage II disease (80.0%), invasive ductal carcinoma (86.7%), and ER+ disease (65.6%). Thirty-seven (41.0%) patients underwent BCT and 53 (59.0%) patients underwent mastectomy. Among the mastectomy patients, 38 (71.7%) patients underwent bilateral mastectomies, specifically 33 (62.0%) patients underwent a NSM and 20 (38.0%) patients underwent a NNSM. The type of surgery that patients underwent stratified by type of neoadjuvant regimen is outlined in the Table 1 below. Most patients who underwent BCT and mastectomy received radiation, including 36 (97.3%) BCT, 24 (72.7%) NSM, and 18 (95.0%) NNSM. Over a median follow-up period of 33 months, 6 patients (6.7%) had recurrences with 2 (2.2%) local recurrences and 4 (4.4%) distant recurrences. The 2 local recurrences occurred in one patient who underwent BCT and one patient who underwent NNSM followed by post-mastectomy radiation. Conclusions: Among mastectomy patients, NSM was more commonly pursued than NNSM. Rates of local recurrence following pertuzumab-containing regimens for HER2-positive localized breast cancer were low overall, regardless of the type of surgery. Data on plastic surgery approaches and complication rates will be presented at the meeting. Table 1.Type of surgery in patients receiving neoadjuvant HER2-directed therapy. AC-THP (N = 45)TCHP (N = 19)THP (N = 26)BCT46.7%47.4%26.9%NNSM26.7%10.5%23.1%NSM26.7%42.1%50.0% Citation Format: Haddad SA, Spring LM, Jimenez RB, Vidula N, Comander A, Shin JA, Coopey SB, Gadd MA, Hughes KS, Taghian A, Smith BL, Isakoff SJ, Moy B, Bardia A, Specht MC. Surgical and long-term outcomes of patients receiving neoadjuvant pertuzumab-containing regimens for HER2-positive localized breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-14-19.

Significance: Surgery is often paramount in the management of many solid organ malignancies because optimal resection is a major factor in disease-specific survival. Cancer surgery has multiple challenges including localizing small lesions, ensuring negative surgical margins around a tumor, adequately staging patients by discriminating positive lymph nodes, and identifying potential synchronous cancers. Intraoperative molecular imaging (IMI) is an emerging potential tool proposed to address these issues. IMI is the process of injecting patients with fluorescenttargeted contrast agents that highlight cancer cells prior to surgery. Over the last 5 to 7 years, enormous progress has been achieved in tracer development, near-infrared camera approvals, and clinical trials. Therefore, a second biennial conference was organized at the University of Pennsylvania to gather surgical oncologists, scientists, and experts to discuss new investigative findings in the field. Our review summarizes the discussions from the conference and highlights findings in various clinical and scientific trials.Aim: Recent advances in IMI were presented, and the importance of each clinical trial for surgical oncology was critically assessed. A major focus was to elaborate on the clinical endpoints that were being utilized in IMI trials to advance the respective surgical subspecialties.Approach: Principal investigators presenting at the Perelman School of Medicine Abramson Cancer Center's second clinical trials update on IMI were selected to discuss their clinical trials and endpoints.Results: Multiple phase III, II, and I trials were discussed during the conference. Since the approval of 5-ALA for commercial use in neurosurgical malignancies, multiple tracers and devices have been developed to address common challenges faced by cancer surgeons across numerous specialties. Discussants also presented tracers that are being developed for delineation of normal anatomic structures that can serve as an adjunct during surgical procedures.Conclusions: IMI is increasingly being recognized as an improvement to standard oncologic surgical resections and will likely advance the art of cancer surgery in the coming years. The endpoints in each individual surgical subspecialty are varied depending on how IMI helps each specialty solve their clinical challenges. (C) The Authors. Published by SPIE under a Creative Commons Attribution 4.0 Unported License.

PURPOSE: We sought to determine whether smartphone GPS data uncovered differences in recovery after breast-conserving surgery (BCS) and mastectomy, and how these data aligned with self-reported quality of life (QoL). METHODS: In a prospective pilot study, adult smartphone-owners undergoing breast surgery downloaded an application that continuously collected smartphone GPS data for 1 week preoperatively and 6 months postoperatively. QoL was assessed with the Short-Form-36 (SF36) via smartphone delivery preoperatively and 4 and 12 weeks postoperatively. Endpoints were trends in daily GPS-derived distance traveled and home time, as well as SF36 Physical (PCS) and Mental Component Scores (MCS) comparing BCS and mastectomy patients. RESULTS: Thirty-one patients were included. Sixteen BCS and fifteen mastectomy patients were followed for a mean of 201 (SD 161) and 174 (107) days, respectively. There were no baseline differences in demographics, PCS/MCS, home time, or distance traveled. Through 12 weeks postoperatively, mastectomy patients spent more time at home [e.g., week 4: 16.7 h 95%CI (14.3,19.6) versus 11.0 h (9.4,12.9), p < 0.001] and traveled shorter distances [e.g., week 4: 52.5 km 95%CI (36.1,76.0) versus 107.7 km (75.8–152.9), p = 0.009] compared with BCS patients. There were no significant QoL differences throughout the study as measured by the MCS [e.g., week 4 difference: 7.83 95%CI (−9.02,24.7), p = 0.362] or PCS [e.g., week 4 difference: 8.14 (−6.67,22.9), p = 0.281]. GPS and QoL trends were uncorrelated (< ± 0.26, p > 0.05). CONCLUSIONS: Differences in BCS and mastectomy recovery were successfully captured using smartphone GPS data. These data may describe currently unmeasured aspects of physical and mental recovery, which could supplement traditional and QoL outcomes to inform shared decision-making.

Purpose:While various studies have highlighted the prognostic significance of pathologic complete response (pCR) after neoadjuvant chemotherapy (NAT), the impact of additional adjuvant therapy after pCR is not known.Experimental Design:PubMed was searched for studies with NAT for breast cancer and individual patient-level data was extracted for analysis using plot digitizer software. HRs, with 95% probability intervals (PI), measuring the association between pCR and overall survival (OS) or event-free survival (EFS), were estimated using Bayesian piece-wise exponential proportional hazards hierarchical models including pCR as predictor.Results:Overall, 52 of 3,209 publications met inclusion criteria, totaling 27,895 patients. Patients with a pCR after NAT had significantly better EFS (HR = 0.31; 95% PI, 0.24–0.39), particularly for triple-negative (HR = 0.18; 95% PI, 0.10–0.31) and HER2+ (HR = 0.32; 95% PI, 0.21–0.47) disease. Similarly, pCR after NAT was also associated with improved survival (HR = 0.22; 95% PI, 0.15–0.30). The association of pCR with improved EFS was similar among patients who received subsequent adjuvant chemotherapy (HR = 0.36; 95% PI, 0.19–0.67) and those without adjuvant chemotherapy (HR = 0.36; 95% PI, 0.27–0.54), with no significant difference between the two groups (P = 0.60).Conclusions:Achieving pCR following NAT is associated with significantly better EFS and OS, particularly for triple-negative and HER2+ breast cancer. The similar outcomes with or without adjuvant chemotherapy in patients who attain pCR likely reflects tumor biology and systemic clearance of micrometastatic disease, highlighting the potential of escalation/deescalation strategies in the adjuvant setting based on neoadjuvant response.See related commentary by Esserman, p. 2771

PURPOSE: Based on improvement in pathologic complete response (pCR) in NeoSphere and TRYPHAENA studies, the FDA approved neoadjuvant pertuzumab for HER2+ localized breast cancer. These studies demonstrated high pCR rates with THP (docetaxel+HP), FEC (5-fluorouracil, epirubicin and cyclophosphamide)-THP, and TCHP (docetaxel, carboplatin+HP). However, in the United States, doxorubicin/cyclophosphamide (AC) is favored over FEC despite no data comparing neoadjuvant AC-THP with AC-TH or TCHP. Here we report outcomes for patients with localized HER2+ breast cancer treated with pertuzumab-containing neoadjuvant regimens and AC-TH. METHODS: We reviewed clinicopathological characteristics of patients with HER2+ breast cancer (Stage I-III) treated with either a neoadjuvant pertuzumab-containing regimen or dosedense (dd) AC-TH, from 2011 to 2016 at a large academic medical institution and two affiliated community sites. pCR was defined as ypT0/is ypN0. Fisher’s exact test and logistic regression analysis were used for statistical analysis. RESULTS: In this study (N = 121), pCR was numerically higher with pertuzumab based regimens, including ddAC-THP (60%), TCHP (63%), THP (55%), as compared with ddAC-TH (46%). THP resulted in significantly less cycle delays due to toxicity compared to the other regimens (p=0.02). THP also resulted in the least dose reductions, lowest rate of hospitalization, and lowest rate of treatment discontinuation. CONCLUSIONS: Pertuzumab based regimens, including THP, resulted in higher pCR rates as compared to ddAC-TH, with the THP regimen associated with the best tolerability among patients with localized HER2+ breast cancer. Given the various neoadjuvant regimens, additional studies are needed to determine optimal treatment sequencing and escalation/de-escalation strategies to personalize neoadjuvant regimens for localized HER2+ breast cancer.

Background: Obtaining tumor-free margins is critical for local control in breast conserving surgery. Currently, 20-40% of lumpectomy patients have positive margins that require surgical re-excision. We assessed the LUM Imaging System for real-time, intraoperative detection of residual tumor in breast cancer patients. The LUM System has the particular advantage of assessing in vivo lumpectomy cavity walls rather than excised specimens, to enable more accurate excision of residual tumor. Methods: Lumpectomy cavity walls of patients undergoing lumpectomy for invasive breast cancer or ductal carcinoma in situ (DCIS), were assessed intraoperatively using the LUM Imaging System (Lumicell Inc., Wellesley MA). LUM015, a cathepsin-activatable fluorescent agent, was given IV 4±2 hrs prior to surgery. Areas of fluorescence generated at potential sites of residual tumor in lumpectomy cavities were evaluated with a sterile hand-held device, displayed on a monitor, excised and correlated with histopathology. Results: In vivo lumpectomy cavities were imaged with the LUM Imaging System in 60 breast cancer patients. 5 were imaged without dye. 55 received LUM015 dye preoperatively and were scanned intraoperatively. Median age was 60 years (range 44-79). Mean tumor size was 1.2cm (0.06-3.5cm) with 71% invasive cancers, 29% DCIS. The test set included 569 cavity margin surfaces assessed intraoperatively and excised. Image acquisition for each margin took approximately 1 second. The LUM Imaging System showed 100% sensitivity and 73% specificity for detection of tumor Conclusions: The LUM Imaging System allows real-time identification of residual tumor in the lumpectomy cavity of breast cancer patients. No sites of residual tumor were missed. Additional studies are underway to optimize this approach for reducing positive margins and second surgeries in breast cancer patients. Table: Margin results in 8 patients with positive margins on initial lumpectomy specimenPositive lumpectomy margin histopathologyLUM cavity wall result (+/- for tumor)Tumor found at re-excisionDCIS++DCIS+-DCIS++IDC++ (Mastectomy)ILC++ (Mastectomy)DCIS+-IDC--DCIS-- Citation Format: Lanahan CR, Gadd MA, Specht MC, Ferrer J, Tang R, Rai U, Merrill AL, Biernacka A, Brachtel E, Smith BL. Real-time, intraoperative detection of residual breast cancer in lumpectomy cavity margins using the LUM imaging system: Results of a feasibility study [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-12-05.

Background Breast-conserving surgery is a critical first step in treatment with the goal of removing all cancer cells while minimizing the removal of healthy tissue. 15% to 25% or more of lumpectomy patients have positive margins and require a second surgery to achieve negative margins and reduce the risk of local recurrences. These positive margins are poorly predictive (35% PPV) of cancer left in the cavity, so most second surgeries find no residual cancer. Better detection tools are needed to identify residual cancer in real time during the initial lumpectomy to reduce the number of second operations. LUM015 is a protease-activated fluorescent imaging agent that accumulates in tumor cells and tumor associated macrophages. The LUM Imaging System camera visualizes the intravenously injected LUM015 in the lumpectomy cavity via a hand-held wide field detector and proprietary tumor detection software. This imaging system was previously tested in multiple single-site studies and a large, prospective multi-site study that enrolled 234 patients and showed good ability to detect residual cancer in the lumpectomy cavity. Trial Design The current prospective, multi-center, randomized, blinded study was designed to demonstrate the clinical efficacy, system accuracy, and safety of the LUM Imaging System. It aims to identify residual cancer in the lumpectomy cavity to reduce the rates of positive margins. This study seeks to enroll women with primary invasive breast cancer (IBC), ductal carcinoma in situ (DCIS) or a combination of IBC/DCIS undergoing a lumpectomy for their breast malignancy. Approximately 310 women at 14 US medical centers will be enrolled. This study is powered by an event-driven design that requires 70 patients to be enrolled that have a ‘truth-standard positive' event, which is the identification of cancer in a protocol defined tissue type. To be eligible, patients must not have a history of allergic reaction to polyethylene glycol, intravenous contrast agents, or systemic therapies to treat their cancer. Use of blue dyes before imaging with the LUM System are not allowed. LUM015 is injected prior to the lumpectomy procedure. Surgeons perform standard of care (SOC) lumpectomy and perform blinded intraoperative imaging of the lumpectomy cavity with the LUM Imaging System in regions where SOC shaves will be taken. The patient is then randomized. If the random assignment is to the device arm, the surgeon is directed to excise margins that the LUM System indicates are positive for cancer. Pathologists are blinded to the type of tissue removed when conducting the pathology assessment. Patient reported outcome data is collected as a quality-of-life survey before and after the subject's lumpectomy. Additional detailed eligibility criteria are in the protocol. To date, 166 patients have participated in this trial. This trial is registered as NCT03686215. Citation Format: Jorge Ferrer, David Carr, Peter Blumencranz, Irene Wapnir, Donna Dyess, Shelly Hwang, Nayana Dekhne, Daleela Dodge, Beth-Ann Lesnikoski, Kelly Hunt, Patricia Clark, Stephanie Valente, M. Catherine Lee, Lynne Clark, Brian Schlossberg, Sean Madden, Alejandra Rodriguez, Kate Smith, Manna Chang, Barbara Smith. Pivotal Study of the LUM Imaging System for assisting intraoperative detection of residual cancer in the tumor bed of female patients with breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT259.

Background: Microscopically tumor-free lumpectomy margins are critical for safe breast conserving surgery. With current tools, 15% to 25% of lumpectomies have positive margins and require a second surgical procedure increasing cost and patient discomfort. In addition, current lumpectomy margin assessment techniques show poor performance in predicting residual disease at re-excision, with a PPV of 35%. Better detection tools are needed to identify residual cancer during the initial lumpectomy and reduce second operations. LUM015 is a protease-activated fluorescent imaging agent that accumulates in tumor cells and tumor associated macrophages injected intravenously before surgery. The LUM Imaging System visualizes the activated LUM015 in the lumpectomy cavity via a hand-held wide field detector and proprietary tumor detection software. This system was previously tested in multiple single-site studies and a large, prospective 234 patient multi-site study that demonstrated successful detection of residual lumpectomy cavity. Initial studies excluded the approximately 20% of breast cancer patients receiving neoadjuvant therapy. Patchy tumor cell death with preoperative therapy can leave small, multifocal deposits of tumor in visible on pre-operative imaging and not palpable or visible during surgery. In this study, we evaluated the LUM Imaging System in this patient population. Trial Design: A prospective, multi-center study was designed to test feasibility of the LUM Imaging System in lumpectomy surgery after neoadjuvant therapy. This will evaluate potential impact of microenvironment changes after treatment and tumor cell death on tumor detection algorithms. Algorithms will be refined if needed. 10 patients will address this objective. A second cohort will further evaluate the feasibility, safety and efficacy of the LUM Imaging System in this patient population. 114 patients with invasive breast cancer and/or ductal carcinoma in situ will enroll at 5 US medical centers. Exclusions include patients allergic to polyethylene glycol or intravenous contrast agents. Use of blue node mapping dyes before imaging with the LUM015 is not allowed. After excision of the main lumpectomy specimen, patients are randomized 1:3 to device or control arms. In the device arm, the cavity is imaged and margins with LUM015 signal are excised. In the control arm, the surgeon records images within the cavity but no LUM015-directed margins are excised. Final comprehensive shave margins are removed in both arms to evaluate extent of residual disease after the use of the LUM Imaging System or after standard lumpectomy resection. Cohort 1 has completed enrollment. No patients have enrolled into cohort 2. This trial is registered as NCT04440982. This study is funded by the NIH through a R01 research grant issued to Massachusetts General Hospital. Citation Format: Jorge Ferrer, Bridget Kelly, Alexandra Webster, Brian Schlossberg, Kate Smith, Manna Chang, Barbara Smith. Feasibility study to evaluate performance of the Lum Imaging System for intraoperative detection of residual tumor in patients with breast cancer receiving neoadjuvant therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT245.

Purpose: Breast cancer in young women is associated with an aggressive tumor biology and higher risk of recurrence. Pathologic complete response (pCR) after neoadjuvant therapy has been shown to be a surrogate marker for disease-free survival (DFS) and overall survival (OS), but the association between pCR and survival outcomes in young women with breast cancer is not well described. Methods: This study included women aged ≤40 years at diagnosis who received neoadjuvant chemotherapy (NAC) for stage II-III invasive breast cancer between 1998 and 2014 at Massachusetts General Hospital. Outcomes were compared between patients who achieved pCR (ypT0/is, ypN0) and those with residual disease. Results: A total of 170 young women were included in the analytical data set, of which 53 (31.2%) achieved pCR after NAC. The 5-year DFS rate for patients with and without pCR was 91% versus 60%, respectively (P

Background Nipple-sparing mastectomy (NSM) has gained popularity for breast cancer treatment and prevention. There are limited data about long-term oncologic safety of this procedure. Study Design We reviewed oncologic outcomes of consecutive therapeutic NSM at a single institution. Nipple-sparing mastectomy was offered to patients with no radiologic or clinical evidence of nipple involvement. Results There were 2,182 NSM performed from 2007 to 2016. Long-term outcomes were assessed in the 311 NSM performed in 2007 to 2012 for Stages 0 to 3 breast cancer; 240 (77%) NSM were for invasive cancer and 71 (23%) were for ductal carcinoma in situ. At 51 months median follow-up, 17 patients developed a recurrence of their cancer. Estimated disease-free survival was 95.7% at 3 years and 92.3% at 5 years. There were 11 (3.7%) locoregional recurrences and 8 (2.7%) distant recurrences; 2 patients had simultaneous locoregional and distant recurrences. There were 2 breast cancer-related deaths in patients with isolated distant recurrences. No patient in the entire 2,182 NSM cohort has had a recurrence in the retained nipple-areola complex. Conclusions Rates of locoregional and distant recurrence are acceptably low after nipple-sparing mastectomy in patients with breast cancer. No patient in our series has had a recurrence involving the retained nipple areola complex.

The aim of this study was to investigate the influence of age at diagnosis of atypical hyperplasia (“atypia”, ductal [ADH], lobular [ALH], or severe ADH) on the risk of developing subsequent invasive breast cancer or ductal carcinoma in situ (DCIS). Using standard survival analysis methods, we retrospectively analyzed 1353 women not treated with chemoprevention among a cohort of 2370 women diagnosed with atypical hyperplasia to determine the risk relationship between age at diagnosis and subsequent breast cancer. For all atypia diagnoses combined, our cohort showed a 5-, 10-, and 15-year risk of invasive breast cancer or DCIS of 0.56, 1.25, and 1.30, respectively, with no significant difference in the (65,75] year age group. For women aged (35,75] years, we observed no significant difference in the 15-year risk of invasive breast cancer or DCIS after atypical hyperplasia, although the baseline risk for a 40-year-old woman is approximately 1/8 the risk of a 70-year-old woman. The risks associated with invasive breast cancer or DCIS for women in our cohort diagnosed with ADH, severe ADH, or ALH, regardless of age, were 7.6% (95% CI 5.9–9.3%) at 5 years, 25.1% (20.7–29.2%) at 10 years, and 40.1% (32.8–46.6%) at 15 years. In contrast to current risk prediction models (e.g., Gail, Tyrer-Cuzick) which assume that the risk of developing breast cancer increases in relation to age at diagnosis of atypia, we found the 15-year cancer risk in our cohort was not significantly different for women between the ages of 35 (excluded) and 75. This implies that the “hits” received by the breast tissue along the “high-risk pathway” to cancer might possibly supersede other factors such as age.

Introduction: Breast cancer treatment costs are rising, and identification of high-value oncology treatment strategies is increasingly needed. We sought to determine the potential cost savings associated with an evidence-based radiation treatment (RT) approach among women with early-stage breast cancer treated in the United States. Patients and Methods: Using the National Cancer Database, we identified women with T1-T2 N0 invasive breast cancers treated with lumpectomy during 2011. Adjuvant RT regimens were categorized as conventionally fractionated whole-breast irradiation, hypofractionated whole-breast irradiation, and omission of RT. National RT patterns were determined, and RT costs were estimated using the Medicare Physician Fee Schedule. Results: Within the 43,247 patient cohort, 64% (n = 27,697) received conventional RT, 13.3% (n = 5,724) received hypofractionated RT, 1.1% (n = 477) received accelerated partial-breast irradiation, and 21.6% (n = 9,349) received no RT. Among patients who were eligible for shorter RT or omission of RT, 57% underwent treatment with longer, more costly regimens. Estimated RT expenditures of the national cohort approximated $420.2 million during 2011, compared with $256.2 million had women been treated with the least expensive regimens for which they were safely eligible. This demonstrated a potential annual savings of $164.0 million, a 39% reduction in associated treatment costs. Conclusion: Among women with early-stage breast cancer after lumpectomy, use of an evidence-based approach illustrates an example of high-value care within oncology. Identification of high-value cancer treatment strategies is critically important to maintaining excellence in cancer care while reducing health care expenditures.

This abstract was withdrawn by the authors.

Purpose Giving an additional radiation dose to the incision or chest wall has been a practice, but it has never been studied in a randomized setting, and it might lead to inferior cosmetic outcomes. This study aims to evaluate whether delivery of a chest wall boost (CWB) to the mastectomy scar or chest wall is independently associated with reconstruction complications and to assess its disease control efficacy in the setting of breast reconstruction. Methods and Materials We conducted a retrospective chart review of 746 patients with breast cancer who underwent mastectomy, breast reconstruction, and PMRT; all underwent treatment at our institution during 1997 to 2016. Various reconstruction techniques were used among this cohort including autologous reconstruction, single-stage direct-to-implant reconstruction, and 2-stage tissue expander implant. Cohorts were divided by administration of CWB. The primary objective was comparing the rate of reconstruction complications including skin necrosis, fat necrosis and infection between groups. Subgroup analysis for patients with implant-based reconstruction was performed to evaluate the effect of CWB on implant-related complications such as capsular contracture, implant exposure, and implant failure. The secondary objective was comparison of the cumulative incidence of local failure between groups overall and within clinically high-risk subgroups. Results The median follow-up was 5.2 years. Most clinicopathologic features were well balanced between the 379 (51%) patients who received CWB and the 367 (49%) who did not. On multivariate analysis, CWB was significantly associated with infection, skin necrosis, and implant exposure. For implant reconstruction patients, CWB independently increased risks of implant failure. CWB administration was not associated with local tumor control benefits, even in high-risk subgroups. Conclusions Our findings suggest that omission of chest wall boost in postmastectomy radiation improves breast reconstruction outcomes without compromising local tumor control.

This study examined the effects of an enhanced recovery program on inpatient opioid requirements and hospital length of stay (LOS) for mastectomy patients undergoing immediate reconstruction. An enhanced recovery program for patients undergoing mastectomy with immediate tissue expander (TE) or implant reconstruction was evaluated by comparing a contemporary cohort of 611 patients in 2016–2018 with a historical cohort of 188 patients in 2010. Opioid use and LOS were compared over time and stratified by laterality, mastectomy type, axillary procedure, and reconstruction. Associations were assessed by uni- and multivariate analyses. In 2010, 95.2% of patients required intravenous (IV) opioids, with a last dose 15.5 h after completion of surgery, compared with 68.7% of patients in 2016–2018, with a last dose 1.8 h after surgery (p

Background Nipple-sparing mastectomies (NSMs) preserve the intact nipple, including nipple duct orifices. Retained orifices might remain patent and communicate with the underlying reconstruction. We report the incidence and outcomes of nipple discharge after NSM in pregnant and nonpregnant women. Patients and Methods Retrospective review of all NSMs at our institution from June 2007 to June 2018 was performed. Subsequent pregnancies and nipple discharge were documented. Patient demographic, operative, histopathology, and cancer treatment data were collected. Descriptive analysis was performed for patients who developed nipple discharge. Results From June 2007 to June 2018, 2778 NSM procedures were performed in 1620 patients, with a mean age of 48 (range, 20-80) years. Fifteen hundred sixty-eight NSMs were therapeutic and 1210 were for risk reduction. Thirty-three subsequent pregnancies were observed in 27 patients, with a mean age of 33 (range, 26-42) years at NSM. Bilateral or unilateral discharge occurred in 6 of 27 (22%) postpartum patients and resolved spontaneously. At 54 months mean follow-up after NSM (range, 16-98 months) and 23 (range, 1-61) months after delivery, no local-regional recurrences were observed. In 1593 patients without subsequent pregnancy, there were 4 patients (0.25%) treated with bilateral NSM with subsequent unilateral watery nipple discharge. There was no evidence of associated malignancy on physical exam, imaging, or cytology, and with 55 to 110 months follow-up, no new or recurrent cancers have been observed. Conclusion Despite extensive removal of nipple and subareolar duct tissue during NSM, milky nipple discharge is possible postpartum. Watery, acellular discharge occurs rarely in nonpregnant patients. To date, no patient with discharge has developed a local recurrence or new breast cancer.

The use of contralateral prophylactic mastectomy (CPM) is increasing among breast cancer patients who are at average or “sporadic” risk for contralateral breast cancer. Because CPM provides no survival benefit for these patients, it is not medically recommended for them. Decision support aids may facilitate more informed, higher quality CPM decision. The purpose of this study was to evaluate the feasibility and acceptability of B-Sure, an online decision support aid to facilitate informed decisions regarding CPM, and to compare the impact of B-Sure in increasing CPM knowledge, reducing decisional conflict, and increasing preparedness to make the CPM decision among breast cancer patients at sporadic risk who are considering CPM. Ninety-three patients with unilateral, nonhereditary breast cancer considering CPM completed a baseline survey, were randomized to receive B-Sure or Usual care, and completed a 4-week follow-up survey assessing decisional conflict, preparedness to make the CPM decision, and CPM knowledge as well as self-efficacy, perceived risk, worry, CPM motivations, and the surgical decision. Study participation was high. B-Sure was viewed by almost 80% of the participants and was evaluated positively. At follow-up, patients assigned to B-Sure reported significantly higher clarity regarding the personal values relevant to the CPM decision and higher knowledge about CPM. B-Sure had smaller effects on other aspects of decisional conflict. B-Sure improved CPM knowledge and reduced decisional conflict. Patients considering CPM may benefit from an online decision support aid, but may be sensitive to approaches that they perceive as biased against CPM.

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. Purpose: Mammoplasty removes random samples of breast tissue from asymptomatic women providing a unique method for evaluating background prevalence of breast pathology in normal population. Our goal was to identify the rate of atypical breast lesions and cancers in women of various ages in the largest mammoplasty cohort reported to date. Methods: We analyzed pathologic reports from patients undergoing bilateral mammoplasty, using natural language processing algorithm, verified by human review. Patients with a prior history of breast cancer or atypia were excluded. Results: A total of 4775 patients were deemed eligible. Median age was 40 (range 13–86) and was higher in patients with any incidental finding compared to patients with normal reports (52 vs. 39 years, p = 0.0001). Pathological findings were detected in 7.06% (337) of procedures. Benign high-risk lesions were found in 299 patients (6.26%). Invasive carcinoma and ductal carcinoma in situ were detected in 15 (0.31%) and 23 (0.48%) patients, respectively. The rate of atypias and cancers increased with age. Conclusion: The overall rate of abnormal findings in asymptomatic patients undergoing mammoplasty was 7.06%, increasing with age. As these results are based on random sample of breast tissue, they likely underestimate the prevalence of abnormal findings in asymptomatic women.

Young age at breast cancer diagnosis has been associated with increased risk of recurrence and mortality. We reevaluated this assumption in a large, modern cohort of women diagnosed with breast cancer at age ≤40 years. We identified women with breast cancer at age ≤40 years at a single institution from 1996–2008. We assessed locoregional recurrence (LRR), distant recurrence, disease-free survival (DFS), and overall survival (OS), and correlated patient and tumor characteristics with outcomes. We identified 584 women aged ≤40 years with breast cancer. Median age was 37 years, and median follow-up was 124 months; 61.5 % were stages 0–I and 38.5 % were stages II–III. Overall, 57.4 % had lumpectomies and 42.5 % mastectomies. DFS was 93 % at 5 years and 84.5 % at 10 years. OS was 93 % at 5 years and 86.5 % at 10 years. On multivariate analysis, worse DFS was associated with positive nodes (p = 0.002); worse OS was associated with larger tumor size (p = 0.042). When stratified by lumpectomy versus mastectomy, there were no significant differences in survival or recurrence. For lumpectomy patients, DFS was 96 % at 5 years and 88 % at 10 years; OS was 96 % at 5 years and 89 % at 10 years. For mastectomy patients, DFS was 89.5 % at 5 years and 79 % at 10 years; OS was 90 % at 5 years and 83 % at 10 years. Lumpectomy LRR rates were 1 % at 5 years and 4 % at 10 years. Mastectomy LRR rates were 3.5 % at 5 years and 8.7 % at 10 years. Outcomes for women with breast cancer at age ≤40 years have improved. Lumpectomy recurrence rates are low, suggesting that lumpectomy is oncologically safe for young breast cancer patients.

When a nipple margin of a nipple-sparing mastectomy (NSM) contains malignancy, current practice includes removal of the nipple or nipple areola complex (NAC). We evaluated rates and trends of positive nipple margins, subsequent management, and oncologic outcomes.A retrospective chart review of all NSM at our institution from 2007 to 2014 was performed. A descriptive analysis was performed of patients with positive nipple/subareolar margins.Among 1,326 NSM, 43 of 642 (6.7%) therapeutic and 3 of 684 (0.4%) prophylactic NSM had positive nipple margins. Nipple or NAC excision was performed for 39 of 46 (85%) positive nipple margins: 20 of 39 (51%) had nipple only and 19 of 39 (49%) had the entire NAC excised. Practice evolved to remove only the nipple and retain the areola for positive nipple margins: in 2007 to 2011, 7 of 17 (41%) underwent nipple-only excision compared with 14 of 22 (64%) in 2012 to 2014. Among 39 excised nipples/NAC, 28 (72%) contained no residual malignancy, while 8 contained ductal carcinoma in situ (DCIS), 2 had invasive lobular carcinoma, and 1 had invasive ductal carcinoma. With experience, rates of positive nipple margins for therapeutic NSM decreased from 11% (17 of 160) in 2007 to 2011 to 5.4% (26 of 482) in 2012 to 2014 (p0.05). At 36 month median follow-up, there were no recurrences in the nipple/NAC.Early results suggest that excision of the nipple with retention of the areola is a safe approach for management of a positive nipple margin after NSM. With experience, low rates of positive nipple margins are possible in therapeutic NSM. Overall risk of nipple/NAC recurrence after NSM remains extremely low.

Standard specimen mammography (SSM) is performed in the radiology department after wire-localized excision of non-palpable breast lesions to confirm the presence of the target and evaluate margins. Alternatively, intra-operative specimen mammography (ISM) allows surgeons to view images in the operating room (OR). We conducted a randomized study comparing ISM and SSM. Women undergoing wire-localized excision for breast malignancy or imaging abnormality were randomized to SSM or ISM. For SSM, the specimen was transported to the radiology department for imaging and interpretation. For ISM, the specimen was imaged in the OR for interpretation by the surgeon and sent for SSM. Interpretation time was from specimen leaving OR until radiologist interpretation for SSM and from placement in ISM device until surgeon interpretation for ISM. Procedure and interpretation times were compared. Concordance between ISM and SSM for target and margins was evaluated. 72 patients were randomized, 36 ISM and 36 SSM. Median procedure times were similar, 48.5 (17-138) min for ISM, and 54 (17-40) min for SSM (p = 0.72), likely since specimens in both groups traveled to radiology for SSM. Median interpretation time was significantly shorter with ISM, 1 (0.5-2.0) and 9 (4-16) min for ISM and SSM, respectively (p

Background: For many women with breast cancer, breast-conserving surgery is a critical first step in treatment with the goal of removing all cancer cells while minimizing the removal of healthy tissue. 15% to 25% or more of lumpectomy patients have positive margins and require a second surgery to achieve negative margins and reduce the risk of local recurrences. These positive margins are poorly predictive (35% PPV) of cancer left in the cavity, so most second surgeries find no residual cancer. Better detection tools are needed to identify residual cancer in real time during the initial lumpectomy to reduce the number of second operations. LUM015 is a protease-activated fluorescent imaging agent that accumulates in tumor cells and tumor associated macrophages. The LUM Imaging System camera visualizes the intravenously injected LUM015 in the lumpectomy cavity via a hand-held wide field detector and proprietary tumor detection software. This imaging system was previously tested in multiple single-site studies and a large, prospective multi-site study that enrolled 234 patients and showed good ability to detect residual cancer in the lumpectomy cavity. Trial Design: The current prospective multi-center, two-arm randomized, blinded study was designed to demonstrate the clinical efficacy, system accuracy, and safety of the LUM Imaging System. It aims to identify residual cancer in the lumpectomy cavity in order to reduce the rates of positive margins. This study seeks to enroll women with confirmed primary invasive breast cancer (IBC), ductal carcinoma in situ (DCIS) or a combination of IBC/DCIS undergoing a lumpectomy for their breast malignancy. The planned enrollment is 170 women being treated at fifteen medical centers across the US. To be eligible, patients must not have a history of allergic reaction to polyethylene glycol, intravenous contrast agents, or systemic therapies to treat their cancer. Use of blue dyes before imaging with the LUM System are not allowed. LUM015 is injected prior to the lumpectomy procedure. Surgeons perform standard of care (SOC) lumpectomy and perform blinded intraoperative imaging of the lumpectomy cavity with the LUM Imaging System in any regions where SOC shaves will be taken. The patient is then randomized either the further use of device or not. If the random assignment is to the device arm, the surgeon is directed to excise margins that the LUM System indicates are positive for cancer. Pathologists are blinded to the type of tissue removed when conducting the pathology assessment. Patient reported outcome data is collected as a quality of life survey before and after the subject's surgery. Additional detailed eligibility criteria are listed in the protocol. To date, 22 subjects have participated in this trial. This trial is registered as NCT03686215. Citation Format: Jorge Ferrer, David Carr, Irene Wapnir, Kelly Hunt, Peter Blumencranz, Nayana Dekhne, Daleela Dodge, Donna Lynn Dyess, Shelley Hwang, Stephanie Valente, Lynne Clark, Beth-Ann Lesnikoski, Anees Chagpar, Paticia Clark, Marie Catherine Lee, Brian Schlossberg, Sean Madden, Livia Gjylameti, Manna Chang, Kate Smith, Barbara Smith. Pivotal study of the LUM Imaging System for assisting intraoperative detection of residual cancer in the tumor bed of female patients with breast cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT281.

Obtaining tumor-free surgical margins is critical to prevent recurrence in breast-conserving surgery but it remains challenging. We assessed the LUM Imaging System for real-time, intraoperative detection of residual tumor. Lumpectomy cavity walls and excised specimens of breast cancer lumpectomy patients were assessed with the LUM Imaging System (Lumicell, Inc., Wellesley MA) with and without intravenous LUM015, a cathepsin-activatable fluorescent agent. Fluorescence at potential sites of residual tumor was evaluated with a sterile hand-held probe, displayed on a monitor and correlated with histopathology. Background autofluorescence was assessed in excised specimens from 9 patients who did not receive LUM015. In vivo lumpectomy cavities and excised specimens were then imaged in 15 women undergoing breast cancer surgery who received no LUM015, 0.5, or 1 mg/kg LUM015 (5 women per dose). Among these, 11 patients had invasive carcinoma with ductal carcinoma in situ (DCIS) and 4 had only DCIS. Image acquisition took 1 s for each 2.6-cm-diameter surface. No significant background normal breast fluorescence was identified. Elevated fluorescent signal was seen from invasive cancers and DCIS. Mean tumor-to-normal signal ratios were 4.70 ± 1.23 at 0.5 mg/kg and 4.22 ± 0.9 at 1.0 mg/kg (p = 0.54). Tumor was distinguished from normal tissue in pre-and postmenopausal women and readings were not affected by breast density. Some benign tissues produced fluorescent signal with LUM015. The LUM Imaging System allows rapid identification of residual tumor in the lumpectomy cavity of breast cancer patients and may reduce rates of positive margins.

Background: While the prognostic significance of pathological complete response (pCR) after neoadjuvant chemotherapy is relatively well established, the impact of adjuvant therapy in modulating relationship between pCR and long term outcomes is less clear. The primary objective of this study was to conduct a systematic review of published neoadjuvant chemotherapy studies to comprehensively evaluate the association between pCR with subsequent breast cancer recurrence and mortality, stratified by breast cancer subtypes and adjuvant chemotherapy usage. Methods: Based on PRISMA guidelines, a search of PubMed from inception until September 2016 was performed to identify eligible studies. Inclusion criteria were clinical trials or studies featuring neoadjuvant chemotherapy that reported pCR results as well as recurrence and/or survival. Hazard Ratios (HRs) and 95% probability intervals (PI) were estimated for endpoints using hierarchical models. We obtained the individual patient-level data for statistical analysis using plot digitizer software. Hazard ratios (HRs), with 95% PIs, measuring the association between pCR and OS or recurrence, were estimated using Bayesian piecewise-exponential proportional hazards hierarchical models including pCR as a predictor. Random effects model was utilized to account for between-study variability in baseline hazards and the variability of the pCR effect between studies. P-value of 0.05 was considered statistically significant. Results: A total of 3,209 citations with associated abstracts were reviewed, and 27,895 patients from 52 studies met inclusion criteria. Attainment of pCR, as compared to absence of pCR, was associated with significantly reduced disease recurrence overall (HR 0.31, 95% PI: 0.24-0.39), and in triple negative (HR 0.18, 95% PI: 0.10-0.31), human epidermal growth factor 2-positive (HER2+) (HR 0.32, 95% PI: 0.21-0.47), and trended towards significance for HR+ breast cancer (HR 0.15, 95% PI: 0.02-1.10). Similarly, pCR after neoadjuvant chemotherapy was also associated with reduced mortality overall (HR 0.22, 95% PI: 0.15-0.30), and among all three major disease subtypes. The association of pCR with reduced recurrence was similar among studies where patients received subsequent adjuvant chemotherapy (HR 0.34, 95% PI: 0.18-0.61) and those without adjuvant chemotherapy (95% HR 0.36, PI: 0.27-0.54). The association between magnitude of pCR change and corresponding change in survival will be presented at the meeting. Conclusion: Achieving pCR following neoadjuvant chemotherapy is associated with significantly improved disease recurrence and survival, particularly for triple negative and HER2+ breast cancer. The similar outcomes with/without adjuvant chemotherapy in patients who attain pCR after neoadjuvant chemotherapy likely reflects tumor biology and suggests adjuvant chemotherapy could potentially be abbreviated in certain circumstances, and highlights the need for further research to evaluate clinical utility of escalation/de-escalation strategies in the adjuvant setting based on neoadjuvant response for patients with localized breast cancer. Citation Format: Spring LM, Fell G, Arfe A, Trippa L, Greenup R, Reynolds K, Smith BL, Moy B, Isakoff SJ, Parmigiani G, Bardia A. Pathological complete response after neoadjuvant chemotherapy and impact on breast cancer recurrence and mortality, stratified by breast cancer subtypes and adjuvant chemotherapy usage: Individual patient-level meta-analyses of over 27,000 patients [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS2-03.

The risk of breast cancer in young women diagnosed with atypical hyperplasia and (LCIS) is not well defined. The objectives were to evaluate outcomes and to help determine guidelines for follow-up in this population. A retrospective review of women under age 35 diagnosed with ADH, ALH, LCIS, and severe ADH from 1987 to 2010 was performed. Patient characteristics, pathology and follow-up were determined from chart review. We identified 58 young women with atypical breast lesions. Median age at diagnosis was 31 years (range 19–34). 34 patients had ADH, 11 had ALH, 8 had LCIS, and 5 had severe ADH. 7 (12%) patients developed breast cancer. The median follow-up was 86 months (range 1–298). Median time to cancer diagnosis was 90 months (range 37–231). 4 cancers were on the same side, 3 were contralateral. 4 were IDC, 1 was ILC, and 2 were DCIS. Cancer was detected by screening mammogram in 4 patients, 2 by clinical exam, and 1 unknown. In the entire cohort, 26 (45%) patients had screening mammograms as part of their follow up, 12 patients had only clinical follow up, and 20 had no additional follow up. 13 patients required subsequent biopsies. Young women with atypical breast lesions are at a markedly increased risk for developing breast cancer and should be followed closely. Based on our findings, we recommend close clinical follow-up, MRI starting at age 25 through age 29, and screening mammograms for those over 30 in this high-risk group of patients.

Background In breast conserving surgery, the concordance between lumpectomy margin (LM) status and the status of the corresponding lumpectomy cavity remains uncertain. Methods We analyzed pathology reports of lumpectomies from 2004 to 2006. We included those which contained both ink-directed LM and complete (≥4) separate corresponding shaved cavity margins (SCMs). SCM pathology was used as a surrogate for lumpectomy cavity status, to determine the predictive value of LM for residual disease. Results Pathology from 1,201 pairs of LM and SCM from 242 patients was compared. LM status predicted corresponding lumpectomy cavity status with 50.9% sensitivity, 69.5% specificity, 35% positive predictive value, and 81.4% negative predictive value, giving an overall accuracy of 64.9%. Conclusions Oriented LMs are not reliable for predicting lumpectomy cavity status, and therefore not reliable for directing re-excision. Taking complete, oriented SCMs at the time of lumpectomy may improve accuracy compared with traditional LM assessment.

BACKGROUND: Breast cancer treatment contributes the greatest proportion of cancer-related health care spending in the United States. Locoregional therapy comprises a significant share of these costs. We hypothesized that among eligible women with early-stage breast cancer treated with lumpectomy, evidence-based utilization of hypofractionated whole breast radiation or omission of radiotherapy could substantially reduce cancer-related treatment costs. METHODS: Using the National Cancer Data Base which captures approximately 70% of all newly diagnosed cancers in the United States, we identified 43,247 women with clinically node-negative, T1-T2 invasive breast cancers treated with lumpectomy during 2011. Women with DCIS, those treated with mastectomy, accelerated partial breast irradiation (APBI), or unknown or questionable radiation regimens were excluded. Adjuvant radiation was categorized into the following regimens: conventionally fractionated whole breast irradiation therapy (CF-WBI) [25-40 fractions, 45-66 Gy], hypofractionated whole-breast irradiation (HF-WBI) [15-24 fractions, 40-58 Gy), and lumpectomy without radiation (no RT). Women were considered eligible for no RT if ≥70 years with T1N0, ER+ breast cancers, and for HF-WBI if ≥50 years, with T1-T2 N0 invasive breast cancer. Treatment costs were calculated using Medicare Physician Fee Schedule payment information for 2011, and based on average current procedural codes billed per regimen. Costs per patient were estimated as follows: CF-WBI $13,358.37, HF-WBI $8,327.98, and lumpectomy without RT $0. Actual treatment costs were compared to evidence-based, reduced-cost radiation regimens for which patients were potentially eligible. RESULTS: Median patient age was 63 years (range 19-90). Median tumor size was 1.2 cm. Of the total study cohort, 84.5% was eligible for HF-WBI, and 22.3% for no RT. Among the 36,562 (84.5%) patients eligible for treatment with HF-WBI, 28,383 (77.6%) received radiation therapy. Of these, 22,653 (79.8%) received CF-WBI, 5,289 (18.6%) received HF-WBI, and 441 (1.6%) received accelerated partial breast irradiation (APBI). Among 9,651 women ≥70 years with ER+ tumors eligible for no-RT, 4,245 (44.0%) received CF-WBI, 1,768 (18.3%) received HF-WBI, 153 (1.6%) received APBI, and 3,485 (36.1%) received no RT. 26% of women received the least expensive evidence-based radiation regimen for which they were eligible, while 67% of patients were treated with more costly radiation regimens. Estimated costs of actual treatment were $420.2 million during 2011, compared to $256.2 million had women been treated with the least expensive radiation regimen for which they were eligible. This translates into an annual cost savings of $164.0 million, a 39% reduction in costs. CONCLUSIONS: Utilization of evidence-based adjuvant radiation following lumpectomy is associated with reductions in cancer-related costs in the locoregional treatment of early-stage breast cancer. Although treatment decisions should not be driven by health care costs alone, consideration of hypofractionated regimens or omission of radiotherapy for patients that fit evidence-based eligibility criteria could translate into dramatic reductions in annual health care spending. Citation Format: Rachel A Greenup, Rachel Blitzblau, Kevin Houck, Janet Horton, Lynn Howie, Manisha Palta, Aimee Mackey, Randy Scheri, Julie A Sosa, Alphonse G Taghian, Jeffrey Peppercorn, Barbara L Smith, E Shelley Hwang. Adjuvant radiation after lumpectomy: A cost comparison of treatment patterns in 43,247 women from the National Cancer Data Base [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-10-02.

Purpose The Radiation Therapy Oncology Group 9804 study identified good-risk patients with ductal carcinoma in situ (DCIS), a breast cancer diagnosis found frequently in mammographically detected cancers, to test the benefit of radiotherapy (RT) after breast-conserving surgery compared with observation. Patients and Methods This prospective randomized trial (1998 to 2006) in women with mammographically detected low- or intermediate-grade DCIS, measuring less than 2.5 cm with margins ≥ 3 mm, compared RT with observation after surgery. The study was designed for 1,790 patients but was closed early because of lower than projected accrual. Six hundred thirty-six patients from the United States and Canada were entered; tamoxifen use (62%) was optional. Ipsilateral local failure (LF) was the primary end point; LF and contralateral failure were estimated using cumulative incidence, and overall and disease-free survival were estimated using the Kaplan-Meier method. Results Median follow-up time was 7.17 years (range, 0.01 to 11.33 years). Two LFs occurred in the RT arm, and 19 occurred in the observation arm. At 7 years, the LF rate was 0.9% (95% CI, 0.0% to 2.2%) in the RT arm versus 6.7% (95% CI, 3.2% to 9.6%) in the observation arm (hazard ratio, 0.11; 95% CI, 0.03 to 0.47; P < .001). Grade 1 to 2 acute toxicities occurred in 30% and 76% of patients in the observation and RT arms, respectively; grade 3 or 4 toxicities occurred in 4.0% and 4.2% of patients, respectively. Late RT toxicity was grade 1 in 30%, grade 2 in 4.6%, and grade 3 in 0.7% of patients. Conclusion In this good-risk subset of patients with DCIS, with a median follow-up of 7 years, the LF rate was low with observation but was decreased significantly with the addition of RT. Longer follow-up is planned because the timeline for LF in this setting seems protracted.

Purpose To present long-term outcomes of a prospective feasibility trial using either protons or 3-dimensional conformal photon-based (accelerated partial-breast irradiation [APBI]) techniques. Methods and Materials From October 2003 to April 2006, 98 evaluable patients with stage I breast cancer were treated with APBI (32 Gy in 8 fractions given twice daily) on a prospective clinical trial: 19 with proton beam therapy (PBT) and 79 with photons or mixed photons/electrons. Median follow-up was 82.5 months (range, 2-104 months). Toxicity and patient satisfaction evaluations were performed at each visit. Results At 7 years, the physician rating of overall cosmesis was good or excellent for 62% of PBT patients, compared with 94% for photon patients ( P =.03). Skin toxicities were more common for the PBT group: telangiectasia, 69% and 16% ( P =.0013); pigmentation changes, 54% and 22% ( P =.02); and other late skin toxicities, 62% and 18% ( P =.029) for PBT and photons, respectively. There were no significant differences between the groups in the incidences of breast pain, edema, fibrosis, fat necrosis, skin desquamation, and rib pain or fracture. Patient-reported cosmetic outcomes at 7 years were good or excellent for 92% and 96% of PBT and photon patients, respectively ( P =.95). Overall patient satisfaction was 93% for the entire cohort. The 7-year local failure rate for all patients was 6%, with 3 local recurrences in the PBT group (7-year rate, 11%) and 2 in photon-treated patients (4%) ( P =.22). Conclusions Local failure rates of 3-dimensional APBI and PBT were similar in this study. However, PBT, as delivered in this study, led to higher rates of long-term telangiectasia, skin color changes, and skin toxicities. We recommend the use of multiple fields and treatment of all fields per treatment session or the use of scanning techniques to minimize skin toxicity.