Positive Nipple Margins in Nipple-Sparing Mastectomy: Management of Nipples Containing Cancer or Atypia.

BACKGROUND: Nipple-sparing mastectomy (NSM) is an oncologically safe approach for breast cancer treatment and prevention; however, there are little long-term data to guide management for patients whose nipple margins contain tumor or atypia. METHODS: NSM patients with tumor or atypia in their nipple margin were identified from a prospectively maintained, single-institution database of consecutive NSMs. Patient and tumor characteristics, treatment, recurrence, and survival data were assessed. RESULTS: A total of 3158 NSMs were performed from June 2007 to August 2019. Nipple margins contained tumor in 117 (3.7%) NSMs and atypia only in 164 (5.2%) NSMs. Among 117 nipple margins that contained tumor, 34 (29%) margins contained invasive cancer, 80 (68%) contained ductal carcinoma in situ only, and 3 (3%) contained lymphatic vessel invasion only. Management included nipple-only excision in 67 (57%) breasts, nipple-areola complex excision in 35 (30%) breasts, and no excision in 15 (13%) breasts. Only 23 (24%) excised nipples contained residual tumor. At 67 months median follow-up, there were 2 (1.8%) recurrences in areolar or peri-areolar skin, both in patients with nipple-only excision. Among 164 nipple margins containing only atypia, 154 (94%) nipples were retained. At 60 months median follow-up, no patient with atypia alone had a nipple or areola recurrence. CONCLUSIONS: Nipple excision is effective management for nipple margins containing tumor. No intervention is required for nipple margins containing only atypia. Our results support broad eligibility for NSM with careful nipple margin assessment.

A Decade of Nipple-Sparing Mastectomy: Lessons Learned in 3035 Immediate Implant-Based Breast Reconstructions.

BACKGROUND: Nipple-sparing mastectomy is commonly performed for breast cancer treatment or prevention. The authors present one of the largest breast reconstruction series in the literature. METHODS: A single-institution retrospective review was conducted from 2007 to 2019. RESULTS: The authors' query identified 3035 implant-based breast reconstructions after nipple-sparing mastectomy, including 2043 direct-to-implant and 992 tissue expander-to-implant reconstructions. The overall major complication rate was 9.15%, and the nipple necrosis rate was 1.20%. Therapeutic mastectomy was associated with higher overall complications and explantations compared with prophylactic mastectomy ( P < 0.01). In comparisons of unilateral and bilateral procedures, bilateral mastectomy had an increased risk for complications (OR, 1.46; 95% CI, 0.997 to 2.145; P = 0.05). Tissue-expander reconstructions had higher rates of nipple necrosis (1.9% versus 0.88%; P = 0.015), infection (4.2% versus 2.8%; P = 0.04), and explantation (5.1% versus 3.5%; P = 0.04) compared with direct-to-implant reconstruction. When assessing plane of reconstruction, the authors found similar rates of complications between subpectoral dual-plane and prepectoral reconstruction. There was no difference in complications between reconstruction with acellular dermal matrix or mesh compared with total or partial muscle coverage without acellular dermal matrix/mesh (OR, 0.749; 95% CI, 0.404 to 1.391; P = 0.361). Multivariable regression analysis revealed preoperative radiotherapy (OR, 2.465; 95% CI, 1.579 to 3.848; P < 0.001), smoking (OR, 2.53; 95% CI, 1.581 to 4.054; P < 0.001), and a periareolar incision (OR, 3.657; 95% CI, 2.276 to 5.875; P < 0.001) to be the strongest predictors of complications and nipple necrosis ( P < 0.05). CONCLUSIONS: Nipple-sparing mastectomy and immediate breast reconstruction has a low rate of complications. In this series, radiation therapy, smoking, and incision choice predicted overall complications and nipple necrosis, whereas direct-to-implant reconstruction and acellular dermal matrix or mesh did not increase risk. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Time to surgery: A health equity metric in breast cancer patients.

BACKGROUND: We evaluated whether time to surgery by race can be a health equity metric of surgical access. METHODS: An observational analysis was performed using the National Cancer Database from 2010 to 2019. Inclusion criteria were women with stage I-III breast cancer. We excluded women with multiple cancers and whose diagnosis was made at a different hospital. The primary outcome variable was surgery within 90 days of diagnosis. RESULTS: A total of 886,840 patients were analyzed, with 76.8% White and 11.7% Black patients. 11.9% of patients experienced delayed surgery, which was significantly more common in Black patients than White patients. On adjusted analysis, Black patients were still significantly less likely to receive surgery within 90 days when compared to White patients (OR 0.61, 95% CI 0.58-0.63). CONCLUSION: The delay in surgery experienced by Black patients highlights the contribution of system factors in cancer inequity and should be a focus for targeted interventions.

Oncologic Safety of Nipple-Sparing Mastectomy for Breast Cancer in BRCA Gene Mutation Carriers: Outcomes at 70 Months Median Follow-Up.

BACKGROUND: Retention of the nipple-areola complex with nipple-sparing mastectomy (NSM) techniques provides a more natural cosmetic result than procedures that sacrifice the nipple. While the oncologic safety of NSM is established by several studies, there is little long-term data on outcomes in BRCA mutation carriers with breast cancer. PATIENTS AND METHODS: BRCA1/2 mutation carriers who underwent NSM and immediate reconstruction from 2008 to 2019 were reviewed and patients with breast cancer on biopsy or final pathology were included. Patient demographics and tumor characteristics, as well as treatment, recurrence, and survival data were collected. RESULTS: A total of 114 therapeutic NSM were performed in 105 BRCA mutation carriers (56 BRCA1, 47 BRCA2, and two women with both mutations). Median age was 45 years. Cancers were 18% stage 0, 52% stage I, 27% stage II, and 3% stage III. Mean invasive tumor size was 1.6 cm and 33 (35%) invasive tumors were triple negative. There were five (4.4%) positive nipple margins on final pathology; all underwent nipple excision. Most patients (80, 76%) received systemic therapy: 65 (62%) received chemotherapy and 48 (46%) received endocrine therapy. At 70 months median follow-up (range 15-150 months), no patient had developed a recurrence in the retained nipple-areola complex or at the site of a nipple excised for a positive margin. The rate of locoregional recurrence outside the nipple was 2.6%, and the rate of distant recurrence was 3.8%. Overall survival was 96%. CONCLUSIONS: NSM is a safe option for BRCA1 and BRCA2 mutation carriers who undergo mastectomy for breast cancer.

Intraoperative Fluorescence Guidance for Breast Cancer Lumpectomy Surgery.

Fluorescence Guidance for Lumpectomy SurgeryThis prospective trial of 406 patients assessed margin status with and without pegulicianine fluorescence-guided surgery (pFGS) for stages 0 to 3 breast cancers. The use of pFGS met prespecified thresholds for removal of residual tumor and specificity but did not meet the prespecified threshold for sensitivity.

Comparison of Wireless Localization Alternatives with Wire Localization for Nonpalpable Breast Lesions.

BACKGROUND: Radiofrequency identification tag localization (TL) and magnetic seed localization (MSL) are alternatives to wire localization (WL) for excision of nonpalpable breast lesions. We sought to compare localization methods with respect to operative time, specimen volume, and re-excision rate. STUDY DESIGN: A retrospective cohort analysis was performed on TL, MSL, and WL lumpectomies and excisional biopsies at a single institution. Association between localization method and operative time, specimen volume, and re-excision rate was assessed by multiple logistic regression using odds ratios (ORs) and 95% CIs. RESULTS: A total of 506 procedures were included: 147 TL (29.0%), 140 MSL (27.7%), and 219 WL (43.3%). On logistic regression analysis, MSL was associated with longer operative times than WL for excisional biopsies only (OR 4.24, 95% CI 1.92 to 9.34, p < 0.001). Mean excisional biopsy time was 39.1 minutes for MSL and 33.0 minutes for WL. Specimen volume did not vary significantly across surgery types between localization methods. In an analysis of all lumpectomies with an indication of carcinoma, marker choice was not associated with rate of re-excision (TL vs WL OR 0.64, 95% CI 0.26 to 1.60, p = 0.342; MSL vs WL OR 1.22, 95% CI 0.60 to 2.49, p = 0.587; TL vs MSL OR 0.65, 95% CI 0.26 to 1.64, p = 0.359). CONCLUSION: TL, MSL, and WL are comparable in performance for excision of nonpalpable breast lesions. Although increased operative time associated with MSL vs WL excisional biopsies is statistically significant, clinical significance warrants additional study. With similar outcomes, physicians may choose the marker most appropriate for the patient and setting.

One-Year Experience of Same-Day Mastectomy and Breast Reconstruction Protocol.

BACKGROUND: The prevalence of same-day mastectomy with reconstruction has continued to increase across the United States in recent years. Prior studies have shown that same-day mastectomy with reconstruction leads to increased patient satisfaction and allows hospitals to use resources better. This study sought to evaluate the implementation of same-day mastectomy with a reconstruction recovery protocol for patients undergoing mastectomy at our institution. METHODS: Under an institutional review board-approved protocol, a retrospective cohort analysis compared patients who underwent mastectomy April 2016 through April 2017 with those who had mastectomy March 2020 through March 2021. Length of stay, postoperative intravenous (IV) opioid administration, safety end points, and cost were the main variables examined. RESULTS: The study compared 457 patients in 2016-2017 with 428 patients in 2020-2021. The median hospital length of stay decreased from 24.6 h in 2016-2017 to 5.5 h in 2020-2021 (p < 0.001). The percentage of patients requiring postoperative IV opioids decreased from 69.1 % in 2016-2017 to 50 % in 2020-2021 (p < 0.001). The rates of unplanned readmissions within 30 days after mastectomy did not differ between the two groups, with a rate of 3.7 % in 2016-2017 and a rate of 5.1 % in 2020-2021 (p = 0.30). Reducing the rate of overnight admissions after mastectomy by 65.8 % resulted in a cost reduction of 65.8 %. CONCLUSIONS: Implementation of same-day mastectomy with a reconstruction protocol across a large academic center and two satellite sites was a safe alternative to conventional mastectomy recovery plans.

Clinical Impact of Intraoperative Margin Assessment in Breast-Conserving Surgery With a Novel Pegulicianine Fluorescence-Guided System: A Nonrandomized Controlled Trial.

Importance: Positive margins following breast-conserving surgery (BCS) are often identified on standard pathology evaluation. Intraoperative assessment of the lumpectomy cavity has the potential to reduce residual disease or reexcision rate following standard of care BCS in real time. Objective: To collect safety and initial efficacy data on the novel pegulicianine fluorescence-guided system (pFGS) when used to identify residual cancer in the tumor bed of female patients undergoing BCS. Design, Setting, and Participants: This prospective single-arm open-label study was conducted as a nonrandomized multicenter controlled trial at 16 academic or community breast centers across the US. Female patients 18 years and older with newly diagnosed primary invasive breast cancer or ductal carcinoma in situ DCIS undergoing BCS were included, excluding those with previous breast cancer surgery and a history of dye allergies. Of 283 consecutive eligible patients recruited, 234 received a pegulicianine injection and were included in the safety analysis; of these, 230 were included in the efficacy analysis. Patients were enrolled between February 6, 2018, and April 10, 2020, and monitored for a 30-day follow-up period. Data were analyzed from April 10, 2020, to August 5, 2021. Interventions: Participants received an injection of a novel imaging agent (pegulicianine) a mean (SD) of 3.2 (0.9) hours prior to surgery at a dose of 1 mg/kg. After completing standard of care (SOC) excision, pFGS was used to scan the lumpectomy cavity to guide the removal of additional shave margins. Main Outcomes and Measures: Adverse events and sensitivity, specificity, and reexcision rate. Results: Of 234 female patients enrolled (median [IQR] age, 62.0 [55.0-69.0] years), 230 completed the trial and 1 patient with a history of allergy to contrast agents had an anaphylactic reaction and recovered without sequelae. Correlation of pFGS with final margin status on a per-margin analysis showed a marked improvement in sensitivity over standard pathology assessment of the main lumpectomy specimen (69.4% vs 38.2%, respectively). On a per-patient level, the false-negative rate of pFGS was 23.7% (9 of 38), and sensitivity was 76.3% (29 of 38). Among 32 patients who underwent excision of pFGS-guided shaves, pFGS averted the need for reexcision in 6 (19%). Conclusions and Relevance: In this pilot feasibility study, the safety profile of pegulicianine was consistent with other imaging agents used in BCS, and was associated with a reduced need for second surgery in patients who underwent intraoperative additional excision of pFGS-guided shaves. These findings support further development and clinical performance assessment of pFGS in a prospective randomized trial. Trial Registration: ClinicalTrials.gov Identifier: NCT03321929.

Magnetic Seeds: An Alternative to Wire Localization for Nonpalpable Breast Lesions.

INTRODUCTION: Magnetic seeds have emerged as an alternative to wires for localization of nonpalpable breast lesions. The purpose of this study was to evaluate the utility of magnetic seeds compared to wires for preoperative localization. MATERIALS AND METHODS: A retrospective cohort analysis of magnetic seed localization (MSL) and wire localization (WL) excisional biopsies and lumpectomies performed at a single institution was conducted. Indication, age, BMI, number of markers, procedure type, operative time, and postoperative opioid administration were reviewed. Impact of localization method on operative time, specimen volume, postoperative opioid administration, and re-excision rate were assessed. RESULTS: A total of 608 MSL procedures in 601 patients were compared to 628 WL procedures in 620 patients. MSL excisional biopsies were significantly longer (37.0 minutes) than WL excisional biopsies (31.9 minutes, P< .001), but in lumpectomies without axillary surgery, MSL procedures (42.3 minutes) were significantly shorter than WL procedures (46.9 minutes, P = .017). Significantly less tissue was excised during MSL lumpectomies (68.5 cm3) and excisional biopsies (32.3 cm3) than WL lumpectomies (78.1 cm3, P = .039) and excisional biopsies (38.7 cm3, P = .018). Postoperative opioid administration was similar for MSL and WL procedures (P = .076). Re-excision rates for MSL lumpectomies were significantly higher for ductal carcinoma in situ (35.3% MSL vs. 18.5% WL, P = .013), but were similar for invasive carcinoma (14.4% MSL vs. 17.7% WL, P = .290). Logistic regression analysis showed no association between localization method and re-excision (OR 1.007, 95% CI 0.681-1.488; P = .973). CONCLUSION: MSL is a feasible alternative to WL for excision of nonpalpable breast lesions with regard to surgical outcomes.

The safety of performing breast reconstruction during the COVID-19 pandemic.

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 versus Skin-Sparing Mastectomy: Does Saving the Nipple Impact Short- and Long-Term Patient Satisfaction?

BACKGROUND: Nipple-sparing mastectomy (NSM) is an oncologically safe alternative to skin-sparing mastectomy (SSM). This study evaluated whether NSM patients were more satisfied than SSM patients in short- and long-term follow-up. METHODS: Women who underwent NSM or SSM between 2009 and 2019 completed a postoperative BREAST-Q survey at least 1 year after surgery and patient characteristics were compared. Patient satisfaction at 1-5 years and 6-10 years after NSM and SSM were analyzed. RESULTS: Overall, 431 patients were included; 247 had NSM and 184 had SSM 1-10 years prior to BREAST-Q survey completion. SSM patients were older, had higher body mass index (BMI), larger breast weight, and more hypertension than NSM patients, but oncologic treatments were similar between groups. BREAST-Q Psychosocial Well-Being and Sexual Well-Being scores were significantly higher in NSM patients compared with SSM patients in the 1-5 years cohort; however, scores attenuated in the 6-10 years cohort. Satisfaction with breasts was nearly significantly higher in NSM patients compared with SSM patients in the 1-5 years cohort (p = 0.056), but no different in the 6-10 years cohort. Receipt of adjuvant chemotherapy, receipt of postmastectomy radiation therapy, and BMI ≥30 were independent risk factors for dissatisfaction with breasts. CONCLUSIONS: Women who are not candidates for NSM should be reassured that long-term qualify of life is not significantly different between SSM and NSM. Dissatisfaction with reconstructed breasts is linked with other factors (besides the nipple), which patients should be made aware of at the time of surgical decision making.

Risk of Developing Breast Reconstruction Complications: A Machine-Learning Nomogram for Individualized Risk Estimation with and without Postmastectomy Radiation Therapy.

BACKGROUND: The purpose of this study 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 débridement. For implant-based patients, complications were defined as 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.

Randomized Phase III Trial Evaluating Radiation Following Surgical Excision for Good-Risk Ductal Carcinoma In Situ: Long-Term Report From NRG Oncology/RTOG 9804.

PURPOSE: To our knowledge, NRG/RTOG 9804 is the only randomized trial to assess the impact of whole breast irradiation (radiation therapy [RT]) versus observation (OBS) in women with good-risk ductal carcinoma in situ (DCIS), following lumpectomy. Long-term results focusing on ipsilateral breast recurrence (IBR), the primary outcome, are presented here. PATIENTS AND METHODS: Eligible patients underwent lumpectomy for DCIS that was mammogram detected, size ≤ 2.5 cm, final margins ≥ 3 mm, and low or intermediate nuclear grade. Consented patients were randomly assigned to RT or OBS. Tamoxifen use was optional. Cumulative incidence was used to estimate IBR, log-rank test and Gray's test to compare treatments, and Fine-Gray regression for hazard ratios (HRs). RESULTS: A total of six hundred thirty-six women were randomly assigned from 1999 to 2006. Median age was 58 years and mean pathologic DCIS size was 0.60 cm. Intention to use tamoxifen was balanced between arms (69%); however, actual receipt of tamoxifen varied, 58% RT versus 66% OBS (P = .05). At 13.9 years' median follow-up, the 15-year cumulative incidence of IBR was 7.1% (95% CI, 4.0 to 11.5) with RT versus 15.1% (95% CI, 10.8 to 20.2) OBS (P = .0007; HR = 0.36; 95% CI, 0.20 to 0.66); and for invasive LR was 5.4% (95% CI, 2.7 to 9.5) RT versus 9.5% (95% CI, 6.0 to 13.9) OBS (P = .027; HR = 0.44; 95% CI, 0.21 to 0.91). On multivariable analysis, only RT (HR = 0.34; 95% CI, 0.19 to 0.64; P = .0007) and tamoxifen use (HR = 0.45; 95% CI, 0.25 to 0.78; P = .0047) were associated with reduced IBR. CONCLUSION: RT significantly reduced all and invasive IBR for good-risk DCIS with durable results at 15 years. These results are not an absolute indication for RT but rather should inform shared patient-physician treatment decisions about ipsilateral breast risk reduction in the long term following lumpectomy.

How Protective are Nipple-Sparing Prophylactic Mastectomies in BRCA1 and BRCA2 Mutation Carriers?

BACKGROUND: 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. METHODS: 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). RESULTS: 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). CONCLUSIONS: 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.

Locally Recurrent Secretory Carcinoma of the Breast with NTRK3 Gene Fusion.

Enhanced understanding of the molecular events underlying oncogenesis has led to the development of "tumor-agnostic" treatment strategies, which aim to target a tumor's genomic profile regardless of its anatomic site of origin. A classic example is the translocation resulting in an ETV6-NTRK3 gene fusion, a characteristic driver of a histologically diverse array of cancers. The chimeric ETV6-NTRK3 fusion protein elicits constitutive activation of the tropomyosin receptor kinase (TRK) C protein, leading to increased cell survival, growth, and proliferation. Two TRK inhibitors, larotrectinib and entrectinib, are currently approved for use in the metastatic setting for the treatment of advanced solid tumors harboring NTRK fusions. Here we report a rare case of recurrent secretory carcinoma of the breast (SCB) with NTRK3 gene fusion. Whereas most cases of SCB represent slow-growing tumors with favorable outcomes, the case detailed here is the first to the authors' knowledge of recurrence within 1 year of surgery. We review the molecular findings and potential clinical significance. KEY POINTS: The translocation resulting in the ETV6-NTRK3 gene fusion is a known oncogenic driver characteristic of secretory carcinoma of the breast (SCB). Whereas most cases of SCB represent slow-growing tumors with favorable outcomes, the case here with ETV6-NTRK3 gene fusion had local recurrence within 1 year of surgery. Two tropomyosin receptor kinase (TRK) inhibitors, larotrectinib and entrectinib, are approved to treat NTRK fusion-positive tumors, demonstrating sustained high overall response rates in the metastatic setting. Approval of TRK inhibitors necessitates optimization of NTRK fusion detection assays, including detection with liquid biopsies.

Performance of a novel protease-activated fluorescent imaging system for intraoperative detection of residual breast cancer during breast conserving surgery.

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 < 2 mm from the adjacent specimen margin. LUM015 signal was stable in vivo at least 6.5 h post injection, and ex vivo at least 4 h post excision. 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.

Smartphone Global Positioning System (GPS) Data Enhances Recovery Assessment After Breast Cancer Surgery.

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) vs. 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) vs. 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 (ρ < ± 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.

Postmastectomy Radiation Therapy on Permanent Implants or Tissue Expanders: Which is Better?

OBJECTIVES: This study evaluates complications and reconstructive failure rates in implant-based reconstruction with radiotherapy. BACKGROUND: Postmastectomy radiotherapy may adversely affect breast reconstructive outcomes. However, the comparative effect of radiotherapy on direct-to-implant versus tissue expander-implant reconstruction has not been examined. METHODS: Single institution retrospective review was performed and patients were followed 2 to 10 years. RESULTS: Of 1566 patients, 265 patients received radiation (149 immediate implants and 116 tissue expanders). Demographics were similar except more smokers in the expander group (7.7% vs 1.3%; P = 0.012). Patients who received radiation with an expander in place had overall more complications (32.8% vs 11.4%; P < 0.001), skin necrosis (10.3% vs 4.0%; P = 0.043), wound breakdown (9.5% vs 2.7%; P = 0.029), and infections (16.4% vs 4.03%; P = 0.001) leading to a higher rate of explantation (16.4% vs 4.0%; P < 0.001). A radiation boost likewise predicted complications [odds ratio (OR) 2.199, 95% confidence interval (CI) 1.154-4.188, P = 0.017]. When comparing reconstructive outcomes, radiated expanders had a higher failure rate (21.6% vs 11.4%; P = 0.025). Revision for capsular contracture was similar between the 2 cohorts (11.4% vs 11.2%; P = 0.959) as were revision rates for contour asymmetry and breast asymmetry. In our multivariable logistic regression analysis, radiation to the expander had a higher risk of reconstruction failure than radiation to the permanent implant (OR 2.020, 95% CI 1.010-4.037, P = 0.047). CONCLUSION: Most patients had successful implant-based reconstructions after mastectomy and radiotherapy. Our study showed radiotherapy after direct-to-implant breast reconstruction had a lower rate of complications and reconstructive failure compared to tissue expander-implant reconstruction.