Reducing the Risk of Needle Tract Seeding or Tumor Cell Dissemination during Needle Biopsy Procedures.

PURPOSE: Many women fear that breast needle biopsies increase the risk of cancer spread. The purpose of this review article is to discuss the breast cancer literature regarding the risk of needle-biopsy-induced cancer cell displacement and its impact on local and regional recurrence and breast cancer survival. METHODS: A literature review is performed to discuss the risks and mitigation of needle-biopsy-induced cancer cell displacement. RESULTS: Needle-biopsy-induced cancer cell displacement is a common event. The risk is influenced by the biopsy technique and the breast cancer type. Evidence suggests that the risk of needle-biopsy-induced cancer cell displacement may potentially increase the odds of local recurrence but has no impact on regional recurrence and long-term survival. CONCLUSIONS: Technical modifications of needle biopsy procedures can reduce the risk of breast needle-biopsy-induced cancer cell displacement and potentially reduce the risk of local recurrence, especially in patients for whom whole breast radiation is to be omitted.

Breast Cancer Cryoablation in the Multidisciplinary Setting: Practical Guidelines for Patients and Physicians.

Breast cancer cryoablation has emerged as a minimally invasive alternative to lumpectomy for treating early-stage breast cancer. However, no consensus exists on what should be considered the standard of care for the multidisciplinary management of patients treated with breast cancer cryoablation. In lieu of national guidelines, this review of the literature provides a multidisciplinary framework and an evidence-based discussion of the integration of "standard of care practices" in the comprehensive management of breast cancer cryoablation patients.

The prevention and treatment of breast cancer- related lymphedema: A review.

Background: Breast cancer- related lymphedema (BCRL) affects about 3 to 5 million patients worldwide, with about 20,000 per year in the United States. As breast cancer mortality is declining due to improved diagnostics and treatments, the long-term effects of treatment for BCRL need to be addressed. Methods: The American Society of Breast Surgeons Lymphatic Surgery Working Group conducted a large review of the literature in order to develop guidelines on BCRL prevention and treatment. This was a comprehensive but not systematic review of the literature. This was inclusive of recent randomized controlled trials, meta-analyses, and reviews evaluating the prevention and treatment of BCRL. There were 25 randomized clinical trials, 13 systemic reviews and meta-analyses, and 87 observational studies included. Results: The findings of our review are detailed in the paper, with each guideline being analyzed with the most recent data that the group found evidence of to suggest these recommendations. Conclusions: Prevention and treatment of BCRL involve a multidisciplinary team. Early detection, before clinically apparent, is crucial to prevent irreversible lymphedema. Awareness of risk factors and appropriate practice adjustments to reduce the risk aids are crucial to decrease the progression of lymphedema. The treatment can be costly, time- consuming, and not always effective, and therefore, the overall goal should be prevention.

Clinical Utility of Universal Germline Genetic Testing for Patients With Breast Cancer.

Importance: National Comprehensive Cancer Network guidelines currently recommend germline testing for high-risk genes in selected patients with breast cancer. The clinical utility of recommending testing all patients with breast cancer with multigene panels is currently under consideration. Objective: To examine the implications of universal testing of patients with breast cancer with respect to clinical decision-making. Design, Setting, and Participants: Patients from a previously reported cohort were assessed as in-criteria or out-of-criteria according to the 2017 guidelines and underwent testing with a multigene germline panel between 2017 to 2018. Patients were women and men aged 18 to 90 years, with a new and/or previous diagnosis of breast cancer who had not undergone either single or multigene testing. Clinicians from 20 community and academic sites documented patient clinical information and changes to clinical recommendations made according to test findings. Association between prevalence of pathogenic or likely pathogenic germline variants and previously unreported clinical features, including scores generated by the BRCAPRO statistical model, was determined. Data were analyzed from April 2020 to May 2022. Exposure: New and/or previous diagnosis of breast cancer. Main Outcomes and Measures: Disease management recommendations that were changed as a result of genetic testing results are reported. Results: Clinicians were asked to assess changes to clinical management as a result of germline genetic testing for 952 patients. Informative clinician-reported recommendations were provided for 939 (467 in-criteria and 472 out-of-criteria) of the patients with breast cancer (936 [99.7%] female; 702 [74.8%] White; mean [SD] age at initial diagnosis, 57.6 [11.5] years). One or more changes were reported for 31 of 37 (83.8%) in-criteria patients and 23 of 34 (67.6%) out-of-criteria patients with a pathogenic or likely pathogenic variant. Recommendations were changed as a result of testing results for 14 of 22 (63.6%) out-of-criteria patients who had a variant in a breast cancer predisposition gene. Clinicians considered testing beneficial for two-thirds of patients with pathogenic or likely pathogenic variants and for one-third of patients with either negative results or variants of uncertain significance. There was no difference in variant rate between patients meeting the BRCAPRO threshold (≥10%) and those who did not (P = .86, Fisher exact test). No changes to clinical recommendations were made for most patients with negative results (345 of 349 patients [98.9%]) or variants of uncertain significance (492 of 509 patients [96.7%]). Conclusions and Relevance: In this cohort study, germline genetic testing was used by clinicians to direct treatment for most out-of-criteria patients with breast cancer with pathogenic or likely pathogenic germline variants, including those with moderate-risk variants. Universal germline testing informs clinical decision-making and provides access to targeted treatments and clinical trials for all patients with breast cancer.

Risk-Stratified Intraoperative Radiation Therapy as a Definitive Adjuvant Radiation Therapy Modality for Women With Early Breast Cancer.

Radiation therapy is an integral component of adjuvant therapy in women who undergo breast conservative surgery, decreasing the likelihood of tumor recurrence and extending survival. The likelihood of tumor recurrence is highest within a proximity of the lumpectomy cavity, which prompted the idea of partial breast irradiation in place of the usual standard-of-care treatment with external beam whole breast radiation therapy. Targeted intraoperative radiation therapy (TARGIT-A) is a multicenter trial initially developed in 1999 and designed as a randomized clinical trial comparing whole breast radiation therapy to risk-adapted intraoperative radiation therapy (IORT). TARGIT-A recruited its first patient in March 2000, with the study concluding in 2012. At a median follow-up of 8.6 years, the prepathology TARGIT-A trial noted results to be noninferior to external beam radiation therapy, with no statistically significant difference in ipsilateral breast tumor recurrence, mastectomy-free survival, distant disease-free survival, or breast cancer-specific mortality. These results are consistent with the majority of retrospective and prospective trials. Risk-adapted IORT, as performed in the prospective randomized TARGIT-A trial, gives level 1 evidence that this approach is a standard option in the treatment of breast cancer.

Mammary Paget's Disease: An Update.

Mammary Paget's Disease is a non-invasive cutaneous malignancy of the breast involving the nipple-areolar complex that is commonly mistaken for benign breast conditions, leading to delay in diagnosis. This review article discusses Paget's disease etiology, clinical presentation, differential diagnosis, diagnostic work-up, natural history and prognosis. This article also discusses evolving strategies for the surgical and non-surgical management of Paget's disease.

New clinical and biological insights from the international TARGIT-A randomised trial of targeted intraoperative radiotherapy during lumpectomy for breast cancer.

BACKGROUND: The TARGIT-A trial reported risk-adapted targeted intraoperative radiotherapy (TARGIT-IORT) during lumpectomy for breast cancer to be as effective as whole-breast external beam radiotherapy (EBRT). Here, we present further detailed analyses. METHODS: In total, 2298 women (≥45 years, invasive ductal carcinoma ≤3.5 cm, cN0-N1) were randomised. We investigated the impact of tumour size, grade, ER, PgR, HER2 and lymph node status on local recurrence-free survival, and of local recurrence on distant relapse and mortality. We analysed the predictive factors for recommending supplemental EBRT after TARGIT-IORT as part of the risk-adapted approach, using regression modelling. Non-breast cancer mortality was compared between TARGIT-IORT plus EBRT vs. EBRT. RESULTS: Local recurrence-free survival was no different between TARGIT-IORT and EBRT, in every tumour subgroup. Unlike in the EBRT arm, local recurrence in the TARGIT-IORT arm was not a predictor of a higher risk of distant relapse or death. Our new predictive tool for recommending supplemental EBRT after TARGIT-IORT is at https://targit.org.uk/addrt . Non-breast cancer mortality was significantly lower in the TARGIT-IORT arm, even when patients received supplemental EBRT, HR 0.38 (95% CI 0.17-0.88) P = 0.0091. CONCLUSION: TARGIT-IORT is as effective as EBRT in all subgroups. Local recurrence after TARGIT-IORT, unlike after EBRT, has a good prognosis. TARGIT-IORT might have a beneficial abscopal effect. TRIAL REGISTRATION: ISRCTN34086741 (21/7/2004), NCT00983684 (24/9/2009).

Targeted Intraoperative Radiotherapy Is a Safe Approach for Patients with Pacemakers: A Case Study and Literature Review.

Case reports detailing the effects of targeted intraoperative radiation therapy (IORT) on patients with cardiac pacemakers (PMs) are rare. This growing population sub-group requiring IORT and lack of standardized guidelines necessitate more practical published research. An 81-year-old patient with clinical stage II, T1 N0 grade III, triple-negative invasive ductal carcinoma and an implanted single-lead chamber PM (VVIR mode, model: Biotronik, type Effecta SR) received targeted intraoperative radiotherapy at the time of wide local excision and sentinel lymph node biopsy. It presents the shortest distance between the outer diameter of the PM and IORT applicator in literature. Target IORT was performed utilizing an Intrabeam device (50 kV, Carl Zeiss Surgical, Oberkochen, Germany). This case elucidates the successful use of targeted IORT for breast-conserving surgery in a patient with a single ipsilateral chamber VVIR mode PM. No device failure or malfunction was reported for the PM before, during, or after the procedure. These findings support the use of targeted IORT for patients diagnosed with early-stage breast carcinomas who have a PM implanted. However, further research is needed to understand the safety of other methods and devices for IORT patients with cardiac implantable electronic devices.

Long term survival and local control outcomes from single dose targeted intraoperative radiotherapy during lumpectomy (TARGIT-IORT) for early breast cancer: TARGIT-A randomised clinical trial.

OBJECTIVE: To determine whether risk adapted intraoperative radiotherapy, delivered as a single dose during lumpectomy, can effectively replace postoperative whole breast external beam radiotherapy for early breast cancer. DESIGN: Prospective, open label, randomised controlled clinical trial. SETTING: 32 centres in 10 countries in the United Kingdom, Europe, Australia, the United States, and Canada. PARTICIPANTS: 2298 women aged 45 years and older with invasive ductal carcinoma up to 3.5 cm in size, cN0-N1, eligible for breast conservation and randomised before lumpectomy (1:1 ratio, blocks stratified by centre) to either risk adapted targeted intraoperative radiotherapy (TARGIT-IORT) or external beam radiotherapy (EBRT). INTERVENTIONS: Random allocation was to the EBRT arm, which consisted of a standard daily fractionated course (three to six weeks) of whole breast radiotherapy, or the TARGIT-IORT arm. TARGIT-IORT was given immediately after lumpectomy under the same anaesthetic and was the only radiotherapy for most patients (around 80%). TARGIT-IORT was supplemented by EBRT when postoperative histopathology found unsuspected higher risk factors (around 20% of patients). MAIN OUTCOME MEASURES: Non-inferiority with a margin of 2.5% for the absolute difference between the five year local recurrence rates of the two arms, and long term survival outcomes. RESULTS: Between 24 March 2000 and 25 June 2012, 1140 patients were randomised to TARGIT-IORT and 1158 to EBRT. TARGIT-IORT was non-inferior to EBRT: the local recurrence risk at five year complete follow-up was 2.11% for TARGIT-IORT compared with 0.95% for EBRT (difference 1.16%, 90% confidence interval 0.32 to 1.99). In the first five years, 13 additional local recurrences were reported (24/1140 v 11/1158) but 14 fewer deaths (42/1140 v 56/1158) for TARGIT-IORT compared with EBRT. With long term follow-up (median 8.6 years, maximum 18.90 years, interquartile range 7.0-10.6) no statistically significant difference was found for local recurrence-free survival (hazard ratio 1.13, 95% confidence interval 0.91 to 1.41, P=0.28), mastectomy-free survival (0.96, 0.78 to 1.19, P=0.74), distant disease-free survival (0.88, 0.69 to 1.12, P=0.30), overall survival (0.82, 0.63 to 1.05, P=0.13), and breast cancer mortality (1.12, 0.78 to 1.60, P=0.54). Mortality from other causes was significantly lower (0.59, 0.40 to 0.86, P=0.005). CONCLUSION: For patients with early breast cancer who met our trial selection criteria, risk adapted immediate single dose TARGIT-IORT during lumpectomy was an effective alternative to EBRT, with comparable long term efficacy for cancer control and lower non-breast cancer mortality. TARGIT-IORT should be discussed with eligible patients when breast conserving surgery is planned. TRIAL REGISTRATION: ISRCTN34086741, NCT00983684.

Breast cancer care during a pandemic: an opportune time for cryoablation?

PURPOSE: Cryoablation is a minimally-invasive percutaneous procedure that is capable of reducing the psychosocial burden of surgical delay while also decreasing the morbidity of breast cancer therapy. The purpose of this editorial is to discuss the potential role of cryoablation for reducing the psychosocial burden of surgical delay during the COVID-19 pandemic by expediting the management of breast cancer while also lessening demand on limited healthcare resources. METHODS: This editorial critiques current expert opinion recommendations that aim to reduce viral transmission and preserve healthcare resources during the COVID-19 pandemic by advocating delay of elective breast cancer surgery. RESULTS: The editorial summarizes the current state of the evidence that supports the selective use of cryoablation as a definite or stopgap measure in the management of breast cancer during the COVID-19 pandemic or when healthcare resources are limited. CONCLUSIONS: As an office-based procedure performed under local anesthesia, cryoablation eliminates the need for operating room personnel and equipment while also reducing the psychosocial impact of delayed breast cancer surgery. By reducing the number of patient and healthcare provider interactions, cryoablation not only decreases the risk of viral transmission but also the need for personal protective devices during resource-limited times.

Autologous mastectomy reconstruction: Communication among the breast surgery team to maximize aesthetic and oncologic outcome.

Mastectomy breast reconstruction with autologous tissue is challenging. Oncologic and aesthetic goals face previous surgical scars, radiation, chemotherapy, or other comorbidities. We describe a simple approach for autologous mastectomy reconstruction so that breast and plastic and reconstructive surgeons can maximize aesthetic outcomes and minimize wound complications. A retrospective chart review was done on patients who underwent mastectomy and autologous reconstruction. The surgical flight plans were reviewed to delineate an approach, and pre- and postoperative photographs were examined to create a step-by-step process. The most encountered mastectomy and autologous flap reconstruction scenarios were categorized to create a step-by-step process. Successful autologous mastectomy reconstruction to optimize aesthetic outcome and minimize complications requires team communication. Creation of a surgical flight plan using information from the physical examination, MRI and adjunctive imaging, and preoperative photographs is imperative. Thoughtful incision choice and exposure approach are paramount.

Effect of Delayed Targeted Intraoperative Radiotherapy vs Whole-Breast Radiotherapy on Local Recurrence and Survival: Long-term Results From the TARGIT-A Randomized Clinical Trial in Early Breast Cancer.

Importance: Conventional adjuvant radiotherapy for breast cancer given daily for several weeks is onerous and expensive. Some patients may be obliged to choose a mastectomy instead, and some may forgo radiotherapy altogether. We proposed a clinical trial to test whether radiotherapy could be safely limited to the tumor bed. Objective: To determine whether delayed second-procedure targeted intraoperative radiotherapy (TARGIT-IORT) is noninferior to whole-breast external beam radiotherapy (EBRT) in terms of local control. Design, Setting, and Participants: In this prospective, randomized (1:1 ratio) noninferiority trial, 1153 patients aged 45 years or older with invasive ductal breast carcinoma smaller than 3.5 cm treated with breast conservation were enrolled from 28 centers in 9 countries. Data were locked in on July 3, 2019. Interventions: The TARGIT-A trial was started in March 2000; patients were randomized after needle biopsy to receive TARGIT-IORT immediately after lumpectomy under the same anesthetic vs EBRT and results have been shown to be noninferior. A parallel study, described in this article, was initiated in 2004; patients who had their cancer excised were randomly allocated using separate randomization tables to receive EBRT or delayed TARGIT-IORT given as a second procedure by reopening the lumpectomy wound. Main Outcomes and Measures: A noninferiority margin for local recurrence rate of 2.5% at 5 years, and long-term survival outcomes. Results: Overall, 581 women (mean [SD] age, 63 [7] years) were randomized to delayed TARGIT-IORT and 572 patients (mean [SD] age, 63 [8] years) were randomized to EBRT. Sixty patients (5%) had tumors larger than 2 cm, or had positive nodes and only 32 (2.7%) were younger than 50 years. Delayed TARGIT-IORT was not noninferior to EBRT. The local recurrence rates at 5-year complete follow-up were: delayed TARGIT-IORT vs EBRT (23/581 [3.96%] vs 6/572 [1.05%], respectively; difference, 2.91%; upper 90% CI, 4.4%). With long-term follow-up (median [IQR], 9.0 [7.5-10.5] years), there was no statistically significant difference in local recurrence-free survival (HR, 0.75; 95% CI, 0.57-1.003; P = .052), mastectomy-free survival (HR, 0.88; 95% CI, 0.65-1.18; P = .38), distant disease-free survival (HR, 1.00; 95% CI, 0.72-1.39; P = .98), or overall survival (HR, 0.96; 95% CI, 0.68-1.35; P = .80). Conclusions and Relevance: These long-term data show that despite an increase in the number of local recurrences with delayed TARGIT-IORT, there was no statistically significant decrease in mastectomy-free survival, distant disease-free survival, or overall survival. Trial Registration: ISRCTN34086741, ClinicalTrials.gov Identifier: NCT00983684.

Targeted Intraoperative Radiotherapy During Breast-conserving Surgery for Breast Cancer in Patients After Implant Augmentation.

BACKGROUND/AIM: Targeted intraoperative radiotherapy (TARGIT IORT) is an option during breast-conserving surgery (BCS). No data have yet been published regarding the safety of TARGIT IORT with implants in situ. TARGIT IORT is an attractive option in this context because of the risk of capsular fibrosis following external beam radiotherapy (EBRT) in such patients. PATIENTS AND METHODS: We are reporting a retrospective analysis of 16 patients who received TARGIT IORT during BCS for early breast cancer after previous implant-based breast augmentation. TARGIT IORT was performed using the Intrabeam™method. RESULTS: Follow-up varied from 98 to 5 months. There were no procedure-related complications. One patient developed local recurrence after 36 months of follow-up. Among the remaining patients (15/16), no breast-cancer-related events occurred. CONCLUSION: This series of patients with TARGIT IORT during BCS after implant-based breast augmentation revealed no safety concerns and gives some confidence in discussing this option with selected patients.

A Consensus Definition and Classification System of Oncoplastic Surgery Developed by the American Society of Breast Surgeons.

BACKGROUND: Several definitions of oncoplastic surgery have been reported in the literature. In an effort to facilitate communication regarding oncoplastic surgery to patients, trainees, and among colleagues, the American Society of Breast Surgeons (ASBrS) aimed to create a consensus definition and classification system for oncoplastic surgery. METHODS: We performed a comprehensive literature search for oncoplastic surgery definitions using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Following this, a consensus definition and classification system was created by the ASBrS. RESULTS: Overall, 30 articles defining oncoplastic surgery were identified, with several articles contradicting each other. The ASBrS definition for oncoplastic surgery defines this set of breast-conserving operations using volume displacement and volume replacement principles as: "Breast conservation surgery incorporating an oncologic partial mastectomy with ipsilateral defect repair using volume displacement or volume replacement techniques with contralateral symmetry surgery as appropriate". Volume displacement is defined as closing the lumpectomy defect and redistributing the resection volume over the preserved breast, and is divided into two levels: level 1 (< 20%) and level 2 (20-50%). Volume replacement includes those situations when volume is added using flaps or implants to correct the partial mastectomy defect. CONCLUSION: The ASBrS oncoplastic surgery definition and classification system provides language to facilitate discussion and teaching of oncoplastic surgery among breast surgeons, trainees, and patients.

Underdiagnosis of Hereditary Breast Cancer: Are Genetic Testing Guidelines a Tool or an Obstacle?

PURPOSE: An estimated 10% of breast and ovarian cancers result from hereditary causes. Current testing guidelines for germ line susceptibility genes in patients with breast carcinoma were developed to identify carriers of BRCA1/ 2 variants and have evolved in the panel-testing era. We evaluated the capability of the National Comprehensive Cancer Network (NCCN) guidelines to identify patients with breast cancer with pathogenic variants in expanded panel testing. METHODS: An institutional review board-approved multicenter prospective registry was initiated with 20 community and academic sites experienced in cancer genetic testing and counseling. Eligibility criteria included patients with a previously or newly diagnosed breast cancer who had not undergone either single- or multigene testing. Consecutive patients 18 to 90 years of age were consented and underwent an 80-gene panel test. Health Insurance Portability and Accountability Act-compliant electronic case report forms collected information on patient demographics, diagnoses, phenotypes, and test results. RESULTS: More than 1,000 patients were enrolled, and data records for 959 patients were analyzed; 49.95% met NCCN criteria, and 50.05% did not. Overall, 8.65% of patients had a pathogenic/likely pathogenic (P/LP) variant. Of patients who met NCCN guidelines with test results, 9.39% had a P/LP variant. Of patients who did not meet guidelines, 7.9% had a P/LP variant. The difference in positive results between these groups was not statistically significant (Fisher's exact test P = .4241). CONCLUSION: Our results indicate that nearly half of patients with breast cancer with a P/LP variant with clinically actionable and/or management guidelines in development are missed by current testing guidelines. We recommend that all patients with a diagnosis of breast cancer undergo expanded panel testing.

Breast conserving surgery with targeted intraoperative radiotherapy for the management of ductal carcinoma in situ.

BACKGROUND: A prospective randomized controlled trial has established the efficacy of targeted intraoperative radiotherapy (TARGIT) in the management of invasive breast cancer treated with breast-conserving surgery (BCS). The purpose of this analysis is to evaluate the efficacy of TARGIT in the management of ductal carcinoma in situ (DCIS). METHODS: A prospective nonrandomized trial was designed to evaluate the success of TARGIT in the management of DCIS, as measured by a low risk of requiring additional surgery or radiotherapy and an acceptable local recurrence rate (LRR). RESULTS: Fifty-five patients with DCIS received BCS and TARGIT from November 2007 to March 2017. Median patient age was 57 years (range, 42-83 years) and median histological lesion size was 14.4 mm (range, 2-51 mm). Four patients required either re-excision and/or whole breast irradiation, yielding a rate of additional therapy of 7.3% (4 of 55). Among 46 women administered TARGIT at the time of initial BCS, two local recurrences were observed yielding a 4.3% (2 of 46) LRR at 46 months median follow-up (range, 4-116 months). There were no clinically significant adverse events. CONCLUSIONS: Preliminary evidence indicates TARGIT can be performed with a low risk of requiring additional therapy (7.3%) and an acceptable LRR (4.3%) when administered at the time of BCS.