Radiation Induced Atypical Vascular Lesion in the Breast.

BACKGROUND AND PURPOSE: Atypical vascular lesion (AVL) became a separate WHO diagnosis in November 2019. Due to a possible risk of developing angiosarcoma, extensive surgery with excision of AVL has been recommended but the benefit from this is questionable. We investigated whether the change in WHO classification has led to an increase in the number of patients diagnosed with AVL, thereby leading to an increase in extensive surgery. METHOD: The Danish National Pathology Databank was used to identify patients diagnosed with AVL between June 1, 2010 to June 31, 2020. The rate of AVL diagnosed before and after change in WHO classification was compared. RESULTS: In total, 13 cases of AVL were identified, 3 cases diagnosed before changes in WHO classification corresponding to 0.025 cases per month, compared to 8 cases, 1.143 cases per month, after the change in WHO classification. This corresponded to a 45-fold increase (95%CI: 10.88-265,31) (P < .0001) in AVL diagnosis. The mean patient age at diagnosis was 67 years. Patients received treatment varying from yearly follow up to extensive surgery. Non developed angiosarcoma in the follow-up period of 22 months. CONCLUSION: The changes in WHO classification of AVL has led to a considerable increase in the number of patients diagnosed with the lesion. No standardized treatment exists for this rare condition, but extensive surgery is often recommended to this frail population despite the lack of evidence for prognostic benefit from the procedure. Prospective follow-up studies are needed to determine the optimal treatment strategy.

ESTRO ACROP consensus guideline for target volume delineation in the setting of postmastectomy radiation therapy after implant-based immediate reconstruction for early stage breast cancer.

Immediate breast reconstruction (IBR) rates after mastectomy are increasing. Postmastectomy radiation therapy (PMRT) contouring guidelines for target volumes in the setting of IBR are lacking. Therefore, many patients who have had IBR receive PMRT to target volumes similar to conventional simulator-based whole breast irradiation. The aim of this paper is to describe delineation guidelines for PMRT after implant-based IBR based on a thorough understanding of the surgical procedures, disease stage, patterns of recurrence and radiation techniques. They are based on a consensus endorsed by a global multidisciplinary group of breast cancer experts.

Radioactive Seed Localization or Wire-guided Localization of Nonpalpable Invasive and In Situ Breast Cancer: A Randomized, Multicenter, Open-label Trial.

OBJECTIVE: To compare the rate of positive resection margins between radioactive seed localization (RSL) and wire-guided localization (WGL) after breast conserving surgery (BCS). BACKGROUND: WGL is the current standard for localization of nonpalpable breast lesions in BCS, but there are several difficulties related to the method. METHODS: From January 1, 2014 to February 4, 2016, patients with nonpalpable invasive breast cancer or DCIS visible on ultrasound were enrolled in this randomized, multicenter, open-label clinical trial, and randomly assigned to RSL or WGL. The primary outcome was margin status after BCS. Secondary outcomes were duration of the surgical procedure, weight of surgical specimen, and patients' pain perception. Analyses were performed by intention-to-treat (ITT) and per protocol. RESULTS: Out of 444 eligible patients, 413 lesions representing 409 patients were randomized; 207 to RSL and 206 to WGL. Twenty-three did not meet inclusion criteria, chose to withdraw, or had a change in surgical management and were excluded. The remaining 390 lesions constituted the ITT population. Here, resection margins were positive in 23 cases (11.8%) in the RSL group compared with 26 cases (13.3%) in the WGL group (P = 0.65). The per-protocol analysis revealed no difference in margin status (P = 0.62). There were no significant differences in the duration of the surgical procedure (P = 0.12), weight of the surgical specimen (P = 0.54) or the patients' pain perception (P = 0.28). CONCLUSION: RSL offers a major logistic advantage, as localization can be done several days before surgery without any increase in positive resection margins compared with WGL.

Reoperation Rates in Ductal Carcinoma In Situ vs Invasive Breast Cancer After Wire-Guided Breast-Conserving Surgery.

Importance: New techniques for preoperative localization of nonpalpable breast lesions may decrease the reoperation rate in breast-conserving surgery (BCS) compared with rates after surgery with the standard wire-guided localization. However, a valid reoperation rate for this procedure needs to be established for comparison, as previous studies on this procedure include a variety of malignant and benign breast lesions. Objectives: To determine the reoperation rate after wire-guided BCS in patients with histologically verified nonpalpable invasive breast cancer (IBC) or ductal carcinoma in situ (DCIS) and to examine whether the risk of reoperation is associated with DCIS or histologic type of the IBC. Design, Setting, and Participants: This nationwide study including women with histologically verified IBC or DCIS having wire-guided BCS performed between January 1, 2010, and December 31, 2013, used data from the Danish National Patient Registry that were cross-checked with the Danish Breast Cancer Group database and the Danish Pathology Register. Main Outcomes and Measures: Reoperation rate after wire-guided BCS in patients with IBC or DCIS. Results: Wire-guided BCS was performed in 4118 women (mean [SD] age, 60.9 [8.7] years). A total of 725 patients (17.6%) underwent a reoperation: 593 were reexcisions (14.4%) and 132 were mastectomies (3.2%). Significantly more patients with DCIS (271 of 727 [37.3%]) than with IBC (454 of 3391 [13.4%]) underwent a reoperation (adjusted odds ratio, 3.82; 95% CI, 3.19-4.58; P < .001). After the first reexcision, positive margins were still present in 97 patients (16.4%). The risk of repeated positive margins was significantly higher in patients with DCIS vs those with IBC (unadjusted odds ratio, 2.21; 95% CI, 1.42-3.43; P < .001). The risk of reoperation was significantly increased in patients with lobular carcinoma vs those with ductal carcinoma (adjusted odds ratio, 1.44; 95% CI 1.06-1.95; P = .02). A total of 202 patients (4.9%) had a subsequent completion mastectomy, but no difference was found in the type of reoperation between patients with DCIS and those with IBC. Conclusions and Relevance: A lower reoperation rate after wire-guided BCS was found in this study than those shown in previous studies. However, the risk of reoperation in patients with DCIS was 3 times higher than in those with IBC. The widespread use of mammographic screening will increase the number of patients diagnosed with DCIS, making a precise localization of nonpalpable DCIS lesions even more important.

Risk of non-sentinel node metastases in patients with symptomatic cancers compared to screen-detected breast cancers.

BACKGROUND: Symptomatic breast cancers may be more aggressive as compared to screen-detected breast cancers. This could favor axillary lymph node dissection (ALND) in patients with symptomatic breast cancer and positive sentinel nodes. METHOD: We identified 955 patients registered in the Danish Breast Cancer Cooperative Group (DBCG) Database in 2008 - 2010 with micrometastases (773) or isolated tumor cells (ITC) (182) in the sentinel node. Patients were cross-checked in the Danish Quality Database of Mammography Screening and 481 patients were identified as screen-detected cancers. The remaining 474 patients were considered as having symptomatic cancers. Multivariate analyses of the risk of non-sentinel node metastases were performed including known risk factors for non-sentinel node metastases as well as method of detection. RESULTS: 18% of the patients had metastases in non-sentinel nodes. This was evenly distributed between patients with symptomatic and screen-detected cancers; 18.5% vs 17.5% (OR 1.07; 95% CI 0.77-1.49; p = 0.69). In patients with micrometastases 21% had non-sentinel node metastases in the group with symptomatic cancers compared to 19% of patients with screen-detected cancers. This difference was not significant (OR 1.16; 95% CI 0.81-1.65, p = 0.43). Neither the multivariate analysis showed an increased risk of non-sentinel node metastases in patients with symptomatic cancers compared to screen-detected cancers (OR 1.12, CI 0.77-1.62, p = 0.55). In patients with ITCs 8% of patients with symptomatic cancers had non-sentinel node metastases compared to 13% of patients with screen-detected cancers. This difference was not significant (OR 0.58; 95% CI 0.22-1.54, p = 0.27). In the multivariate analysis, the risk of non-sentinel node metastases was still not significantly increased in patients with symptomatic cancers compared to screen-detected cancers (OR 0.45; 95% CI 0.16-1.27, p = 0.13). CONCLUSION: We did not find any clinically relevant difference in the risk of non-sentinel node metastases between patients with symptomatic and screen-detected cancers with micrometastases or ITC in the sentinel node.

Robust and validated models to predict high risk of non-sentinel node metastases in breast cancer patients with micrometastases or isolated tumor cells in the sentinel node.

BACKGROUND: Benefit from axillary lymph node dissection in sentinel node positive breast cancer patients is under debate. Based on data from 1820 Danish breast cancer patients operated in 2002-2008, we have developed two models to predict high risk of non-sentinel node metastases when micrometastases or isolated tumor cells are found in sentinel node. The aim of this study was to validate these models in an independent Danish dataset. MATERIAL AND METHODS: We included 720 breast cancer patients with micrometastases and 180 with isolated tumor cells in sentinel node operated in 2009-2010 from the Danish Breast Cancer Cooperative Group database. Accuracy of the models was tested in this cohort by calculating area under the receiver operating characteristic curve (AUC) as well as sensitivity and specificity. RESULTS: AUC for the model for patients with micrometastases was comparable to AUC in the original cohort: 0.63 and 0.64, respectively. The sensitivity and specificity for predicting risk of non-sentinel node metastases over 30% was 0.36 and 0.81, respectively, in the validation cohort. AUC for the model for patients with isolated tumor cells decreased from 0.73 in the original cohort to 0.60 in the validation cohort. When dividing patients with isolated tumor cells into high and low risk of non-sentinel node metastases according to number of risk factors present, 37% in the high-risk group had non-sentinel node metastases. Specificity and sensitivity was 0.48 and 0.88, respectively, in the validation cohort when using this cut-point. CONCLUSION: In this independent dataset, the model for patients with micrometastases was robust with accuracy similar to the original cohort, while the model for patients with isolated tumor cells was less accurate. The models may be used to identify patients where axillary lymph node dissection should still be considered.

Quantifying the number of lymph nodes identified in one-stage versus two-stage axillary dissection in breast cancer.

PURPOSE: To establish whether a different number of lymph nodes is identified in a delayed versus an immediate axillary lymph node dissection (ALND) in breast cancer patients. METHODS: Using data from the Danish National Patient Register and the Danish Breast Cancer Cooperative Group Database we identified 864 breast cancer patients with sentinel lymph node dissection (SLND) and delayed ALND and 7393 breast cancer patients with SLND and immediate ALND operated between 2002 and 2010. We compared the number of lymph nodes identified in the two groups by a student's t-test. RESULTS: The mean number of lymph nodes identified in patients with immediate and delayed ALND was 16.55 and 15.59, respectively. This difference was statistically significant (P < 0.0001). CONCLUSION: The number of lymph nodes identified in breast cancer patients is slightly reduced if delayed ALND is performed. However, the difference is small and considered to be without clinical significance.

International multicenter tool to predict the risk of nonsentinel node metastases in breast cancer.

BACKGROUND: Axillary treatment of breast cancer patients is undergoing a paradigm shift, as completion axillary lymph node dissections (ALNDs) are being questioned in the treatment of patients with tumor-positive sentinel nodes. This study aims to develop a novel multi-institutional predictive tool to calculate patient-specific risk of residual axillary disease after tumor-positive sentinel node biopsy. METHODS: Breast cancer patients with a tumor-positive sentinel node and a completion ALND from five European centers formed the original patient series (N = 1000). Statistically significant variables predicting nonsentinel node involvement were identified in logistic regression analysis. A multivariable predictive model was developed and validated by area under the receiver operating characteristics curve (AUC), first internally in 500 additional patients and then externally in 1068 patients from other centers. All statistical tests were two-sided. RESULTS: Nine tumor- and sentinel node-specific variables were identified as statistically significant factors predicting nonsentinel node involvement in logistic regression analysis. A resulting predictive model applied to the internal validation series resulted in an AUC of 0.714 (95% confidence interval [CI] = 0.665 to 0.763). For the external validation series, the AUC was 0.719 (95% CI = 0.689 to 0.750). The model was well calibrated in the external validation series. CONCLUSIONS: We present a novel, international, multicenter, predictive tool to assess the risk of additional axillary metastases after tumor-positive sentinel node biopsy in breast cancer. The predictive model performed well in internal and external validation but needs to be further studied in each center before application to clinical use.

Iatrogenic displacement of tumor cells to the sentinel node after surgical excision in primary breast cancer.

Isolated tumor cells (ITC) are more common in the sentinel node (SN) after needle biopsy of a breast cancer, indicating iatrogenic displacement of tumor cells. We here investigate whether similar iatrogenic displacement occurs after surgical excision of a breast tumor. We compared the incidence of ITC in the SN of 414 breast cancer patients with recent surgical excision to a group of 16,960 patients without recent surgical procedure in a multivariate analysis by linking data from the Danish Breast Cancer Cooperative Group database and the Danish National Health Register. Moreover, the incidence of spread to non-SNs in patients with ITC in the SN after recent surgical excision was analyzed. We found an adjusted odds ratio on 3.73 (95% CI 2.57-5.43; P < 0.0001) for having ITC in the SN after surgical excision. The increase in ITC after surgical excision was especially seen in patients with ductal carcinomas (OR 4.66; 95% CI 3.03-7.19). None of the patients with ITC in SN after surgical excision had further spread to non-SNs compared to 12% in the group without recent surgical excision (P = 0.09). The nearly fourfold increase in ITC in the SN after surgical excision indicates that this procedure induces iatrogenic displacement of tumor cells. This displacement was more common in ductal carcinomas. We found no further dissemination to non-SNs in patients with ITC in the SN after recent surgical excision, and it is questioned whether these patients benefit from an axillary lymph node dissection.