Society of Surgical Oncology Breast Disease Site Working Group Statement on Contralateral Mastectomy: Indications, Outcomes, and Risks.

Rates of contralateral mastectomy (CM) among patients with unilateral breast cancer have been increasing in the United States. In this Society of Surgical Oncology position statement, we review the literature addressing the indications, risks, and benefits of CM since the society's 2017 statement. We held a virtual meeting to outline key topics and then conducted a literature search using PubMed to identify relevant articles. We reviewed the articles and made recommendations based on group consensus. Patients consider CM for many reasons, including concerns regarding the risk of contralateral breast cancer (CBC), desire for improved cosmesis and symmetry, and preferences to avoid ongoing screening, whereas surgeons primarily consider CBC risk when making a recommendation for CM. For patients with a high risk of CBC, CM reduces the risk of new breast cancer, however it is not known to convey an overall survival benefit. Studies evaluating patient satisfaction with CM and reconstruction have yielded mixed results. Imaging with mammography within 12 months before CM is recommended, but routine preoperative breast magnetic resonance imaging is not; there is also no evidence to support routine postmastectomy imaging surveillance. Because the likelihood of identifying an occult malignancy during CM is low, routine sentinel lymph node surgery is not recommended. Data on the rates of postoperative complications are conflicting, and such complications may not be directly related to CM. Adjuvant therapy delays due to complications have not been reported. Surgeons can reduce CM rates by encouraging shared decision making and informed discussions incorporating patient preferences.

Partial breast irradiation for patients with early-stage invasive breast cancer or ductal carcinoma in situ: an ASTRO clinical practice guideline

This guideline provides evidence-based recommendations on appropriate indications and techniques for partial breast irradiation (PBI) for patients with early-stage invasive breast cancer and ductal carcinoma in situ. ASTRO convened a task force to address 4 key questions focused on the appropriate indications and techniques for PBI as an alternative to whole breast irradiation (WBI) to result in similar rates of ipsilateral breast recurrence (IBR) and toxicity outcomes. Also addressed were aspects related to the technical delivery of PBI, including dose-fractionation regimens, target volumes, and treatment parameters for different PBI techniques. The guideline is based on a systematic review provided by the Agency for Healthcare Research and Quality. Recommendations were created using a predefined consensus-building methodology and system for grading evidence quality and recommendation strength. PBI delivered using 3-dimensional conformal radiation therapy, intensity modulated radiation therapy, multicatheter brachytherapy, and single-entry brachytherapy results in similar IBR as WBI with long-term follow-up. Some patient characteristics and tumor features were underrepresented in the randomized controlled trials, making it difficult to fully define IBR risks for patients with these features. Appropriate dose-fractionation regimens, target volume delineation, and treatment planning parameters for delivery of PBI are outlined. Intraoperative radiation therapy alone is associated with a higher IBR rate compared with WBI. A daily or every-other-day external beam PBI regimen is preferred over twice-daily regimens due to late toxicity concerns.

Germline Testing in Patients With Breast Cancer: ASCO-Society of Surgical Oncology Guideline.

PURPOSE: To develop recommendations for germline mutation testing for patients with breast cancer. METHODS: An ASCO-Society of Surgical Oncology (SSO) panel convened to develop recommendations based on a systematic review and formal consensus process. RESULTS: Forty-seven articles met eligibility criteria for the germline mutation testing recommendations; 18 for the genetic counseling recommendations. RECOMMENDATIONS: BRCA1/2 mutation testing should be offered to all newly diagnosed patients with breast cancer ≤65 years and select patients >65 years based on personal history, family history, ancestry, or eligibility for poly(ADP-ribose) polymerase (PARP) inhibitor therapy. All patients with recurrent breast cancer who are candidates for PARP inhibitor therapy should be offered BRCA1/2 testing, regardless of family history. BRCA1/2 testing should be offered to women who develop a second primary cancer in the ipsilateral or contralateral breast. For patients with prior history of breast cancer and without active disease, testing should be offered to patients diagnosed ≤65 years and selectively in patients diagnosed after 65 years, if it will inform personal and family risk. Testing for high-penetrance cancer susceptibility genes beyond BRCA1/2 should be offered to those with supportive family histories; testing for moderate-penetrance genes may be offered if necessary to inform personal and family cancer risk. Patients should be provided enough pretest information for informed consent; those with pathogenic variants should receive individualized post-test counseling. Variants of uncertain significance should not impact management, and patients with such variants should be followed for reclassification. Referral to providers experienced in clinical cancer genetics may help facilitate patient selection and interpretation of expanded testing, and provide counseling of individuals without pathogenic germline variants but with significant family history.Additional information is available at www.asco.org/breast-cancer-guidelines.

Partial Breast Irradiation for Patients With Early-Stage Invasive Breast Cancer or Ductal Carcinoma In Situ: An ASTRO Clinical Practice Guideline.

PURPOSE: This guideline provides evidence-based recommendations on appropriate indications and techniques for partial breast irradiation (PBI) for patients with early-stage invasive breast cancer and ductal carcinoma in situ. METHODS: ASTRO convened a task force to address 4 key questions focused on the appropriate indications and techniques for PBI as an alternative to whole breast irradiation (WBI) to result in similar rates of ipsilateral breast recurrence (IBR) and toxicity outcomes. Also addressed were aspects related to the technical delivery of PBI, including dose-fractionation regimens, target volumes, and treatment parameters for different PBI techniques. The guideline is based on a systematic review provided by the Agency for Healthcare Research and Quality. Recommendations were created using a predefined consensus-building methodology and system for grading evidence quality and recommendation strength. RESULTS: PBI delivered using 3-dimensional conformal radiation therapy, intensity modulated radiation therapy, multicatheter brachytherapy, and single-entry brachytherapy results in similar IBR as WBI with long-term follow-up. Some patient characteristics and tumor features were underrepresented in the randomized controlled trials, making it difficult to fully define IBR risks for patients with these features. Appropriate dose-fractionation regimens, target volume delineation, and treatment planning parameters for delivery of PBI are outlined. Intraoperative radiation therapy alone is associated with a higher IBR rate compared with WBI. A daily or every-other-day external beam PBI regimen is preferred over twice-daily regimens due to late toxicity concerns. CONCLUSIONS: Based on published data, the ASTRO task force has proposed recommendations to inform best clinical practices on the use of PBI.

Factors Associated With Node-Positive Disease in Estrogen Receptor-Positive Breast Cancer Patients.

INTRODUCTION: Larger tumor size and shorter tumor-to-nipple distance at diagnosis are associated with greater risk of lymph node involvement in breast cancer. However, the relationship between receptor subtype status and lymph node metastasis remains unclear. Our objective was to examine the association between primary tumor size, location, and nodal metastasis across estrogen receptor (ER)+/ progesterone receptor (PR)+/ human epidermal growth factor receptor 2 (HER2)-, ER+/PR-/HER2-, ER+/PR+/HER2+, and ER+/PR-/HER2+ tumors. METHODS: A single-institution retrospective chart review was conducted of breast cancer patients diagnosed between 1998 and 2019 who underwent nodal evaluation during primary surgery. Neoadjuvant chemotherapy, pure ductal carcinoma in situ, inflammatory, recurrent, metastatic, bilateral, multicentric, and multifocal disease were excluded. Descriptive statistics (proportions and frequencies for categorical variables and medians [Q1-Q3] for continuous variables) were used to summarize patient characteristics. Kruskal-Wallis test was applied to test the association of outcome variables and continuous variables. Chi-square test or Fisher exact test was applied to test the association of outcome variables and categorical variables. RESULTS: Six hundred eighteen ER + patients had a median tumor size of 1.7 cm (1.1-2.5 cm). Two hundred ninety six out of 618 (47.9%) were node-positive and 188/618 (30.4%) had axillary dissection. Eighty four point three percent of patients were ER+/PR+/HER2-, 6.31% were ER+/PR-/HER2-, 6.96% were ER+/PR+/HER2+, and 1.13% were ER+/PR-/HER2+. Median tumor size was significantly larger in node-positive cases compared to node-negative cases in ER+/PR+/HER2-, ER+/PR+/HER2+, and ER+/PR-/HER2- subgroups. In ER+/PR+/HER2-patients, median tumor-nipple distance was significantly shorter in node-positive patients compared to node-negative patients. Upper outer quadrant location was significantly associated with nodal positivity in ER+/PR-/HER2- patients. CONCLUSIONS: Across ER + patients, the significance between tumor size, location, and lymph node positivity varied significantly when differentiating by PR and HER2 status.

Factors Predictive of Positive Lymph Nodes for Breast Cancer.

BACKGROUND: Axillary node status is an important prognostic factor in breast cancer. The primary aim was to evaluate tumor size and other characteristics relative to axillary disease. MATERIALS AND METHODS: Single institution retrospective chart review of stage I-III breast cancer patients collected demographic and clinical/pathologic data from 1998-2019. Student's t-test, Chi-squared test (or Fisher exact test if applicable), and logistic regression models were used for testing the association of pN+ to predictive variables. RESULTS: Of 728 patients (mean age 59 yrs) with mean follow up of 50 months, 86% were estrogen receptor +, 10% Her2+, 78% ER+HER2-negative, and 10% triple-negative. In total, 351/728 (48.2%) were pN+ and mean tumor size was larger in pN+ cases compared to pN- cases (mean = 27.7 mm versus 15.5 mm) (p < 0.001). By univariate analysis, pN+ was associated with lymphovascular invasion (LVI), higher grade, Her2, and histology (p < 0.005). Tumor-to-nipple distance was shorter in pN+ compared to pN- (45 mm v. 62 mm; p< 0.001). Age < 60, LVI, recurrence, mastectomy, larger tumor size, and shorter tumor-nipple distance were associated with 3+ positive nodes (p < 0.05). CONCLUSIONS: Larger tumor size and shorter tumor-nipple distance were associated with higher lymph node positivity. Age less than 60, LVI, recurrence, mastectomy, larger tumor size, and shorter tumor-nipple distance were all associated with 3+ positive lymph nodes.

NCCN Guidelines® Insights: Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic, Version 2.2024.

The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic focus primarily on assessment of pathogenic/likely pathogenic (P/LP) variants associated with increased risk of breast, ovarian, pancreatic, and prostate cancer, including BRCA1, BRCA2, CDH1, PALB2, PTEN, and TP53, and recommended approaches to genetic counseling/testing and care strategies in individuals with these P/LP variants. These NCCN Guidelines Insights summarize important updates regarding: (1) a new section for transgender, nonbinary and gender diverse people who have a hereditary predisposition to cancer focused on risk reduction strategies for ovarian cancer, uterine cancer, prostate cancer, and breast cancer; and (2) testing criteria and management associated with TP53 P/LP variants and Li-Fraumeni syndrome.

Tumor Characteristics Associated with Axillary Nodal Positivity in Triple Negative Breast Cancer.

Larger-size primary tumors are correlated with axillary metastases and worse outcomes. We evaluated the relationships among tumor size, location, and distance to nipple relative to axillary node metastases in triple-negative breast cancer (TNBC) patients, as well as the predictive capacity of imaging. We conducted a single-institution, retrospective chart review of stage I-III TNBC patients diagnosed from 1998 to 2019 who underwent upfront surgery. Seventy-three patients had a mean tumor size of 20 mm (range 1-53 mm). All patients were clinically node negative. Thirty-two patients were sentinel lymph node positive, of whom 25 underwent axillary lymph node dissection. Larger tumor size was associated with positive nodes (p < 0.001): the mean tumor size was 14.30 mm in node negative patients and 27.31 mm in node positive patients. Tumor to nipple distance was shorter in node positive patients (51.0 mm) vs. node negative patients (73.3 mm) (p = 0.005). The presence of LVI was associated with nodal positivity (p < 0.001). Tumor quadrant was not associated with nodal metastasis. Ultrasound yielded the largest number of suspicious findings (21/49), with sensitivity of 0.25 and specificity of 0.40. On univariate analysis, age younger than 60 at diagnosis was also associated with nodal positivity (p < 0.002). Comparative analyses with other subtypes may identify biologic determinants.

Surgical Management of the Axilla in HR+/HER2- Breast Cancer in the Z1071 Era: A Propensity Score-Matched Analysis of the National Cancer Database.

BACKGROUND: Axillary management varies between sentinel lymph node biopsy (SLNB) and axillary lymph node dissection (ALND) for patients with clinical N1 (cN1), hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)/neu-negative (HER2-), infiltrative ductal carcinoma (IDC) who achieve a complete clinical response (cCR) to neoadjuvant systemic therapy (NAST). This study sought to evaluate clinical practice patterns and survival outcomes of SLNB versus ALND in this patient subset. METHODS: Patients with cN1, HR+/HER2-, unilateral IDC demonstrating a cCR to NAST were identified from the 2012-2017 National Cancer Database (NCDB) and stratified based on final axillary surgery management (SLNB vs ALND). After propensity score-matching, overall survival (OS) was compared using a Kaplan-Meier analysis, and significant OS predictors were identified using Cox regression. RESULTS: Of the 1676 patients selected for this study, 593 (35.4%) underwent SLNB and 1083 (64.6%) underwent ALND. Use of SLNB increased by 28 % between 2012 and 2017. Among a total of 584 matched patients, 461 matched ypN0 patients, and 108 matched ypN+ patients, mean OS did not differ between SLNB and ALND (all patients [92.1 ± 0.8 vs 90.2 ± 1.0 months; p = 0.157], ypN0 patients [92.4 ± 0.8 vs 89.9 ± 0.9 months; p = 0.105], ypN+ patients [83.5 ± 2.3 vs 91.7 ± 2.7 months; p ± 0.963). Cox regression identified age, Charlson score, clinical T stage, and pathologic nodal status as significant predictors of OS. CONCLUSION: The final surgical management strategy used for cN1, HR+/HER2- IDC patients who achieved a cCR to NAST did not have a significant impact on survival outcomes in this analysis. Potential opportunities for de-escalation of axillary management among this patient subset exist, and validation studies are needed.

Factors Influencing Lymph Node Positivity in HER2/neu+ Breast Cancer Patients.

Axillary lymph node metastases are a key prognostic factor in breast cancer treatment. Our aim was to evaluate how tumor size, tumor location, and imaging results correlate to axillary lymph node diseases for patients with stage I-III HER2/neu+ breast cancer. This is a single-institution retrospective chart review of female breast cancer patients diagnosed with primary invasive Her2/neu+ breast cancer who were treated with upfront surgical resection from 2000-2021. Of 75 cases, 44/75 (58.7%) had nodal metastasis, and there was a significant association of larger tumor size to nodal metastases (p ≤ 0.001). Patients with negative nodes had a smaller mean tumor size (n = 30; 15.10 mm) than patients with positive nodes (n = 45; 23.9 mm) (p = 0.002). Preoperative imaging detected suspicious nodes in 36 patients, and ultrasound detected the most positive nodes (14/18; p = 0.027). Our data confirms that tumor size at diagnosis is correlated with a higher likelihood of axillary involvement in patients with Her2/neu+ breast cancer; notably, a large proportion of Her2/neu+ breast cancers have metastatic involvement of axillary lymph nodes even with small primary lesions.

Oncolytic T-VEC virotherapy plus neoadjuvant chemotherapy in nonmetastatic triple-negative breast cancer: a phase 2 trial.

Talimogene laherparepvec (T-VEC) is an oncolytic virus hypothesized to enhance triple-negative breast cancer (TNBC) responses to neoadjuvant chemotherapy (NAC). This article describes the phase 2 trial of T-VEC plus NAC (ClinicalTrials.gov ID: NCT02779855 ). Patients with stage 2-3 TNBC received five intratumoral T-VEC injections with paclitaxel followed by doxorubicin and cyclophosphamide and surgery to assess residual cancer burden index (RCB). The primary end point was RCB0 rate. Secondary end points were RCB0-1 rate, recurrence rate, toxicity and immune correlates. Thirty-seven patients were evaluated. Common T-VEC toxicities were fevers, chills, headache, fatigue and injection site pain. NAC toxicities were as expected. Four thromboembolic events occurred. The primary end point was met with an estimated RCB0 rate = 45.9% and RCB0-1 descriptive rate = 65%. The 2-year disease-free rate is equal to 89% with no recurrences in RCB0-1 patients. Immune activation during treatment correlated with response. T-VEC plus NAC in TNBC may increase RCB0-1 rates. These results support continued investigation of T-VEC plus NAC for TNBC.

Integrating age, BMI, and serum N-glycans detected by MALDI mass spectrometry to classify suspicious mammogram findings as benign lesions or breast cancer.

While mammograms are the standard tool for breast cancer screening, there remains challenges for mammography to effectively distinguish benign lesions from breast cancers, leading to many unnecessary biopsy procedures. A blood-based biomarker could provide a minimally invasive supplemental assay to increase the specificity of breast cancer screening. Serum N-glycosylation alterations have associations with many cancers and several of the clinical characteristics of breast cancer. The current study utilized a high-throughput mass spectrometry workflow to identify serum N-glycans with differences in intensities between patients that had a benign lesion from patients with breast cancer. The overall N-glycan profiles of the two patient groups had no differences, but there were several individual N-glycans with significant differences in intensities between patients with benign lesions and ductal carcinoma in situ (DCIS). Many N-glycans had strong associations with age and/or body mass index, but there were several of these associations that differed between the patients with benign lesions and breast cancer. Accordingly, the samples were stratified by the patient's age and body mass index, and N-glycans with significant differences between these subsets were identified. For women aged 50-74 with a body mass index of 18.5-24.9, a model including the intensities of two N-glycans, 1850.666 m/z and 2163.743 m/z, age, and BMI were able to clearly distinguish the breast cancer patients from the patients with benign lesions with an AUROC of 0.899 and an optimal cutoff with 82% sensitivity and 84% specificity. This study indicates that serum N-glycan profiling is a promising approach for providing clarity for breast cancer screening, especially within the subset of healthy weight women in the age group recommended for mammograms.

Surgical Management of the Axilla in Invasive Lobular Carcinoma in the Z1071 Era: A Propensity-Score Matched Analysis of the National Cancer Database.

In patients with invasive lobular carcinoma (ILC) and clinically positive nodes (cN1) who demonstrate an axillary clinical response to neoadjuvant-chemotherapy (NAC), the outcomes of sentinel lymph node biopsy (SLNB) compared to axillary lymph node dissection (ALND) are not well studied. We sought to evaluate axillary surgery practice patterns and the resultant impact on overall survival (OS) in cN1 ILC. The National Cancer Database (NCDB) was queried (2012-2017) for women with cN1 ILC who were treated with NAC followed by surgery. Propensity-score matching was performed between SLNB and ALND cohorts. Kaplan-Meier and Cox regression analyses were performed to identify predictors of OS. Of 1390 patients, 1192 were luminal A ILCs (85.8%). 143 patients (10.3%) had a complete axillary clinical response, while 1247 (89.7%) had a partial clinical response in the axilla. Definitive axillary surgery was SLNB in 211 patients (15.2%). Utilization of SLNB for definitive axillary management increased from 8% to 16% during the study period. Among 201 propensity-score matched patients stratified by SLNB vs. ALND, mean OS did not significantly differ (81.6 ± 1.8 vs. 81.4 ± 2.0 months; p = 0.56). Cox regression analysis of the entire cohort demonstrated that increasing age, grade, HER2+ and triple-negative tumors, and partial clinical response were unfavorable OS predictors (p < 0.02 each). The definitive axillary operation and administration of adjuvant axillary radiation did not influence OS. In cN1 ILC patients with a clinical response to NAC in the axilla, SLNB vs. ALND did not affect OS. Further axillary therapy may be warranted with ypN+ disease.

Neoadjuvant systemic therapy in geriatric breast cancer patients: a National Cancer Database (NCDB) analysis.

PURPOSE: Neoadjuvant systemic therapy (NAST) can be an effective treatment option for patients with HER2 + or triple negative breast cancer (TNBC). However, its use in geriatric patients is largely understudied. Our aim is to investigate the effect of NAST in both septuagenarians and octogenarians with HER2 + or TNBC to better understand its role in the geriatric patient population. METHODS: We utilized the National Cancer Database (NCDB) to analyze female patients with HER2 + or TNBC between 70 and 89 years. We compared the baseline demographic and clinical characteristics of septuagenarians and octogenarians using mixed-effect modeling for continuous variables and conditional logistic regressions for categorical variables. Overall survival (OS) between several subgroups was compared based on a propensity score model. Kaplan-Meier method was used to calculate OS between the subgroups, and log-rank test was used to compare OS results. RESULTS: A total of 16,443 patients met inclusion/exclusion criteria, of which 92.9% had infiltrative ductal carcinoma and 73.5% were TNBC. Most patients received NAST as a first course of therapy (58.8%). Septuagenarians were more likely to receive NAST (65.9%), whereas octogenarians were more likely to receive upfront surgical resection (67.7%). Our analysis demonstrated OS benefit with NAST among patients who received surgical resection. However, in patients who received NAST, decline during therapy was associated with a significantly poorer OS outcomes in general. CONCLUSION: When combined with surgical resection, NAST is an effective treatment option in both septuagenarians and octogenarians. Nonetheless, careful selection of NAST recipients in this population remains critical to optimize patient outcome.

Effect of Microporous Polysaccharide Particles in Patients Undergoing Mastectomy.

BACKGROUND: Microporous polysaccharide particles (MPP, proprietary name "Arista AH"), derived from purified plant starch, are used to augment hemostasis at surgery. The effect of MPP regarding short-term complications after mastectomy remains an area of ongoing investigation. PATIENTS AND METHODS: A single-institution, retrospective chart review of patients undergoing unilateral mastectomy without reconstruction from January 2019 to 2021 was performed. Primary endpoints included antibiotic prescription, seroma or abscess drainage, readmission, wound dehiscence, and time to drain removal within 30 days of initial surgery. Wilcoxon rank sum test or Student t test was used for group comparisons for continuous variables; Chi-square test or Fisher exact test was used to evaluate the associations among categorical variables. RESULTS: One hundred ninety patients were included; 119 received MPP and 71 did not. There was no difference in antibiotic prescription, infection drainage, hematoma, readmission, dehiscence, or time to drain removal with regards to MPP use. MPP treated patients were older (65.8 years vs. 59.1, P < .001) and had lower albumin levels (4.1 g/dL vs. 4.3, P = .025). Patients who underwent abscess drainage had higher body mass index ( mean 36.1 vs. 30.1 P = .036). Patients requiring seroma drainage were more likely to be diabetic (12.8% vs. 4%, P = .035) and to have been treated with lymphovenous anastomosis (LVA, 15.6% vs. 3.8%, P = .009). Patients who had LVA were significantly less likely to receive MPP when compared to other groups (3.1% vs. 74.7% P < .001). CONCLUSION: Consider utilizing MPP in patients at higher risk of seroma, such as those undergoing axillary surgery including LVA.