Is Choosing Wisely Wise for Lobular Carcinoma in Patients Over 70 Years of Age? A National Cancer Database Analysis of Sentinel Node Practice Patterns.

BACKGROUND: Controversy continues in the treatment of breast cancer in women over 70 years of age. In 2016, the Society of Surgical Oncology recommended against routine use of sentinel lymph node biopsy (SLNBx) as part of the 'Choosing Wisely Campaign'. This study examines the oncologic safety of avoidance of routine SLNBx in patients over 70 years of age with invasive lobular carcinoma (ILC). METHODS: The National Cancer Database was used to identify women with invasive ductal carcinoma (IDC) and ILC diagnosed between 2012 and 2020. Clinical and pathological staging, axillary staging, surgery type, and lymph node positivity between patients with IDC or ILC were compared. RESULTS: Among women with T1 tumors, 85,949 (79.6%) patients with IDC and 12,761 (81.5%) patients with ILC underwent SLNBx (p < 0.001). Among patients who underwent SLNBx, those with IDC were more likely to have positive nodes (n = 7535, 8.8%) than those with ILC (n = 1041, 8.2%; p = 0.02). During the time interval of interest, for both IDC and ILC patients, the rate of axillary lymph node dissection decreased and rates of SLNBx or no axillary staging increased. On multivariate analysis, ILC histology was associated with use of SLNBx, but without nodal positivity. CONCLUSION: A trend de-escalation of axillary staging was identified in this study, however the majority of patients meeting the 'Choosing Wisely' criteria are still undergoing SLNBx. No increased risk of nodal positivity was identified among patients with ILC, suggesting that surgeons can continue to choose wisely and limit the use of SLNBx in women over 70 years of age with T1 ILC tumors.

Accurate genome-wide genotyping from archival tissue to explore the contribution of common genetic variants to pre-cancer outcomes.

PURPOSE: The contribution of common genetic variants to pre-cancer progression is understudied due to long follow-up time, rarity of poor outcomes and lack of available germline DNA collection. Alternatively, DNA from diagnostic archival tissue is available, but its somatic nature, limited quantity and suboptimal quality would require an accurate cost-effective genome-wide germline genotyping methodology. EXPERIMENTAL DESIGN: Blood and tissue DNA from 10 individuals were used to benchmark the accuracy of Single Nucleotide Polymorphisms (SNP) genotypes, Polygenic Risk Scores (PRS) or HLA haplotypes using low-coverage whole-genome sequencing (lc-WGS) and genotype imputation. Tissue-derived PRS were further evaluated for 36 breast cancer patients (11.7 years median follow-up time) diagnosed with DCIS and used to model the risk of Breast Cancer Subsequent Events (BCSE). RESULTS: Tissue-derived germline DNA profiling resulted in accurate genotypes at common SNPs (blood correlation r2 > 0.94) and across 22 disease-related polygenic risk scores (PRS, mean correlation r = 0.93). Imputed Class I and II HLA haplotypes were 96.7% and 82.5% concordant with clinical-grade blood HLA haplotypes, respectively. In DCIS patients, tissue-derived PRS was significantly associated with BCSE (HR = 2, 95% CI 1.2-3.8). The top and bottom decile patients had an estimated 28% and 5% chance of BCSE at 10 years, respectively. CONCLUSIONS: Archival tissue DNA germline profiling using lc-WGS and imputation, represents a cost and resource-effective alternative in the retrospective design of long-term disease genetic studies. Initial results in breast cancer suggest that common risk variants contribute to pre-cancer progression.

Large and diffuse ductal carcinoma in situ: potentially lethal subtypes of "preinvasive" disease.

PURPOSE: Trials for DCIS have not explored whether outcomes for patients with large disease burden requiring mastectomy are comparable to those of patients with lumpectomy-amenable disease. We aim to identify whether patients with DCIS larger than 5 cm and diffuse-type DCIS differ in breast cancer mortality (BCM) from patients with disease less than 5 cm. METHODS: Patients diagnosed with DCIS in the SEER program were assessed to identify factors prognostic of breast-cancer-specific survival using competing risks regression. RESULTS: 44,849 patients met criteria for the cumulative incidence estimate. On competing risks cumulative incidence approximation, the 10-year estimate for BCM for each group was 1.3%, 1.3%, 2.3%, and 5.1%, respectively, and the difference among groups was significant (p = 0.017). On competing risks regression of patients with known covariates, both diffuse-type disease and disease larger than 5 cm (hazard ratio [HR] = 6.2 and 1.7, p = 0.013 and p = 0.042, respectively) were associated with increased risk of BCM. After matching, DCIS > 5 cm and diffuse disease were associated with increased BCM relative to disease < 5 cm (HR = 1.69, p = 0.04). Among patients undergoing mastectomy for disease larger than 5 cm or diffuse disease, the 10-year cumulative incidence for BCM was 0.5% among patients undergoing bilateral mastectomy and 2.4% for patients undergoing unilateral mastectomy. CONCLUSION: Patients with large and diffuse DCIS represent uncommon but poorly studied DCIS subgroups with worse prognoses than patients with disease smaller than 5 cm. Further studies are needed to elucidate the appropriate treatment for these patients.

Ductal carcinoma in situ in patients younger than 30 years: differences in adjuvant endocrine therapy and outcomes.

PURPOSE: To use the National Cancer Database to assess treatment patterns in very young women with ductal carcinoma in situ (DCIS) given their propensity for higher risk features and increased risk of recurrence. METHODS: We used the NCDB to identify female patients who underwent surgery for a first cancer diagnosis of DCIS within three different age groups: ≤30, 31-50, and >50. Demographic information, tumor characteristics, and initial treatment patterns were characterized and compared. Univariable and multivariable logistic regression of individuals with hormone-receptor-positive disease who underwent breast-conserving surgery (BCS) was conducted to assess for group differences in adjuvant endocrine therapy utilization. Survival analysis was conducted via Kaplan-Meier method and Cox regression. RESULTS: We identified 236,832 patients meeting inclusion criteria. Individuals in the youngest group were more likely to be a minority, had better Charlson-Deyo scores, lived further from their treatment facility, and were less often insured. This group also had more unfavorable tumor features and were more likely to undergo bilateral mastectomy. In subgroup analysis of patients with hormone-receptor-positive disease who underwent BCS, the youngest group was significantly less likely to have received endocrine therapy. There was also a trend toward worse overall survival in the youngest group. CONCLUSION: We report differences in demographics, tumor characteristics, and treatment of very young women with DCIS. Given the known reduction in recurrence with use of adjuvant endocrine therapy, there may be room for increasing therapy rates or otherwise altering guidelines for treatment of young women with hormone-receptor-positive DCIS who undergo BCS.

Modernizing Surgical Quality: A Novel Approach to Improving Detection of Surgical Site Infections in the Veteran Population.

Introduction: Surgical site infections (SSIs) are an important quality measure. Identifying SSIs often relies upon a time-intensive manual review of a sample of common surgical cases. In this study, we sought to develop a predictive model for SSI identification using antibiotic pharmacy data extracted from the electronic medical record (EMR). Methods: A retrospective analysis was performed on all surgeries at a Veteran Affair's Medical Center between January 9, 2020 and January 9, 2022. Patients receiving outpatient antibiotics within 30 days of their surgery were identified, and chart review was performed to detect instances of SSI as defined by VA Surgery Quality Improvement Program criteria. Binomial logistic regression was used to select variables to include in the model, which was trained using k-fold cross validation. Results: Of the 8,253 surgeries performed during the study period, patients in 793 (9.6%) cases were prescribed outpatient antibiotics within 30 days of their procedure; SSI was diagnosed in 128 (1.6%) patients. Logistic regression identified time from surgery to antibiotic prescription, ordering location of the prescription, length of prescription, type of antibiotic, and operating service as important variables to include in the model. On testing, the final model demonstrated good predictive value with c-statistic of 0.81 (confidence interval: 0.71-0.90). Hosmer-Lemeshow testing demonstrated good fit of the model with p value of 0.97. Conclusion: We propose a model that uses readily attainable data from the EMR to identify SSI occurrences. In conjunction with local case-by-case reporting, this tool can improve the accuracy and efficiency of SSI identification.

Distance of Biopsy-Confirmed High-Risk Breast Lesion from Concurrently Identified Breast Malignancy Associated with Risk of Carcinoma at the High-Risk Lesion Site.

High-risk breast lesions including incidental intraductal papilloma without atypia (IPA), lobular hyperplasia (LCIS or ALH), flat epithelial atypia (FEA) and complex sclerosing lesion (CSL) are not routinely excised due to low upgrade rates to carcinoma. We aim to identify features of these lesions predictive of upgrade when identified concurrently with invasive disease. Methods: A single-center retrospective cohort study was performed for patients who underwent multi-site lumpectomies with invasive disease at one site and a high-risk lesion at another site between 2006 and 2021. A multinomial logistic regression was performed. Results: Sixty-five patients met the inclusion criteria. Four patients (6.2%) had an upgrade to in situ disease (DCIS) and one (1.5%) to invasive carcinoma. Three upgraded high-risk lesions were ipsilateral to the concurrent carcinoma and two were contralateral. In the multivariate model, a high-risk lesion within 5 cm of an ipsilateral malignancy was associated with increased risk of upgrade. The 3.8% upgrade rate for high-risk lesions located greater than 5 cm from ipsilateral malignancy or in the contralateral breast suggests that omission of excisional biopsy may be considered. Excisional biopsy of lesions within 5 cm of ipsilateral malignancy is recommended given the 25% upgrade risk in our series.

Duration of Endocrine Treatment for DCIS impacts second events: Insights from a large cohort of cases at two academic medical centers.

Ductal carcinoma in situ (DCIS) incidence has risen rapidly with the introduction of screening mammography, yet it is unclear who benefits from both the amount and type of adjuvant treatment (radiation therapy, (RT), endocrine therapy (ET)) versus what constitutes over-treatment. Our goal was to identify the effects of adjuvant RT, or ET+/- RT versus breast conservation surgery (BCS) alone in a large multi-center registry of retrospective DCIS cases (N = 1,916) with median follow up of 8.2 years. We show that patients with DCIS who took less than 2 years of adjuvant ET alone have a similar second event rate as BCS. However, patients who took more than 2 years of ET show a significantly reduced second event rate, similar to those who received either RT or combined ET+RT, which was independent of age, tumor size, grade, or period of diagnosis. This highlights the importance of ET duration for risk reduction.

Bilateral mastectomy associated with higher breast cancer mortality among patients with estrogen receptor positive progesterone receptor negative localized breast cancer.

BACKGROUND: Rates of mastectomy for patients with localized breast cancer remain high despite decades of evidence that breast conservation therapy is equally effective. The impact of progesterone receptor (PR) status on the relative efficacy of surgical extent for localized estrogen receptor (ER) positive breast cancer on breast cancer mortality has not been studied. METHODS: This retrospective cohort study included patients diagnosed with breast cancer between 1998 and 2015 using data from the Surveillance, Epidemiology and End Results (SEER) program. Female patients aged 40-70 with T1-2N0M0 ER positive breast cancer were included. Patients in this study either underwent lumpectomy without radiation, lumpectomy with radiation, unilateral mastectomy without radiation, or bilateral mastectomy without radiation for their disease. Breast cancer specific mortality was the main outcome of interest, calculated using competing risks methods to estimate cumulative incidence and hazard ratios among the treatment groups. RESULTS: After one-to-one matching, 23,080 patients were included with median follow-up time 7.6 years (interquartile range, 4.0-8.3 years). Median age at diagnosis was 52 years (interquartile range, 47-59 years). Among patients, 19,996 (86.6%) had PR+ disease and 3,084 (13.4%) of patients had PR-. Among patients with PR- disease, bilateral mastectomy was associated with higher cumulative incidence of breast cancer mortality relative to patients undergoing lumpectomy with radiation, with 10-year cumulative incidences of 9.2% [95% confidence interval (CI): 6.6-12.7%] vs. 4.4% (95% CI: 3.0-6.6%). This difference was significant in the adjusted multivariate model [hazard ratio (HR) =1.77; 95% CI: 1.12-2.82; P=0.02]. CONCLUSIONS: Bilateral mastectomy was associated with significantly increased risk of breast cancer mortality relative to lumpectomy with radiation for patients with PR- disease. Unilateral mastectomy and lumpectomy without radiation were associated with increased risk for breast cancer mortality relative to lumpectomy with radiation for patients with PR+ disease.

Correlation of tangible quality parameters of vegetable-based transformer fluids.

Due to the inherent environmental footprint of petroleum derived transformer fluids, the power industry is gradually exploring the potential of vegetable oils as alternatives. The impetus comes mostly from vegetable oils renewability and their inherent biodegradability. However, the major drawback in the use of vegetable oils as dielectric fluids is their lower oxidative stability and higher kinematic viscosity compared to mineral oils. The results obtained clearly demonstrate the correlation between spectroscopic data induction time, kinematic viscosity, acid value, and peroxide value. Quantitatively, the absorption frequencies of functional groups in vegetable oil transformer fluids that can be correlated to the mentioned quality parameters show noticeable changes with aging/oxidative degradation. The study also demonstrates the utility of integrating spectroscopic data to understand trends in induction time and kinematic viscosity of oil samples heated under transformer service conditions.

Risk factors for breast cancer mortality after ductal carcinoma in situ diagnosis differ from those for invasive recurrence.

BACKGROUND: Breast cancer mortality after ductal carcinoma in situ is rare, making it difficult to predict which patients are at risk and to identify whether risk factors for this outcome are the same as those for invasive recurrence. We aimed to identify whether risk factors for invasive recurrences are similar to those for breast cancer death after a diagnosis of pure ductal carcinoma in situ. METHODS: The Surveillance, Epidemiology, and End Results Program was queried for female patients diagnosed with pure ductal carcinoma in situ. Cumulative incidence was estimated by treatment group using competing risks. Competing risks regression was then performed for the development of in-breast invasive recurrence with competing risks of breast and non-breast cancer death. Competing risks regression was then again performed for development of breast cancer mortality with the competing risk of non-breast cancer death. RESULTS: A total of 29,515 patients were identified. Of them, 164 patients suffered breast cancer mortality without an intervening invasive recurrence, and 44 suffered breast cancer mortality after an invasive in-breast recurrence. On competing risks analysis for invasive in-breast recurrence, significant factors included lesion size >5 cm (hazard ratio = 1.59, 95% confidence interval 1.24-2.04, P < .001), diffuse disease (hazard ratio = 0.0005, 95% confidence interval 0.0003-0.0007, P < .001), other race (hazard ratio = 1.29, 95% confidence interval 1.10-1.52, P = .002), Black race (hazard ratio = 1.21, 95% confidence interval 1.01-1.46, P = .04), age at diagnosis (hazard ratio = 0.99, confidence interval 0.98-1.00, P = .02), low-grade disease (hazard ratio = 0.79, 95% confidence interval 0.64-0.96, P = .02), lumpectomy with radiation (hazard ratio = 0.67, 95% confidence interval 0.58-0.77, P < .001), and mastectomy (hazard ratio = 0.36, 95% confidence interval 0.30-0.44, P < .001). Significant factors for breast cancer mortality included age at diagnosis (hazard ratio = 1.04, 95% confidence interval 1.03-1.05, P < .001), Black race (hazard ratio = 2.88, 95% confidence interval 2.08-3.99, P < .001), diffuse disease (hazard ratio = 6.02, 95% confidence interval 1.39-26.07, P = .02), lumpectomy with radiation (hazard ratio = 0.51, 95% confidence interval 0.36-0.72, P < .001), and mastectomy (hazard ratio = 0.60, 95% confidence interval 0.50-0.92, P = .02). CONCLUSION: Our results suggested that risk factors for in-breast invasive recurrence after a diagnosis of pure ductal carcinoma in situ differ from risk factors for breast cancer mortality and development of metastatic recurrence. In-breast invasive recurrence is not the only consideration for breast cancer specific mortality in ductal carcinoma in situ patients.

Glucocorticoid receptor regulates the epithelial-mesenchymal transition process through GR/ZEB1/E-cad and is involved in breast cancer endocrine drug resistance-a bioinformatics analysis.

Background: Studies have shown that there is a connection between estrogen receptor (ER) and glucocorticoid receptor (GR), which can impact the epithelial-mesenchymal transition (EMT) process and contribute to endocrine resistance in breast cancer. However, the specific mechanism is unclear. It is crucial to investigate this mechanism further. Methods: This study aimed to confirm the role of GR in breast cancer endocrine resistance. Based on our hypothesis, GR is linked to a gene involved in the EMT process, and thus contributes to endocrine resistance in breast cancer. We obtained survival data and GR expression data from Molecular Taxonomy of Breast Cancer International Consortium (METABRIC). Additionally, we gathered GR expression data from Gene Expression Omnibus (GEO). Using Cytoscape, we constructed a protein-protein interaction (PPI) network and identified key genes. Data of Vimentin, E-cad, and Wnt/ß-catenin expression were obtained from The Cancer Genome Atlas (TCGA). We used the co-expression method to identify key proteins. UALCAN and cBioPortal were utilized to verify the function of the key protein. Results: In ER+ breast cancer, GR (P=3.12780899271121E-08) and zinc finger E-box binding homeobox 1 (ZEB1) (P=1.716157E-01) were lowly expressed and down-regulated genes of GR differentially expressed genes were enriched in cell adhesion molecules. We screened for the key protein ZEB1 and found high levels of it was positively associated with prolonged recurrence-free survival (RFS) in patients receiving endocrine therapy (P=0.0024), while high levels of E-cad were negatively associated (P=0.0038). GR expression was positively associated with ZEB1 (Spearman =0.29, P=8.50e-21), negatively associated with E-cad (Spearman =-0.13, P=5.17e-5), and negatively associated with the SETD1B (Spearman =-0.14, P=1.527e-5), a gene downstream of ZEB1. In contrast, ZEB1 expression was negatively correlated with E-cad (Spearman =-0.081, P=3.132e-3) and negatively correlated with SET domain-containing 1B (SETD1B) (Spearman =-0.177, P=9.07e-11). Conclusions: In ER+ breast cancers, GR expression is suppressed, and the EMT process is inhibited by suppressing ZEB1 expression and thus promoting E-cad expression. For the investigation of endocrine medication resistance in breast cancer, it is crucial to identify the mechanisms by how GR participates in the EMT process.

Histopathological growth distribution of ductal carcinoma in situ: tumor size is not "one size fits all".

Background: Ductal carcinoma in situ (DCIS) is a group of preinvasive breast neoplasms. Studies have shown excellent survival among patients with lumpectomy-amenable disease. Patients requiring mastectomy have been less well characterized. We aim to characterize this cohort and identify whether growth distribution pattern is associated with sentinel lymph node involvement at time of surgery or subsequent development of metastatic disease. Methods: Patients were identified using local cancer registry data and were chart reviewed using electronic medical records. Growth pattern was classified as unifocal, multifocal, or diffuse. Chi-squared, Analysis of Variance (ANOVA), and Kaplan-Meier analyses were performed. Results: Two hundred and twenty-six patients were identified with median age at diagnosis 49 and follow up 7.1 years. 42 had unifocal, 51 had multifocal and 20 had diffuse lesions. 3/20 patients with diffuse type lesions developed subsequent distant metastatic disease, while none of the patients with unifocal or multifocal lesions did. 1/20 patients with diffuse and 2/51 with multifocal disease had sentinel lymph node involvement (SLNI) at surgery. Tumor extent was not associated with sentinel lymph node involvement or distant metastatic disease (P=0.2, Kaplan-Meier analysis) but growth pattern was (P=0.01). It was also associated on Kaplan-Meier with development of distant metastatic disease alone (P=0.01). Conclusions: Patients with diffuse growth pattern DCIS were more likely to have SLNI or development of distant metastatic disease. Our findings suggest that patients with diffuse type lesions are at greater risk of metastatic disease and therefore breast cancer death from DCIS. Optimal therapy for these patients will need further elucidation.

The breast pre-cancer atlas illustrates the molecular and micro-environmental diversity of ductal carcinoma in situ.

Microenvironmental and molecular factors mediating the progression of Breast Ductal Carcinoma In Situ (DCIS) are not well understood, impeding the development of prevention strategies and the safe testing of treatment de-escalation. We addressed methodological barriers and characterized the mutational, transcriptional, histological, and microenvironmental landscape across 85 multiple microdissected regions from 39 cases. Most somatic alterations, including whole-genome duplications, were clonal, but genetic divergence increased with physical distance. Phenotypic and subtype heterogeneity was frequently associated with underlying genetic heterogeneity and regions with low-risk features preceded those with high-risk features according to the inferred phylogeny. B- and T-lymphocytes spatial analysis identified three immune states, including an epithelial excluded state located preferentially at DCIS regions, and characterized by histological and molecular features of immune escape, independently from molecular subtypes. Such breast pre-cancer atlas with uniquely integrated observations will help scope future expansion studies and build finer models of outcomes and progression risk.

Efficacy and safety of neoadjuvant pertuzumab plus trastuzumab in combination with chemotherapy regimen in Chinese patients with HER2-positive early breast cancer: a real-world retrospective multi-center cohort study.

Background: Pertuzumab plus trastuzumab combined with chemotherapy has become a standard neoadjuvant therapy option for patients with high-risk human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC). There is still not enough evidence for the efficacy and safety of neoadjuvant pertuzumab and trastuzumab plus chemotherapy in HER2-positive BC patients in China, both in clinical trials and real-world settings. This study aimed to assess the efficacy and safety of neoadjuvant pertuzumab plus trastuzumab in combination with chemotherapy in Chinese patients with HER2-positive BC in real-world clinical application. Methods: We retrospectively collected the data from the electronic medical records of HER2-positive patients treated with neoadjuvant trastuzumab and pertuzumab plus chemotherapy from December 2018 to May 2021 at 21 hospitals located in Hunan Province, China, including age, American Joint Committee on Cancer (AJCC) stage, clinical tumor size, clinical lymph node status, pathological characteristics (before neoadjuvant systemic therapy), treatment approach, adverse events to neoadjuvant therapy, and achievement of pathological complete response (pCR). The primary endpoint was the total rate of pCR, and the secondary endpoints were the rate of pCR of each subgroup and the safety of dual anti-HER2 therapy. Results: A total of 188 patients met the inclusion criteria and were included in the analysis. Of the 188 patients, 119 (63.3%) were diagnosed at stage II and 64 (34.0%) at stage III; 163 (86.7%) were cT2-3; 149 patients (79.3%) were ≥ cN1; 84 patients (44.7%) were hormone receptor (HR)-positive. pCR was observed in 88 of 188 patients (46.8%). The pCR rate of HR-negative patients (54.8%) was higher (P=0.014) than that of HR-positive patients (36.9%). Patients with Ki-67 <15% achieved a higher (P=0.033) pCR rate (68.2%) than those with Ki-67 ≥15% (44.0%). Anemia was the most common adverse event (63.4%), and the most common grade 3-4 adverse event was nausea and vomiting (8.5%). Conclusions: Our study confirmed the benefit of neoadjuvant pertuzumab plus trastuzumab in combination with chemotherapy on pCR with a tolerable safety profile in routine clinical practice in Chinese patients with HER2-positive BC. HR-negativity and Ki-67 <15% were associated with pCR in these patients.

Clinical and radiographic evaluation of a monoblock tibial component.

Modular tibial components are the clinical standard in total knee arthroplasty despite the lack of evidence of improved function and longevity when compared with monoblock implants. This study describes the minimum 5-year outcomes for 125 total knee arthroplasties performed with monoblock tibial components in 101 patients. No patients were lost to follow-up. Average Knee Society Score was 87.1 at a mean follow-up of 5.2 years. Clinical and radiographic follow-up showed all components to be stable, no implants at risk of loosening, no observable osteolysis, and no observed change in bone density. Survivorship free of revision for tibial component loosening was 100% at 5 years. These results show excellent midterm durability of a partially cemented porous tantalum monoblock implant with uncemented pegs.

HER2-Overexpressing Ductal Carcinoma In Situ Associated with Increased Risk of Ipsilateral Invasive Recurrence, Receptor Discordance with Recurrence.

The impact of HER2 status in ductal carcinoma in situ (DCIS) on the risk of progression to invasive ductal carcinoma (IDC) has been debated. We aim to use a national database to identify patients with known HER2 status to elucidate the effect of HER2 overexpression on ipsilateral IDC (iIDC) development. We performed survival analysis on patient-level data using the U.S. NCI's Surveillance Epidemiology and End Results program. We identified patients diagnosed with DCIS who underwent lumpectomy and had known HER2 status. Competing risks analysis was performed. A total of 1,540 patients had known HER2 status and met inclusion criteria. Median age at diagnosis was 60, median follow-up time was 44.5 months. A total of 417 (27.1%) patients were HER2 positive and 1,035 (67.2%) were HER2 negative. Twenty-two (1.4%) patients developed iIDC and 27 (1.8%) developed ipsilateral in situ or contralateral disease. The estimated cumulative incidence of iIDC at 5 years was 1.9% for all patients, 1.2% for HER2-negative and borderline patients, and 3.9% for HER2-positive patients. On multivariate competing risks regression, two factors were significant for iIDC: radiation (protective) therapy within 24 months (HR, 0.05; P = 0.00006) and HER2 overexpression (increased likelihood; HR, 2.72; P = 0.044). Patients with HER2-positive DCIS were more likely to have recurrences with receptor discordance. HER2 may serve as a prognostic factor for invasive recurrence and was the only lesion-related factor to significantly relate to iIDC development. It may also be associated with receptor discordance of recurrences. Further large studies will be needed to confirm these results.