Inhibiting Pathological Calcium Phosphate Mineralization: Implications for Disease Progression.

Pathological calcifications, especially calcium phosphate microcalcifications (MCs), appear in most early breast cancer lesions, and their formation correlates with more aggressive tumors and a poorer prognosis. Hydroxyapatite (HA) is a key MC component that crystallizes in the tumor microenvironment. It is often associated with malignant breast cancer lesions and can trigger tumorigenesis in vitro. Here, we investigate the impact of additives on HA crystallization and inhibition, and how precancerous breast cells respond to minerals that are deposited in the presence of these additives. We show that nonstoichiometric HA spontaneously crystallizes in a solution simulating the tumor microenvironmental fluids and exhibits lump-like morphology similar to breast cancer MCs. In this system, the effectiveness of poly(aspartic acid) and poly(acrylic acid) (PAA) to inhibit HA is examined as a potential route to improve cancer prognosis. In the presence of additives, the formation of HA lumps is associated with the promotion or only minimal inhibition of mineralization, whereas the formation of amorphous calcium phosphate (ACP) lumps is followed by inhibition of mineralization. PAA emerges as a robust HA inhibitor by forming spherical ACP particles. When precancerous breast cells are exposed to various HA and ACP minerals, the most influential factors on cell proliferation are the mineral phase and whether the mineral is in the form of discrete particles or particle aggregates. The tumorigenic effects on cells, ranging from cytotoxicity and suppression of proliferation to triggering of proliferation, can be summarized as HA particles < HA aggregates < ACP particles < ACP aggregates. The cellular response to minerals can be attributed to a combination of factors, including mineral phase, crystallinity, morphology, surface texture, aggregation state, and surface potential. These findings have implications for understanding mineral-cell interactions within the tumor microenvironment and suggest that, in some cases, the byproducts of HA inhibition can contribute to disease progression more than HA itself.

Systematic review and meta-analysis of prognostic characteristics for breast cancers in populations with digital versus film mammography indicate the transition may have increased both early detection and overdiagnosis.

OBJECTIVE: Film mammography has replaced digital mammography in breast screening programs globally. This led to a small increase in the rate of detection, but whether the detection of clinically important cancers increased is uncertain. We aimed to assess the impact on tumour characteristics of screen-detected and interval breast cancers. STUDY DESIGN AND SETTING: We searched seven databases from inception to 08 October 2023 for publications comparing film and digital mammography within the same population of asymptomatic women at population (average) risk of breast cancer. We recorded reported tumour characteristics and assessed risk of bias using the ROBINS-I tool. We synthesized results using meta-analyses of random effects. RESULTS: Eighteen studies were included in the analysis from 8 countries, including 11,592,225 screening examinations (8,117,781 film; 3,474,444 digital). There were no differences in tumour size, morphology, grade, node status, receptor status, or stage in the pooled differences for screen-detected and interval invasive cancer tumour characteristics. There were statistically significant increases in screen-detected DCIS across all grades: 0.05 (0.00-0.11), 0.14 (0.05-0.22), and 0.19 (0.05-0.33) per 1,000 screens for low, intermediate, and high grade DCIS respectively. There were similar (non-statistically significant) increases in screen-detected invasive cancer across all grades. CONCLUSION: The increased detection of all grades of DCIS and invasive cancer may indicate both increased early detection of more aggressive disease and increased overdiagnosis. FUNDING: Australian National Health and Medical Research Council and the National Breast Cancer Foundation. REGISTRATION: PROSPERO 2017:CRD42017070601.

Outcomes of atypical (B3) core biopsy lesions diagnosed across BreastScreen NSW, Australia.

INTRODUCTION: Atypical or B3 lesions comprise a heterogeneous group of uncertain malignant potential. B3 lesions diagnosed on core biopsy are usually recommended for diagnostic open biopsy. Identifying factors which could allow conservative management of B3 lesions would be helpful in avoiding unnecessary surgery. The aim of this study was to identify the upgrade rate to malignancy for B3 core biopsy lesions and to compare characteristics of lesions which were malignant and benign at excision. METHOD: This retrospective study used data from BreastScreen New South Wales (NSW), Australia, of women who were diagnosed with B3 lesions on needle biopsy from 2011 to 2019. RESULTS: During the study period, 1927 B3 lesions were included. The upgrade rate to malignancy was 26.4%. Of the malignant lesions on excision, 29.6% were invasive and 69.2% were in situ. The rates of upgrade to invasive cancer and DCIS varied substantially with the core biopsy lesion type. Lesions with atypia on core biopsy had significantly higher upgrade rates to malignancy at 34.7% compared to 13.6% for lesions without atypia (p < 0.0001). Lesions with malignant pathology were significantly larger than those with benign pathology (difference = 5.1 mm (95% CI 2.7-7.5 mm), p < 0.001). CONCLUSIONS: The overall upgrade rate of B3 lesions to malignancy was 26.4%. The majority of the lesions were upgraded to DCIS instead of invasive cancer. Upgrade rates varied by lesion type. Lesions with atypia had significantly higher upgrade rates to cancer compared to lesions without atypia. Malignant lesions were significantly larger than benign lesions.

Tools to Guide Radiation Oncologists in the Management of DCIS.

Similar to invasive breast cancer, ductal carcinoma in situ is also going through a phase of changes not only from a technical but also a conceptual standpoint. From prescribing radiotherapy to everyone to personalized approaches, including radiotherapy omission, there is still a lack of a comprehensive framework to guide radiation oncologists in decision making. Many pieces of the puzzle are finding their place as high-quality data mature and are disseminated, but very often, the interpretation of risk factors and the perception of risk remain very highly subjective. Sharing the therapeutic choice with patients requires effective communication for an understanding of risks and benefits, facilitating an informed decision that does not increase anxiety and concerns about prognosis. The purpose of this narrative review is to summarize the current state of knowledge to highlight the tools available to radiation oncologists for managing DCIS, with an outlook on future developments.

Expression of immune-related genes and breast cancer recurrence in women with ductal carcinoma in situ.

BACKGROUND AND AIM: Ductal carcinoma in situ (DCIS) is a non-obligate precursor of invasive breast cancer with highly variable clinical behavior, but risk stratification is still challenging. We sought to identify immune-related gene expression signatures of pure DCIS associated with different risks of breast cancer recurrence. METHODS: A retrospective nested case-control study of 143 pure DCIS was performed including 70 women with subsequent ipsilateral breast event (IBE, in situ or invasive; cases) and 73 DCIS women with no IBE and matched for age, tumor size, treatment, hormone receptors/HER2 status, and follow-up time (controls). RNA was extracted from DCIS samples and subjected to next-generation sequencing gene expression analysis of 395 immune-related genes. Correlations between DCIS immune-related gene expression and IBE were analyzed using weighted Cox regression for nested case-control data. RESULTS: Eight immune-related genes were differentially expressed between cases and controls. MAGEA10 expression (present vs. absent) and high expression levels of IFNA17 and CBLB (Q4 vs. Q1) were observed more frequently in DCIS of women with subsequent IBE, mainly invasive (p-valueFDR < 0.05). Conversely, expression of IL3RA1, TAGAP, TNFAIP8, and high expression levels of CCL2 and LRP1 were associated with a lower risk of IBE (p-valueFDR < 0.05). CONCLUSION: This exploratory analysis of pure DCIS showed significant differences in immune-related gene expression profiles between women with and with no subsequent IBE, particularly as invasive IBE. These results, after additional validation, could improve risk stratification and management of DCIS patients.

Nipple-Sparing Mastectomy and Adequate Margins for Patients With Ductal Carcinoma In Situ.

BACKGROUND: For patients with ductal carcinoma in situ (DCIS) undergoing breast conservation surgery (BCS), guidelines advise a margin width of at least 2 mm, with studies demonstrating decreased recurrence risk compared to narrower margins. However, limited data exist establishing if this margin is appropriate in mastectomies, and specifically for nipple-sparing mastectomy (NSM). Consequently, we evaluated the margins of DCIS patients undergoing NSM and resulting oncologic outcomes. METHODS: A single-institution retrospective review was performed in patients with DCIS or DCIS with microinvasion (DCIS + MI) undergoing NSM from April 2010 to December 2021. Patient and tumor characteristics, margin status, treatment, and outcomes information were collected. The association between margins and local-regional (LRR) and distant recurrence (DR) were examined. RESULTS: 161 patients were included, comprising 284 NSM (164 therapeutic, 120 prophylactic). 153 patients had DCIS and 8 had DCIS + MI. Most patients had hormone sensitive, 123 (76.4%), and nuclear grade 2, 72 (44.7%), disease. In total, 35 (21.7%) patients had positive or <2 mm margins. Of these, 21 (60%) involved the anterior margin. At a median follow-up of 45 months (range 0-151), 2.5% (n = 4) had a LRR and .6% (n = 1) had a DR. Of patients with a recurrence, only 2 had positive or <2 mm margins, 1 had received endocrine therapy, and none received adjuvant radiation. DISCUSSION: No specific margin status was found to correlate with recurrence for patients with DCIS or DCIS + MI undergoing NSM, with an altogether low recurrence risk. Overall, this suggests that recommended DCIS margins in BCS doesn't necessarily apply in NSM, where margins of <2 mm may be acceptable.

Assessing the malignancy of suspicious breast microcalcifications: the role of contrast enhanced mammography.

PURPOSE: To assess the role of contrast-enhanced mammography (CEM) in predicting the malignancy of breast calcifications. MATERIAL AND METHODS: We retrospectively evaluated patients with suspicious calcifications (BIRADS 4) who underwent CEM and stereotactic vacuum-assisted biopsy (VAB) at our institution. We assessed the sensitivity (SE), specificity (SP), positive predictive value (PPV) and negative predictive value (NPV) of CEM in predicting malignancy of microcalcifications with a 95% confidence interval; we performed an overall analysis and a subgroup analysis stratified into group A-low risk (BIRADS 4a) and group B-medium/high risk (BIRADS 4b-4c). We then evaluated the correlation between enhancement and tumour proliferation index (Ki-67) for all malignant lesions. RESULTS: Data from 182 patients with 184 lesions were collected. Overall the SE of CEM in predicting the malignancy of microcalcifications was 0.70, SP was 0.85, the PPV was 0.82, the NPV was 0.76 and AUC was 0.78. SE in group A was 0.89, SP was 0.89, PPV was 0.57, NPV was 0.98 and AUC was 0.75. SE in group B was 0.68, SP was 0.80, PPV was 0.87, NPV was 0.57 and AUC was 0.75. Among malignant microcalcifications that showed enhancement (N = 52), 61.5% had Ki-67 ≥ 20% and 38.5% had low Ki-67 values. Among the lesions that did not show enhancement (N = 22), 90.9% had Ki-67 < 20% and 9.1% showed high Ki-67 values 20%. CONCLUSIONS: The absence of enhancement can be used as an indicative parameter for the absence of disease in cases of low-suspicious microcalcifications, but not in intermediate-high suspicious ones for which biopsy remains mandatory and can be used to distinguish indolent lesions from more aggressive neoplasms, with consequent reduction of overdiagnosis and overtreatment.

Development of erlotinib-loaded nanotransferosomal gel for the topical treatment of ductal carcinoma in situ.

Aims: This study was aimed to formulate erlotinib (ERL)-loaded transferosomal gel (ERL@TG) intended for topical application for the treatment of ductal carcinoma in situ. Materials & methods: The optimized process involved a thin-film hydration method to generate ERL-loaded transferosomes (ERL@TFS), which was incorporated into a carbopol gel matrix to generate ERL@TG. The optimized formulation was characterized in vitro followed by cytotoxicity evaluation on MCF-7 breast cancer cell lines and acute toxicity and skin irritation studies was performed in vivo. Results: In a comparative assessment against plain ERL, ERL@TG displayed enhanced efficacy against MCF-7 cell lines, reflected in considerably lower IC50 values with an enhanced safety profile. Conclusion: Optimized ERL@TG was identified as a promising avenue for addressing ductal carcinoma in situ breast cancer.

Despite progress, breast cancer remains a significant cause of death. This study aimed to revolutionize the treatment of noninvasive ductal carcinoma in situ, a type of breast cancer, by developing a special gel that can be applied directly to the breast. The developed gel was in the nanoform, a 'nanotransfersomal' gel that contained erlotinib, a potent drug for breast cancer. To ensure its effectiveness, we evaluated the erlotinib-loaded transfersomal gel through various tests. The results confirmed that the gel was nano-sized and loaded with a high amount of erlotinib. Animal studies were conducted to check if the prepared gel caused any skin irritation and interestingly, there was no irritation observed on the animals' skin. Furthermore, we treated breast cancer cells with the developed gel using a method called MTT assay and the results showed improved cell-killing activity in comparison to plain drug. In conclusion, this special gel represents a breakthrough in breast cancer treatment. It offers hope for better outcomes in the fight against this disease. This innovative approach involves directly applying the gel on the affected area topically to increase patient compliance and decreasing side effects of drugs. This could potentially transform ductal carcinoma in situ breast cancer treatment, bringing us closer to improved treatments and outcomes.

Changing trends in the management of ductal carcinoma in situ in Republic of Korea: a comprehensive analysis using Health Insurance Review and Assessment data [2009-2020].

Background: Increasing rates of diagnosis of ductal carcinoma in situ (DCIS), given the widespread use of mammography, is a global trend. Various attempts have been made in the selection of surgical methods and application of radiation therapy (RT), and the prevalence of infectious diseases has also affected these attempts. This study aimed to investigate evolving treatment patterns and trends in the management of DCIS in South Korea. Methods: We conducted a comprehensive search of the Korean Health Insurance Review and Assessment Service-National Patient Sample (HIRA-NPS) database and selected patients who underwent breast surgery following a DCIS diagnosis between 2009 and 2020. Based on this sample, the analyses were weighted according to the Korean population. We examined annual variations in mastectomy types, reconstructive procedures, and RT utilization from a multidisciplinary perspective. Results: In our weighted sample, 43,780 patients with DCIS underwent surgery, with a consistent annual increase of 10%. The proportion of lumpectomy procedures increased from 56.7% to 65.4%, showing a greater growth rate than that of total mastectomies (TMs). Following the availability of reconstruction data in 2015, shifts have emerged toward a preference for implant-based autologous tissue reconstruction. As we transitioned to the latter part of our study, the trend was marked by the increasing adoption of hypofractionated RT and omission of RT. Of the patients who underwent lumpectomy in 2020, 25.6% adopted hypofractionated RT and 53.8% omitted RT. This transformation was particularly evident among older patients, individuals treated in metropolitan areas, and those treated in small-sized healthcare facilities. Conclusions: Our study sheds light on the changing landscape of DCIS treatment in South Korea incorporating perspectives from surgeons, plastic surgeons, and radiation oncologists. We observed an increase in the rates of lumpectomy and implant-based reconstruction. Adoption of hypofractionated RT and omission of RT showed increasing trends.

Paget's Presentation of High-Grade Ductal Carcinoma In Situ (DCIS) in a Very Young Female With Breast Cancer 2 (BRCA2) Mutation.

This is a case of a previously healthy 29-year-old female with erythema and skin excoriations of the left breast nipple-areolar complex (NAC). After a repeat trial and failure of topical hydrocortisone, a diagnostic mammogram and nipple biopsy revealed Paget's disease (PD) of the nipple with ductal carcinoma in situ (DCIS). A subsequent genetic analysis found a breast cancer 2 (BRCA2) gene mutation. Treatment consisted of a left breast skin-sparing simple mastectomy with sentinel lymph node (SLN) biopsy and immediate tissue expander placement for implant reconstruction. Further management involved right breast short-interval surveillance with annual mammography and magnetic resonance imaging (MRI) with the possibility of prophylactic surgery along with oophorectomy after childbearing.

Breast tissue imaging atlas using ultra-fast confocal microscopy to identify cancer lesions.

New generation ultra-fast fluorescence confocal microscopy (UFCM) allows to image histological architecture of fresh breast tissue and may be used for ex vivo intraoperative analysis for margin status. The criteria to identify breast tumoral and non-tumoral tissues in UFCM images are still objects of investigation. The objective of the study was to create an atlas of ex vivo UFCM images of breast tissues and breast carcinomas based on the first extensive collection of large field-of-view UFCM breast images. One hundred sixty patients who underwent conserving surgery for breast cancer were included. Their fresh surgical specimens were sliced, stained with acridine orange, and imaged at high resolution with large-field-of-view UFCM. The resulting images were digitally false colored to resemble frozen sections. Each UFCM image was correlated with the corresponding definitive histology. Representative images of normal tissue, inflammation, benign lesions, invasive carcinoma (IC), and ductal carcinoma in situ (DCIS) were collected. A total of 320 large-field images were recorded from 58 IC of no special type, 44 invasive lobular carcinomas, 1 invasive mucinous carcinoma, 47 DCIS, 2 lobular carcinomas in situ, and 8 specimens without cancer. Representative images of the main components of the normal breast and the main types of ICs and DCIS were annotated to establish an UFCM atlas. UFCM enables the imaging of the fresh breast tissue sections. Main morphological criteria defined in traditional histopathology such as tissue architecture and cell features can be applied to describe UFCM images content. The generated atlas of the main normal or tumoral tissue features will support the adoption of this optical technology for the intraoperative examination of breast specimens in clinical practice as it can be used to train physicians on UFCM images and develop artificial intelligence algorithms. Further studies are needed to document rare breast lesions.

Rate of residual tumor after repeat surgery for positive margins in ductal carcinoma in Situ, and predictive factors.

AIMS: To evaluate the rate of residual tumor in re-excision specimen of patients with positive margins in ductal carcinoma in situ (DCIS) following breast-conservative surgery, and to identify predictive factors of residual tumor. MATERIAL AND METHODS: We conducted a monocentric, retrospective study, from January 2010 to December 2020. All 103 patients who underwent re-excision for positive margins in DCIS following breast-conservative surgery for in situ or invasive breast carcinoma were included. Positive margins were defined as inferior to 2 mm from the DCIS component. Two groups were defined, depending on the presence of residual tumor or not, and were compared on their clinical and histopathological characteristics to identify predictive factors of residual tumor. RESULTS: Residual tumor was found in re-excision specimen of 46 patients (44.7 %). The risk of residual tumor was increased in patients with more than 2 tumor foci (aOR: 12.4; 95 % CI: 1.2 -124.1; p = 0.032) and in those with extensive margin involvement (aOR: 3.2; 95 % CI: 1.3-8.2; p = 0.013). Finally, surgery performed after 2013 was associated with a lower risk of residual tumor (aOR: 0.23; 95 % CI: 0.09-0.058; p = 0.002). CONCLUSION: The rate of residual tumor in re-excision specimen of patients with positive margins in DCIS is high. Both the number of tumor foci and the extension of positive margins were identified as risk factors. Finally, the surgical learning curve for this procedure seems to be significantly correlated with the risk of residual tumor and needs to be considered.

Benign Adenomyoepithelioma: An Unrecognised Precursor of Ductal Carcinoma in Situ in Patient With Lynch Syndrome.

Currently, there is no robust evidence demonstrating a clear association between Lynch syndrome and non-malignant breast pathology such as adenomyoepithelioma. We report a case of benign breast adenomyoepithelioma, which after recurrence was associated with ductal carcinoma in-situ (DCIS) in a 41-year-old woman with Lynch syndrome, who lacked significant family history of breast or ovarian cancer. Both, the adenomyoepithelioma and DCIS were found to have nuclear loss of MSH2/MSH6 by immunohistochemistry, while germline testing confirmed MSH2 gene mutation. Concordant loss of MSH2 in both lesions in the context of a MSH2 pathogenic variant in this patient with Lynch syndrome illustrates that the benign adenomyoepithelioma behaved as a likely precursor of DCIS. Our report provides a novel perspective that in some patients with Lynch syndrome adenomyoepithelioma may represent a pre-malignant precursor lesion of DCIS.

Surgical margin and local recurrence of ductal carcinoma in situ.

PURPOSE: This study aims to evaluate the association between surgical margin status and local recurrence of DCIS. METHODS: A retrospective analysis of a prospectively maintained 20-year DCIS database was performed. >=2 mm margin was defined as clear margin. Local relapse rate between the patients with clear versus close margins were analyzed with Kaplan-Meier analyses. RESULTS: 654 patients were analyzed. Median age was 46.5 (Range 18 - 80). 205 (31.3%) were high grade, 194 (29.7%) were intermediate grade, 143 (21.9%) were low grade. 112 (18.3%) were unknown. 202 (30.9%) were estrogen receptor positive, 49 (7.4%) were negative, 403 (61.6%) patients were unknown. 403 (61.6%) patients received mastectomy while 251 (38.4%) patients received BCS and radiotherapy. 549 (83.9%) patients had clear surgical margin, 50 (7.7%) patients had involved (positive) resection margin, 55 (8.4%) had close margin (<2 mm margin). All patients with involved margin received re-excision of margin, while 21 patients (out of 55 who had close resection margins) received re-excision of margin. Negative surgical margins were achieved after the re-excision. 34 patients with close resection margin decided not to receive re-excision but to undergo adjuvant radiotherapy. After median follow-up of 128 months, the 10-year ipsilateral breast tumor relapse (IBTR) was 4.5% (N = 28), Of which 27 (96.4%) patients had clear margin after the initial surgical treatment of DCIS. 1 (3.6%) patient had close surgical margin. Difference in IBTR between the two groups was not statistically significant (p = 0.692). CONCLUSION: Close surgical margin for DCIS is not associated with increased risk of IBTR.

Spatial Engineering of Mammary Epithelial Cell Cultures with 3D Bioprinting Reveals Growth Control by Branch Point Proximity.

The three-dimensional (3D) structure of the ductal epithelium and the surrounding extracellular matrix (ECM) are integral aspects of the breast tissue, and they have important roles during mammary gland development, function and malignancy. However, the architecture of the branched mammary epithelial network is poorly recapitulated in the current in vitro models. 3D bioprinting is an emerging approach to improve tissue-mimicry in cell culture. Here, we developed and optimized a protocol for 3D bioprinting of normal and cancerous mammary epithelial cells into a branched Y-shape to study the role of cell positioning in the regulation of cell proliferation and invasion. Non-cancerous cells formed continuous 3D cell networks with several organotypic features, whereas the ductal carcinoma in situ (DCIS) -like cancer cells exhibited aberrant basal polarization and defective formation of the basement membrane (BM). Quantitative analysis over time demonstrated that both normal and cancerous cells proliferate more at the branch tips compared to the trunk region of the 3D-bioprinted cultures, and particularly at the tip further away from the branch point. The location-specific rate of proliferation was independent of TGFß signaling but invasion of the DCIS-like breast cancer cells was reduced upon the inhibition of TGFß. Thus, our data demonstrate that the 3D-bioprinted cells can sense their position in the branched network of cells and proliferate at the tips, thus recapitulating this feature of mammary epithelial branching morphogenesis. In all, our results demonstrate the capacity of the developed 3D bioprinting method for quantitative analysis of the relationships between tissue structure and cell behavior in breast morphogenesis and cancer.

Ductal carcinoma in situ and invasive carcinoma originating in a Fibroadenoma with concurrent benign phyllodes tumor: A case report.

INTRODUCTION AND IMPORTANCE: This case report presents a rare occurrence of multiple bilateral breast fibroadenomas, one evolving into ductal carcinoma in situ (DCIS) and invasive carcinoma, occurring simultaneously with a benign phyllodes tumor in the same breast. The importance of this case lies in emphasizing the crucial need for surveillance in patients with a long history of fibroadenomas and the necessity to investigate any rapid change in the size of fibroadenoma. CASE PRESENTATION: A 35-year-old multiparous female with a 17 year history of bilateral multiple breast lumps presented with recent onset of right breast pain and yellowish nipple discharge. Two lumps in her right breast had demonstrated an increase in size. Examination revealed a significant mass in the retroareolar region of the right breast and another at the 2 o'clock position. Histopathological examination of the biopsy specimens revealed fibroadenoma and benign phyllodes tumor. The patient underwent a bilateral breast lumpectomy. Further histopathological examination revealed ductal carcinoma in situ and invasive carcinoma within a complex fibroadenoma in the right breast and benign phyllodes tumor. Sentinel lymph node biopsy was negative. She had adjuvant radiations and trastuzumab. Regular follow-ups show no recurrence. CLINICAL DISCUSSION: Fibroadenomas are usually benign but rarely undergo malignant change. Quick response to size changes and early detection greatly enhance patient results. CONCLUSION: Ductal carcinoma in situ and invasive breast cancer, a rare malignancy found within a fibroadenoma, necessitates histopathological specimens and immunohistochemical results for accurate diagnosis. Survival rates are significantly enhanced through a multidisciplinary approach.

Contemporary Analysis of Reexcision and Conversion to Mastectomy Rates and Associated Healthcare Costs for Women Undergoing Breast-Conserving Surgery.

PURPOSE: This study was designed to provide a comprehensive and up-to-date understanding of population-level reoperation rates and incremental healthcare costs associated with reoperation for patients who underwent breast-conserving surgery (BCS). METHODS: This is a retrospective cohort study using Merative™ MarketScan® commercial insurance data and Medicare 5% fee-for-service claims data. The study included females aged 18-64 years in the commercial cohort and females aged 18 years and older in the Medicare cohort, who underwent initial BCS for breast cancer in 2017-2019. Reoperation rates within a year of the initial BCS and overall 1-year healthcare costs stratified by reoperation status were measured. RESULTS: The commercial cohort included 17,129 women with a median age of 55 (interquartile range [IQR] 49-59) years, and the Medicare cohort included 6977 women with a median age of 73 (IQR 69-78) years. Overall reoperation rates were 21.1% (95% confidence interval [CI] 20.5-21.8%) for the commercial cohort and 14.9% (95% CI 14.1-15.7%) for the Medicare cohort. In both cohorts, reoperation rates decreased as age increased, and conversion to mastectomy was more prevalent among younger women in the commercial cohort. The mean healthcare costs during 1 year of follow-up from the initial BCS were $95,165 for the commercial cohort and $36,313 for the Medicare cohort. Reoperations were associated with 24% higher costs in both the commercial and Medicare cohorts, which translated into $21,607 and $8559 incremental costs, respectively. CONCLUSIONS: The rates of reoperation after BCS have remained high and have contributed to increased healthcare costs. Continuing efforts to reduce reoperation need more attention.

Radiotherapy statements of the 18th St. Gallen International Breast Cancer Consensus Conference-a German expert perspective.

PURPOSE: To summarize the radiotherapy-relevant statements of the 18th St. Gallen Breast Cancer Consensus Conference and interpret the findings in light of German guideline recommendations. METHODS: Statements and voting results from the 18th St. Gallen International Breast Cancer Consensus Conference were collected and analyzed according to their relevance for the radiation oncology community. The voting results were discussed in two hybrid meetings among the authors of this manuscript on March 18 and 19, 2023, in light of the German S3 guideline and the 2023 version of the Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) guidelines. RESULTS AND CONCLUSION: There was a high level of agreement between the radiotherapy-related statements of the 18th St. Gallen International Breast Cancer Consensus Conference and the German S3 and AGO guidelines. Discrepancies include the impact of number of lymph node metastases for the indication for postmastectomy radiotherapy.

Age and race/ethnicity differences in decisional conflict in women diagnosed with ductal carcinoma in situ.

PURPOSE: Women diagnosed with ductal carcinoma in situ (DCIS) face confusion and uncertainty about treatment options. The objective of this study was to determine whether there are differences in decisional conflict about treatment by age and race/ethnicity. METHODS: A cross-sectional survey was conducted of women (age ≥ 18) diagnosed with DCIS enrolled at Kaiser Permanente of Southern California. The Decisional Conflict Scale (DCS) measured personal perceptions of decision uncertainty, values clarity, and effective decision-making. We used a multivariable regression to study whether age, race, and ethnicity were associated with patient-reported DCS. RESULTS: 45% (N = 1395) of women who received the online survey, participated. The mean age was 56 (± 9.6) years, the majority were white. Compared to women younger than 50, women aged 60-69 reported lower overall DCS scores (-5.4; 95% CI -1.5 to -9.3). Women > 70 had lower values clarity scores (-9.0; 95% CI -2.8 to -15.2) about their treatment compared to women aged 50-59 and 60-69 (-7.1; 95% CI -2.9 to -11.3 and - 7.2; 95% CI -2.9 to -11.5) and likewise, lower effective decision-making scores (-5.4; 95% CI -1.7 to -9.2 and - 5.2; 95% CI -1.4 to -9.0) compared to women < 50. Compared to whites, blacks reported lower decision conflict (-4.4; 95% CI 0.04 to -8.8) and lower informed decision (-5.2; 95% CI -0.18 to -10.3) about DCIS treatment. CONCLUSION: Younger women reported higher decisional conflict about DCIS treatment, compared to older women (> 70). Age based tailored discussions about treatment options, health education, and supportive decision-making interventions/tools may reduce decision conflict in future DCIS patients. TRADE REGISTRATION: The IRB number is 10678.

Surgical De-Escalation for Re-Excision in Patients with a Margin Less Than 2 mm and a Diagnosis of DCIS.

The current surgical guidelines recommend an optimal margin width of 2 mm for the management of patients diagnosed with ductal carcinoma in situ (DCIS). However, there are still many controversies regarding re-excision when the optimal margin criteria are not met in the first resection. The purpose of this study is to understand the importance of surgical margin width, re-excision, and treatments to avoid additional surgery on locoregional recurrence (LRR). The study is retrospective and analyzed surgical margins, adjuvant treatments, re-excision, and LRR in patients with DCIS who underwent breast-conserving surgery (BCS). A total of 197 patients were enrolled. Re-operation for a close margin rate was 13.5%, and the 3-year recurrence was 7.6%. No difference in the LRR was reported among the patients subjected to BCS regardless of the margin width (p = 0.295). The recurrence rate according to margin status was not significant (p = 0.484). Approximately 36.9% (n: 79) patients had resection margins < 2 mm. A sub-analysis of patients with margins < 2 mm showed no difference in the recurrence between the patients treated with a second surgery and those treated with radiation (p = 0.091). The recurrence rate according to margin status in patients with margins < 2 mm was not significant (p = 0.161). The margin was not a predictive factor of LRR p = 0.999. Surgical re-excision should be avoided in patients with a focally positive margin and no evidence of the disease at post-surgical imaging.