Unsupervised representation learning of chromatin images identifies changes in cell state and tissue organization in DCIS.

Ductal carcinoma in situ (DCIS) is a pre-invasive tumor that can progress to invasive breast cancer, a leading cause of cancer death. We generate a large-scale tissue microarray dataset of chromatin images, from 560 samples from 122 female patients in 3 disease stages and 11 phenotypic categories. Using representation learning on chromatin images alone, without multiplexed staining or high-throughput sequencing, we identify eight morphological cell states and tissue features marking DCIS. All cell states are observed in all disease stages with different proportions, indicating that cell states enriched in invasive cancer exist in small fractions in normal breast tissue. Tissue-level analysis reveals significant changes in the spatial organization of cell states across disease stages, which is predictive of disease stage and phenotypic category. Taken together, we show that chromatin imaging represents a powerful measure of cell state and disease stage of DCIS, providing a simple and effective tumor biomarker.

Extramammary breast cancer of the vulva.

A woman in her 70s was seen in the gynaecology outpatient clinic with a swelling on the right side of the vulva. Surgical excision of the lesion revealed unexpectedly an extensive ductal carcinoma in situ with a focus of a grade 2 invasive ductal carcinoma arising in extramammary breast tissue of the vulva. Postoperative staging studies showed normal breasts, with no evidence of disease elsewhere. The patient underwent a wider excision of the right vulva and sentinel node biopsy of the right inguinal region, which revealed no further disease. The patient is currently taking adjuvant hormonal therapy and has remained disease free at 2-year follow-up. This case underscores the importance of considering rare presentations of vulvar malignancies and the necessity for a multidisciplinary approach in managing such cases.

Predictors of residual disease after breast conservation surgery for ductal carcinoma in situ: A retrospective study.

BACKGROUND: Breast-conserving therapy is the standard of care for ductal carcinoma in situ (DCIS). Debate on what constitutes a satisfactory margin persists. This study aimed to identify predictors of residual disease at re-excision. METHODS: This is a population-based retrospective cohort study of women with DCIS who underwent a lumpectomy between 2007 and 2017 in Manitoba, with close (≤2 mm) or positive margins that led to re-excision. RESULTS: The DCIS re-excision rate was 29.3% for 1001 patients. 63.2% of patients were found to have residual disease on re-excision. On univariable analysis, the size, margin status, number of positive margins, type of second surgery, and Van Nuys Prognostic Index score were associated with residual disease on re-excision. The size of DCIS and the number of positive margins remained statistically significant on multivariable analysis. CONCLUSIONS: Re-excision should be rationalized by considering the predictors of residual disease in conjunction with other factors.

Ductal Carcinoma In Situ.

In breast cancer (BC) pathogenesis models, normal cells acquire somatic mutations and there is a stepwise progression from high-risk lesions and ductal carcinoma in situ to invasive cancer. The precancer biology of mammary tissue warrants better characterization to understand how different BC subtypes emerge. Primary methods for BC prevention or risk reduction include lifestyle changes, surgery, and chemoprevention. Surgical intervention for BC prevention involves risk-reducing prophylactic mastectomy, typically performed either synchronously with the treatment of a primary tumor or as a bilateral procedure in high-risk women. Chemoprevention with endocrine therapy carries adherence-limiting toxicity.

Stromal lymphocytes are associated with upgrade of B3 breast lesions.

Various histopathological, clinical and imaging parameters have been evaluated to identify a subset of women diagnosed with lesions with uncertain malignant potential (B3 or BIRADS 3/4A lesions) who could safely be observed rather than being treated with surgical excision, with little impact on clinical practice. The primary reason for surgery is to rule out an upgrade to either ductal carcinoma in situ or invasive breast cancer, which occurs in up to 30% of patients. We hypothesised that the stromal immune microenvironment could indicate the presence of carcinoma associated with a ductal B3 lesion and that this could be detected in biopsies by counting lymphocytes as a predictive biomarker for upgrade. A higher number of lymphocytes in the surrounding specialised stroma was observed in upgraded ductal and papillary B3 lesions than non-upgraded (p < 0.01, negative binomial model, n = 307). We developed a model using lymphocytes combined with age and the type of lesion, which was predictive of upgrade with an area under the curve of 0.82 [95% confidence interval 0.77-0.87]. The model can identify some patients at risk of upgrade with high sensitivity, but with limited specificity. Assessing the tumour microenvironment including stromal lymphocytes may contribute to reducing unnecessary surgeries in the clinic, but additional predictive features are needed.

Long-term Outcome After Helical Tomotherapy Following Breast Conserving Surgery for Ductal Carcinoma In Situ.

Background: This retrospective study aimed to investigate the outcomes and adverse events (AEs) associated with adjuvant radiotherapy with helical tomotherapy (hT) after breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS). Methods: Twenty-eight patients with DCIS underwent postoperative hT between 2011 and 2020. hT was chosen since it provided optimal target coverage and tolerable organ-at-risk doses to the lungs and heart when tangential 3-dimensional conformal radiotherapy (3D-CRT) was presumed to provide unfavorable dosimetry. The median total (single) dose was 50.4 Gy (1.8 Gy). The median time between BCS and the start of hT was 5 weeks (range, 4-38 weeks). Statistical analysis included local recurrence-free survival, overall survival (OS), and secondary cancer-free survival. AEs were classified according to the Common Toxicity Criteria for Adverse Events, version 5. Results: The patients' median age was 58 years. The median follow-up period was 61 months (range, 3-123 months). The 1-, 3-, and 5-year OS rates were 100% each. None of the patients developed secondary cancer, local recurrence, or invasive breast cancer during follow-up. The most common acute AEs were dermatitis (n = 27), fatigue (n = 4), hyperpigmentation (n = 3), and thrombocytopenia (n = 4). The late AE primarily included surgical scars (n = 7) and hyperpigmentation (n = 5). None of the patients experienced acute or late AEs > grade 3. The mean conformity and homogeneity indices were 0.9 (range, 0.86-0.96) and 0.056 (range, 0.05-0.06), respectively. Conclusion: hT after BCS for DCIS is a feasible and safe form of adjuvant radiotherapy for patients in whom 3D-CRT is contraindicated due to unfavorable dosimetry. During follow-up, there were no recurrences, invasive breast cancer diagnoses, or secondary cancers, while the adverse effects were mild.

Intraductal photothermal ablation: a noninvasive approach for early breast cancer treatment and prevention.

Background: Innovative treatment strategies for early-stage breast cancer (BC) are urgently needed. Tumors originating from mammary ductal cells present an opportunity for targeted intervention. Methods: We explored intraductal therapy via natural nipple openings as a promising non-invasive approach for early BC. Using functional Near-infrared II (NIR-II) nanomaterials, specifically NIR-IIb quantum dots conjugated with Epep polypeptide for ductal cell targeting, we conducted in situ imaging and photothermal ablation of mammary ducts. Intraductal administration was followed by stimulation with an 808 nm laser. Results: This method achieved precise ductal destruction and heightened immunological responses in the microenvironment. The technique was validated in mouse models of triple-negative BC and a rat model of ductal carcinoma in situ, demonstrating promising therapeutic potential for localized BC treatment and prevention. Conclusion: Our study demonstrated the effectiveness of NIR-II nanoprobes in guiding non-invasive photothermal ablation of mammary ducts, offering a compelling avenue for early-stage BC therapy.

Meta-analysis on axillary lymph node metastasis rate in ductal carcinoma in situ with microinvasion.

OBJECTIVE: To address the question of axillary lymph node staging in ductal carcinoma in situ with microinvasion (DCIS-MI), we retrospectively evaluated axillary lymph nodes metastasis (ALNM) rate in a cohort of postsurgical DCIS-MI patients. By analyzing these data, we aimed to generate clinically relevant insights to inform treatment decision-making for this patient population. METHODS: A systematic search was conducted on PubMed, Web of Science, Embase, The Cochrane Library, CNKI, Wanfang Database, Wipe, and China Biomedical Literature Database to identify relevant publications in any language. All the analyses were performed using Stata 16.0 software. RESULTS: Among the 28 studies involving 8279 patients, the pooled analysis revealed an ALNM rate of 8% (95% CI, 7% to 10%) in patients with DCIS-MI. Furthermore, the rates of axillary lymph node macrometastasis, micrometastasis, and ITC in patients with DCIS-MI were 2% (95% CI, 2% to 3%), 3% (95% CI, 2% to 4%), and 2% (95% CI, 1% to 3%), respectively. Moreover, 13 studies investigated the non-sentinel lymph node (Non-SLN) metastasis rate, encompassing a total of 1236 DCIS-MI cases. The pooled analysis identified a Non-SLN metastasis rate of 33% (95% CI, 14% to 55%) in patients with DCIS-MI. CONCLUSION: The SLNB for patients with DCIS-MI is justifiable and could provide a novel therapeutic basis for systemic treatment decisions.

Pure Apocrine Intraductal Carcinoma of Salivary Glands: Reassessment of Molecular Underpinnings and Behavior.

BACKGROUND: Intraductal carcinoma (IDC) of the salivary glands is a confounding entity, our understanding of which continues to evolve. At least four forms have been elucidated based on histomorphology, immunophenotype, and molecular profile: (1) intercalated duct-like, S100/SOX10+ with frequent NCOA4::RET fusions; (2) oncocytic, S100/SOX10+ with TRIM33::RET, NCOA4::RET, and BRAF V600E; (3) apocrine, AR+ with PI3 kinase pathway mutations; and (4) mixed/hybrid intercalated duct-like/apocrine, with S100/SOX10+ and AR+ areas and frequent TRIM27::RET. The revelation that myoepithelial cells harbor the same fusion as luminal cells suggested that fusion-positive cases are not in situ carcinomas as previously believed. To this point, purely apocrine IDC with entirely intraductal growth has not been found to harbor fusions, but very few cases have been tested. METHODS: IDCs with pure apocrine morphology, entirely intraductal growth, and no precursor lesion (pleomorphic adenoma or sclerosing polycystic adenoma) were retrieved from the authors' archives. Several immunostains (S100, SOX10, GCDFP-15, AR, p40/SMA) and targeted next generation sequencing (NGS) panel including 1425 cancer-related genes were performed. RESULTS: Seven entirely IDC with pure apocrine type were collected. The cases arose in the parotid glands (mean, 1.9 cm) of 5 men and 2 women ranging from 51 to 84 years (mean, 69.7 years). Histologically, tumors consisted of rounded to angulated ductal cysts lined by epithelial cells with abundant finely granular eosinophilic cytoplasm and large nuclei with prominent nucleoli. Pleomorphism was mild to moderate, the mitotic rate was low, and necrosis was absent. Conventionally invasive foci or areas of intercalated duct-like morphology were not identified. In all cases, luminal cells were diffusely positive for AR and GCDFP-15 while negative for S100/SOX10, and the ducts were completely surrounded by myoepithelial cells highlighted by p40 and SMA. Molecular analysis was successful in 6 cases. Three harbored fusions: one with NCOA4::RET, another with STRN::ALK and one with both CDKN2A::CNTRL and TANC1::YY1AP1. The three fusion-negative cases all harbored HRAS mutations; additional mutations (PIK3CA, SPEN, ATM) were found in 2 of 3 cases. All patients were treated by surgery alone. Six of them are currently free of disease (follow up 12-190 months), but the case harboring NCOA4::RET developed lymph nodes metastasis in the form of a fusion-positive invasive salivary duct carcinoma. CONCLUSIONS: Purely apocrine IDC is a heterogeneous disease. A subset seems to be genetically similar to salivary duct carcinoma and may indeed represent carcinoma in situ. The other group harbors fusions, similar to other forms of IDC. Moreover, the occurrence of lymph node metastasis discredits the idea that any fusion-positive IDC with a complete myoepithelial cell layer has no metastatic potential. With the wide use of RET-and ALK-based targeted therapies, our findings further underscore the importance of fusion analysis for IDC.

Multicentric reticulohistiocytosis revealing a ductal breast cancer in situ: A case report with dermoscopic and histopathological findings. / Reticulohistiocitosis multicéntrica reveladora de cáncer de mama ductal in situ: reporte de caso con aspectos dermatoscópicos e histopatológicos.

Multicentric reticulohistiocytosis is a rare non-Langerhans cell histiocytosis of unknown etiology. It is classified as multicentric because of multisystem involvement. The disease predominantly affects the skin and joints, but visceral involvement is possible. Multiple erythematous-brownish, pruritic nodules and papules on the face, hands, neck, and trunk are characteristic. It is associated with autoimmune diseases, or malignant neoplasms are seen in 20% to 30% of patients with multicentric reticulohistiocytosis. The diagnosis is based on histopathology of affected tissues. As it is an underreported disease, there is no standardized treatment. A case of multicentric reticulohistiocytosis is reported as a paraneoplastic manifestation of ductal breast cancer, being successfully treated with no recurrence after two years of follow-up. Few cases of multicentric reticulohistiocytosis associated with breast cancer have been reported in the literature.

La reticulohistiocitosis multicéntrica es una enfermedad inflamatoria, una histiocitosis de células no Langerhans, poco frecuente y de etiología desconocida. Se clasifica como multicéntrica al presentar compromiso multisistémico. La enfermedad afecta predominantemente a la piel y las articulaciones, pero es posible la afectación visceral. Las manifestaciones cutáneas se caracterizan por múltiples nódulos y pápulas de color eritemato-marronáceas, pruriginosas en la cara, manos, cuello y tronco. Se asocia a enfermedades autoinmunes y neoplasias malignas, observándose entre el 20 y el 30% de los pacientes con reticulohistiocitosis multicéntrica. Su diagnóstico se realiza sobre la base de la histopatología de tejidos afectados. Al ser una enfermedad poco reportada, no existe tratamiento estandarizado. Se reporta un caso de reticulohistiocitosis multicéntrica como manifestación paraneoplásica a un cáncer ductal de mama, siendo tratadas con éxito, sin recidivas luego de dos años de seguimiento. Pocos casos se han reportado en la literatura de reticulohistiocitosis multicéntrica asociado a cáncer mamario.

Extracellular Microenvironment Alterations in Ductal Carcinoma In Situ and Invasive Breast Cancer Pathologies by Multiplexed Spatial Proteomics.

Ductal carcinoma in situ (DCIS) is a heterogeneous breast disease that remains challenging to treat due to its unpredictable progression to invasive breast cancer (IBC). Contemporary literature has become increasingly focused on extracellular matrix (ECM) alterations with breast cancer progression. However, the spatial regulation of the ECM proteome in DCIS has yet to be investigated in relation to IBC. We hypothesized that DCIS and IBC present distinct ECM proteomes that could discriminate between these pathologies. Tissue sections of pure DCIS, mixed DCIS-IBC, or pure IBC (n = 22) with detailed pathological annotations were investigated by multiplexed spatial proteomics. Across tissues, 1,005 ECM peptides were detected in pathologically annotated regions and their surrounding extracellular microenvironments. A comparison of DCIS to IBC pathologies demonstrated 43 significantly altered ECM peptides. Notably, eight fibrillar collagen peptides could distinguish with high specificity and sensitivity between DCIS and IBC. Lesion-targeted proteomic imaging revealed heterogeneity of the ECM proteome surrounding individual DCIS lesions. Multiplexed spatial proteomics reported an invasive cancer field effect, in which DCIS lesions in closer proximity to IBC shared a more similar ECM profile to IBC than distal counterparts. Defining the ECM proteomic microenvironment provides novel molecular insights relating to DCIS and IBC.

Adenocarcinoma of anogenital mammary gland type arising from encapsulated papillary carcinoma: A rare vulvar tumor mimicking breast carcinoma.

Anogenital mammary-like glands are normal structures of the anogenital region. Tumors originating from these glands often exhibit a striking resemblance to their mammary gland counterparts. Herein, we present a rare case of adenocarcinoma of mammary gland type in the vulva of a 69-year-old female. Histopathologic examination revealed a complex lesion, which included a large encapsulated papillary carcinoma (EPC) with associated invasive carcinoma of mammary gland type and ductal carcinoma in situ (DCIS). The invasive component consisted mostly of invasive ductal carcinoma of no special type, with a notable focus of invasive mucinous carcinoma. p40 immunostain demonstrated a lack of myoepithelial cells in both the EPC and invasive carcinoma, but such cells expressed p40 around the ducts involved by DCIS. The main component of this lesion, EPC, was characterized by a papillary proliferation within a cystic space surrounded by a fibrous capsule without a myoepithelial layer. The histopathologic features of anogenital EPC closely resemble cutaneous hidradenoma papilliferum. Indeed, there have been a few reports in the literature describing cases where in situ and invasive carcinoma arose from a preexisting hidradenoma papilliferum. As tumors of anogenital mammary-like glands bear a closer resemblance to breast lesions than to skin tumors, we recommend that they be aligned with the classification of well-established breast lesions rather than cutaneous adnexal tumors.

Ductal carcinoma in situ and cause-specific mortality among younger and older postmenopausal women: the Women's Health Initiative.

BACKGROUND: Whether DCIS is associated with higher breast cancer-specific and all-cause mortality is unclear with few studies in older women. Therefore, we examined DCIS and breast cancer-specific, cardiovascular (CVD)-specific, and all-cause mortality among Women's Health Initiative (WHI) Clinical Trial participants overall and by age (< 70 versus ≥ 70 years). METHODS: Of 68,132 WHI participants, included were 781 postmenopausal women with incident DCIS and 781 matched controls. Serial screening mammography was mandated with high adherence. DCIS cases were confirmed by central medical record review. Adjusted multivariable Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI). Kaplan Meier (KM) plots were used to assess 10-year and 20-year mortality rates. RESULTS: After 20.3 years total, and 13.2 years median post-diagnosis follow-up, compared to controls, DCIS was associated with higher breast cancer-specific mortality (HR 3.29; CI = 1.32-8.22, P = 0.01). The absolute difference in 20-year breast cancer mortality was 1.2% without DCIS and 3.4% after DCIS, log-rank P = 0.026. Findings were similar by age (< 70 versus ≥ 70 years) with no interaction (P interaction = 0.80). Incident DCIS was not associated with CVD-specific mortality (HR 0.77; CI-0.54-1.09, P = 0.14) or with all-cause mortality (HR 0.96; CI = 0.80-1.16, P = 0.68) with similar findings by age. CONCLUSIONS: In postmenopausal women, incident DCIS was associated with over three-fold higher breast cancer-specific mortality, with similar findings in younger and older postmenopausal women. These finding suggest caution in using age to adjust DCIS clinical management or research strategies.

B3 Breast Lesions: Positive Predictive Value and Follow-Up on a Large Single-Institution Series.

INTRODUCTION: Lesions of uncertain malignant potential (B3) represent 10% of core needle biopsies (CNBs) or vacuum-assisted breast biopsies (VABBs). Traditionally, B3 lesions are operated on. This study investigated the association between B3 subtypes and malignancy to determine the best management. METHODS: Pre- and postoperative histological reports from 226 patients, who had undergone excisional surgery for B3 lesions, following CNB or VABB, were retrospectively analyzed. The correlation between the CNB/VABB diagnosis and the final pathology was investigated, along with the correlation between malignancy upgrade and the type of mammographic lesion. The positive predictive value (PPV) of malignancy of B3 lesions was calculated by simple logistic regression. Patients without cancer diagnosis underwent a 7-y follow-up. RESULTS: Pathology showed 171 (75.6%) benign and 55 (24.3%) malignant lesions. The PPV was 24.3% (P = 0.043), including 31 (13.7%) ductal carcinomas in situ and 24 (10.6%) invasive carcinomas. The most frequently upgraded lesions were atypical ductal hyperplasia, 34.2% (P = 0.004), followed by lobular intraepithelial neoplasia, 27.5% (P = 0.025). The median diameter of mammographic lesions was 1.5 [0.9-2.5] cm, while for surgical specimens, it was 5 [4-7] cm (P < 0.0001). Mammographic findings and histology showed a significant correlation (P = 0.038). After a 7-y follow-up, 15 (8.9%) patients developed carcinoma, and 7 patients (4%) developed a new B3 lesion. CONCLUSIONS: We can conclude that atypical ductal hyperplasia and lobular intraepithelial neoplasia still require surgery for a significant PPV. Other types that lacked significance or confidence intervals were too wide to draw any conclusion.

Ductal carcinoma in situ of the breast: finding the balance between overtreatment and undertreatment.

Ductal carcinoma in situ (DCIS) accounts for 15-25% of all breast cancer diagnoses. Its prognosis is excellent overall, the main risk being the occurrence of local breast events, as most cases of DCIS do not progress to invasive cancer. Systematic screening has greatly increased the incidence of this non-obligate precursor of invasion, lending urgency to the need to identify DCIS that is prone to invasive progression and distinguish it from non-invasion-prone DCIS, as the latter can be overdiagnosed and therefore overtreated. Treatment strategies, including surgery, radiotherapy, and optional endocrine therapy, decrease the risk of local events, but have no effect on survival outcomes. Active surveillance is being evaluated as a possible new option for low-risk DCIS. Considerable efforts to decipher the biology of DCIS have led to a better understanding of the factors that determine its variable natural history. Given this variability, shared decision making regarding optimal, personalised treatment strategies is the most appropriate course of action. Well designed, risk-based de-escalation studies remain a major need in this field.

Multi-omics portrait of ductal carcinoma in situ in young women.

BACKGROUND: Young patients with breast ductal carcinoma in situ (DCIS) often face a poorer prognosis. The genomic intricacies in young-onset DCIS, however, remain underexplored. METHODS: To address this gap, we undertook a comprehensive study encompassing exome, transcriptome, and vmethylome analyses. Our investigation included 20 DCIS samples (including 15 young-onset DCIS) and paired samples of normal breast tissue and blood. RESULTS: Through RNA sequencing, we identified two distinct DCIS subgroups: "immune hot" and "immune cold". The "immune hot" subgroup was characterized by increased infiltration of lymphocytes and macrophages, elevated expression of PDCD1 and CTLA4, and reduced GATA3 expression. This group also exhibited active immunerelated transcriptional regulators. Mutational analysis revealed alterations in TP53 (38%), GATA3 (25%), and TTN (19%), with two cases showing mutations in APC, ERBB2, and SMARCC1. Common genomic alterations, irrespective of immune status, included gains in copy numbers at 1q, 8q, 17q, and 20q, and losses at 11q, 17p, and 22q. Signature analysis highlighted the predominance of signatures 2 and 1, with "immune cold" samples showing a significant presence of signature 8. Our methylome study on 13 DCIS samples identified 328 hyperdifferentially methylated regions (DMRs) and 521 hypo-DMRs, with "immune cold" cases generally showing lower levels of methylation. CONCLUSION: In summary, the molecular characteristics of young-onset DCIS share similarities with invasive breast cancer (IBC), potentially indicating a poor prognosis. Understanding these characteristics, especially the immune microenvironment of DCIS, could be pivotal in identifying new therapeutic targets and preventive strategies for breast cancer.

Potential rapid intraoperative cancer diagnosis using dynamic full-field optical coherence tomography and deep learning: A prospective cohort study in breast cancer patients.

An intraoperative diagnosis is critical for precise cancer surgery. However, traditional intraoperative assessments based on hematoxylin and eosin (H&E) histology, such as frozen section, are time-, resource-, and labor-intensive, and involve specimen-consuming concerns. Here, we report a near-real-time automated cancer diagnosis workflow for breast cancer that combines dynamic full-field optical coherence tomography (D-FFOCT), a label-free optical imaging method, and deep learning for bedside tumor diagnosis during surgery. To classify the benign and malignant breast tissues, we conducted a prospective cohort trial. In the modeling group (n = 182), D-FFOCT images were captured from April 26 to June 20, 2018, encompassing 48 benign lesions, 114 invasive ductal carcinoma (IDC), 10 invasive lobular carcinoma, 4 ductal carcinoma in situ (DCIS), and 6 rare tumors. Deep learning model was built up and fine-tuned in 10,357 D-FFOCT patches. Subsequently, from June 22 to August 17, 2018, independent tests (n = 42) were conducted on 10 benign lesions, 29 IDC, 1 DCIS, and 2 rare tumors. The model yielded excellent performance, with an accuracy of 97.62%, sensitivity of 96.88% and specificity of 100%; only one IDC was misclassified. Meanwhile, the acquisition of the D-FFOCT images was non-destructive and did not require any tissue preparation or staining procedures. In the simulated intraoperative margin evaluation procedure, the time required for our novel workflow (approximately 3 min) was significantly shorter than that required for traditional procedures (approximately 30 min). These findings indicate that the combination of D-FFOCT and deep learning algorithms can streamline intraoperative cancer diagnosis independently of traditional pathology laboratory procedures.

Pushing the envelope in breast conserving surgery - is multiple-wire localization (3 or more wires) associated with increased risk of compromised margins and long-term recurrence?

INTRODUCTION: In the last two decades there has been a paradigm shift with breast conserving surgery (BCS) being applied to larger and more extensive breast malignancies. The aim of this study is to examine the success of BCS being performed in patients with extensive breast malignancies requiring at least 3 wires for localization, and to assess possible risk factors for failure. MATERIALS AND METHODS: We performed a retrospective single center review of 232 patients who underwent BCS between 2010 and 2020 requiring at least 3 wires for localization, thus comprising the multi-wire group (MWG). The cohort included a control group of 232 single-wire BCS patients (SWG) chronologically matched with the MWG. Patients with either invasive malignancy or ductal carcinoma in situ (DCIS) were included in the study. Clinical, radiological, and pathological data was collected. Proportions of positive surgical margins, re-lumpectomies and conversion to mastectomy were calculated. Survival analysis for locoregional and distant recurrence was performed. RESULTS: Women in the MWG were younger (mean age 57 vs. 63.1, P < 0.001), had larger tumor size (mean size 5.1 cm vs. 1.3 cm, p < 0.001), a higher prevalence of calcifications on mammograms (72 % vs. 17 %, P < 0.001), a higher proportion of positive lymph nodes (75 % vs. 45 %, P = 0.019), and an elevated incidence of a ductal carcinoma in situ (DCIS) component (72 % vs. 38 %, P < 0.001). Positive surgical margins were higher in the MWG (13 % vs 7 %, P = 0.03), which lead to higher proportions of re-lumpectomies or conversion to mastectomies (7 % vs 4 %, P = 0.17). On multivariate analysis of the entire cohort, patients with positive margins were more likely to have a DCIS component (77 % vs 53 %, P = 0.001), an infiltrating lobular carcinoma (ILC) component (15 % vs 9 %, P = 0.013), and positive ER hormonal status (94 % vs 85 %, p = 0.05). The number of wires was not an independent predictor of positive margins. On long-term analysis, the locoregional disease-free survival was similar between the SWG and MWG (P = 0.1). However, the MWG showed higher rates of distant metastasis (12 % vs 4 %, P = 0.006). CONCLUSIONS: BCS requiring 3 or more wires is associated with a slightly higher proportion of positive margins. The increased risk of positive margins appears to be related to the type of tumor (DCIS component, ILC component and ER status) rather than to the number of wires. The number of wires does not significantly impact locoregional disease-free survival.

Evaluation of the Efficacy of Postoperative Adjuvant Therapy for HER2-Positive Ductal Carcinoma in Situ with Microinvasion.

A retrospective study on 90 eligible HER2+ ductal carcinoma in situ with microinvasion (DCIS-MI) patients was performed with a median follow-up time of 57 months. The baseline was consistent between the 4-cycle and 6-cycle chemotherapy groups. There were more patients with multiple foci of micrometastasis in the target therapy group in the two groups with or without target therapy (p < 0.01). Postoperative chemotherapy with a 4-cycle regimen can achieve the expected therapeutic effect in patients with HER2+ DCIS-MI, but the role of target therapy in HER2+ DCIS-MI patients has not been confirmed.