Presence Of Comedonecrosis Research Articles

Evaluation of tumor infiltrating lymphocytes as a prognostic biomarker in patients with ductal carcinoma in situ of the breast.

To assess the association between tumor-infiltrating lymphocytes (TILs) in ductal carcinoma in situ (DCIS) samples and disease recurrence. This retrospective cohort study included women aged 18years and older who underwent treatment between January 2007 and December 2020. Male patients, individuals diagnosed with invasive or microinvasive disease based on anatomopathological examination of surgical specimens, and those with a personal history of any other cancers were excluded. Additionally, the presence of "touching TILs" (lymphocytes in direct contact with tumor cells) and periductal desmoplasia were evaluated as complementary methods to represent the immunological microenvironment. The primary outcome was relapse-free survival based on TIL quantification adjusted for potential confounders. Pathologists assessed TILs in the sample with the highest tumor representation and quantified them as a percentage. Survival was evaluated using Kaplan‒Meier curves, log-rank tests, and Cox regression models. A total of 191 patients met the eligibility criteria. The mean follow-up duration was 77.2months, with a recurrence rate of 9.2%. Patients with TILs ≥ 17% had a greater risk of recurrence (HR 2.97, 95% CI 1.17-7.51; p = 0.02). Additionally, focal necrosis (HR 6.4, 95% CI 1.39-34.71; p = 0.018) or comedonecrosis (HR 4.53, 95% CI 1.34-15.28; p = 0.015) were associated with increased recurrence risk. According to the multivariate model, comedonecrosis and TILs ≥ 17% were significantly associated with recurrence (p = 0.034 and p = 0.035, respectively). Regarding the evaluations of "touching TILs" and periductal desmoplasia, no statistical significance was found when assessing their association with disease recurrence. In our cohort, a high percentage of TILs (≥ 17%) and the presence of comedonecrosis were independently associated with DCIS recurrence.

The Predictive Role of Mammography, Dynamic Contrast-Enhanced Breast Magnetic Resonance Imaging and Diffusion-Weighted Imaging in Hormone Receptor Status of Pure Ductal Carcinoma In Situ Lesions.

The aim of this retrospective study was to analyze the predictive capabilities of preoperative mammography, dynamic contrast-enhanced-magnetic resonance imaging (DCE-MRI), and diffusion-weighted imaging (DWI) in determining hormone receptor (HRc) status for pure ductal carcinoma in situ (DCIS) lesions. The study included a total of 79 patients who underwent preoperative mammography (MG) and MRI between December 2018 and December 2023 and were subsequently diagnosed with pure DCIS after surgery. The correlation between MG, DCE-MRI, and DWI features and estrogen receptor (ER) and progesterone receptor (PR) status was examined. Among the lesions, 44 were double HRc-positive (ER and PR-positive), 13 were single HRc-positive (ER-positive and PR-negative or ER-negative and PR-positive) and 22 were double HRc-negative (ER and PR-negative). The presence of symptom (p = 0.029), the presence of comedo necrosis (p = 0.005) and high histological grade (p<0.001) were found to be associated with ER and PR negativity. Amorphous microcalcifications were more commonly observed in the double HRc-negative group, while linear calcifications were more prevalent in both double and single HRc-positive groups (p = 0.020). Non-mass enhancement (NME) with a linear distribution was significantly more common in double HRc-negative lesions (38%), and NME with a segmental distribution in both double (43%) and single (50%) receptor-positive lesions (p = 0.042). Evaluation of DWI findings revealed that a higher lesion-to-normal breast parenchyma apparent diffusion coefficient (ADC) ratio statistically increased the probability of HRc positivity (p = 0.033). Certain clinicopathological, mammography, and MRI features, along with the lesion-to-normal breast parenchyma ADC ratio, can serve as predictors for HRc status in DCIS lesions.

Abstract PO4-17-05: Patterns of care: radiotherapy after breast conserving surgery and the use of endocrine therapy for screen-detected ductal carcinoma in situ (DCIS) in the UK

Abstract Background The use of adjuvant radiotherapy (RT) and endocrine therapy (ET) in the management of pure ductal carcinoma in situ (DCIS) remains controversial. We investigate how the use of adjuvant RT after breast conserving surgery (BCS) and use of adjuvant ET (in BCS and mastectomy patients) has changed over time. Methods A prospective cohort SQL database of 11,284 patients (the Sloane Project) diagnosed 2003-2012 with screen-detected DCIS in the UK was interrogated for use of adjuvant RT and ET over time and association with factors reported to be predictive of recurrence (patient age, DCIS nuclear grade, size, comedo necrosis, resection margins), as well as institution of surgery, travel time to radiotherapy facility, Index of Multiple Deprivation and outcome (provided by the National Disease Registration Service, NDRS). RT data by site were confirmed with more recent data from the National Audit of Breast Cancer in Older Patients (NABCOP), which looked at patterns of care and outcomes for women aged 70 years and over, compared with those aged 50-64 in England and Wales. Results Among the 7,949 women (70.6%) treated by BCS, post-operative adjuvant RT was given to 4,939 (62.1%); RT use after BCS increased over time (R2 =0.92; p&amp;lt; 0.01). RT use was associated with year of diagnosis (p &amp;lt; 0.01), younger age at diagnosis (p &amp;lt; 0.01), larger DCIS size (p &amp;lt; 0.01), presence of comedo necrosis (p &amp;lt; 0.01), higher nuclear grade (p &amp;lt; 0.01) and presence of microinvasion (p &amp;lt; 0.01). Adjusted analyses showed the most significant factor for RT after BCS was the surgery institution. Travel time to RT facility, Index of Multiple Deprivation and final radial margin were not associated with RT use. When compared with the more recent data from the NABCOP, a marked variation in radiotherapy use across hospitals remains. Ipsilateral recurrence rate varied significantly by hospital, with some of the difference associated with RT utilisation. ET was prescribed in 1313 women (12%), more often following BCS than mastectomy (p &amp;lt; 0.001), with significant variation by institution and a decline in the use of ET over time. Conclusion Marked geographic variation in the use of RT and ET after surgery for DCIS persists in the UK and is likely due to physician choice rather than other factors such as travel times to RT facilities. This is contributing to geographic variation in ipsilateral recurrence rates, suggesting the need for adoption of more authoritative guidelines to support clinical decision-making. Consistent national practice could provide auditable performance standards for adjuvant therapy of screen detected DCIS and contribute to more uniform patient care. Citation Format: Karen Clements, David Dodwell, Elinor Sawyer, Ramsey Cutress, Nisha Sharma, Abeer Shaaban, Alastair Thompson. Patterns of care: radiotherapy after breast conserving surgery and the use of endocrine therapy for screen-detected ductal carcinoma in situ (DCIS) in the UK [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-17-05.

Abstract PO4-26-02: Evaluation of Tumor Infiltrating Lymphocytes as a predictive biomarker of recurrence in patients with Ductal Carcinoma In Situ of the breast

Abstract Introduction: Ductal carcinoma in situ (DCIS) represents around 20% of early breast cancer diagnoses globally. Some studies evaluated risk factors associated with DCIS recurrence. Among these, age, surgical margins, comedonecrosis (CN), high nuclear grade, negative hormone receptors and HER2 expression stand out. Recent approaches have been evaluating the role of the immune microenvironment and its association with recurrence and progression of DCIS. Objective: To evaluate the association between Tumor Infiltrating Lymphocytes (TILs) in DCIS samples and disease recurrence. To characterize the immunological microenvironment of DCIS, analyzing the presence of TILs, “touching TILs” and desmoplastic reaction and their association with recurrence. Epidemiological, clinical, histological and immunohistochemical (IHC) characteristics were also evaluated. Methods: This is a retrospective cohort study with patients diagnosed with DCIS and treated at Sao Paulo State Cancer Institute and Hospital das Clinicas of University of Sao Paulo. We included women over 18 years old with a diagnosis of DCIS who underwent treatment from Jan/2007 to Dec/2020. Male patients, patients with a diagnosis of invasive or microinvasive disease in the anatomopathological examination of the surgical specimen or patients with history of any neoplasm were excluded. The main outcome was survival analysis according to the quantification of TILs, adjusted for potential confounders. For that, we collected data on age, presence of palpable mass, imaging findings, histological and IHC characteristics, such as expression of estrogen receptor (ER), progesterone receptor (PR) and hyperexpression of HER2, type of surgical approach, type of radiation therapy, use of endocrine therapy, length of follow-up, recurrence, and its type. Two pathologists evaluated TILS in the sample with the highest tumor representation and numerically quantified it as percentage. They also evaluated the presence of “touching tils” (lymphocytes in contact with the basement membrane) and desmoplastic reaction in the tumor stroma. Kaplan-Meier curves, log-rank tests and Cox regression models were used to evaluate survival. Chi-square tests were used to evaluate the association between categorical variables. Results: 283 patients met the eligibility criteria. Mean age of patients was 55 years. 15% had a palpable nodule at physical examination. Clustered amorphous microcalcifications were the most prevalent mammographic presentation, found in 41% of the patients. The most frequent histological and IHC features were cribriform presentation (73%) and ER positivity (86%), respectively. Desmoplastic reaction was absent in 10.5%, discreet in 51.9%, moderate in 24% and intense in 13.6% of the patients. Breast conserving surgery was performed in 189 patients, and 100 of them received adjuvant radiation therapy. Mean follow-up was 77.2 months, with a recurrence rate of 9.2%. We observed that tumors with focal necrosis (HR 6.4 [1.39-34.71] p 0.018) or CN (HR 4.53 [1.34 – 15.28] p 0.015) had higher risks of recurrence. Patients with a percentage value of TILs greater than or equal to 17% also had a higher risks of recurrence (HR 2.97 (1.17-7.51) p 0.02). These patients were mostly under 65 years of age (OR 0.45 [0.21 - 0.97] p 0.049). In a multivariate model, CN and TILs&amp;gt;17% remained significantly associated with recurrence (p=0.034 and p=0.035 respectively). There was a trend for invasive recurrence in 76.9% of the patients that relapsed when TILS were greater than or equal to 17% (p 0.062). “Touching TILs” were present in 12.9% of the patients but were not associated with recurrence (p=0.575). Conclusion: In our cohort, high value of TILs (&amp;gt;= 17%) and presence of CN were independently associated with DCIS recurrence. Our findings suggest that TILS are a prognostic immunological biomarker in DCIS and warrant further investigation in prospective trials to determine the most adequate cut-point. Citation Format: Camila Pasetto, Fernando Aguiar, Marcella Peixoto, Maira Doria, Bruna Mota, Jonathan Maesaka, Jose Roberto Filassi, Edmund Baracat, Rodrigo Gonçalves. Evaluation of Tumor Infiltrating Lymphocytes as a predictive biomarker of recurrence in patients with Ductal Carcinoma In Situ of the breast [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-26-02.

Brain Metastases from Breast Cancer Histologically Exhibit Solid Growth Pattern with at Least Focal Comedonecrosis: A Histopathologic Study on a Monocentric Series of 30 Cases.

Since there are no morphological clues capable of making a pathologist suspect a possible mammary origin of a metastatic lesion without adequate clinical information, the histologic diagnosis of brain metastasis from BC is still based on the immunohistochemical expression of mammary gland markers such as GATA-3, ERs, PgRs and HER-2. The present retrospective study aimed to select purely morphological features capable of suggesting the mammary origin of a metastatic carcinoma in the brain. The following histological features were collected from a series of 30 cases of brain metastases from breast cancer: (i) a solid growth pattern; (ii) the presence of comedonecrosis; and (iii) glandular differentiation. Our results showed that most cases histologically exhibited a solid growth pattern with at least focal comedonecrosis, producing an overall morphology closely reminiscent of mammary high-grade ductal carcinoma in situ. Although the above-mentioned morphological parameters are not strictly specific to a mammary origin, they may have an important diagnostic utility for leading pathologists to suspect a possible breast primary tumor and to include GATA-3, ERs, PgRs and HER-2 in the immunohistochemical panel.

Impact of comedonecrosis on prostate cancer outcome: a systematic review.

Cribriform architecture has been recognised as an independent parameter for prostate cancer outcome. Little is yet known on the added value of individual Gleason 5 growth patterns. Comedonecrosis is assigned Gleason pattern 5 and can occur in both invasive and intraductal carcinoma. The aim of this study is to systematically review the literature for the prognostic value of comedonecrosis in prostate cancer. A systematic literature search of Medline, Web of Science, Cochrane library and Google scholar was performed according to the Preferred reporting items for systematic reviews and meta-analysis (PRISMA)guidelines. After identification and screening of all relevant studies published up to July 2022, 12 manuscripts were included. Clinicopathological data were extracted and the presence of comedonecrosis in either invasive, intraductal or ductal carcinoma was associated with at least one clinical outcome measure. No meta-analysis was performed. Eight of 11 studies showed that comedonecrosis was significantly associated with biochemical recurrence and two studies with metastasis or death. The only studies using metastasis-free and disease specific-free survival as an endpoint both found comedonecrosis to be an independent prognostic parameter in multivariate analysis. The studies were all retrospective and demonstrated considerable heterogeneity with regard to clinical specimen, tumour type, grade group, correction for confounding factors and endpoints. This systematic review demonstrates weak evidence for comedonecrosis to be associated with adverse prostate cancer outcome. Study heterogeneity and lack of correction for confounding factors prohibit drawing of definitive conclusions.

Upgrade Rate of Ductal Carcinoma In Situ to Invasive Carcinoma and the Clinicopathological Factors Predicting the Upgrade Following a Mastectomy: A Retrospective Study.

Background The rate of upgrading ductal carcinoma in situ (DCIS) to invasive cancer varies widely in the literature with no consensus regarding sentinel lymph node biopsy (SLNB) for DCIS; however, some guidelines do recommend it in the event of a mastectomy. The primary aim of this study was to determine the upgrade rate of DCIS to invasive carcinoma (IC) in patients undergoing mastectomy for DCIS and identify the clinicopathological predicting factors for the upgrade. The secondary aim was to determine the SLNB positivity rate. Methodology We retrospectively analysed consecutive patients with DCIS diagnosed through a biopsy who then underwent mastectomy over a 10-year period (2010 to 2020). Clinical, radiological, and histological variables were collected from medical records. Results We studied 143 women (mean age = 57.4 years, range = 26-85 years) who underwent mastectomy for DCIS identified on biopsy.Almost two-thirds (62.9%, 90/143) of the patients were detected on screening mammography, while 35.6% (51/143) were diagnosed following presentation with either an area of palpable concern or nipple discharge.The most common mammographic presentation of DCIS was calcification (83.9%, 120/143), and, in 85.9% of the patients, the mammographic lesion was more than 20 mm. High-grade DCIS was noted in 76.9% of preoperative biopsy results, while the rest was either low or intermediate-grade DCIS. Overall, 24.5% (35/143) were upgraded to IC (upgraded group) on postoperative histology, whereas 108/143 remained DCIS postoperatively (pure DCIS group).The positivity rate of SLNB was 4.8%. Multifocality was the only significant predictor of IC on multivariate analyses of clinicopathological predictors (odds ratio = 3.0, 95% confidence interval = 1.0-8.7). The presence of comedonecrosis was higher in the upgraded group compared to the pure DCIS group (42.9% vs. 27.8%), but this was not statistically significant. Conclusions In our study cohort, nearly one in four (24.5%) patients were upgraded from DCIS to IC on postoperative histology, with an SLNB positivity rate of 4.8%. This is important when counselling patients regarding the risk of coincident occult IC and the importance of SLNB at the time of mastectomy. Multifocality on preoperative imaging was the only significant predictive factor. Based on this result, we recommend that SLNB should also be considered if patients have multifocal DCIS and planned for oncoplastic breast-conserving surgery. However, further studies are required to investigate the association between multifocal DCIS and the risk of upgrading to IC.

Abstract PR001: Spatial proximity between CD8+ T cells and tumor cells correlates with invasive recurrence in DCIS

Abstract Purpose: The immune microenvironment in ductal carcinoma in situ (DCIS) and its significance are not well established. In this study, we characterized the immune microenvironment of DCIS to determine if immune cell densities, or their spatial relationships with tumor cells, are predictive of recurrence with invasive breast cancer. Methods: One hundred thirty-two cases of DCIS were included in this study. Seventy (53%) cases were high grade, 72 (54%) were HER2+, and 91 (69%) were HR+. Twenty cases recurred with invasive breast cancer. Immune infiltrates were characterized by multiplex immunofluorescence staining of FFPE sections using two 6-plex panels. Panel IP1.2 included markers for CD3, CD20, Foxp3, pan-cytokeratins, Ki67, and HLADR. Panel IP2.2 included markers for CD3, CD8, CD68, pan-cytokeratins, PD-1, and PD-L1. Staining was performed on a Leica Bond autostainer and images were acquired on a Vectra Polaris imaging system. Image analysis was performed utilizing inForm and QuPath software packages, as well as R scripts. Counts for each cell population were determined and spatial point pattern analyses were performed to quantitate the spatial relationships between tumor cells and various immune cell types. Results: High infiltrates of T cells, CD8+ T cells (Tc), Foxp3+ T cells, and B cells were associated with high grade, hormone receptor (HR) negativity, HER2 positivity, and the presence of comedonecrosis. PD-1+ T cells and PD-1+ Tc were associated with high grade, HR negativity, and HER2 positivity. PD-L1+ immune cells, but not PD-L1+ tumor cells, were also associated with high grade, HR negativity, and HER2 positivity. None of the cell populations were associated with invasive recurrence. However, the spatial proximity of tumor cells with T cells, in particular Tc, was significantly associated with a subsequent invasive event. Patients whose DCIS had a high tumor-to-Tc proximity score (indicating close proximity of tumor and Tc) were less likely to have an invasive recurrence. Conclusion: These findings suggest that the tumor immune microenvironment is an important factor in identifying DCIS cases at risk for invasive recurrence and that manipulating the immune microenvironment may be an efficacious strategy to alter or prevent disease progression. Citation Format: Michael J. Campbell, Nicole Schindler, Alexa Glencer, Jennifer Bolen, Hidetoshi Mori, Tristan Loveday, Harriet Rothschild, Gillian Hirst, Scott Vandenberg, Alexander Borowsky, Laura Esserman. Spatial proximity between CD8+ T cells and tumor cells correlates with invasive recurrence in DCIS [abstract]. In: Proceedings of the AACR Special Conference on Rethinking DCIS: An Opportunity for Prevention?; 2022 Sep 8-11; Philadelphia, PA. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_1): Abstract nr PR001.

The Use of Optical Coherence Tomography for Gross Examination and Sampling of Fixed Breast Specimens: A Pilot Study.

Thorough gross examination of breast cancer specimens is critical in order to sample relevant portions for subsequent microscopic examination. This task would benefit from an imaging tool which permits targeted and accurate block selection. Optical coherence tomography (OCT) is a non-destructive imaging technique that visualizes tissue architecture and has the potential to be an adjunct at the gross bench. Our objectives were: (1) to familiarize pathologists with the appearance of breast tissue entities on OCT; and (2) to evaluate the yield and quality of OCT images of unprocessed, formalin-fixed breast specimens for the purpose of learning and establishment of an OCT–histopathology library. Methods: Firstly, 175 samples from 40 formalin-fixed, unprocessed breast specimens with residual tissue after final diagnosis were imaged with OCT and then processed into histology slides. Histology findings were correlated with features on OCT. Results: Residual malignancy was seen in 30% of tissue samples. Corresponding OCT images demonstrated that tumor can be differentiated from fibrous stroma, based on features such as irregular boundary, heterogeneous texture and reduced penetration depth. Ductal carcinoma in situ can be subtle, and it is made more recognizable by the presence of comedo necrosis and calcifications. OCT features of benign and malignant breast entities were compiled in a granular but user-friendly reference tool. Conclusion: OCT images of fixed breast tissue were of sufficient quality to reproduce features of breast entities previously described in fresh tissue specimens. Our findings support the use of readily available unprocessed, fixed breast specimens for the establishment of an OCT–histopathology library.

Microinvasive breast cancer and the role of sentinel lymph node biopsy

Whether sentinel lymph node biopsy (SLNB) should be performed in patients with microinvasive breast cancer (MIBC) has been a matter of debate over the last decade. MIBC has a favorable prognosis and while metastasis to the axilla is rare, it can impact treatment recommendations. In this study we evaluated clinical and histological features in both MIBC and background DCIS including ER, PR, and HER-2, number of foci of MIBC, the extent of the DCIS, nuclear grade, presence of comedo necrosis, as well as surgical procedures, adjuvant treatment and follow up to identify variables which predict disease free survival (DFS), as well as the factors which influence clinical decision making. Our study included 72 MIBC patients with a mean patient follow-up time of 55 months. Three patients with MIBC had recurrence, and two deceased, leaving five patients in total with poor long-term outcomes and a DFS rate of 93.1%. Performing mastectomy, high nuclear grade, and negativity for ER and HER-2 were found to be associated with the use of SLNB, although none of these variables were found to be associated with DFS. One positive lymph node case was discovered following SLNB in our study. This suggests the use of SLNB may provide diagnostic information to some patients, although these are the anomalies. When comparing patients who had undergone SLNB to those which had not there was no difference in DFS. Certainly, the use of SLNB in MIBC is quite the conundrum. It is important to acknowledge that surgical complications have been reported, and traditional metrics used for risk assessment in invasive breast cancer may not hold true in the setting of microinvasion.

Abstract P3-12-36: The diagnosis and prognosis of ductal carcinoma in situ (DCIS) with microinvasion - Results from the United Kingdom Sloane project

Abstract Background/objectives The natural history of microinvasive carcinoma of the breast (one or more foci of invasion of 1mm or less) and its optimal management remain controversial. We analysed the frequency and outcome of patients with DCIS plus microinvasion within a large prospective cohort of screen-detected DCIS. Methods Patients with screen-detected DCIS diagnosed between 2003 and 2012 with or without microinvasion in the final surgical specimen were identified from the UK Sloane Project database. Comprehensive imaging, surgical, pathology, oncology and subsequent outcome data were collected with a median follow-up of 9 years. Results Among 11285 DCIS patients diagnosed in the UK, microinvasion was reported in 521 (4.6%). The frequency of reported microinvasion varied considerably among screening units (0-25%) but overall decreased from 7% in 2003/04 to 3% in 2011/12.As reported elsewhere, microinvasion was significantly associated with high grade DCIS (5.9% of 7182 cases) compared to 2.9% of intermediate grade and &amp;lt;1% of low grade DCIS (p&amp;lt;0.001, Chi square test). Microinvasion was associated with larger DCIS size (p&amp;lt;0.001) 2.2% of DCIS &amp;lt;10mm, 3.9% of DCIS 10-20mm, 5.8% of DCIS 20-30mm, 5.2% of DCIS 30-40mm and 8.0% of DCIS &amp;gt;40mm had microinvasive foci reported. Microinvasion was also associated with the presence of comedo necrosis (p&amp;lt;0.001), and solid (p&amp;lt;0.001), cribriform (p&amp;lt;0.001) or flat (p=0.03) DCIS architecture.Microinvasion was identified more frequently in patients who underwent mastectomy (6.9%) than in those who had breast conserving surgery (BCS) (3.6%; p&amp;lt;0.001). Axillary nodal surgery was more commonly performed for microinvasion (60.4% compared to 30.3%) including for patients undergoing BCS (43.4% vs 8.5% of all patients with BCS; p&amp;lt;0.001). The rate of nodal metastasis was, however, low and not statistically significantly different between those with and without microinvasion (0.4% and 0.1% respectively, p=0.27).Patients with microinvasion who underwent BCS were also more likely to receive radiotherapy (p&amp;lt;0.001). There was no significant association between the presence or absence of microinvasion with margin status or width. Subsequent events data for England showed that microinvasion was associated with a low rate of ipsilateral subsequent events, with 2.3% of patients having recurrent DCIS and 4.2% developing invasive carcinoma. This was not statistically significantly different from DCIS without microinvasion. All subsequent ipsilateral DCIS events in patients with microinvasion were of high grade. The majority (71.4%) of subsequent ipsilateral invasive carcinomas were of grade 3 compared with only 30.4% of grade 3 carcinomas in patients with DCIS without microinvasion (p=0.02). Breast cancer mortality was significantly higher in women whose tumours showed microinvasion (2.1%) compared with those without it (0.8%; p=0.005). Conclusions Microinvasion was most commonly identified within high-grade DCIS and in larger DCIS lesions, and was associated with comedo necrosis. Its pathological reporting decreased over a 10-year period, but there was significant variation between departments, which requires further evaluation. Patients with DCIS plus microinvasion were more likely to have undergone mastectomy, axillary node surgery and to receive radiotherapy after BCS. Microinvasive breast carcinoma was associated with a low rate of subsequent in situ/invasive events and had a good prognosis but, nevertheless, a higher breast cancer mortality than DCIS without microinvasion. Citation Format: Abeer M Shaaban, Bridget Hilton, Karen Clements, David Dodwell, Nisha Sharma, Cliona Kirwan, Elinor Sawyer, Anthony Maxwell, Matthew Wallis, Hilary Stobart, Senthurun Mylvaganam, Janet.Litherland Litherland, Samantha Brace-Mcdonnell, Joanne Dulson-Cox, Olive Kearins, Elena Provenzano, Sarah Pinder, Alastair Thompson. The diagnosis and prognosis of ductal carcinoma in situ (DCIS) with microinvasion - Results from the United Kingdom Sloane project [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-12-36.

Biological features of ductal carcinoma in situ: clinical role and basis for treatment individualization

Ductal carcinoma in situ (DCIS) is an extremely heterogeneous disease in terms of clinical manifestations, morphological changes, and expression of biomarkers, which determine the risk of subsequent development of an invasive breast cancer (BC). Diagnosis and treatment of DCIS prevents the development of invasive tumors (which reduces the potential risk of death from BC); however, the prognostic value of local treatment depends on the biological characteristics of its. The tumor grade, presence of comedonecrosis and expression of estrogen receptors are the key prognostic factors in DCIS for the treatment tactics and prognosis. The clinical symptoms of DCIS are very scarce, the most of tumors is diagnosed by screening mammography; the typical sign of DCIS is malignant microcalcifications or changes of breast architectonic. The sensitivity of mammography, ultrasound and MRI directly depend on the biological characteristics of DCIS. Surgical treatment (breast-conserving surgery or mastectomy) significantly reduces the risk of BC death in women with DCIS G2/G3, and radiotherapy after breast-conserving surgery reduce the risk of local recurrence of non-invasive and invasive BC. The choice of the local treatment (breast-conserving surgery radiation therapy vs mastectomy) depend on such factors as: tumor size, localization, clear margins, and biological characteristics of DCIS. In contrast to invasive cancers, the negative margin in DCIS is more than 2 mm from the tumor. Regional lymph node involvement in DCIS occurs in less than 1% of cases; however, microinvasion is found in analyze the surgical specimen in 15% of patients, which raises the question about regional staging. Risk factors for microinvasion in DCIS are age less than 55 years, tumor lesion size more than 4.0 cm, DCIS grade G3, and tumor palpability. Adjuvant endocrine therapy with tamoxifen significantly reduces the 10-year risk of invasive recurrence by 51%, the risk of contralateral BC by 50% and the risk of death by 40%, but only for hormone-positive DCIS. HER2 overexpression is found in DCIS significantly often (up to 40% of cases) than in invasive BC, HER2+ status correlates with DCIS high grade G3, the presence of comedonecrosis and with increased risk of relapse (both non-invasive and invasive) but is not a reason for anti-HER2 therapy. DCIS low risk and DCIS high risk have not only different morphological characteristics, but also different models of biological behavior, which must be considered in the different choice of treatment tactics.

Disparities in surveillance imaging after breast conserving surgery for primary DCIS.

6516 Background: Due to the elevated risk of ipsilateral invasive breast cancer (iIBC) after diagnosis with primary ductal carcinoma in situ (DCIS), professional guidelines recommend surveillance screening within 6-12 months (mo) after completion of initial local treatment and annually thereafter. To characterize adherence to these guidelines, we explored longitudinal patterns of utilization and factors associated with the use of surveillance imaging (mammography, MRI, ultrasound) for women with primary DCIS treated with breast conserving surgery (BCS) ± radiotherapy (RT) within 6 mo of diagnosis. Methods: A treatment-stratified random sample of patients diagnosed with screen-detected and biopsy-confirmed DCIS in 2008-15 was selected from 1,330 Commission on Cancer-accredited facilities (up to 20/site) in the US. All imaging exams coded as asymptomatic were collected from 6 mo up to 10 years (yr) post-diagnosis. Time was defined according to 12-mo long surveillance periods. To be included in a given surveillance period, women had to be alive and free of a new breast cancer diagnosis through the end of the period. Women were classified as “consistent” screeners if they had at least one surveillance screen during each period, for the first 5 yr post-treatment or until censoring, whichever occurred first. Repeated measures multivariable logistic regression with generalized estimating equations was used to model receipt of surveillance breast imaging over time. The model included clinical and socioeconomic features. Results: The final analytic cohort contained 12,559 women; 8,989 (71.6%) received RT after BCS. Median age was 60 yr (interquartile range: 52-69) and median follow-up was 5.6 yr (95% confidence interval [CI] 5.6-5.7). Among women who received BCS (instead of BCS+RT), 62.5% (79.7%) underwent surveillance imaging within 6-18 mo after diagnosis. 38.7% (54.0%) were categorized as “consistent” screeners. Compared to white women, Black women were less likely to receive surveillance screening after treatment for primary DCIS (odds ratio [OR] 0.85, 95% CI 0.77-0.94). Hispanic ethnicity had a similar association (OR 0.86, 95% CI 0.74-0.99) compared to non-Hispanic ethnicity. Women with private insurance, compared to government insurance, were more likely to receive screening (OR 1.20, 95% CI 1.11-1.30). Prognostic tumor features indicative of a higher risk of subsequent iIBC, including higher grade, presence of comedonecrosis, and hormone receptor-negative DCIS, were not associated with screening uptake. Conclusions: Despite guidelines recommending annual surveillance imaging, many women with primary DCIS do not undergo regular imaging after BCS. The findings from this US-based study suggest that disparities in screening uptake are associated with race/ethnicity and insurance status rather than prognostic tumor features.

Criteria for Excision of Suspicious Calcifications Using the Breast Lesion Excision System (BLES)

Background: The aim of the study was to retrospectively evaluate possible imaging and histopathology criteria that can be used in a clinical basis to assess the success of excision of suspicious calcifications using the breast lesion excision system (BLES).Methods: We investigated 400 BLES stereotactic biopsies of suspicious calcifications with the mean size of 15.38 mm (st. dev.= 13.579 mm, range 3-78 mm) using a 20 mm probe performed in our department between January 2014 and 2016. The mean age of our population was 58.5 years old (range 39-78 years). The pathology results of BLES specimens were compared with the final surgical results to assess excision success rates. Possible imaging and histopathology criteria for removal were statistically analyzed (mammographic size, disease free margins, grade, comedo phenotype, molecular type).Results: The results showed that 90/400 (22.5%) biopsies were cancers (80% DCIS) and 38/400 were lesions with cell atypia (9.5%) of which 29/38 had subsequent surgery and were included in the study. Excision was achieved in 31/90 cancers (34.4%) and in 23/29 lesions with cell atypia (76.3%). The imaging and histopathology criteria for BLES excision that could be potentially clinically assessed were the initial mammographic size (p&lt;0.001), the distance of the lesion from the specimen margins (p&lt;0.001), the presence of comedo necrosis (p=0.014) and the grade of the cancers (p=0.021). The underestimation rate was 15.5%. Conclusion: the mammographic size, grade, comedo presence and disease-free margins, were the main criteria for BLES success rate of excision of suspicious calcifications.

Abstract PD5-05: Including a 21-gene assay recurrence score in multivariable predictive model generation improves prediction of local recurrence after breast conserving surgery for ductal carcinoma-in-situ

Abstract Introduction Accurate prediction of local recurrence (LR) after breast conserving surgery (BCS) for ductal carcinoma-in-situ (DCIS) is crucial to personalize recommendations for adjuvant radiotherapy (RT). The 21-gene recurrence score (RS) predicts for distant metastases for woman with invasive breast cancer. We hypothesised that the RS could improve prediction of LR after BCS for DCIS. Methods We performed a population-based analysis of 1226 woman aged ≤74 treated with BCS ± RT for pure DCIS. Expert pathology review was obtained for all cases, as was the RS. Treatment and outcomes were obtained by deterministic linkage to administrative databases and chart review. Clinico-pathologic features obtained included: age, tumor size, nuclear grade, presence of comedonecrosis, multifocality, margins, and adjuvant radiation. The outcome assessed was local recurrence by 10 years from diagnosis of DCIS. The LR prediction model was developed using multivariable Cox regression, where a non-parametric approach was implemented to estimate the baseline hazard function. The proportional hazards assumption was assessed and time-interaction terms were included with each covariate in the model. Models were ranked based on c-statistic, log-likelihood estimate, and Akaike information criterion (AIC). Backward selection was used to obtain the final reduced model with time-interaction terms. Calibration for the best model was examined by grouping predicted 10-year risk of LR into deciles and plotting against observed 10-year risk of LR based on mean Kaplan-Meier estimates. Internal validation was performed by bootstrapping. Results Of the 1226 woman included, 514 were treated with BCS alone and 712 received adjuvant RT. Median follow up from time of treatment was 16 years (interquartile range (IQR): 14-18). The median age was 56 years (IQR: 49-64). Margins were negative in 90.5% of cases. Tumor size was ≤1cm in 430 (35.1%), 1-2.5cm in 633 (51.6%), and &amp;gt;2.5cm in 163 (13.3%). The median RS was 15 (IQR: 8-30) and the mean RS was 21.37 (SD 18.93). The best predictive model included the RS and had a c-statistic of 0.68 as well as the lowest AIC. This model included the following variables: RS, age, tumor size, nuclear grade, margin status, comedonecrosis (≤30% vs higher), multifocality, and treatment (BCS vs BCS+RT); it also included the following interaction terms: treatment and time, RS and time, comedonecrosis and time, and treatment and tumor size. Due to the non-linear relationship between certain characteristics and the risk of LR, quadratic terms for RS and age were also included. This model was well calibrated overall, especially in the lower risk range around the 10% risk threshold. It was also well calibrated in this risk range in the subset of woman who were treated with BCS alone. Conclusion The best performing model generated to predict LR after BCS for DCIS includes the RS. Work is ongoing to compare RS and the 12-gene DCIS score in terms of prediction of LR, as well as prediction of invasive LR specifically. This work can help guide future clinical de-escalation trials by better identifying woman with truly low risk of LR after BCS for DCIS. Citation Format: Ezra Hahn, Rinku Sutradhar, Sumei Gu, Lawrence Paszat, Danielle Rodin, Sharon Nofech-Mozes, Cindy Fong, Eileen Rakovitch. Including a 21-gene assay recurrence score in multivariable predictive model generation improves prediction of local recurrence after breast conserving surgery for ductal carcinoma-in-situ [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD5-05.

Abstract P3-08-19: Biomarkers associated with dcis related breast cancer death

Abstract Introduction In primary ductal carcinoma in situ of the breast (DCIS) tumour biological features associated with risk of invasive recurrence and metastasis may already be present at the pre-invasive stage. The aim of this study was to investigate the correlation of biological markers in DCIS and the risk of subsequent breast cancer death. Patients and methods A nested case-control study was conducted in a population based cohort of women diagnosed with primary DCIS between 1992 and 2012. Women who later died from breast cancer were identified. Four controls per case were selected randomly by incidence density sampling from the same cohort. Tumour blocks were retrieved for histopathological reevaluation and immunohistochemical analysis (IHC) of Oestrogen Receptor (ER), Progesterone Receptor (PR), Human Epidermal Growth Receptor 2 (HER2) and Ki67 expression. Odds ratios (OR) for risk of breast cancer death with 95% CI was calculated using conditional logistic regression. Results From a cohort of 6964 women with primary DCIS, tumour specimens were available for 66 patients who died from breast cancer and these were compared to samples from 195 controls. DCIS with intense lymphocytic infiltration was associated with an increased risk of breast cancer related death in univariate analysis (OR 2.25; 95%CI 1.02-4.99). None of the biomarkers were individually related to increased risk. In multivariable analysis and stepwise adjusting for age, tumour size and treatment; PR negativity in combination with lymphocytic infiltration (OR 4.40; 95%CI 1.20-16.14), PR negativity, lymphocytic infiltration and presence of comedonecrosis (OR 5.48; 95%CI 1.71-17.57) and the combination of PR negativity, lymphocytic infiltration, comedonecrosis and HER2 positivity (OR 7.54; 95%CI 2.00-28.43) were all independently associated with increased risk of breast cancer related death. Conclusion In the present study, the combination of PR negativity and periductal lymphocytic infiltration was associated with risk of breast cancer related death after primary DCIS. Combining biomarker expressions in DCIS with features in the peritumoural stroma may be useful tools for prognostication. Citation Format: Charlotta Wadsten, Johan Hartman, Irma Fredriksson, Hans Garmo, Fredrik Wärnberg, Malin Sund. Biomarkers associated with dcis related breast cancer death [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-19.

Ductal carcinoma in situ of the breast: correlation of architectural, cytological, IHC findings and recurrence analysis

ABSTRACT Objective: This study evaluated the histopathological features of ductal carcinoma in situ (DCIS), including cytological grade, architectural pattern and immunohistochemistry (IHC) in pure DCIS and DCIS associated with invasive carcinoma of no special type (ICNST). Methods: We evaluated a series of 232 cases of pure DCIS and DCIS associated with ICNST from a total of 399 breast carcinomas from a population consisting by women diagnosed with breast cancer and submitted to breast surgery from 2011 to 2015. Results: DCIS presented a mixed architectural pattern in most cases (56%); the solid subtype was the most common morphology (30%). High-grade DCIS was identified in 84/221 cases (38%), and comedonecrosis was present in 106/221 cases (48%). High-grade was more common in the solid subtype (61/155 cases, 39%, p < 0.001). Tumor size was greater in the presence of comedonecrosis than in the absence (mean 27 vs 20 mm, p = 0.009). Estrogen receptor (ER) was positive in 81% of cases with a cribriform pattern (p = 0.013). Greater locoregional recurrence was found in the comedonecrosis (15%) and micropapillary (19%) subtypes in DCIS associated with ICNST. Conclusion: We observed a greater relationship of ER with the low nuclear grade, while Ki-67 was related to the high-grade. DCIS presented a higher nuclear grade compared to ICNST. The less common pure pattern was the micropapillary, and the most common, the solid. Comedonecrosis was more frequent in the solid pattern. Our results showed that high-grade was more common in the solid and comedo subtype, and low-grade was more frequent in the cribriform.

Ductal Carcinoma In Situ (DCIS) at Breast MRI: Predictors of Upgrade to Invasive Carcinoma

To determine the upgrade rate of magnetic resonance imaging (MRI)-detected ductal carcinoma in situ (DCIS) and to identify patient, imaging, and pathologic features that may predict the risk of upgrade. Medical chart review from January 2007 to December 2016 identified 60 patients with 61 cases of MRI-detected DCIS and negative mammographic evaluations within 1 year prior to the MRI. Imaging and pathology reports were reviewed. Standard statistical tests, including Student's t-tests and chi-square tests, were used to compare patient, imaging, and pathologic features between the cases of DCIS that did and did not upgrade to invasive carcinoma at surgery. Over a 10-year period, 60 patients (mean age 52 years, range 30-76 years) were diagnosed with 61 cases of MRI-detected DCIS. Two-thirds of DCIS cases were detected on MRI examinations that were performed for purposes of high-risk screening (67.2%, 41/61). MRI features that led to the DCIS diagnosis were nonmass enhancement in 78.7% (48/61), enhancing mass in 16.4% (10/61), nonmass enhancement and enhancing mass in 3.3% (2/61), and enhancing focus in 1.6% (1/61). Thirteen cases (21.3%, 13/61) were upgraded to invasive ductal carcinoma at surgery. DCIS cases that upgraded were larger on MRI (40 mm vs 17 mm, p < 0.01) and more likely to be associated with comedonecrosis at biopsy (38.5% [5/13] vs 6.3% [3/48], p < 0.01). The upgrade rate of MRI-detected DCIS to invasive ductal carcinoma at surgery is 21.3%. Features that are associated with upgrade include large size on MRI and the presence of comedonecrosis at biopsy.

Variability in diagnostic threshold for comedo necrosis among breast pathologists: implications for patient eligibility for active surveillance trials of ductal carcinoma in situ

Active surveillance trials for low-risk ductal carcinoma in situ (DCIS) are in progress in the United States and Europe. In some of these trials, the presence of comedo necrosis in the DCIS has been an exclusion criterion for trial entry. However, the minimum amount of necrosis required by pathologists for a diagnosis of comedo necrosis is not well-defined. We surveyed 35 experienced breast pathologists to assess their diagnostic threshold for comedo necrosis. Pink circles representing necrosis ranging in extent from 10 to 80% of the duct diameter were superimposed on eight replicate histologic images of a single duct involved by low nuclear grade, solid pattern DCIS. These images were circulated by e-mail to the participating pathologists who were asked to select the image that represents the minimum amount of necrosis that they require for a diagnosis of comedo necrosis. Among the 35 participants, the minimum extent of the duct diameter required for a diagnosis of comedo necrosis was 10% for 4 pathologists, 20% for 5, 30% for 11, 40% for 7, 50% for 6, 60% for 1 and 70% for 1. There was no single threshold about which more than one-third of the pathologists agreed met the minimal criteria for comedo necrosis. We conclude that even among experienced breast pathologists, the threshold for comedo necrosis is highly variable. Our findings highlight the need for a standardized definition of comedo necrosis as a trial criterion, and more generally where it may be used as a marker of increased risk of recurrence for therapeutic decision making.

Thioredoxin-interacting protein is an independent risk stratifier for breast ductal carcinoma in situ

Current clinicopathological parameters are useful predictors of breast ductal carcinoma in situ behavior, but they are insufficient to define high-risk patients for disease progression precisely. Thioredoxin-interacting protein (TXNIP) is a key player of oxidative stress. This study aims to evaluate the role of TXNIP as a predictor of ductal carcinoma in situ progression. Tissue microarrays from 776 pure ductal carcinoma in situ and 239 mixed ductal carcinoma in situ and invasive tumors were constructed. All patients were treated at a single institution with a long-term follow-up and TXNIP expression was assessed using immunohistochemistry. TXNIP expression was investigated in terms of associations with clinicopathological and molecular features and patient outcome. Loss/reduced cytoplasmic expression of TXNIP was associated with features of aggressiveness including high nuclear grade (p = 1.6 × 10−5), presence of comedo necrosis (p = 0.001), and estrogen receptor negative (ER−)/HER2− ductal carcinoma in situ (p = 4.6 × 10−5). Univariate analysis showed an inverse association between TXNIP expression and outcome in terms of shorter local recurrence-free survival (p = 0.009). Multivariable analyses showed that independent predictors of ductal carcinoma in situ recurrence were low TXNIP expression (p = 0.005, HR = 0.51, and 95% CI: 0.32–0.81), larger ductal carcinoma in situ size, and high nuclear grade. TXNIP functions as a tumor suppressor gene with loss of its expression associated with ductal carcinoma in situ recurrence. TXNIP can be used as a potentially useful marker in prognostic stratification of ductal carcinoma in situ for management decisions.