Breast Surgical Specimens Research Articles

Impact of the COVID-19 pandemic on the pathologic diagnosis and treatment of breast cancer in a university hospital in Brazil

PurposeThe COVID-19 pandemic has led to the need for extraordinary restrictions and adjustments in health services, which may have compromised cancer screening and oncological treatments. The aim of our retrospective study was to evaluate the impact of the COVID-19 pandemic on breast cancer pathologic diagnosis, presentation, and treatment in a university hospital in Brazil.Materials and methodsWe extracted data from the medical records of all patients who were diagnosed with breast cancer and underwent treatment in a Southeast University Hospital in Brazil from March to December between 2018 and 2021. The primary objective was to compare breast cancer diagnosis, stage, and oncology treatments during the COVID-19 pandemic (2020–2021) with a prepandemic control cohort (2018–2019).ResultsWe collected data for 116 patients and 500 breast surgical specimens. There was a -12% decline in the diagnosis of new cases of breast cancer during the pandemic. The decrease was most pronounced when comparing 2019 and 2020 (-50%), and a recovery in the number of diagnoses was noted in 2021 compared to 2019 (+ 7.1%). In terms of therapeutic surgical approaches, an increase of 29.73% occurred during the pandemic period. The increase was most pronounced when comparing 2018 and 2020 (+ 41.18%). Overall, stage distribution and other tumor characteristics did not show statistically significant differences between the pandemic and prepandemic cohorts.ConclusionsOur results showed a decrease in the number of new breast cancer diagnoses (-12%) during the pandemic compared to the prepandemic period. However, the number of therapeutic surgical approaches performed increased, and a recovery in the number of breast cancer diagnoses during 2021 has been noticed. Concerted measures are needed to minimize the long-term negative impact of the COVID-19 pandemic on delayed diagnosis.

Abstract PR009: Effect of testosterone therapy on quantitative breast lobular atrophy in transmasculine individuals

Abstract Background. Most transmasculine (TM) individuals pursue gender-affirming testosterone therapy (TT). The health outcomes associated with long-term TT use remains unclear. We previously reported that TT is associated with breast lobular atrophy (i.e., shrinking) when assessed by pathologists. Breast lobules are the main sites whereby cancer develops, and there are ongoing research to clarify the association between lobular atrophy and breast cancer risk. As such, TT may influence breast cancer risk in TM individuals. This study investigated the quantitative relationship between length of TT use and lobular atrophy. Materials and Methods. Breast surgical specimens were obtained from 417 TM subjects who had gender affirming chest-contouring surgery. Clinical data were retrieved from medical records. Each subject had one to six H&E slides that were reviewed by pathologists and digitized at 20× (n=1073 whole slide images (WSIs)). We applied our deep-learning computational pathology method that detects and quantifies acini and breast lobules to the WSIs. For each WSI, our method extracted total tissue area (mm2), fat area (mm2), number of breast lobules, area (mm2) and span (mm) of each lobule, and the number of acini in each lobule. Multiple WSIs for each subject were combined to compute four measures of lobular atrophy—1) median lobule size (mm2), 2) median acini counts per lobule, 3) number of lobules per mm2 of tissue area, and 4) % lobular area. We evaluated the relationship between quantitative measures of lobular atrophy for every six months of TT use with linear regression models, adjusting for age, year of surgery, race/ethnicity, BMI, chest binding, whether the subject removed their ovaries, and TT dose. Patients who did not use TT prior to surgery were assigned as zero months of TT. In order to improve the interpretability of the beta coefficient, we back transformed the natural log beta coefficients. Results. The size of breast lobules in TM individuals shrank by 3.9 % for every six months of TT use (adjusted p<0.001). The results of the other three measures were similar: the median number of acini in each breast lobule decreased by 5.5%, the number of lobules per mm2 of breast tissue decreased by 4.9%, and the % of lobular area in the breast was reduced by 10.0%, for every six months that a patient received TT (all adjusted p≤0.001). Conclusions. This is the first study to investigate the quantitative relationship between duration of TT and lobular atrophy. For every six months of TT, the breast lobules of TM subjects decreased in size and numbers at an approximate rate of 5%, after accounting for potential confounders. This work will support the understanding of breast cancer risk in the TM population, and contributes to reducing healthcare disparities in the transgender community. Citation Format: Gabrielle M. Baker, Yaileen D. Guzman-Arocho, Vanessa C. Bret-Mounet, Mitko Veta, Suzanne C. Wetstein, Brittany M. Charlton, Sarah S. Jackson, Gerburg M. Wulf, Yujing Jan Heng. Effect of testosterone therapy on quantitative breast lobular atrophy in transmasculine individuals [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr PR009.

Effectiveness of Carbon Localization for Invasive Breast Cancer: An Institutional Experience.

The final oncological and aesthetic results of breast-conserving surgery (BCS) are influenced by the precise localization of breast cancer (BC) tumors and by the quality of the intraoperative margin assessment technique. This study aimed to assess the effectiveness of the carbon localization (CL) technique by determining the success rate of BC identification and the proportion of adequate complete resection of BC lesions. We conducted a cross-sectional retrospective study of patients treated with primary BCS for invasive BC who underwent CL of their BC lesion at the Jules Bordet Institute between January 2015 and December 2017. Descriptive statistics with categorical and continuous variables were used. The success rate of tumor identification and the rate of adequate excision were calculated using the test of percentages for independent dichotomous data. This study included 542 patients with 564 nonpalpable BC lesions. The median pathological tumor size was 12 mm. Of these, 460 were invasive ductal carcinomas. Most of the tumors were of the luminal subtype. CL was performed using ultrasound guidance in 98.5% of cases. The median delay between CL and surgery was 5 days, with 46% of the patients having CL one day before surgery. The lumpectomy weighed 38 g on average, with a median diameter of the surgical sample at 6 cm and a median volume of 44 cm3 (6-369). One-stage complete resection was successfully performed in 93.4% of cases. In 36% of cases, an intraoperative re-excision was performed, based on intraoperative macroscopic pathological margin evaluation. The tumor was identified in 98.9% of cases in the breast surgical specimen. This study demonstrated high success rates for BC tumor identification (99%) and one-stage complete resection (93.4%) after BCS and CL. These results show that CL is an effective, simple, and inexpensive localization technique for successful excision of BC lesions during BCS.

Automatic diagnosis and classification of breast surgical samples with dynamic full-field OCT and machine learning.

The adoption of emerging imaging technologies in the medical community is often hampered when they provide a new unfamiliar contrast that requires experience to be interpreted. Dynamic full-field optical coherence tomography (D-FF-OCT) microscopy is such an emerging technique. It provides fast, high-resolution images of excised tissues with a contrast comparable to H&E histology but without any tissue preparation and alteration. We designed and compared two machine learning approaches to support interpretation of D-FF-OCT images of breast surgical specimens and thus provide tools to facilitate medical adoption. We conducted a pilot study on 51 breast lumpectomy and mastectomy surgical specimens and more than 1000 individual images and compared with standard H&E histology diagnosis. Using our automatic diagnosis algorithms, we obtained an accuracy above 88% at the image level () and above 96% at the specimen level (above ). Altogether, these results demonstrate the high potential of D-FF-OCT coupled to machine learning to provide a rapid, automatic, and accurate histopathology diagnosis with minimal sample alteration.

Breast carcinoma detection in ex vivo fresh human breast surgical specimens using a fast slide-free confocal microscopy scanner: HIBISCUSS project.

New generation ultra-fast fluorescence confocal microscopy allows the ex vivo intraoperative analysis of fresh tissue. The High resolution Imaging for Breast carcInoma detection in ex vivo Specimens after breast Conserving sUrgery by hiStolog Scanner (HIBISCUSS) project aimed to develop an online learning program to recognize the main breast tissue features on ultra-fast fluorescence confocal microscopy images and to evaluate the performance of surgeons and pathologists in diagnosing cancerous and non-cancerous breast tissue in ultra-fast fluorescence confocal microscopy images. Patients who underwent conservative surgery or mastectomy for breast carcinoma (invasive or in situ lesions) were included. The fresh specimens were stained with a fluorescent dye and imaged using a large field-of-view (20 cm2) ultra-fast fluorescence confocal microscope. One hundred and eighty-one patients were included. The images from 55 patients were annotated to generate learning sheets and images from 126 patients were blindly interpreted by seven surgeons and two pathologists. The time for tissue processing and ultra-fast fluorescence confocal microscopy imaging was between 8 and 10 min. The training program was composed of 110 images divided into nine learning sessions. The final database for blind performance assessment comprised 300 images. The mean duration for one training session and one performance round was 17 and 27 min respectively. The performance of pathologists was almost perfect with 99.6 per cent (standard deviation (s.d.) 5.4 per cent) accuracy. Surgeons' accuracy significantly increased (P = 0.001) from 83 per cent (s.d. 8.4 per cent) in round 1 to 98 per cent (s.d. 4.1 per cent) in round 7 as well as the sensitivity (P = 0.004). Specificity increased without significance from 84 per cent (s.d. 16.7 per cent) in round 1 to 87 per cent (s.d. 16.4 per cent) in round 7 (P = 0.060). Pathologists and surgeons showed a short learning curve in differentiating breast cancer from non-cancerous tissue in ultra-fast fluorescence confocal microscopy images. Performance assessment for both specialties supports ultra-fast fluorescence confocal microscopy evaluation for intraoperative management. NCT04976556 (http://www.clinicaltrials.gov).

Abstract P5-01-08: Steps toward noninvasive lymph node staging (NILS) in clinically node negative patients: Artificial neural network model to preoperatively predict lymphovascular invasion

Abstract Background: Lymphovascular invasion (LVI) is one of the most important predictors for nodal status in breast cancer patients [1]. Multiple models have been published for prediction of preoperatively disease-free axillary using i.a. LVI [1-2]. However, LVI detection in preoperative core needle biopsy has been reported with a failure rate of 30% [3] and the analysis is not routinely performed in Sweden. Thus, a preoperative model of LVI status would be useful in prediction models for noninvasive lymph node staging (NILS). The purpose of this study was to develop an artificial neural network (ANN) model for LVI prediction using only clinicopathological variables that are routinely available in the preoperative setting. Methods: Data gathered prospectively during 2009-2012 in Lund, Sweden from 761 clinically node negative breast cancer patients were retrospectively extracted. Inclusion criteria were female sex, primary breast cancer and that each patient was scheduled for primary surgery. Patients with metastatic disease, bilateral cancer, tumor size greater than 50 mm, previous ipsilateral breast or axillary surgery, patients omitted of standard axillary staging procedure by SLNB or ALND, and those who had neoadjuvant treatment were excluded. LVI was assessed on surgical breast specimens and was defined as the presence of tumor cells within endothelium-lined vascular channels. Out of the 761 patients in the cohort, 613 patients were documented with LVI status. The LVI full case dataset was split 80/20 for training and validation. The remaining 148 patients were set aside for model testing. Since the test dataset did not contain information on LVI status, it was used to compare the predicted fraction of LVI positive patients to that of the development dataset. Only variables possible to obtain in the preoperative setting were included in the prediction models, comprising age, menopausal status, mode of detection (mammography screening or symptomatic representation), tumor size, multifocality (yes/no), histopathological type, histological grade, ki-67 percentage, estrogen receptor status, progesterone receptor status, and human epidermal growth factor receptor 2 status. An ensemble approach was used, where each ensemble constituted 30 ANNs that were trained and validated using 5-fold cross validation. For every ensemble model, different model parameters, such as L2-regularization and the number of hidden nodes, were tested. Model selection was based on validation AUC. Results: The study cohort included female clinically node negative breast cancer patients scheduled for primary surgery. Data from 613 patients (lymph node stages N0: 67.4%, N1: 26.9%, N2+: 5.7%) were used to develop the model, and 148 patients (N0: 56.8%, N1: 35.8%, N2+: 7.4%) constituted the internal test cohort. Fifteen percentage of the patients in the development dataset were LVI positive. The selected ensemble model achieved a validation AUC of 0.80 (CI 0.75-0.85). This model predicted an LVI positive rate of 16.2% in the test dataset. Conclusion: LVI was predicted with high accuracy using an ANN model based on routine preoperative clinicopathological variables. The result of validation AUC 0.80 (CI 0.75-0.85) indicates a potential for preoperative prediction of LVI, and the model can putatively be useful when applying preoperative nodal prediction models in patients without known LVI status. To confirm these results, verification in an external dataset is needed. Validation of the LVI-model in an independent dataset from the National Breast Cancer Registry will be performed, as well as an evaluation of the usefulness of the LVI-model as an imputation in a nodal prediction model. [1] Dihge, L. et al. BMC Cancer (2019). PMID: 31226956 [2] Bevilacqua, J. L. et al. J Clin Oncol. (2007). PMID: 17664461 [3] Harris, G. C. et al. Am J Surg Pathol. (2003). PMID: 12502923 Citation Format: Malin Hjärtström, Looket Dihge, Pär-Ola Bendahl, Mattias Ohlsson, Lisa Rydén. Steps toward noninvasive lymph node staging (NILS) in clinically node negative patients: Artificial neural network model to preoperatively predict lymphovascular invasion [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-01-08.

Abstract PD15-01: PD15-01 AXILLARY NODAL RECURRENCE IS RARE IN PATIENTS WITH NODE-POSITIVE BREAST CANCER UNDERGOING SLNB FOLLOWING NEOADJUVANT CHEMOTHERAPY : EARLY RESULTS OF THE NEOSENTITURK-TRIAL/MF-18-03

Abstract Background: Whether axillary lymph node dissection (ALND) following sentinel lymph node biopsy (SLNB) could be spared in patients with initially clinically positive axilla after neoadjuvant chemotherapy (NAC) is still controversial even though recent studies indicate that axillary recurrence seems to be a rare event. Our aim is to find out whether omitting ALND could be oncologically safe in patients undergoing SLNB after NAC. Material and Methods: Of patients presented with c T1-4N1-3M0 disease, those undergoing SLNB after NAC were included in the prospective multicentre registry trial " MF18-03/BHWG" (ClinicalTrials.gov/NCT04250129). Cases with inflammatory breast cancer, distant metastases, pregnancy, bilateral breast cancer, or other cancers and those without adjuvant nodal radiotherapy were excluded from the study. The end points of the present report are the axillary nodal recurrence (AR) and locoregional recurrence (LRR) rates at a median follow-up more than 2 years, and determine factors associated with AR and LRR . The locoregional recurrences included ipsilateral, and contralateral axillary recurrences, infra-and supraclavicular recurrences, and recurrences in the mammaria interna region. Results: Between January 2018 to January 2021, 2358 patients with cN(+) disease, who became cN0 after NAC, and underwent SLNB, were analyzed. Median age was 47 (range, 21-86). Of those, the majority of patients had cT1-2 (80.5%) and N1 (80.3%) disease. Following NAC, half of the patients (50%) had breast conserving surgery, whereas the remaining half had mastectomy (50%). Of 2358 patients, 908 (38.5%) had ALND following SLN (ypN+, 85%) and 1450 (61.5%) underwent SLNB alone (ypN0, 72%). SLNB was performed by using the blue dye technique-alone in 66.6% of patients and by targeted axillary dissection in 659 patients (27.9%). Of those, 819 (34.8%) were HER2(+) and 373 (15.8%) were triple negative. The pCR rates for the axilla, breast and both for the axilla and breast were 50%, 35% and 28%, respectively. At a median follow-up time of 28 months (range, 12-62), the LRR, AR and isolated AR rates were 0.6% (n=14), 0.25% (n=6) and 0.13% (n=3), respectively. Furthermore, no significant difference could be found in LRR- and AR- rates between SLNB-alone and ALND groups regardless of the definitive nodal pathology (Table 1). Nodal recurrences were seen at a median of 12 months after the surgery. Of 6 cases with AR, 3 had synchronous local recurrences in breast, and 2 of them also had lung metastases in addition to local recurrence. All patients with AR were interestingly found to have HER2(+) or triple negative breast cancer at the initial diagnosis, and had residual invasive cancer in the breast surgical specimen. Logistic regression analyses revealed that patients with AR were significantly more likely to be younger than 45 (RR=7.81 ; 95% CI, 0.91-66.91) and have a cN2-3 (RR=4.1; 95% CI, 0.83-20.38), and non-luminal breast cancer (RR=12.47; 95% CI, 1.45-106.9) at the initial diagnosis (Table 2). Similarly, patients with LRR were more likely to present with cN2-3 disease (RR=3.09; 95% CI, 1.07-8.94) and non-luminal pathology (RR=6.27; 95%CI, 1.96-20.06) . Conclusion: This large prospective registry data also suggest that nodal recurrences can be detected at very low rates within 3 years after surgery in patients with clinically node-positive disease following NAC regardless of the extent of axillary surgery or nodal pathology as long as regional nodal radiation is provided. Since patients with early nodal recurrences have an agressive tumor biology with a potential of systemic recurrences, effective adjuvant systemic therapies should be considered in those with HER2(+) or triple negative residual breast cancer after surgery following adjuvant nodal radiation. Table 1. Local locoregoinal and systemic recurrences in cT1-4N1-3 patients with ypN0/ypN(+) diseases (n =2358) Table 2. Factors associated with axillary and locoregoinal recurrences (AR = axillary recurrences, LRR = locoregoinal recurrences, pCR = pathologic complete response) Citation Format: Neslihan Cabıoğlu, Hasan Karanlik, Mehmet Ali Gulcelik, Abdullah İgci, Mahmut Muslumanoglu, Havva Belma Kocer, Cihan Uras, Gokhan Giray Akgul, Mustafa Tukenmez, Serkan Ilgun, Didem Can Trabulus, Guldeniz Karadeniz Cakmak, Ahmet Dağ, Nilufer Yıldirim, Baha Zengel, Ebru Sen Oran, Kazim Senol, Halil Kara, Selman Emiroglu, M. Umit Ugurlu, Bulent Citgez, Yeliz Emine Ersoy, Atilla Celik, Ece Dilege, Yasemin Bolukbaşı, Niyazi Karaman, Gul Basaran, Aykut Soyder, Ayfer Kamali Polat, Gurhan Sakman, Serdar Ozbas, Ayse Altınok, Leyla Zer, Alper Akcan, Ibrahim Ali Ozemir, Levent Yeniay, N. Zafer Utkan, Lutfi Dogan, Mutlu Dogan, Mehmet Velidedeoglu, Beyza Ozcinar, Fazilet Erozgen, Abut Kebudi, Kemal Atahan, Vafa Valiyeva, Serdar Yormaz, Ali Sevinc, Cumhur Arici, Atilla Soran, Vahit Ozmen. PD15-01 AXILLARY NODAL RECURRENCE IS RARE IN PATIENTS WITH NODE-POSITIVE BREAST CANCER UNDERGOING SLNB FOLLOWING NEOADJUVANT CHEMOTHERAPY : EARLY RESULTS OF THE NEOSENTITURK-TRIAL/MF-18-03 [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD15-01.

Can surgeons detect breast carcinoma in ex-vivo fresh human breast surgical specimens? A feasibility study using ultra-fast slide-free confocal microscopy

Can surgeons detect breast carcinoma in ex-vivo fresh human breast surgical specimens? A feasibility study using ultra-fast slide-free confocal microscopy

Next Generation Sequencing of Reactive Stroma and Residual Breast Cancer Cells in Tumor Bed after Neoadjuvant Chemotherapy.

Primary systemic or neoadjuvant chemotherapy of breast cancer has become a standard therapy option in locally advanced or predefined intrinsic subtypes such as triple negative or Her2 positive breast cancer. Neoadjuvant chemotherapy can result in complete pathological response without residual tumor cells (tumor bed) or partial response and non-response with different amounts of reactive stroma and residual tumor cells. The interaction between therapy regimens and tumoral driver mutations have been extensively studied, although the reactive stroma of the tumor bed received less attention. In this study, we characterized the mutational status of residual breast cancer cells and reactive tumor stroma devoid of residual tumor cells in partial or non-responders using next generation sequencing. Twenty-one post-therapeutic breast surgical specimens after neoadjuvant chemotherapy underwent pathogenic driver-mutation screening using microdissected residual breast cancer cells and in reactive stroma adjacent to tumor bed areas. In reactive stroma, no mutations could be validated. In residual breast cancer cells, mutations were detected in sixteen of twenty-one cases (76%). In nine of these twenty-one cases (43%), pathogenic driver mutations (PIK3CA, PTEN, TP53, FN1, PLAG1) were identified. Pathogenic driver-mutations are exclusively restricted to residual carcinoma cells and are absent in reactive stroma independently from intrinsic breast cancer subtypes or tumor stage. These data suggest that the absence of pathogenic mutations in a tumor bed without residual tumor cells may have prognostic implications after neoadjuvant chemotherapy.

Tumor bed extending to margins in breast cancer specimens after neoadjuvant chemotherapy: Incidence and clinical significance

BackgroundPathologic examination of post-neoadjuvant chemotherapy (NAC) breast surgical specimens includes assessment of margins. It has been recommended that tumor bed (TB) changes extending to margins should be documented; however, its' incidence and clinical significance have not yet been established. The aim of our study was to gather prognostic data on this histological finding. DesignWe retrospectively identified all cases where TB was reported at margin. Cases where margins were also positive for invasive carcinoma or DCIS were excluded. ResultsFrom 2016 to 2019, 115 cases of NAC treated breast cancers were identified with 21 having at least one margin positive for TB after initial surgery (incidence of 18.3 %). Five cases were estrogen receptor (ER)-/HER2-, 9 were HER2+ and 7 were ER+/HER2-. Nineteen patients underwent partial mastectomy and 2 underwent total mastectomy. Nine patients had a pathological complete response (pCR).Ten cases had more than one positive margin for TB. None of the 21 patients underwent a second surgery for margin re-excision. Twenty patients received adjuvant therapy. With an average follow-up of 28.1 months, there has been one local recurrence. Four other patients developed metastatic disease, one of which died of the disease. The rates of locoregional and distant recurrence and mortality were statistically similar to those from patients whose margins were negative for TB. ConclusionsOur results suggest low risk of local recurrence when a positive margin for TB is not re-excised. Further data and follow-up will be needed to confirm the adequacy of conservative management in this setting.

Abstract P4-07-30: Residual lymphovascular invasion: Predicts the outcome of neoadjuvant chemotherapy in locally advanced breast cancer

Abstract Background: Lymphovascular invasion (LVI) is known to be associated with a poor outcome in breast cancer patients. It indicates a highly proliferative cancer. Few studies examined the value of LVI as a predictor for outcome after neoadjuvant chemotherapy (NAC). The aim of this study to look for an association between survival outcomes and clinicopathological features in locally advanced breast cancer patients treated with NAC and to identify the predictors of nodal pathologic complete response (PCR). Methods:This study is a retrospective analysis of 224 women with locally advanced breast cancer who underwent NAC between 2011-2020. Kaplan-Meier analyses were used to assess the associations between disease-free survival (DFS) and overall survival (OS) and all clinicopathological variables including LVI in breast surgical specimens following NAC. Associations between nodal PCR and all clinicopathologic variables were assessed Results:Median follow-up was 29.9 months. Absence of nodal PCR (p.000), positive family history (p .027), clinical T4 (p.049), pathological TNM staging (p.016), high tumor grade (p .020),triple negative disease(p .016) and absence of tumor PCR (p.001) were associated with worse disease free survival. Absence of nodal PCR (p.002), high BMI (p.039), multicentric disease (p.026), high tumor grade, triple negative disease (p.018), and absence of tumor PCR (p.005) were associated with worse overall survival. LVI was found in 53 of surgical specimens (23.7%). It was associated with worse DFS (HR) (2.967) 95% CI (1.7-4.9), p.000 and overall survival (HR) (3.05) 95% CI (1.525-6.09), p.002). Nodal PCR significantly correlated with T stage (p .013), LVI (p.000), ER status (p.004), PR status (p.003), Her2neu status and IHC score (p.000), tumor subtype (p.000), tumor PCR (p.000), DFS (p.000), and OS (p.000). Conclusion:LVI is significantly associated with worse DFS and OS in locally advanced breast cancer patients treated with NAC. This data confirmed the previously published recommendation to add LVI to the pathological staging system. LVI may be further explored as a guide for adjuvant treatment options in clinical trials. Nodal PCR is another significant predictor of outcome and is associated significantly with tumor PCR and LVI. Both tumor PCR and LVI can be used as criteria for axillary surgery omission in future trials. Citation Format: Omima Elemam, Khaled Elnaghi, Ziad Emarah, Hossam Alghanami, Seham Abdelkhalek. Residual lymphovascular invasion: Predicts the outcome of neoadjuvant chemotherapy in locally advanced breast cancer [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 P4-07-30.

Abstract P1-02-01: Deep learning identifies morphological changes in whole slide images of treatment-resistant TNBC

Abstract Deep learning has become an important methodology for analyzing hematoxylin and eosin (H&E) stained whole slide images (WSIs), with high accuracy in detecting tumors, distinguishing cancer subtypes, and stratifying patients by survival risk in certain cancers [1,2,3]. However, machine-learning based evaluations of post-treatment tumors have been limited, e.g. focusing on user-defined features such as cellularity [4] rather than data-driven approaches. We analyzed 80 WSIs to determine if treatment-naïve TNBC, treatment-resistant TNBC, and treatment resistant growth factor and hormone receptor expressing tumors could be distinguished from each other (36 treatment naïve TNBC, 25 resistant TNBC, and 19 resistant non-TNBC WSIs corresponding to 31, 22, and 16 patients, respectively). All resistant patients received chemotherapy, except for one ER+ patient who only received medication to block hormone production. Our deep learning image-based models were able to separate treatment naive and treatment resistant TNBC tumors with high accuracy (AUC=0.85). We further developed a 3-way classifier that was able to distinguish resistant non-TNBC tumors from TNBC treatment-resistant and treatment-naïve samples (AUC=0.74). Removing deep learning features differentiating between TNBC and non-TNBC resistant samples, we find treatment-naïve and resistant samples can be separated irrespective of breast cancer subtype (AUC=0.77). Our results show that post chemotherapy, breast tumors are morphologically distinguishable by machine learning methods from treatment naïve tumors. While some treatment-related morphological changes are present across subtypes, some are unique to TNBC.

Optical scatter imaging of resected breast tumor structures matches the patterns of micro-computed tomography

In patients undergoing breast-conserving surgery (BCS), the rate of re-excision procedures to remove residual tumor left behind after initial resection can be high. Projection radiography, and recently, volumetric x-ray imaging are used to assess margin adequacy, but x-ray imaging lacks contrast between healthy, abnormal benign, and malignant fibrous tissues important for surgical decision making. The purpose of this study was to compare micro-CT and optical scatter imagery of surgical breast specimens and to demonstrate enhanced contrast-to intra-tumoral morphologies and tumor boundary features revealed by optical scatter imaging. A total of 57 breast tumor slices from 57 patients were imaged ex vivo by spatially co-registered micro-CT and optical scatter scanning. Optical scatter exhibited greater similarity with micro-CT in 89% (51/57) of specimens versus diffuse white light (DWL) luminance using mutual information (mean ± standard deviation of 0.48 ± 0.21 versus 0.24 ± 0.12; p < 0.001) and in 81% (46/57) of specimens using the Sørensen–Dice coefficient (0.48 ± 0.21 versus 0.33 ± 0.18; p < 0.001). The coefficient of variation (CV) quantified the feature content in each image. Optical scatter exhibited the highest CV in every specimen (optical scatter: 0.70 ± 0.17; diffuse luminance: 0.24 ± 01; micro-CT: 0.15 ± 0.03 for micro-CT; p < 0.001). Optical scatter also exhibited the highest contrast ratios across representative tumor boundaries with adjacent healthy/benign fibrous tissues (1.5–3.7 for optical scatter; 1.0–1.1 for diffuse luminance; 1.0–1.1 for micro-CT). The two main findings from this study were: first, optical scatter contrast was in general similar to the radiological view of the tissue relative to DWL imaging; and second, optical scatter revealed additional features associated with fibrous tissue structures of similar radiodensity that may be relevant to diagnosis. The value of micro-CT lies in its rapid three-dimensional scanning of specimen morphology, and combined with optical scatter imaging with sensitivity to fibrous surface tissues, may be an attractive solution for margin assessment during BCS.

Testosterone therapy and breast histopathological features in transgender individuals

Testosterone therapy (TT) is administered to enhance masculinization in transgender individuals. The long-term effect of exogenous testosterone on breast tissues remains unclear. Our study evaluated the modulation of breast morphology by TT in transgender individuals with special attention to duration of TT. We reviewed 447 breast surgical specimens from gender affirming chest-contouring surgery, and compared histopathological findings including degree of lobular atrophy, and atypical and non-atypical proliferations between subjects who did (n = 367) and did not (n = 79) receive TT. TT for one patient was unknown. TT for >12 months was associated with seven histopathological features. Longer duration of TT was significantly associated with higher degrees of lobular atrophy (p < 0.001). This relationship remained significant after accounting for age at surgery, ethnicity, body mass index, and presurgical oophorectomy (adjusted p < 0.001). Four types of lesions were more likely to be absent in breast tissues exposed to longer durations of TT: cysts (median = 16.2 months; p < 0.01; adjusted p = 0.01), fibroadenoma (median = 14.8 months; p = 0.02; adjusted p = 0.07), pseudoangiomatous stromal hyperplasia (median = 17.0 months; p < 0.001; adjusted p < 0.001), and papillomas (median = 14.7 months; p = 0.04; adjusted p = 0.20). Columnar cell change and mild inflammation were also less likely to occur in subjects receiving TT (p < 0.05), but were not linked to the duration of TT. Atypia and ductal carcinoma in situ were detected in 11 subjects (2.5%) all of whom received TT ranging from 10.1 to 64.1 months. The incidental findings of high-risk lesions and carcinoma as well as the risk of cancer in residual breast tissue after chest-contouring surgery warrant the consideration of culturally sensitive routine breast cancer screening protocols for transgender men and masculine-centered gender nonconforming individuals. Long-term follow-up studies and molecular investigations are needed to understand the breast cancer risk of transgender individuals who receive TT.

Learning from the wastage: histomorphology of columnar cell lesions and other changes in surgical pathology breast specimens

Introduction: In recent few decades, widespread use of mammography has resulted in increased detection of precursor and preinvasive breast lesions such as atypical ductal hyperplasia, ductal carcinoma in situ and, a type of breast lesion termed, ‘Flat epithelial atypia” which belongs to the group of columnar cell lesions with atypia. Although in India, invasive breast cancer is still most common presentation than early preinvasive lesions, with advanced diagnostic set up and increased awareness, early detection of preinvasive lesions is bound to be increased in future. For their accurate diagnosis, it is very necessary to be aware and alert about the morphology of these lesions. Objectives: Present study was undertaken to study the morphology of Columnar Cell Lesion and other changes in Surgical Biopsy specimens received in Histopathology laboratory of a tertiary health care centre. Materials and Methods: Excessive sections were taken from breast tissue surrounding the primary lesion in mastectomy or wide local excision specimens received over two-year duration and were examined for various changes in the epithelium and in the stroma especially columnar cell lesions and other precursor lesions. Results: A spectrum of precursor lesions including columnar cell lesions could be commonly seen in most of the specimens. Their morphology and differential diagnosis could be studied in details in these sections which otherwise are wasted usually. Conclusion: The tissue surrounding primary lesion in surgical pathology breast specimens is a good source to study the detailed morphology of columnar cell lesions and other lesions to get familiar with them for their accurate detection and early diagnosis in future. Keywords: Precursor breast lesions, Columnar cell lesions, Flat epithelial atypia, Ductal hyperplasia.

Rapid assessment of breast tumor margins using deep ultraviolet fluorescence scanning microscopy.

.Significance: Re-excision rates for women with invasive breast cancer undergoing breast conserving surgery (or lumpectomy) have decreased in the past decade but remain substantial. This is mainly due to the inability to assess the entire surface of an excised lumpectomy specimen efficiently and accurately during surgery.Aim: The goal of this study was to develop a deep-ultraviolet scanning fluorescence microscope (DUV-FSM) that can be used to accurately and rapidly detect cancer cells on the surface of excised breast tissue.Approach: A DUV-FSM was used to image the surfaces of 47 (31 malignant and 16 normal/benign) fresh breast tissue samples stained in propidium iodide and eosin Y solutions. A set of fluorescence images were obtained from each sample using low magnification () and fully automated scanning. The images were stitched to form a color image. Three nonmedical evaluators were trained to interpret and assess the fluorescence images. Nuclear–cytoplasm ratio (N/C) was calculated and used for tissue classification.Results: DUV-FSM images a breast sample with subcellular resolution at a speed of . Fluorescence images show excellent visual contrast in color, tissue texture, cell density, and shape between invasive carcinomas and their normal counterparts. Visual interpretation of fluorescence images by nonmedical evaluators was able to distinguish invasive carcinoma from normal samples with high sensitivity (97.62%) and specificity (92.86%). Using N/C alone was able to differentiate patch-level invasive carcinoma from normal breast tissues with reasonable sensitivity (81.5%) and specificity (78.5%).Conclusions: DUV-FSM achieved a good balance between imaging speed and spatial resolution with excellent contrast, which allows either visual or quantitative detection of invasive cancer cells on the surfaces of a breast surgical specimen.

3D microcalcification detection using a color Doppler twinkling artifact with optimized transmit conditions: Preliminary results.

Mammography is the only method that has been proven to detect breast microcalcifications (MCs), but the sensitivity of mammography varies according to breast density. This paper proposes an ultrasound (US) color Doppler twinkling artifact (CDTA) method with optimized transmit conditions to identify breast MCs without ionizing radiation. The transmit conditions for US color Doppler imaging (CDI) were optimized to enhance the sensitivity of the twinkling artifact (TA) that arises from random scattering on rough surfaces of breast MCs. To validate the proposed breast MC detection method, a chicken breast phantom with MC particles (groups of particles <400 and <240 ) was fabricated and scanned by a digital mammography system and an US research platform by an L11-5v linear array probe with a three-dimensional (3D) motion tracking system. From the phantom experiment, the proposed 3D CDTA imaging method with optimized transmit conditions (i.e., a center frequency of 5.0MHz, an f-number of 1.3, and a peak negative pressure of 1.83MPa) successfully detected all 16 MC particles, comparable to detection with mammography. For a human breast surgical specimen in the ex vivo study, all 10 MC clusters, marked by a radiologist on the mammogram, were identified with the proposed 3D CDTA imaging method. In the phantom and ex vivo breast specimen studies, the proposed 3D CDTA imaging method successfully detected MCs, and the spatial localization was highly correlated with the mammogram results. These results indicate that the proposed 3D CDTA imaging method has great potential for the detection of MCs without ionizing radiation.

Raman Spectroscopy for Rapid Evaluation of Surgical Margins during Breast Cancer Lumpectomy

Failure to precisely distinguish malignant from healthy tissue has severe implications for breast cancer surgical outcomes. Clinical prognoses depend on precisely distinguishing healthy from malignant tissue during surgery. Laser Raman spectroscopy (LRS) has been previously shown to differentiate benign from malignant tissue in real time. However, the cost, assembly effort, and technical expertise needed for construction and implementation of the technique have prohibited widespread adoption. Recently, Raman spectrometers have been developed for non-medical uses and have become commercially available and affordable. Here we demonstrate that this current generation of Raman spectrometers can readily identify cancer in breast surgical specimens. We evaluated two commercially available, portable, near-infrared Raman systems operating at excitation wavelengths of either 785 nm or 1064 nm, collecting a total of 164 Raman spectra from cancerous, benign, and transitional regions of resected breast tissue from six patients undergoing mastectomy. The spectra were classified using standard multivariate statistical techniques. We identified a minimal set of spectral bands sufficient to reliably distinguish between healthy and malignant tissue using either the 1064 nm or 785 nm system. Our results indicate that current generation Raman spectrometers can be used as a rapid diagnostic technique distinguishing benign from malignant tissue during surgery.

Adequacy of Tissue Sampling in Breast Specimen

Abstract Objectives Due to inadequate sampling concerns, pathologists frequently request additional tissue sections (ie, more tissue sections in addition to initial representative sections) in breast specimens. This study explores the effectiveness of the additional tissue sections in the breast specimens. Methods Breast specimens received in our institution on which additional tissue sections were requested were included in the study. Pathology reports and glass slides for these specimens were reviewed. Additional tissue sections were considered effective if they changed the final diagnosis altogether, changed a benign entity to borderline or malignant category, changed pathologic tumor stage, changed margin status, changed tumor focality, or if lymphovascular invasion was identified. Results A total of 325 specimens were identified. Of these, 98 (30.1%) were benign while 224 (68.9%) were malignant. Among malignant cases, 53 (23.7%) had neoadjuvant therapy. Overall mean initial representative sections submitted were 15.1 ± 8.7 while additional tissue sections were 10.7 ± 8.0. There was no difference in additional sections submitted for benign versus malignant cases (9.8 ± 7.7 vs 11.2 ± 8.0; P = .96). Also there was no difference in additional sections submitted for cases with neoadjuvant therapy versus those without any therapy (10.4 ± 6.9 vs 11.6 ± 8.4; P = .36). Twenty-five (7.7%) specimens benefited from submission of additional tissue sections. All 25 cases were malignant; 7 had neoadjuvant therapy while 18 did not. No tumor was identified in initial representative sections in 6 cases, pathologic tumor stage was changed in 12 cases, margin status changed in 2 cases, tumor focality changed in 4 cases, and an extra positive lymph node was identified in 1 case. Conclusion Additional tissue sections contributed to final diagnosis in 7.7% cases. Surgical pathology breast specimens require specialized handling and thorough sampling for accurate diagnosis and staging.

A new breast tomosynthesis imaging method: Continuous Sync-and-Shoot – technical feasibility and initial experience

BackgroundDigital breast tomosynthesis (DBT) is gaining popularity in breast imaging. There are several different technical approaches for conducting DBT imaging.PurposeTo determine optimal imaging parameters, test patient friendliness, evaluate the initial diagnostic performance, and describe diagnostic advances possible with the new Continuous Sync-and-Shoot method.Material and MethodsThirty-six surgical breast specimens were imaged with digital mammography (DM) and a prototype of a DBT system (Planmed Oy, Helsinki, Finland). We tested the patient friendliness of the sync-and-shoot movement without radiation exposure in eight volunteers. Different imaging parameters were tested with 20 specimens to identify the optimal combination: angular range 30°, 40°, and 60°; pixel binning; Rhodium (Rh) and Silver (Ag) filtrations; and different kV and mAs values. Two breast radiologists evaluated 16 DM and DBT image pairs and rated six different image properties. Imaging modalities were compared with paired t-test.ResultsThe Continuous Sync-and-Shoot method produced diagnostically valid images. Five out of eight volunteers felt no/minimal discomfort, three experienced mild discomfort from the tilting movement of the detector, with the motion being barely recognized. The combination of 30°, Ag filtering, and 2 × 2 pixel binning produced the best image quality at an acceptable dose level. DBT was significantly better in all six evaluated properties (P < 0.05). Mean DoseDBT/DoseDM ratio was 1.22 (SD = 0.42).ConclusionThe evaluated imaging method is feasible for imaging and analysing surgical breast specimens and DBT is significantly better than DM in image evaluation.