bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract PS19-24: Low expression MicroRNA-195 enriched the cell cycle and cell proliferation gene sets and is associated with advanced grades and worse overall survival of ER positive breast cancer patients
Authors: Tokumaru Yoshihisa , Oshi Masanori , Katsuta Eriko , Matsuhashi Nobuhisa , Futamura Manabu , Yoshida Kazuhiro , Takabe Kazuaki
Published: February 2021

Background: MicroRNA-195 (miR-195) exerts the tumor suppressive functions in various cancers, including breast cancer, by targeting and inhibiting the expressions of the cell cycle and cell proliferation associated genes. In this study, we hypothesized that miR-195 low expressing tumors associate with high proliferative characteristics and poor survival. Material and Methods: We obtained the clinicopathological data and survival information of breast cancer patients from two large publicly available databases; The Cancer Genome Atlas (TCGA) and The Molecular Taxonomy of Breast Cancer International Consortium (METARBRIC). Total of 755 and 1287 patients’ data were obtained from TCGA and METABRIC respectively. Survival analysis, Overall survival (OS) and Disease-free survival (DFS) was performed by comparing the high and low expression groups. CYT score, xCell, and other immunological factors were used to evaluate intratumoral immune cell composition. Also, gene set enrichment analysis (GSEA) was performed between miR-195 high and low expression groups. Results: The patients were divided into miR-195 high and low groups by utilizing median cutoff. Advanced grades were significantly associated with lower expression of miR-195 in ER positive/HER2 negative (ER+/HER2) subtype with both TCGA and METABRIC cohorts (p<0.001 and p<0.001, respectively). On the contrary this was not consistent with other subtypes, HER2+ and triple negative (TN). Also, Low miR-195 expressing tumors demonstrated higher MKI67 expressions in ER+/HER2- subtype with TCGA (p<0.001). This was validated with METABRIC cohort (p<0.001). Furthermore, GSEA demonstrated that low miR-195 expressing tumors enriched the gene sets related with cell cycle or cell proliferation, such as MYC signaling, mTOR signaling, E2F signaling, G2M Checkpoint signaling and PI3K_Akt_mTOR signaling, compared with high miR-195 expressing tumors in ER+/HER2-. Conclusion: Low expression of miR-195 was associated with improved OS in ER positive breast cancer patients. Also, low miR-195 expressing tumors were found to associate with advanced grades as well as enriching the genes relating to cell proliferation and cell cycle, which may explain the poor survival of low miR-195 expressing patients in ER positive breast cancer.

Citation Format: Yoshihisa Tokumaru, Masanori Oshi, Eriko Katsuta, Nobuhisa Matsuhashi, Manabu Futamura, Kazuhiro Yoshida, Kazuaki Takabe. Low expression MicroRNA-195 enriched the cell cycle and cell proliferation gene sets and is associated with advanced grades and worse overall survival of ER positive breast cancer patients [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 PS19-24.
Abstract PS19-28: Thymoquinone and tamoxifen co-treatment synergistically inhibit proliferation, invasion and induce apoptosis in human breast cancer cell lines in vitro and in vivo
Authors: Yahiya Islam , Helmy Heba , Sultan Ahmed
Published: February 2021

Epidemiological studies and experimental analysis indicate that dietary factors influence thedevelopment of breast cancer, suggesting the role of natural products as modifying factors againstbreast cancer. Thymoquinone (TQ) (a dietary phytochemical compound) the main active ingredientof the volatile oil of black seed (Nigella sativa) has been used to be safe when administered to awide variety of normal cells. In addition, Tamoxifen (TAM), a nonsteroidal triphenylethylene derivateand selective ER modulator, has been used as a single agent in the treatment of ER positive breastcancer.In the present study, we report the possible chemo-sensitizing effect of TQ as a promisingconventional chemotherapeutic agent, using a panel of human breast cancer cell lines, MCF-7, ZR-75-1, T-47D and BT-20 respectively in vitro and in vivo.Our data revealed that TQ, TAM or combined treatments significantly inhibited cell viability of MCF-7, T-47D, ZR-75-1 but slightly of BT-20 cell lines consistently with down-regulation of signaltransducer and activator of transcription 3 (STAT 3), mTOR, cyclin D1, oncogenic β-catenin,signaling a specific transcription factor and PPAR-gamma in a dose dependent manner. Mostimportantly, combined treatment enhanced inhibition of cell viability, DNA fragmentation andapoptosis induction through Caspase-3 activation and Bcl-2 down regulation in all tested cell linesbut this effect was limited in BT-20 cells compared to controls. Moreover, our data was supported bymicroscopic examination using electron scanning microscopy that revealed many apoptoticalterations after combined treatment compared to each TQ or TAM. Furthermore, confocalfluorescence microscopy examination revealed that only combined treatment showed a significantinhibition of filopodia formation as a sign of invasion inhibition in both BT-20 and MCF-7 humanbreast cancer cell lines. In vivo, tumor xenotransplants of human ZR-75-1 cells revealed that onlycombined treatment showed a significant regression in tumor size by 53% after 72h and enhancedE-cadherin expression as analyzed by immunohistochemistry and confocal fluorescencemicroscopy.Taken together, our findings provide strong in vitro and in vivo molecular evidences in support ofour hypothesis that Thymoquinone synchronized as chemo-preventive agent with Tamoxifen to inhibithuman breast cancer cell lines proliferation, invasion and induce apoptosis that might have a potentialimplication in breast cancer prevention and treatment.

Citation Format: Islam Yahiya, Heba Helmy, Ahmed Sultan. Thymoquinone and tamoxifen co-treatment synergistically inhibit proliferation, invasion and induce apoptosis in human breast cancer cell lines in vitro and in vivo [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 PS19-28.
Abstract PS2-39: A peninsular experience - developing a non-biopsy protocol for the female cohort 25-29 years with clinically typical fibroadenoma conforming to maxwell criteria on ultrasound
Authors: Arif Tahera , Absar Mohammed Shameem , Vinayagam Raman
Published: February 2021

Abstract.Abstract1:

IntroAim: The aim of this study was to introduce a non -biopsy protocol in our department for benign breast lump referrals confirmed as typical U2/3 fibroadenoma on imaging. The cohort of women between 25-29 years of age with sonographic features (Maxwell non-biopsy criteria) U2/3 typical of fibroadenoma does not miss malignancy. Current UK guidance is not to biopsy sonographically typical fibroadenomas in women under 25 years. We have studied our population extending the radiological Maxwell criteria reflecting histologically benign outcomes even in this group of 25-29 years.MethodsMethods: Retrospectively data was collected of all women between 25-29 years of age undergoing core biopsy for ultrasound confirmed both simple and complex fibroadenomas at Clatterbridge General Hospital between 2014 and 2019 over a period of five years. The number of cancers picked up was compared with the number of referrals and the discordance between radiological diagnosis of fibroadenoma and histopathological confirmation of malignancy was recorded.ResultsResults: We saw increment in referrals in this group of young women from n=260 to n=386 over the five year study period. A total of 1707 referrals were made across five years. n=175 image guided core biopsies were carried out for U2,U3,U4 lesions appearing as fibroadenoma on ultrasound. Out of these (n=175), all lesions coded U2/3 (n=165) based on Maxwell criteria on ultrasound were negative for cancer. U4 lesions on ultrasound were confirmed as cancers mimicking fibroadenoma(n=10).ConclusionConclusion: This retrospective audit of 1707 patients provides sound evidence for safe non-biopsy of typical fibroadenomas in women 25-29 years when clinical and sonographic features meet strict criteria. We started using the non-biopsy protocol using Maxwell criteria for U2/3 lesions. We discharged women in this group if they met all the protocol criteria, i.e., their lesion does not appear suspicious clinically, has all the ultrasound appearances typical of a fibroadenoma U2/3, and they do not have any compounding circumstances (e.g., family history, genetic predisposition). As routine, we advise all women who are discharged without follow-up to examine their breasts regularly and return if they detect any changes including increase in lesion size. We need data to be audited prospectively and provide level 1 evidence to the same effect.

Citation Format: Tahera Arif, Mohammed Shameem Absar, Raman Vinayagam. A peninsular experience - developing a non-biopsy protocol for the female cohort 25-29 years with clinically typical fibroadenoma conforming to maxwell criteria on ultrasound [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 PS2-39.
Abstract PS3-20: Rapid beside diagnosis of breast core needle biopsies using stimulated raman histology
Authors: Orringer Daniel Avram , Chen Thomas , Pastore Steve , Darvishian Farbod , Toth Hildegard , Schnabel Freya
Published: February 2021

Image-guided core needle biopsy plays a central role in the diagnosis and management of a wide range of breast lesions. After collection, tissue cylinders are transported from a biopsy suite to a pathology laboratory for analysis. The existing workflow for microscopic diagnosis of tissue specimens precludes the option of using histologic data to inform clinical decision-making at the time of biopsy. Here, we introduce stimulated Raman histology (SRH), a rapid label-free optical imaging method that enables microscopic imaging of unprocessed breast biopsy specimens in the biopsy suite within minutes of sample collection. SRH has been thoroughly validated for use in the detection and diagnosis of brain tumors but its use has not been validated in breast lesions. In our study, we collected core needle biopsy specimens and allocated a 2mm portion of the tissue sample for SRH imaging. Each specimen was imaged with SRH and subsequently fixed in formalin, embedded, stained and sectioned in a conventional manner. A board-certified breast pathologist first analyzed the diagnostic features of the imaged specimens with SRH and then with conventional H&E-stained sections. In a pilot series of six patients, we found that SRH could differentiate between lesions that can mimic cancer such as a radial scar from neoplastic ones like invasive ductal carcinoma. SRH also demonstrated histologic differences between a benign tumor like a fibroadenoma and a malignant tumor like an invasive ductal carcinoma. We also observed diagnostic differences amongst benign processes such as radial scar and pseudoangiomatous stromal hyperplasia. Importantly, we showed that SRH is non-consumptive and the imaged tissue can be used for downstream histologic and immunohistochemical analysis. Our data provide proof of concept that SRH can reveal the diagnostic features of tissue collected in breast core needle biopsies, supporting further validation of this technology. Ultimately, we envision the use of SRH to create new, efficient workflows for managing patients with breast lesions, especially those in which fine needle aspiration is of limited value, and where rapid diagnosis of tissue biopsies could streamline care and increase patient satisfaction.

Citation Format: Daniel Avram Orringer, Thomas Chen, Steve Pastore, Farbod Darvishian, Hildegard Toth, Freya Schnabel. Rapid beside diagnosis of breast core needle biopsies using stimulated raman histology [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 PS3-20.
Abstract PS3-25: Quantitation of serum thioredoxin 1 could mitigate difficulty to detect breast cancer from dense breasts by mammography
Authors: Suh Kyoung Hoon , Choi Bo Bae , Lee Youn Ju , Kim Je Ryoong , Lee Jin Sun , Kim Young
Published: February 2021

Background: Even though almost half of women have dense breasts (DB), the density of breasts has been an obstacle to detect breast cancer (BC) correctly by the gold standard of screening, mammography. It is strongly recommended to take consideration of breast density in analyzing mammogram. We have reported the possibility of serum level of thioredoxin 1 (Trx1) as a novel means to assess the risk of BC regardless of various conditions of breasts. In present study, we have evaluated how serum level of Trx1 can mitigate the difficulty to detect BC from dense breast by mammography. Methods: We have generated monoclonal antibodies against Trx1 and developed an ELISA kit that quantitates Trx1 in serum. The level of Trx1 was determined in each serum from BC patients (n=106) who had been confirmed as BC by various examinations including mammography as well as surgery. Each Trx1 level was analyzed with corresponding patient’s mammography results such as patterns, asymmetry, shapes, margin, and density. The analyzed results were compared with those from other biomarker tests including CA15-5 and CEA to evaluate the clinical validity of Trx1 in this study. Each test was duplicated two times, and test results were analyzed by ROC analysis, one-way ANOVA tests, and unpaired t-tests.Results: Most of BC patients (82.6%, n=86) was classified as mammography pattern 3 and 4, and BI-RADS score higher than 4 (74.0%, n=77). More than half of patients’ breast density was in high density group (54.8%, n=57), whereas 5.8% of iso density (n=6) and 39.4% of not determined (n=41). The blood Trx1 levels of patients were higher than the cut-off value of 14 U/ml indicating BC regardless of characteristics of breasts. Although other breast cancer biomarker tests such as CA15-3 and CEA could not identify BC, Trx1 level could correctly detect BC even in the cases that mammography could not show the mass clearly. The sensitivity/specificity of mammography and Trx1 test were 75.2%/74.0% and 96.2%/99.0%, respectively. When mammography and Trx1 test were combined, the whole sensitivity/specificity was 99.3%/100.0%. Conclusion: Even though it is obvious that larger size of further study necessary, the serum Trx1 level showed that it could identify BC in dense breasts easily. These results indicated that serum Trx1 level could efficiently mitigate the difficulty to detect BC from dense breasts by mammography. Keywords: Thioredoxin 1, Breast cancer, Dense breast, Diagnostics, Sensitivity, Specificity, Blood

Citation Format: Kyoung Hoon Suh, Bo Bae Choi, Youn Ju Lee, Je Ryoong Kim, Jin Sun Lee, Young Kim. Quantitation of serum thioredoxin 1 could mitigate difficulty to detect breast cancer from dense breasts by mammography [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 PS3-25.
Abstract PS4-43: Prediction of breast ductal carcinoma in situ recurrence using histomics analysis of stromal features from hematoxylin and eosin stain-based images
Authors: Upadhaya Taman , Balassanian Ronald , Morin Olivier , Park Catherine
Published: February 2021

OBJECTIVE

It remains a challenge to predict individual risk for recurrence after primary treatment of ductal carcinoma in situ (DCIS). While DCIS is contained within the duct, prior studies have pointed to the importance of stromal collagen in cancer progression. Using hematoxylin and eosin (H&E) stain-based images, we studied the collagen structure surrounding DCIS in a case-control cohort of women to determine whether stromal collagen could provide additional risk information.

METHODS

We present a quantitative histology image analysis pipeline (termed “histomics”) that consists of collagen segmentation, quantitative feature extraction and statistical analysis to predict recurrence. A cohort of 73 patients with DCIS (33 cases with recurrence matched with 40 controls) were retrospectively analyzed. H&E images were obtained from pathologic slides and regions-of-interest (ROI) of the collagen in the stroma adjacent to DCIS was automatically segmented using an in-house trained deep learning algorithm. A total of 123 histomics features (intensity, statistical and textural) were then extracted from the segmented ROI for each patient. Kruskal-Wallis test and receiver-operating characteristic methodology was used to assess performance of the features to differentiate patients with and without recurrence.

RESULTS

We found substantial variations in recorded H&E signal between samples, and the intensity and statistical features did not reach statistical significance. However, twelve percent of the textural features had an AUC between 0.62 to 0.61 with p-value between 0.06 to 0.08. Two textural histomics features in particular were significantly associated with DCIS patient recurrence; inverse variance (AUC: 0.64, p-value: 0.046) feature based on grey-level cooccurrences matrix (GLCM) and complexity (AUC 0.65, p-value: 0.025) feature based on neighborhood grey tone difference matrix (NGTDM).

CONCLUSION

Textural stromal features extracted from H&E image-based histomics indicate association of some features with tumor progression in DCIS. H&E image based histomics features can be a promising quantitative tool to develop predictive signatures of recurrence in patients with DCIS. We are processing additional patients through our quantitative image analysis pipeline to determine the significance of histomics features compared to conventional clinical features for the prediction of DCIS recurrence.

Citation Format: Taman Upadhaya, Ronald Balassanian, Olivier Morin, Catherine Park. Prediction of breast ductal carcinoma in situ recurrence using histomics analysis of stromal features from hematoxylin and eosin stain-based images [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 PS4-43.
Abstract PS5-41: Machine learning model of gut microbiota predicts neratinib induced diarrhea in patients with breast cancer
Authors: Wong Chi Wah , Yost Susan E. , Lee Jin Sun , Gillece John D. , Folkerts Megan , Reining Lauren , Highlander Sarah K. , Eftekhari Zahra , Mortimer Joanne , Yuan Yuan
Published: February 2021

Background: Neratinib is a potent small molecule tyrosine kinase inhibitor (TKI) of human epidermal growth factor receptors (HER1,2,4). One of the major side effects of neratinib is diarrhea. The human gut contains a dense microbiome ecosystem that is essential in maintaining a healthy host physiology, and its disruption may lead to increased risk of toxicities from cancer therapy. In this study, we aimed to develop a machine learning model based on analysis of gut microbiota data to predict neratinib-induced diarrhea.

Methods: Patients were enrolled in a phase II trial evaluating safety and tolerability of neratinib in older adults with HER2+ breast cancer (NCT02673398). Neratinib was administered as single agent, 240 mg oral daily in a 28-day cycle. Stool samples were collected at baseline and during treatment for 16S rRNA gene sequencing. Using microbial relative abundance data, we developed gradient-boosted tree models with two nested loops of cross validations to classify whether diarrhea would occur or not after treatment onset. For the inner validation loop, we used ten-fold cross validation to determine the optimal model from hyper-parameters including regularization. For the outer validation loop, we utilized a leave-one-patient-out cross validation to test this model on the hold-out patient’s baseline data and the predictions were used for model assessment.

Results: A total of 11 patients and 50 longitudinal stool samples were collected. The median age was 66 years. 73% developed grade ≥ 1 diarrhea attributed to neratinib. Shannon diversity index of gut microbiome was not associated with diarrhea. For predictive modeling, the outer validation loop Area Under the Receiver Operating Characteristic Curve (AUROC) and Area Under the Precision Recall Curve (AUPRC) were 0.92 and 0.97, respectively. The two most important taxa predictive of protection from diarrhea were Ruminiclostridium 9, and Bacteroides sp. HPS0048. We found that patients with a larger relative abundance of Ruminiclostridium 9 and Bacteroides sp. HPS0048 have reduced risk of neratinib-related diarrhea.

Conclusions: The machine learning model can identify breast cancer patients at risk of diarrhea prior to neratinib use. Future studies are required to validate this finding.

Citation Format: Chi Wah Wong, Susan E. Yost, Jin Sun Lee, John D. Gillece, Megan Folkerts, Lauren Reining, Sarah K. Highlander, Zahra Eftekhari, Joanne Mortimer, Yuan Yuan. Machine learning model of gut microbiota predicts neratinib induced diarrhea in patients with breast cancer [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 PS5-41.
Abstract PS5-45: The impact of progesterone receptor negativity on oncologic outcomes in estrogen receptor positive breast cancer
Authors: Davey Matthew G , Ryan Éanna J , Folan Padraig J , O'Halloran Niamh , Boland Michael R , Barry Michael Kevin , Sweeney Karl J , Malone Carmel M , McLaughlin Ray J , Kerin Michael J , Lowery Aoife J
Published: February 2021

BACKGROUND: Estrogen receptor (ER) status provides invaluable prognostic and therapeutic information in breast cancer (BC). When clinical decision making is driven by ER status, the value of assessing progesterone receptor (PgR) status is less certain. AIM: To describe the clinicopathologic features of ER positive (ER+) /PgR negative (PgR-) BC and to determine the effect of PgR negativity on oncologic outcomes in ER+ disease.METHODS: Consecutive female patients with ER+ BC managed in a single institution between 2005-2015 were included. Clinicopathological features of PgR- BC were determined. Factors associated with PgR- disease were assessed using binary logistic regression. Oncological outcome was assessed using Kaplan-Meier curves and Cox regression analysis.RESULTS: 2660 patients were included with a median age of 59.6±13.3 years (21-99). Median follow-up was 97.2 months (3.0-181.2). 2208 cases were PgR+ (83.0%) and 452 were PgR- (17.0%). Being postmenopausal (OR:1.656, 95% Confidence interval (CI):1.249-2.195, P<0.001), presenting with symptoms (OR:1.712, 95% CI:1.302-2.249, P<0.001), invasive ductal subtype (OR:1.514, 95% CI:1.166-1.966, P=0.002) and grade 3 tumours (OR:2.198, 95% CI:1.683-2.870, P<0.001) were all associated with PgR- status. In patients receiving neoadjuvant chemotherapy (n=308), pathological complete response rates were 10.1% (25/247) in patients with PgR+ disease, versus 18.0% in those with PgR- disease (11/61) (P=0.050). PgR negativity independently predicted worse disease-free (HR:1.632, 95%CI:1.209-2.204, P=0.001) and overall survival (OS) (HR:1.774, 95%CI:1.324-2.375, P<0.001), as well as worse OS in ER+/HER2- disease (P=0.004). CONCLUSIONS: In ER+ disease, PgR- tumours have more aggressive clinicopathological features and worse oncological outcomes. Neoadjuvant and adjuvant therapeutic strategies should be tailored according to PgR status.

Citation Format: Matthew G Davey, Éanna J Ryan, Padraig J Folan, Niamh O'Halloran, Michael R Boland, Michael Kevin Barry, Karl J Sweeney, Carmel M Malone, Ray J McLaughlin, Michael J Kerin, Aoife J Lowery. The impact of progesterone receptor negativity on oncologic outcomes in estrogen receptor positive breast cancer [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 PS5-45.
Abstract PS6-09: An AI-digital breast cancer risk discrimination platform (PreciseDx) using a representative H&E image and selected clinical variables accurately categorized patients with oncotype Dx low risk recurrence scores (RS)
Authors: Donovan Michael Joseph , Shpalensky Nina , Prastawa Marcel , Abishek SM , Scott Richard , Sawyer Mary , Zeineh Jack , Fernandez Gerardo
Published: February 2021

Background: Clinical practice guidelines emphasize the critical importance of grading and stage in breast cancer treatment. Although histologic grade is subjective, non-quantitative, skill-dependent, and oftentimes inaccurate it remains an independent prognostic feature and therefore plays a direct role in patient management including neoadjuvant therapy vs surgery, and interpretation of genomic studies. We developed an AI-based platform which combines digital H&E features with select clinical variables to assess risk of breast cancer recurrence and evaluated ability to predict Oncotype low risk RS categorization. Methods: Retrospective study to identify a subset of Mt. Sinai, NY invasive ductal breast cancer (IDC) patients from 2010-2016 with H&E stained slides, clinical features and OncotypeDx recurrence scores (RS). Recurrence endpoint(s): local- regional, distant-recurrence free and overall survival. Digital images generated with Philips scanning system; reviewed by two pathologist for tumor content and quality prior to image analysis and feature extraction. Support vector machine learning models were used for initial feature performance and final models generated. Positive predictive value (PPV), sensitivity (S) and likelihood ratios (LR) were used for performance. Results: 391 patients: mean age 57 years, 100% Stage I/II, 59% Grade 2, and 6% LN+ve 0-3; 97% IDC, 100% ER+ve, 94% PR+ve, 0% Her2 amplified; median follow-up 61 months; 323 (83%) low risk (</=25) RS and 68 (17%) high risk RS (>25). There were 23 events (6%) and 13 (56%) were locoregional recurrence. PreciseDx model with age, and PR levels combined with imaging features reflective of mitotic activity and nuclear characteristics (clinical grade not selected) correctly identified LR RS categorization: PPV of 91%, [95CI 0.87-0.94], Se 92% [0.86-0.95] and positive / negative likelihood ratio : 6.8, and 0.5, respectively. Conclusions: Application of an AI-digital breast cancer risk assessment platform using only the H&E image and limited clinical data successfully classified low risk RS patients with high accuracy. Future models will extend outcome to 10 years and evaluate treatment selection and duration

Citation Format: Michael Joseph Donovan, Nina Shpalensky, Marcel Prastawa, SM Abishek, Richard Scott, Mary Sawyer, Jack Zeineh, Gerardo Fernandez. An AI-digital breast cancer risk discrimination platform (PreciseDx) using a representative H&E image and selected clinical variables accurately categorized patients with oncotype Dx low risk recurrence scores (RS) [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 PS6-09.
Abstract PS6-21: High expression of MicroRNA-223 indicates better prognosis in triple negative breast cancer
Authors: Chen Li , Zhu Xiuzhi , Yao Ling , Wang Zonghua
Published: February 2021

Background: MicroRNAs (miRNAs) can influence many biological processes and also show promise as biomarkers for cancer. Few researches have focused on the expression of microRNA-223 (miR-223) and its precise role in breast cancer (BC). We aimed to examine the expression level of miR-223 and further explored the prognostic value in BC.Methods: Tissue microarray-based miRNA detection in situ hybridization with LNA probe was used to detect miR-223 expression in 450 BC tissue. Overall survival (OS) and disease-free survival (DFS) were compared between two groups using the Kaplan-Meier method and Cox regression model.Results: Better OS and DFS were observed in the high-miR-223 expression patients compared to those of low expression patients (P < 0.0001 and P = 0.017, respectively), especially in the triple-negative breast cancer (TNBC) subtype (P = 0.046and P < 0.001, respectively). Combined with the univariate and multivariate Cox regression analysis, TNM stage (p = 0.008), molecular subtype (p =0.049) and miR-223 (p < 0.001) were independently linked to OS and DFS. External validation was performed in METABRIC and TCGA database via online webtool and consistent with the data above.Conclusions: This study provided evidence that high-miR-223 expression at diagnosis was associated with better DFS and OS for BC, especially for the TNBC subtype. miR-223 is a valid and independent prognostic biomarker in BC.

Table Univariate and multivariate survival analysis for disease-free survivalUnivariate MultivariateVariableHR95% CIP valueHR95% CIP valueAge0.594≤40 vs >601.3510.626-2.9140.44440-60 vs >600.9940.548-1.8030.984Menopausal statuspre vs post0.7370.487-1.1130.147DifferentiationII vs III0.7300.457-1.1640.186TNM stage0.0080.008II vs I1.4210.860-2.3460.1701.4850.887-2.4850.132III vs I2.7581.446-5.2590.0022.8581.469-5.5630.002Molecular subtype0.1940.049Luminal B vs Luminal A1.1060.580-2.1070.7600.8130.415-1.5930.546HER2+ vs Luminal A0.9860.497-1.9560.9670.7010.337-1.4580.342Triple-negative vs Luminal A1.6260.930-2.8430.0881.4930.849-2.6260.164MicroRNA-223low vs high3.9602.201-7.126<0.0013.7892.098-6.843<0.001Abbreviations: CI, confidence interval; HR, hazard ratio.The covariates in the Cox model were all categorical variables, and the adjusted p value and HR were derived from the model.

Citation Format: Li Chen, Xiuzhi Zhu, Ling Yao, Zonghua Wang. High expression of MicroRNA-223 indicates better prognosis in triple negative breast cancer [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 PS6-21.
Abstract PS6-44: The significance of body mass index and absolute lymphocyte count as a prognostic factor for disease-free survival in Korean breast cancer patients
Authors: Ko Sung Min
Published: February 2021

Introduction: The purpose of our study is to identify the association between body mass index (BMI) and absolute lymphocyte count (ALC), and to determine the effect of these two factors on the prognosis of breast cancer patients.Methods: We retrospectively identified 16,375 healthy female and 1,226 primary invasive breast cancer patients from Gangnam Severance Hospital. BMI and complete blood count (CBC) information at the time of diagnosed was collected. A multivariate Cox proportional hazard model was used to variable associated with disease-free survival (DFS).Results: BMI and ALC has positive correlation in breast cancer patients as well as health female (both P < .001). However, the effect of BMI and ALC on prognosis was the opposite. Overweight and obese had worse DFS (HR, 2.00; 95% CIs, 1.36-2.96; P < .001) than underweight or normal weight, but patients with high ALC had better DFS than those with low ALC (HR, 0.42; 95% CIs, 0.28-0.63; P < .001). When the risk stratification group was divided according to BMI /ALC, the high-risk group who had high BMI and low ALC had worse DFS than low-risk group (HR, 2.61; 95% CIs, 1.51-4.51; P = .001). In subgroup analysis, Her2-overexpressing and early stage tumor was more affected by BMI/ALC.Conclusions: The impact of BMI and ALC on prognosis in breast cancer was the opposite although BMI and ALC had positive correlation. Patients with high BMI and low ALC had worse DFS than others. Weight management is essential to breast cancer patients, and additional study about correlation between BMI and ALC affecting prognosis is needed in the future.

Citation Format: Sung Min Ko. The significance of body mass index and absolute lymphocyte count as a prognostic factor for disease-free survival in Korean breast cancer patients [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 PS6-44.
Abstract PS6-48: Clinicopathologic features and follow-up outcomes of breast cancers with HER2 FISH group 3 Results: A single institution experience
Authors: Zhang Huina , Ajabnoor Rana , Hicks David , Turner Bradley
Published: February 2021

INTRODUCTION: There is dearth information on the long-term outcome and role of HER2 targeted therapy in breast cancer patients in the HER2 FISH group 3 category, which is defined as breast cancer with a HER2/CEP17 ratio < 2 and HER2 copy number ≥ 6 signals/cell. In this study, we report the clinicopathologic features and outcomes of breast cancer patients in the HER2 FISH group 3 category at our institution. METHODS: We identified 52/2,874 (1.8%) breast cancer patients with HER2 FISH group 3 results between 1/2007 and 3/2020. 28 of these 52 patients had available detailed clinicopathologic and follow-up data, with an average follow-up of 38.5 months. RESULTS: Most of the cases with group 3 FISH results were high grade ductal carcinomas with positive hormonal receptor expressions and equivocal HER2 expression by immunohistochemistry. Among all the clinicopathologic variables, only tumor size (p=0.048) significantly contributed to the poor clinical outcomes. HER2 copy number failed to show any significant association with histologic grade, tumor size, clinical stage, hormonal receptor status or disease outcomes. There was no statistically significant difference in disease outcome between patients who were treated with HER2 targeted therapy and patients who did not receive HER2 targeted therapy, regardless of the HER2 copy number or clinical stage (Table 1). CONCLUSION: Our preliminary findings suggest that certain patients with HER2 FISH group 3 category breast cancer may not need HER-2 targeted therapy. Larger-scale studies are needed to further evaluate which HER2 FISH group 3 results are more likely to benefit from the HER-2 targeted therapy.

Table 1. Response to HER2 targeted therapy in HER2 FISH group 3 breast cancer patients based on HER2 copy numbers and clinical stageHER 2 targeted therapyp-valueGivenNot givenTotal populationGood outcome (n=21)1380.371Bad outcome (n=7)61HER2 copy number < 10Good outcome (n=16)1060.366Bad outcome (n=7)61HER2 copy number ≥ 10Good outcome (n=5)321.000Bad outcome (n=0)00Stage I-IIGood outcome (n=16)970.737Bad outcome (n=3)21Stage III-IVGood outcome (n=5)410.343Bad outcome (n=4)40*Good outcome = No evidence of disease**Bad outcome = Local recurrence, distant metastasis, and/or died of disease

Citation Format: Huina Zhang, Rana Ajabnoor, David Hicks, Bradley Turner. Clinicopathologic features and follow-up outcomes of breast cancers with HER2 FISH group 3 Results: A single institution experience [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 PS6-48.
Abstract PS6-51: Identification of a low-risk luminal breast cancer cohort that may not benefit from multi-gene testing
Authors: Lei Lei , Chan Han-Ching , Lu Tzu-Pin , Miao Xian-Yuan , Yang Zi-Yan , Huang Jia-Huan , Wang Xiao-Jia , Cheng Hung-Chun Skye
Published: February 2021

Purpose: Dutch clinical risk criteria (low-risk definition: age > 35 years and (grade 1 with tumor ≤3cm, grade 2 with tumor ≤2cm, or grade 3 with tumor ≤1cm) have been used to stratify the benefit of MammaPrint and Oncotype DX for the decision-making regarding adjuvant chemotherapy for early-stage luminal breast cancer. We propose that the criteria could help to identify low-risk patients who could barely benefit from multi-gene testing. Materials and methods: Breast cancer patients from Taiwan Cancer Database initially treated with primary surgeries between 2008 and 2012 who met the following criteria: (1) pathologic node-negative, (2) hormone receptor-positive, (3) HER2-negative, (4) undergone hormonal therapy, and (5) a minimum follow-up time of 5-year if free from any event, were enrolled in this study. Out of the total 2679 eligible patients, 1074 (40.1%) patients received adjuvant chemotherapy in addition to endocrine therapy. The study endpoints included breast cancer-specific survival (BCSS) and overall survival (OS). Kaplan-Meier statistics estimated the difference between clinical outcomes in low- and high-risk groups. Results: The median follow-up time of BSCC and OS was 5.9 years (range, 0-7 years) and 5.8 years (range, 0-7 years), respectively. There were statistical significances of 5-year BCSS (n=2679) and 5-year OS (n=2636) between low-risk and high-risk groups (in both endpoints, P < 0.0001). According to the Dutch criteria, low-risk patients with and without adjuvant chemotherapy had a 5-year BCSS of 99.0% vs. 99.2% and a 5-year OS of 98.4% vs. 97.4%, respectively. High-risk patients with and without adjuvant chemotherapy had a 5-year BCSS of 97.7% vs. 98.1% and a 5-year OS of 96.4% vs. 95.3%, respectively. Conclusion: The benefit of chemotherapy in low-risk patients classified by Dutch criteria might be very small since the breast cancer mortality was less than 1% with a minimum of 5-year follow-up. Dutch criteria cannot identify high-risk patients who would benefit from chemotherapy. We assumed that multi-gene testing in low-risk patients would not be cost-effective.

Citation Format: Lei Lei, Han-Ching Chan, Tzu-Pin Lu, Xian-Yuan Miao, Zi-Yan Yang, Jia-Huan Huang, Xiao-Jia Wang, Hung-Chun Skye Cheng. Identification of a low-risk luminal breast cancer cohort that may not benefit from multi-gene testing [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 PS6-51.
Abstract PS6-53: Higher clinical lymph node stage predicts worse survival in patients with breast cancer who achieve a pathologic complete response after neoadjuvant chemotherapy
Authors: Xie Li-Yun , Wang Kun , Shi Yan-Xia , Chen Hai-Lu , Huang Jian-Hao , Fan Yang-Hang , Qiu Si-Qi , Wu Zhi-Yong
Published: February 2021

Background: Despite patients with breast cancer who achieve a pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) generally demonstrate improved survival, some of these patients will develop breast cancer recurrence. Identification of factors associated with recurrence in patients with pCR after NAC would be helpful to optimize treatment strategies in breast cancer. In this study, we aim to particularly explore the factors associated with the prognosis of this patient population.Methods: Data of patients from three tertiary hospitals and treated with NAC between 2005 and 2019 were retrospectively collected. A pCR was defined as no invasive tumor in the breast and no tumor in the lymph node (ypT0/is, ypN0). Factors associated with pCR were analyzed using univariable and multivariable logistic regression analyses. Disease-free survival (DFS) and overall survival (OS) were analyzed using the Kaplan-Meier method. The

prognostic value of clinicopathological factors regarding DFS and OS were determined by univariable and multivariable Cox regression analyses.Results: A total of 897 patients were used for the analysis, including 287 patients with a pCR and 610 patients without pCR. Clinical TNM stage, histological grade, estrogen receptor (ER) status, progesterone receptor (PR) status, human epidermal growth factor receptor 2 (HER2) status, Ki67, molecular subtype, NAC regimen and NAC cycles were associated with pCR status, with TNM stage and molecular subtype as independent predictors of pCR. Patients with a pCR had a superior DFS (pCR vs non-pCR, hazard ratio [HR] 0.26 (95% confidence interval [CI] 0.15-0.45, P<0.001) and OS (pCR vs non-pCR, hazard ratio [HR] 0.13 (95% confidence interval [CI] 0.05-0.35, P<0.001). In patients with pCR, clinical T stage, N stage and TNM stage were associated with DFS and OS, with higher N stage as an independent predictor of a worse DFS and OS.Conclusions:Clinical N stage of breast cancer is an independent predictor of worse DFS and OS in patients with a pCR after NAC. Possible this could support treatment escalation in this patient population in the future.

Citation Format: Li-Yun Xie, Kun Wang, Yan-Xia Shi, Hai-Lu Chen, Jian-Hao Huang, Yang-Hang Fan, Si-Qi Qiu, Zhi-Yong Wu. Higher clinical lymph node stage predicts worse survival in patients with breast cancer who achieve a pathologic complete response after neoadjuvant chemotherapy [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 PS6-53.
Abstract PS6-58: The impact of baseline modified glasgow prognostic score (mGPS) on survival outcomes in in indigenous and non-indigenous patients with advanced breast cancer patients of Western Australia
Authors: Khan Azim , Martin Hilary , Spalding Lisa , Redfern Andrew
Published: February 2021

Introduction: The modified Glasgow prognostic score (mGPS) is known to be useful in prognostication of multiple cancers. The mGPS, which integrates albumin and C-reactive protein, could assist as a possible prognostic marker in breast cancer. Indigenous women have inferior breast cancer survival to non-Indigenous women and may also have a differing inflammatory environment. Here, we examine the utility and impact of baseline mGPS on survival outcomes in women with metastatic breast cancer by Indigenous status.

Methods: We retrospectively collected data from the Western Australian Cancer Registry and electronic records for patients diagnosed with breast cancer between 2001 and 2016 with confirmed metastatic disease. Overall survival (OS) were measured from the date of diagnosis until death. mGPS comprised scores of one point given for CRP > 10 mg/L and/or albumin < 3.5 g/dL, therefore having a value of 0 to 2.

Results: Of 152 patients with metastatic breast cancer, 89 patients had all relevant data available and were included with a median follow up of 120 months. The median age was 55.3 years. Baseline mGPS was 0 in 46.6 %, 1 in 34.8 % and 2 in 18.6 %.

Median OS across Indigenous and non-Indigenous patients combined was significantly worse moving from the mGPS-0 group through mGPS-1 to mGPS 2, 50.0 v 30.0 v 8.0 months respectively (p<0.0001). Looking at the groups separately, both cohorts separately demonstrated inferior median OS in mGPS-2 compared to mGPS-1 patients, 9 v 32 months (p=0.02) for Indigenous patients, and 2.0 vs 25.0 months for non_Indigenous patients (p=0.001).

The correlation between mGPS and the neutrophil-to-lymphocyte ratio (NLR) was weak with a Pearson correlation R-value of 0.184 (p=0.085)

Conclusion: The study shows that the mGPS is an independent prognostic factor in advanced-stage disease. A higher baseline mGPS score was associated with worse survival in Indigenous and non-Indigenous patients. A larger prospective study is needed to validate the results, inclusive of assessing links between mGPS and OS in different breast cancer sub-types.

Citation Format: Azim Khan, Hilary Martin, Lisa Spalding, Andrew Redfern. The impact of baseline modified glasgow prognostic score (mGPS) on survival outcomes in in indigenous and non-indigenous patients with advanced breast cancer patients of Western Australia [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 PS6-58.
Abstract PS7-40: Triple negative breast cancer in New Orleans, part deux
Authors: Loch Michelle M , Hsieh Mei-Chin , Reske Thomas , Chen Vivien , Wu Xiao-Cheng
Published: February 2021

Version 7/7/2020 with edit Triple-Negative Breast Cancer in New Orleans – part deaux Objectives: To update our previously reported findings with more current data from SEER 18 registries to compare race-specific incidence rates of triple-negative breast cancer (TNBC) in New Orleans (NO) and Louisiana (LA) with other SEER metro areas and identify the predictors of TNBC. Background: We previously reported significantly increased incidence rates of TNBC in black women (BW) in NO and LA than other SEER metro areas. Methods: We analyzed tumor characteristics of invasive female breast cancers diagnosed from 2011-2017 from SEER 18 for BW and white women (WW). We compared LA data with SEER 18 and metropolitan areas (Atlanta, Detroit, Los Angeles and San Francisco) as we did with our previous data set. Predictors of TNBC in NO and LA were identified in multivariate logistic regression adjusting for age, BMI, poverty, insurance, tumor size, Bloom-Richardson grade and AJCC stage. Results: The overall incidence rate of TNBC in BW was again significantly higher in NO (29.8 per 100,000) than any metro area and the SEER metro areas combined (23.9 per 100,000). Detroit again had the second highest rate (27.2) followed by San Francisco/Oakland (23.8) Los Angeles (22.3) and Atlanta (22.1). The multivariable analysis showed that younger age, large tumor size, high grade were associated with increased risk of TNBC in BW. Conclusions: The incidence rates of TNBC in BW in NO continue to be consistently higher compared to LA and other SEER 18 metro areas. This data reiterates the importance of ongoing translational research to broaden the understanding and optimize the treatment of this aggressive disease, especially in this vulnerable population.

Citation Format: Michelle M Loch, Mei-Chin Hsieh, Thomas Reske, Vivien Chen, Xiao-Cheng Wu. Triple negative breast cancer in New Orleans, part deux [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 PS7-40.
Abstract PS7-54: Racial differences in age-related DNA methylation changes in normal breast tissue
Authors: He Chunyan , Castle James , Lin Nan , Liu Yunlong , Wang Chi
Published: February 2021

Age is a well-established risk factor for breast cancer development. While age-related epigenetic changes are believed to contribute to overall breast cancer risk, the underlying molecular mechanisms are poorly understood. In addition, racial disparity in breast cancer is well recognized. Compared to European American (EA) women, African American (AA) women are more often diagnosed with breast cancer at younger ages, have a more advanced or aggressive disease, and have poorer outcomes. We hypothesize that age-related DNA methylation (DNAm) may contribute to breast cancer risk differently for distinct racial groups. We investigated epigenome-wide age-related DNAm in normal breast tissue from 178 EA and 272 AA women separately using the Illumina TruSeq Methyl Capture EPIC library and NGS technology. We identified 3,944 and 506 CpG loci that were significantly associated with chronological age, of which 3,534 and 504 CpGs were increasingly hypermethylated with older ages and 410 and 2 loci were increasingly hypomethylated with older ages, in EA and AA women, respectively. Despite the different number, all 506 loci that were significantly associated with age in AA women were also significant for EA women. The low number age-related DNAm loci identified in AA women may reflect a more complex interplay of factors on epigenetic mechanisms in this racial group. Pathway analyses suggested these age-related loci are enriched in biological processes including cell communication, signaling, proliferation, and adhesion. We further examined 181 CpG loci that were previously reported to be associated with age in normal breast tissue but found that only six loci were replicated in our dataset. Our results suggested age-related biological pathways that potentially implicated in breast cancer development and a more complex epigenetic mechanisms in AA women.

Citation Format: Chunyan He, James Castle, Nan Lin, Yunlong Liu, Chi Wang. Racial differences in age-related DNA methylation changes in normal breast tissue [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 PS7-54.