Triple-negative Phenotype Research Articles

Epithelial-Mesenchymal Transition Indexes in Triple-Negative Breast Cancer Progression and Metastases.

Background Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer characterized by the lack of expression of estrogen and progesterone receptors and the absence of HER2 protein overexpression or gene amplification. How TNBC becomes so aggressive at the molecular level is not yet fully understood. The epithelial-mesenchymal transition (EMT) has been increasingly recognized as playing a pivotal role in cancer progression and metastasis. This study aimed to elucidate the connection between TNBC progression with EMT-related markers, including vimentin, beta-catenin, and E-cadherin. Methodology Rigorous immunohistochemical analysis was employed to assess the expression of vimentin, beta-catenin, and E-cadherin in primary tumors, tumor buds, and lymph node metastases (LNMs) from 137 cases with an invasive ductal carcinoma triple-negative phenotype diagnosed between 2018 and 2024. The EMT index, which was especially important in our work, is the sum of vimentin and beta-catenin expression divided by that of E-cadherin. Estimated Pearson correlation, multiple linear regression, and Kruskal-Wallis tests were used to determine the relationships of the EMT index with tumor buds and tumor-infiltrating lymphocytes (TILs). Results Vimentin highly correlated within separate regions of interest with Pearson correlation ranging from 0.90 to 0.92 (p < 0.001). Strong negative correlations between E-cadherin and vimentin (r = -0.81 to - 0.89, p < 0.001) showed its role in preserving the epithelial phenotype. The presence of tumor buds, aggregates, or clusters of cancer cells shed from the primary tumor mass invading the connective tissue showed very strong associations with the EMT index (r = 0.91, p < 0.001). Its presence is suggestive of aggressive disease and may identify a high-risk subpopulation that may benefit from more active surveillance or adjuvant treatment. Similarly, TILs correlated inversely with the EMT index (r = -0.90, p < 0.001). The most significant predictor of the EMT index, i.e., vimentin, had a model R-squared value of 1.000 in the regression analysis. Conclusions This study brings to light the importance of EMT-related markers in TNBC progression, with special emphasis on tumor buds as possible prognostic indicators for aggressive disease. The negative correlation of TILs with the EMT index indicates that an effective immune response could antagonize EMT-mediated tumor progression. These results suggest that EMT-based treatments in TNBC should be designed from a multimarker perspective by including interactions among several markers to optimize predictions and therapeutics. The results hold the potential to set future research directions and actionable outcomes that could influence clinical utility in the battle against TNBC.

Tamoxifen metabolites treatment promotes ERα+ transition to triple negative phenotype in vitro, effects of LDL in chemoresistance.

Estrogen receptor-positive (ER+) breast cancer represents about 80% of cases, tamoxifen is the election neoadjuvant chemotherapy. However, a large percentage of patients develop chemoresistance, compromising recovery. Clinical evidence suggests that high plasmatic levels of low-density lipoproteins (LDL) could promote cancer progression. The present study analyzed the effect of LDL on the primary plasmatic active Tamoxifen's metabolites resistance acquisition, 4-hydroxytamoxifen (4OH-Tam) and 4-hydroxy-N-desmethyl-tamoxifen (endoxifen), in breast cancer ERα + cells (MCF-7). Two resistant cellular variants, MCF-7Var-H and MCF-7Var-I, were generated by a novel strategy and their phenotype features were evaluated. Phenotypic assessment was performed by MTT assays, cytometry, immunofluorescence microscopy, zymography and protein expression analysis. MCF-7Var-H, generated only with tamoxifen metabolites, showed a critical down-regulation in hormone receptors, augmented migration capacity, metalloprotease 9 extracellular medium excretion, and a mesenchymal morphology in contrast with native MCF-7, suggesting the transition towards Triple-negative breast cancer (TNBC) phenotype. In contrast, MCF-7Var-I which was generated in a high LDL media, showed only a slight upregulation in ER and other less noticeable metabolic adaptations. Results suggest a potential role of transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) in phenotypic differences observed among variants. LDL high or low concentrations during Tamoxifen´s metabolites chemoresistance acquisition leads to different cellular mechanisms related to chemoresistance. A novel adaptative cellular response associated with Nrf2 activity could be implicated.

Prognostic Evaluation of Piezo2 Channels in Mammary Gland Carcinoma.

In the last decade, a group of Ca2+ channels called Piezo were discovered, demonstrating a decisive role in the cellular response to mechanical stimuli and being essential in the biological behavior of cells regarding the extracellular compartment. Several investigations have suggested a potential role in carcinogenesis, with a tumor suppressor role in some cases but increased expression in several high-grade neoplasms. Regarding Piezo2 expression in mammary gland neoplasms, a protective role for Piezo2 was initially suggested, but a subsequent study demonstrated a relationship between Piezo2 expression and the highly aggressive triple-negative phenotype of breast carcinoma. A cohort of 125 patients with clinical follow-up was chosen to study Piezo2 expression and clarify its clinical implications using the same immunohistochemical evaluation performed for other breast carcinoma parameters. Fisher's exact test was chosen to identify potential relationships between the different variables. A significant association was found with the Ki67 proliferation index, but not with mitoses. The tendency of most proliferative tumors was to have an increased score for Piezo2. A similar association was found between Piezo2 expression and perineural invasion.

P53 protein expression patterns associated with TP53 mutations in breast carcinoma

PurposeThe importance of a TP53 mutation has been demonstrated in several tumor types, including breast cancer (BC). However, the accuracy of p53 protein expression as a predictor of gene mutation has not been well studied in BC. Therefore, we evaluated p53 protein expression associated with TP53 mutations in breast cancers from 64 patients.MethodsTP53 mutation was examined using next-generation sequencing (NGS). p53 protein expression was examined using immunohistochemistry (IHC).ResultsAmong the 64 BCs, 55% demonstrated abnormal expression patterns including 27% overexpression, 22% null, 6% equivocal with 45% having a wild-type pattern. A TP53 mutation was present in 53% (34/64) of tumors including 30% (19/64) demonstrating a missense mutation, 11% (7/64) with a frameshift mutation, 11% (7/64) with a nonsense mutation, and 3% (1/64) with a splice site mutation. Abnormal expression of p53 protein was present in 33 of 34 (97%) tumors carrying a TP53 mutation; conversely, a wild-type pattern was present in 28 of 30 (93%) tumors without a detectable mutation (p < 0.0001). The majority of BCs with a p53 IHC overexpression pattern (15/17, 88%) contained a missense TP53 mutation; while the majority of BCs with a null pattern (12/14, 86%) contained a truncating mutation (p < 0.0001). The BCs with a null pattern are associated with a high Nottingham histological grade and a triple-negative phenotype when compared to those demonstrating overexpression (p < 0.05).ConclusionThese findings suggest that p53 IHC can be a potential surrogate for TP53 mutations in BC. Different p53 expression patterns may correlate with specific TP53 genetic mutations in BC.

Radiogenomics of homologous recombination deficiency (HRD) in breast cancer: Radiomics-based image biomarker for HRD.

554 Background: Homologous recombination deficiency (HRD) in breast cancer is an actionable target, with treatment efficacy potentially linked to timely detection. Notably, BRCA1 and BRCA2 are key genes implicated in HRD, and their pathogenic germline mutations are crucial criteria for the use of poly (ADP-ribose) polymerase inhibitors (PARPi). Although germline BRCA1/2 mutations are detectable in only a small fraction (1-5%) of breast cancers, recent whole-genome sequencing (WGS) studies have revealed that up to 22% of breast cancers also exhibit HRD-like genomic characteristics, suggesting a broader potential for HRD-targeted therapy. This has spurred the development of genomic-feature-based HRD identification methods. However, the invasive and costly nature of these methods poses a challenge. This has prompted our investigation into non-invasive image biomarkers for HRD identification. Methods: Invasive breast cancer patients were recruited from March 2021 to August 2022. Eligibility criteria included availability of fresh-frozen tumor tissue for WGS and suitability for dynamic contrast-enhanced (DCE) MRI to facilitate radiomics analysis. The association between HRD and radiomic features as well as clinicopathologic factors was investigated through rigorous genomic and statistical analysis. Results: This study encompassed 145 patients aged 20 to 69 years, of whom 16.6% (24 out of 145) were genomically identified as HRD. All patients harboring pathogenic germline mutations in BRCA1 (n=3) or BRCA2 (n=2), along with concomitant somatic LOH, exhibited HRD. A comprehensive analysis of 214 radiomic features revealed that tumor sphericity, informational measure of correlation 1 (IMC1), size-zone non-uniformity normalized (SZNN), and small area emphasis (SAE) derived from subtracted early dynamic T1-weighted imaging were significantly correlated with HRD. Moreover, these radiomic features demonstrated substantial diagnostic value, as evidenced by their ROC-AUC and PR-AUC performance against baseline models: Sphericity (ROC: 0.62, p=0.055; PR: 0.22, p=0.053), SAE (ROC: 0.63, p=0.052; PR: 0.32, p=0.007), SZNN (ROC: 0.63, p=0.04; PR: 0.30, p=0.007), and IMC1 (ROC: 0.62, p=0.067; PR: 0.29, p=0.02). Additionally, our findings suggest that these radiomic features are more directly related to HRD than to the triple-negative phenotype, which is commonly linked to HRD. Conclusions: We found that four radiomic features from MRI have significant predictive value for identifying HRD in breast cancer. Given their fair predictability and immediate availability, these features are ideally suited for a screening approach, potentially identifying more patients eligible for targeted treatment. This finding represents a significant advancement in the fields of radiology and precision oncology, opening new avenues for patient-specific treatment strategies.

The efficacy of PARP inhibitors in the treatment of patients with synchronous breast cancer.

e13041 Background: Currently, the role of BRCA1/2 in the development of primary and multiple malignant breast tumors is under discussion, along with the effectiveness of targeted therapy for this oncopathology. At the same time, there is a lack of sufficient research dedicated to the treatment of patients with synchronous breast cancer (BC) concurrent with ovarian cancer (OC) and the outcomes of using PARP inhibitors in this patient population. Methods: A retrospective analysis of treatment outcomes based on long-term survival indicators was conducted for 23 patients with synchronous BC, where the second tumor was OC. These patients underwent evaluation and treatment between 2017 and 2022. The average age of the patients was 45.3±5.6 years, with a prevalence of patients in stages IIb-IIIa of BC and IIb-IIIc of OC. Germline mutations in the BRCA1/2 genes were detected in 8 patients, among whom 5 exhibited the triple-negative phenotype of BC. The 1st group included 11 (47.8%) patients without BRCA1/2 mutations, who received neoadjuvant chemotherapy with paclitaxel 175 mg/m2 + carboplatin AUC 6 once every 3 weeks. In the 2nd group, consisting of 12 (52.2%) patients, olaparib 800 mg was added to this chemotherapy regimen. This group also included 8 patients with BRCA1/2 mutations. Results: In the majority of patients in both groups, a significant elevation in CA125 levels in serum was observed, averaging 563 U/mL, with practically normal CA153 levels at 32 U/mL. Identified mutations included 5382insC and 4154delA mutations in the BRCA1 gene, as well as the 6174delT mutation in the BRCA2 gene. Patients underwent three courses of treatment, and four weeks after completing the last course, surgical intervention was performed in the form of radical mastectomy, hysterectomy, bilateral salpingo-oophorectomy, and omentectomy. Following surgical treatment, patients received adjuvant chemotherapy following the same regimens. In the 2nd group, patients continued to receive olaparib for one year, and no signs of unacceptable toxicity were reported. The median overall survival in the first group of patients was 34.2 months (95% CI: 28.6-37.5), while in the second group, it was 36.8 months (95% CI: 31.4-41.1). The addition of bevacizumab significantly increased the median time to progression from 13.8 months (95% CI: 11.8-14.5) to 15.2 months (95% CI: 12.4-15.8), p=0.042. Lethal outcomes primarily occurred due to the progression of ovarian cancer. Conclusions: Thus, the addition of the PARP inhibitor olaparib to a platinum-based chemotherapy regimen in patients with synchronous breast cancer, associated with germline mutations in BRCA1/2 genes and the presence of ovarian cancer as a second tumor, has a positive impact on treatment outcomes. This contributes to the resectability of patients and significantly increases the median time to progression.

Effects of Garlic on Breast Tumor Cells with a Triple Negative Phenotype: Peculiar Subtype-Dependent Down-Modulation of Akt Signaling.

Breast cancer includes tumor subgroups with morphological, molecular, and clinical differences. Intrinsic heterogeneity especially characterizes breast tumors with a triple negative phenotype, often leading to the failure of even the most advanced therapeutic strategies. To improve breast cancer treatment, the use of natural agents to integrate conventional therapies is the subject of ever-increasing attention. In this context, garlic (Allium sativum) shows anti-cancerous potential, interfering with the proliferation, motility, and malignant progression of both non-invasive and invasive breast tumor cells. As heterogeneity could be at the basis of variable effects, the main objective of our study was to evaluate the anti-tumoral activity of a garlic extract in breast cancer cells with a triple negative phenotype. Established triple negative breast cancer (TNBC) cell lines from patient-derived xenografts (PDXs) were used, revealing subtype-dependent effects on morphology, cell cycle, and invasive potential, correlated with the peculiar down-modulation of Akt signaling, a crucial regulator in solid tumors. Our results first demonstrate that the effects of garlic on TNBC breast cancer are not unique and suggest that only more precise knowledge of the mechanisms activated by this natural compound in each tumor will allow for the inclusion of garlic in personalized therapeutic approaches to breast cancer.

Clinical, Histopathological, and Immunohistochemical Characteristics of Predictive Biomarkers of Breast Cancer: A Retrospective Study.

Breast cancer is a complex disease with variability in clinical manifestation, response to current therapy, and biochemical and histological features among various subgroups. Histologic grading and immuno-histochemical evaluation of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2), and Ki-67 proliferation index play a crucial role in increasing the differential diagnostic value among various types of breast carcinoma. The aim of this study was to determine the histopathological and immuno-histochemical characteristics of breast tumors from a University Laboratory of Pathology in Greece. The study included female patients over 18 years of age, whose histopathological and immunohistochemical reports were stored in the archives of the First Department of Pathology of National and Kapodistrian University of Athens. The study involved 197 female patients with a median age of 70 years and median tumor size of 2.6 cm. Most tumors were located at the left breast and ductal carcinoma was the most common histologic type (35.5%). Most tumors had histologic grade 2 (106, 53.8%), and were classified as TNM stage IIA (65, 33%). Most grade 1 and 2 tumors exhibited high expression of PR, whereas most grade 3 tumors had no PR expression. Moreover, patients with triple-negative cancer presented with grades 2 and 3 at a lower percentage compared to patients without a triple-negative phenotype (p=0.001). The study provided valuable insights into the histopathological and immuno-histochemical characteristics involved in the development and progression of breast cancer.

Abstract PO5-26-12: Optimizing Treatment Decisions in Microinvasive Ductal Carcinoma in Situ: Evaluating the Need for Surgical Axillary Staging

Abstract Background: Surgical axillary staging is often debated in patients with microinvasive ductal carcinoma in situ (T1mi) due to the low occurrence of nodal metastasis. Axillary surgery (ASx) is associated with risks like seroma, wound complications, lymphedema, and sensory deficits. This study aims to assess the utility of surgical axillary staging in clinically node-negative (cN0) T1mi breast cancer patients and provide insights for optimizing high value surgical treatment and subsequent decision-making. Methods: This retrospective cohort study analyzed data from the National Cancer Database (NCDB) to investigate axillary status of patients with cT1mi breast cancer between 2012 and 2019. Patient demographics, clinical characteristics, treatment methods and pathologic findings were collected. Comparisons were made between those who did and did not undergo ASx, and of those who did, between patients who were pathologically node-positive (pN+) vs. node-negative (pN-). Results: Of 10,843 patients analyzed, 9,220 (85.0%) underwent ASx while 1,623 (15.0%) did not. Mean age of patients undergoing ASx and those who did not was 59.2±11.2 and 66.3±12.8 years, respectively (p&amp;lt; 0.001). On univariate analysis, other factors associated with undergoing ASx were having private insurance, fewer medical comorbidities, having a HER2+ or triple negative phenotype, higher grade, presence of lymphovascular invasion and undergoing mastectomy (all p&amp;lt; 0.05). Sentinel lymphadenectomy was performed in 83% of patients while axillary lymph node dissection (ALND) was performed in 17% of patients. Final pathology demonstrated an upgrade to a true invasive cancer (T1 or greater) in 29.3% of cases. Of 9,069 patients who underwent ASx with known pathologic nodal status, 8,512 (93.9%) were pN- and 557 (6.1%) were pN+. Factors independently associated with increased odds of having positive nodes were younger age (OR 1.02, 95% CI 1.01-1.03, p&amp;lt; 0.001), Black race (OR 1.51, 95% CI 1.12-2.10, p=0.007), lymphovascular invasion (OR 13.72, 95% CI 10.25-18.36, p&amp;lt; 0.001), and undergoing mastectomy (OR 1.98, 95% CI 1.57-2.51, p&amp;lt; 0.001). Among the pN+ patients, only 64 (0.7%) had ≥3 total positive nodes and would require ALND. On subset analysis of the 4,190 patients undergoing mastectomy, 244 (5.8%) did not undergo ASx, while 3,946 (94.2%) did, of whom 373 (9%) were pN+. Regarding adjuvant treatments in this group, more patients who underwent ASx received chemotherapy (12% v. 8%, p&amp;lt; 0.001), and among those who did undergo surgery those who were pN+ were much more likely to receive chemotherapy (58% v. 12%, p&amp;lt; 0.001). However, similar proportions of patients who did and did not undergo ASx received adjuvant radiation (5% v. 4%, p=0.65), while, as expected, among those undergoing ASx, a higher proportion who were pN+ underwent radiation (32% v. 5%, p&amp;lt; 0.001). Conclusion: Surgical axillary staging for T1mi breast cancer is common, but many patients are node-negative. More patients are undergoing ALND than necessary based on pathology. Nodal status influences adjuvant therapy decisions. Identifying factors linked to upgrade and higher pN+ probabilities can enable personalized surgical treatments, reducing morbidity for most patients. Citation Format: Christian Lava, Karen Li, Lauren Berger, Daisy Spoer, Lindy Rosal, Austin Williams, Monika Masanam, Ian Greenwalt, Jennifer Son, Lucy De La Cruz. Optimizing Treatment Decisions in Microinvasive Ductal Carcinoma in Situ: Evaluating the Need for Surgical Axillary Staging [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-26-12.

Abstract PO3-03-04: Metaplastic breast cancer: a single center retrospective study

Abstract Background: Metaplastic breast cancer (MBC) is a rare malignancy that accounts for up to 1% of all primary invasive breast carcinomas (BC). It is histologically heterogeneous, usually presents with a triple-negative phenotype and comprises low-grade and high-grade (HG) variants. HG variants have a higher risk of recurrence and a shorter disease-free and overall survival compared to other BC subtypes. Our research aimed to estimate the prevalence of HG-MBC among the Slovenian population and determine the characteristics of patients (pts) and tumours and the disease outcome. Patients and methods: Our retrospective study included pts diagnosed with HG-MBC at the Institute of Oncology Ljubljana from January 1983 until January 2021. Clinicopathologic characteristics such as tumour subtype, size and grade, nodal status, hormonal receptors (HR) and HER-2 status, lymphovascular invasion (LVI), tumour-infiltrating lymphocytes (TIL) and presence of germline BRCA mutation status were determined. The survival analyses were performed using the Kaplan-Meier method. The Cox proportional hazard model examined the association between risk factors and survival outcomes. Results: We evaluated 113 HG-MBC pts among a total of 27700 pts diagnosed with BC over 38 years (0.41%). The median age was 61.6 years (range 29.7 -93.9), majority of pts were postmenopausal (78.69%). The median follow-up was 15.5 years. The most common tumour subtype in our cohort was mixed MBC (53 cases, 46.9%), followed by MBC with mesenchymal differentiation (24 cases, 21.2%), squamous cell carcinoma (20 cases, 17.7%) and spindle cell carcinoma (16 cases, 14.2%). From the 113 evaluated pts, we obtained data about the stage in 105 pts, pathological tumour size in 100 pts, number of positive lymph nodes in 99 pts, HR status in 95 pts, HER2 status in 76 pts, grade in 97 pts, LVI in 85 pts, MIB-1 in 41 pts and TIL in 77 pts. At diagnosis, 17/105 pts (16.2%) had stage I disease, 59/105 pts (56.2%) stage II, 25/105 pts (23.8%) stage III and 4/105 pts (3,8%) stage IV. Most tumours were poorly differentiated (90/97, 92.2%) without LVI (60/85, 70.6%). Only 6/95 (6,3%) pts had positive HR, 7/76 (9.2%) pts had positive HER-2 status and 8/77(10.4%) pts intensive TIL. Overall, 13 pts were tested for BRCA germline mutation, among which only 1 (7,7%) had BRCA1 mutation. Modified radical mastectomy was the most frequent type of surgery (63.5%); 49.5% of the patients received radiotherapy. In total, 66/113 pts received CT: from 1983 to 2000, 16/36 (44.4%), and after 2000 50/77 (74.9%). In the first period, most pts received CMF (14/16; 87.5%) and anthracyclines and taxanes (27/50; 54%) in the second period. The disease progressed at 37 pts. At 19 pts, new malignancies were found. 55 pts died, 37 of them because of BC. Five- and 10-year disease-free survival (DFS) was 61.7% and 54.1%, while 5-and 10-year overall survival (OS) was 67.1 % and 56.7%, respectively. However, DFS and OS did not differ between the pre-2000 and post-2000 periods. The best outcome was found in pts with squamous cell carcinoma (5- and 10-year DFS 83.5% and 77.0% and 5-and 10- year OS 89.4 % and 83.0%). A subtype of MBC (squamous cell vs other) was the only predictive factor in multivariate analysis for both DFS (HR 0.21; 95% CI 0.05-0.92; p = 0.038 and OS (HR 0.27; 95%CI 0.09-0.78; p = 0.016), no association was seen between survival and tumour size, nodal status, stage, HR and HER2 status, grade, LVI and TILs. Visceral organs were the most common localization of distant metastases (21/37, 56.8%). Metastases in CNS occurred in 9/37 (24.3%) pts. Median OS after the first progression was only 0.9 years. Conclusions: The proportion of HG-MBC in our cohort of pts is 0.41%. Disease outcomes are poor; the 10-year OS of pts with early HG-MBC is only 56.6% and has not improved during the last decades. Squamous cell differentiation predicts a better outcome and is the only independent predictive factor of DFS and OS among HG-MBC pts. Citation Format: Maša Auprih, Gorana Gasljevic, Eva Setina, Anja Zizek, Simona Borstnar. Metaplastic breast cancer: a single center retrospective study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-03-04.

Abstract PO5-25-02: Microenvironment based co-culture dependence of breast cancer and immune cell interactions on functional outcomes

Abstract The tumour microenvironment (TME) includes physical forces from interstitial fluid flow and cell-cell interactions that modulate cancer development and progression through activation of multiple oncogenic pathways leading to tumor growth and metastatic spreading. We previously reported on the role of physical forces on epithelial to mesenchymal transition (EMT) and S100 gene family expression and cell to cell adhesion properties with implications to normal breast development and cancer. Signals from the tumor exit the local tumor environment through interstitial fluid transport and cell migration where they can be found in the blood stream. We developed a whole blood RNA gene expression biomarker panel coupled with proprietary software capable of identifying the presence of an active breast cancer signature at early stages of disease with clinical study results previously reported. Here we report on results from transcriptomic and function studies with cell interaction models. Cancer cells can influence immune cells through direct contact or via secreted molecules causing the immune cells to undergo functional changes. To investigate mechanisms involved in the induction of these alterations in a model system, we performed co-culture studies with human monocytic cells and breast cancer cells. Interaction of human monocytic cells with the breast cancer cells caused significant changes in both behavior and transcriptomes. Moreover, using RNAseq and pathway analysis we demonstrated that the changes induced through the exposure to the more aggressive triple negative (TNBC) phenotype were distinct from the alterations triggered upon contact with an ER+ breast cancer cell line. We also show that cancer-immune crosstalk triggers EMT as well as activation of multiple oncogenic pathways associated with cell migration and invasion, cell chemotaxis and cell-to-cell interactions. As the interplay between cancer and immune cells plays an important role in cancer progression, these findings provide important insight into key mechanisms controlling these outcomes. Citation Format: Karen Norek, Jacob Kennard, Kenneth Fuh, Robert Shepherd, Kristina Rinker, Olesya Kharenko. Microenvironment based co-culture dependence of breast cancer and immune cell interactions on functional outcomes [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-25-02.

Abstract PO5-21-07: Mitomycin: its developmental role in the treatment of patients with BRCA - associated triple-negative early and locally advanced breast cancer

Abstract Rationale. BRCA-associated triple-negative breast cancer (TNBC) is one of the most aggressive subtypes of breast cancer with high sensitivity to chemotherapy, which leads to increased interest in the development of new strategies for neoadjuvant treatment of patients with a triple-negative tumor phenotype. The aim of the study is to determine the role of adding platinum to standard neoadjuvant systemic therapy in patients with primary BRCA-associated TNBC, to evaluate the effect of platinum preparations on relapse-free survival in patients of this category, to determine the role of adding mitomycin to platinum in patients with primary BRCA-associated TNBC. Materials and methods. The study included 80 patients diagnosed with primary BRCA - associated TNBC, divided into 3 groups according to the treatment. Each group was subdivided depending on the final pathomorphological result and the presence of relapses. Results. 80 patients with primary BRCA-associated TNBC were divided into 3 groups depending on the ongoing neoadjuvant chemotherapy (NACT). Group I included 48 (60%) patients who received the AC-T regimen, in group II — NAC according to the AC-TCarb regimen, 27 (33.75%) patients, in group III — NAC with mitomycin in combination with cisplatin, 5 (6.25%) of patients. A comparative analysis of the results of the frequency of achieving complete pathomorphological regression (pCR), depending on the addition of a platinum drug to standard NAC, showed the advantage of group II compared to group I (73.7% vs. 41.2%, respectively, p = 0.0433). Taking into account the ongoing NAC regimens, with a median follow-up of 20.7 months, patients of group I had a slightly higher risk of relapse compared to patients of group II (p = 0.099). Patients of group III demonstrated the achievement of pCR in 66.6% of cases (2/3) during the full course of NAC, 2 patients of group III did not complete the planned course of NAC for medical reasons, due to the development of a pronounced nephrotoxic effect. During the observation period of group III, no cases of relapse were recorded. Conclusions.The addition of platinum drugs to the standard anthracycline/taxane NAPCT regimen in patients with primary BRCA-associated TNBC, results in a higher pCR rate, which entails a reduced risk of disease recurrence.The use of the new NAC regimen with mitomycin in combination with platinum compounds has promising results in patients with this oncopathology, which deserves a more detailed clinical evaluation.Performinga full course of planned NAC has a positive tendency in achieving pCR in patients of this category. Keywords: BRCA1/2 mutation; triple negative breast cancer; platinum preparations; mitomycin; neoadjuvant chemotherapy. Citation Format: Petr Krivorotko, Evgeniy Imyanitov, Diana Enaldieva, Elena Zhiltsova, Roman Donskih, Anna Sokolenko, Laysan Shaikhelislamova, Larisa Gigolaeva, Tengiz Tabagua, Alexander Komyakhov, Kirill Nikolaev, Konstantin Zernov, Sergey Yerechshenko, Roman Pesotsky, Nikolay Amirov, Alexander Emelyanov, Viktoria Mortada, Yana Bondarchuk, Vladislav Semiglazov. Mitomycin: its developmental role in the treatment of patients with BRCA - associated triple-negative early and locally advanced breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-21-07.

Abstract PO1-27-07: Is HER2-low a biologically distinct breast cancer (BC) subtype? Prognosis and pathological complete response rate after neoadjuvant treatment (NAT) in early breast cancer (BC) HER2 negative

Abstract Background: Overexpression of HER2 is a significant prognostic and predictive factor in early breast cancer. HER2 positive tumors are those scored by immunohistochemistry (IHC) 3+ or 2+ with amplification by in situ hybridization (ISH). These tumors may benefit from HER2-targeted treatment and additionally, in early HER2-positive BC, achieving a complete pathological response after neoadjuvant treatment improves patient survival. In recent years, new anti-HER2 antibody-drug conjugates have proven effective for HER2 low BC (defined as IHC score 1+ or 2+ not amplified) in the metastatic disease setting; however, in HER2-low early BC, studies testing novel anti-HER2 antibody-drug conjugates as neoadjuvant therapy (NAT) are ongoing. Currently, we don´t know exactly whether HER2 expression can influence the pathological response rate after NAT or disease-free survival (DFS) in these patients compared to HER2-zero (IHC 0). The aim of our study is to determine the impact on response rate to NAT and survival outcomes in early HER2-negative BC. Methods: We conducted a retrospective study in two hospitals in Andalucia, Spain. Patients with early HER2 negative BC treated with NAT from January 2015 to June 2022 were included. Patients were divided into HER2 low patients (IHC 1+ or 2+ not amplified) and HER2 0 (IHC 0). We collected clinical and pathological characteristics, pathological response rate using the Residual Cancer Burden (RCB) system where a complete pathological response (pCR) was defined as ypT0/ypTis and ypN0, and survival outcomes. The primary objective of the study was to analyze the pCR rate after NAT according to HER2 score, and secondary objectives were to assess disease-free survival and overall survival (DFS and OS rates). Results: 574 patients were included (100% women). 397 patients had hormone receptors (luminal BC) on these tumors, and 177 did not have them, i.e., triple-negative BC (TNBC). 225 patients were HER2-zero, and 312 patients were HER2-low (253/312 patients had luminal BC and 59/312 patients were TNBC). The pCR in HER2-low patients was 17.3% and 23.1% in HER2-zero patients (p=0.047). For luminal BC patients, the pCR was 16.7% in HER2-low tumors and 13.7% in HER2-zero tumors (p=0.29). Similarly, there was no difference in pCR rates in TNBC patients (45.8% in HER2-low and 53.8% in HER2-zero tumors, respectively, (p=0.958). The overall survival (OS) at 96 months was 88.7% (95% CI 85.6%-92%). Regarding survival outcomes, neither HER2 expression level was associated with higher 8-year DFS: 81.1% in HER2-low patients (95% CI 75.7%-86.8%) and 74.9% in HER2-zero patients (95% CI 62.3%-90.1%) p=0.64. There was no difference between histological subtypes at 8-years regarding DFS rate: 80.5% (95% CI 74.3%-87.2%) in luminal HER2-low patients and 76.3% (95% CI 60.8%-95.7%) in luminal HER2-zero patients, p=0.22; 83.8% in TNBC HER2-low (95% CI 74.5%-94.2%) and 77.5% in TNBC HER2-zero patients (95% CI 69.4%-86.6%) p=0.26. We also didn´t find significant differences in terms of OS. For HER2-low patients, the 8-year OS was 90.9% (95% CI 87%-94.9%) and for HER2-zero patients, it was 86.4% (95% CI 80.8%- 92.5%) p=0.46. There were also no differences in OS for different histological subgroups with an 8-year OS in luminal HER2-low breast cancer patients of 92.5% (95% CI 88%-96.7%) and 87% in HER2-zero (95% CI 78.9%-96.1%) p=0.91. In patients with triple-negative breast cancer phenotype, the OS was 84.2% for HER2-low (95% CI 74.5%-95.2%) and 85.3% for HER2-zero (95% CI 77.9%-93.4%) p=1. Conclusions: We found no difference in survival outcomes and response rate to conventional NAT between HER2-low and HER2-zero expression levels. Therefore, our data do not support the hypothesis of HER2-low as a biologically specific breast cancer subtype. Further research on this approach with HER2 antibody-drug conjugate schemes as an alternative to traditional NAT schemes is warranted. Citation Format: Ana Gil-Torralvo, Yeray Rodriguez, Alejandro Falcon, David Morales, Mónica Cejuela, Isabel Miras, Marta Amérigo, Manuel Ruíz - Borrego, Juan Bayo, Francisco Javier Salvador Bofill. Is HER2-low a biologically distinct breast cancer (BC) subtype? Prognosis and pathological complete response rate after neoadjuvant treatment (NAT) in early breast cancer (BC) HER2 negative [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-27-07.

Abstract PO4-15-02: ApoE polymorphism is associated with aggressive tumor phenotypes for breast cancer patients

Abstract Introduction: Apolipoprotein E (APOE) is implicated in several biological processes, such as protein synthesis, cell growth and differentiation, cholesterol transport, lipid metabolism, and tissue repair. APOE has different isoforms (E2, E3, and E4) that combine conflicting relations with cancer risk. This study aimed to evaluate the distribution of different isoforms of APOE among suspected HBOC (Hereditary Breast and Ovarian Cancer Syndrome) patients. Methodology: DNA was extracted from the blood cells of 108 patients. The detection was performed using qPCR after amplifying specific regions containing the polymorphisms. It was considered that all the amplicons containing Cq amplification &amp;lt; 35. The melting curve for each patient was analyzed to determine the frequency of the isoforms E2, E3, E4, and genotypes E2/E2, E2/E3, E2E4, E3/E3, and E3/E4. The allele and genotype were also correlated with hereditary variants previously identified by genetic tests for germline mutations and with tumoral phenotype. The data were expressed in frequency and associated using chi-square tests or Fisher's exact test (SPSS v20.0, p&amp;lt; 0.05). Results A total of 108 patients filling criteria for HBOC syndrome were evaluated. Among them, 15 (13.9%) had a mutation in BRCA1, 5 (4.6%) in BRCA2, and 2 (1.9%) in TP53. Most patients were under 45 years old (n=76, 70.4%), female (n=104, 96.3%), had a high school education (n=44, 44.0%), were non-smokers (n=79, 80.6%) or drinkers (n=76, 78.4%), and had no comorbidities (n=66, 64.1%). Overweight at diagnosis was observed in 61 (68.5%) individuals. The most frequent tumor phenotype and stage were luminal B (n=46, 43.4%) and stage IIIA (n=22, 26.2%), respectively. Neoadjuvant chemotherapy was performed in 40 (47.1%) with a high rate of complete and partial response 18 (36.7%) and 22 (44.9%), respectively. Regarding ApoE polymorphisms, the E2 allele showed the lowest frequency (n=7, 6.5%), E3 was present in 103 (95.4%) cases, while E4 was present in 39 (36.1%). The most frequent genotype was E3/E3 (n=64, 58.3%), followed by E3/E4 (n=34, 31.5%), E2/E3 (n=6, 5.6%), E4 (n=4, 3.7%), and E2/E4 (n=1, 0.9%). No cases of E2/E2 genotype were observed. The presence of E2 was inversely associated with comorbidity frequency (p=0.040) but directly associated with TP53 mutation (p=0.012) and triple-negative tumor phenotype (p=0.027). E3 was not associated with clinical characteristics, but E4 was associated with low Ki-67 immunoreactivity (p=0.033). The E2/E3 phenotype was directly associated with triple-negative tumors (p=0.044) and heterozygous tumors (p=0.011). Conclusion: The ApoE polymorphism, particularly the presence of the E2 allele in heterozygosity, is associated with TP53 mutation and a more aggressive tumor phenotype. Citation Format: Maria Claudia Luciano, Rosane Sant' Ana, Valeska Lima, Paulo Goberlanio Silva, Clarissa Albuquerquye, Flavio Bitencourt, Maria Julia Bezerra, Francisca Fernanda Oliveira, José Fernando De Moura, Isabelle Joyce Fernandes, Fernanda Leite. ApoE polymorphism is associated with aggressive tumor phenotypes for breast cancer patients [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-15-02.

Abstract PO3-20-09: METACHRONOUS METAPLASTIC BREAST CARCINOMA IN A 55-YEAR-OLD PATIENT WITH SEROUS OVARIAN CARCINOMA

Abstract Metaplastic breast carcinoma is a rare histologic subtype of breast carcinoma, accounting for only 0.2 to 2% of all breast cancers. It is comprised of a heterogeneous histology involving mesenchymal and epithelial components. Metaplastic breast carcinoma usually harbors a triple-negative phenotype, but carries a worse prognosis compared to other breast cancer subtypes. Due to its unique histopathological and molecular characteristics, there has been limited data on the optimal management of metaplastic breast carcinoma. Moreover, the presence of a secondary breast neoplasm in the background of a prior ovarian carcinoma represents a diagnostic and therapeutic challenge. We report a case of a 55-year-old female with a previous history of serous ovarian carcinoma six years ago, who presented with an enlarging right breast mass. Digital mammography showed a right retro-areolar mass, 5.7 x 4.8 x 5.4 cm, BIRADS 4C. Initial biopsy done showed presence of atypical cells in a background of cystic change. The patient underwent modified radical mastectomy with incision biopsy and frozen section. Final histopathologic diagnosis was consistent with metaplastic breast carcinoma, mixed epithelial and mesenchymal type, Nottingham grade 2, with no lymphovascular invasion identified, pT2N0. Tumor was ER negative, PR negative, Her 2 neu negative, with Ki-67 of 10% on immunohistochemistry. She then underwent adjuvant treatment with 6 cycles of paclitaxel and carboplatin. Six years prior, the patient was likewise diagnosed with high-grade serous ovarian carcinoma. She had total abdominal hysterectomy with bilateral salpingo-oophorectomy and adjuvant chemotherapy with 6 cycles of Paclitaxel and Carboplatin was given. She had recurrence in the paraaortic lymph node after 3 years and underwent cytoreductive surgery with excision of nodule and hyperthermic intraperitoneal chemotherapy with cisplatin. Currently, the patient has no evidence of disease in the recent positron emission tomography scan, with normal serum CA-125 level. The current standard of care for metaplastic breast carcinoma follows that of triple-negative breast cancer. However, previous literature has shown that metaplastic breast carcinoma is more chemo-refractory compared to triple-negative breast cancer, with more response seen with taxane-based chemotherapy. Due to poor response rates to neoadjuvant chemotherapy, surgical management for early-stage disease is warranted. Targeting molecular alterations is necessary to improve the prognosis of this subtype. Genomic features of homologous recombination deficiency were also found to be more prevalent in metaplastic breast cancer, thus genomic testing is warranted, especially in the setting of a prior history of ovarian carcinoma. Citation Format: Raye Angeli Abella, Carlos Dy. METACHRONOUS METAPLASTIC BREAST CARCINOMA IN A 55-YEAR-OLD PATIENT WITH SEROUS OVARIAN CARCINOMA [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-20-09.

Abstract PO4-06-03: A comparative study between RECIST 1.1 using MRI and PERCIST 1.0 using PET/CT to evaluate the response in patients of carcinoma breast receiving neoadjuvant chemotherapy

Abstract Introduction: Breast cancer is the most common cancer in women leading to the major public health problem with an estimated new cases of 2,261,419 (11.7%). Depending upon the stage at presentation, the primary modalities vary. Presently, the primary option for HER2-positive, Triple negative cancers of size more than 2cm or nodal involvement and locally advanced breast cancer is neoadjuvant chemotherapy (NACT). Accurate assessment of the tumor response and residual cancer after undergoing NACT is considered crucial for reducing the number of local recurrence cases and to predict the prognosis as patients who achieve pathological complete response (pCR) after NACT have a longer disease free period and better overall survival as compared to non-responders. In our study we have compared the two commonly used criteria i.e. RECIST 1.0 and PERCIST 1.0. Methodology: 70 patients diagnosed with breast cancer requiring neoadjuvant chemotherapy were recruited in the study conducted in the department of surgical disciplines, AIIMS Delhi from January 2021 to December 2022. Each patient underwent a contrast enhanced MRI breast and whole body FDG PET/CT at the beginning of chemotherapy and after completion of chemotherapy within a stipuated time of two to three weeks. For RECIST 1.1 criteria, response assessment was done using MRI and PERCIST used PET/CT. The response was compared with the gold standard histopathological size. Results: Concordance between the RECIST 1.1 and PERCIST 1.0 response classifications was seen in 27 (39.1%) cases, while discordance was seen in 42 (60.8%). A significant difference was observed between RECIST 1.1 and PERCIST 1.0 (k=0.1309, p&amp;lt; 0.0001) for response classification. Tumor response was upgraded in 32 and downgraded in 2 patients using PERCIST 1.0 as compared to RECIST 1.1. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy to predict pCR along with comparison among different molecular subtypes is shown in the table below. Conclusion: RECIST 1.1 showed high specificity, PPV and accuracy in predicting pathological complete response but tends to underestimate it whereas PERCIST 1.0 showed higher sensitivity with a tendency to overestimate. RECIST 1.1 had a high level of specificity and NPV as compared to the PERCIST 1.0, which showed a high level of sensitivity and PPV. Thus, they act as complementary modalities for predicting pathological complete response. The accuracy to predict pCR was higher for the triple-negative phenotype and Her2 neu enriched with PERCIST 1.0 as compared to RECIST 1.1, while that of PERCIST 1.0 was lower for luminal type. Table. Comparison of RECIST 1.1 and PERCIST 1.0. Citation Format: Anita Dhar, Kanika Sharma. A comparative study between RECIST 1.1 using MRI and PERCIST 1.0 using PET/CT to evaluate the response in patients of carcinoma breast receiving neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-06-03.

Abstract PO5-27-12: TALL CELL CARCINOMA WITH REVERSED POLARITY: A RARE SUBTYPE OF INVASIVE BREAST CARCINOMA WITH UNUSUAL ONCOGENIC DRIVER MUTATION R132C IN IDH1 GENE

Abstract Introduction: Tall cell carcinoma with reversed polarity (TCCRP) is a rare subtype of invasive breast carcinoma with a distinguishing morphogical feature, which is the predilection of nuclei to polarize to the apical pole of tall columnar epithelial cells. These tumours are most commonly associated with IDH2 p.Arg172 hotspot mutations. All reported cases of TCCRP affected women ranging from 39 to 89 years (mean age of 64 years). The tumours presented as a mammographic or palpable mass, only rarely associated with axillary lymph node metastases. TCCRP are usually associated with an indolent clinical course and a favourable prognosis. Morphologically, TCCRP is composed of circumscribed nests of epithelial cells often exhibiting delicate fibrovascular cores, conveying a solid papillary pattern. True papillae and cystic structures containing colloid-like material may be observed in some cases. The tumour cells are tall and columnar, with abundant eosinophilic cytoplasm, containing bland, round to ovoid nuclei disposed at the apical pole of the columnar epithelial cells. Mitotic figures are rare. Most TCCRPs exhibit a triple-negative phenotype and a low (&amp;lt; 20%) Ki-67 proliferation index. Molecular features of TCCRP comprise IDH2 p.Arg172 hotspot mutations, reported in about 84% of the cases studied, as well as PIK3CA missense mutations, identified in about 68% of these tumours. Only one case of TCCRP was associated with IDH1 gene mutations according to the literature. Case report: A 62 year old woman presented with a palpable mass and no axillary adenopathy was identified. Hematoxylin-eosin (HE) stain showed an invasive breast carcinoma, with epithelial tumour cells arranged in a solid and papillary pattern with thin fibrovascular cores. Neoplastic cells are tall and columnar, with abundant eosinophilic cytoplasm and round to ovoid nuclei, exhibiting no pleomorphism and disposed in the apical pole of the cells. Mitotic figures were not detected. Considering the highly suggestive morphology on HE stain, biopsy sample was sent for molecular analysis by next generation sequencing (NGS). Results and discussion: Molecular analysis by NGS using the TruSight Oncology 500 panel (Illumina) revealed the presence of the oncogenic mutations R132C and H1047R in IDH1 and PIK3CA genes, respectively. Contrary to what occurs in almost all cases of Tall cell carcinoma with reversed polarity (TCCRP), in which an oncogenic mutation is described in codon R172 of the IDH2 gene, in this case a mutation was observed in the IDH1 gene. Such a mutation has been described in only one case diagnosed with TCCRP according to the literature, this being the second reported case. Conclusion: This case report aims to warn of the possibility that other driver mutations may be associated with the diagnosis of TCCRP, such as IDH1 R132 and not just IDH2 R172, and that a comprehensive testing approach of the IDH1/2 genes might be more accurate in these cases. Citation Format: Karla Prigenzi, Luiz Gustavo Ferreira Cortes, Paulo Vidal Campregher, João Bosco de Oliveira Filho, Nestor Andrade Piva. TALL CELL CARCINOMA WITH REVERSED POLARITY: A RARE SUBTYPE OF INVASIVE BREAST CARCINOMA WITH UNUSUAL ONCOGENIC DRIVER MUTATION R132C IN IDH1 GENE [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-27-12.

Abstract A065: Single cell transcriptomics reveals putative tumor promoting subpopulation in Brca1 mutant breast cancer mouse model

Abstract Women with BRCA1 (B1) mutations have an exceptionally high risk of developing breast cancer. The only effective preventive strategy currently offered to these women is the life altering prophylactic mastectomy. Considering the limited treatment options available, it is critical that new preventive strategies be identified. Design of such strategies requires an understanding of early events in the breast cells that drive tumorigenesis. B1 heterozygous mouse models can help us identify these early changes however, despite the well-established association between B1 heterozygosity and cancer predisposition in humans, there are currently no such B1 mouse models that faithfully recapitulate this high risk of tumor formation. We have now established a mouse model that induces mammary tumors in B1 heterozygous (Brca1wt/flx,Trp53flx/flx,K14cre) mice upon replication stress (RS). Our approach is based on our published work that reveals haploinsufficiency for RS suppression in B1 heterozygous cells. We find that increasing RS in B1 heterozygous mice results in accelerated mammary tumorigenesis. RS in this mouse model was delivered by injecting DNA-adduct forming 4-nitroquinoline-1-oxide (4NQO) via mammary intraductal injections over a course of 4 weeks. RS served as an efficient and abnormally rapid driver of tumor formation (30 days post completion of injection regimen) in B1 heterozygous mice. B1 heterozygous mice formed mammary adenocarcinoma. These tumors exhibit a triple negative breast cancer phenotype similar to that found in human BRCA1 mutant breast cancer. Our scRNAseq-based analysis of 42,000 cells from mouse mammary tissue collected at different time points during tumorigenesis has identified early transcriptomic changes that occur in different mammary cell types (e.g., luminal and basal) as they respond to RS. We find that in response to RS, a population of trans-differentiated cells accumulates in the mammary tissue. This population is bi-potent (expresses both luminal progenitor and basal epithelial markers), is specifically enriched in Brca1 heterozygous mammary tissue and expresses certain prognostic markers with a strong correlation to poor outcome in human breast cancer. This population is also enriched for proliferation markers. We suspect that this transdifferentiated population, which is primarily enriched in B1 heterozygous mammary tissue undergoing RS, marks the earliest cancer promoting cell population. Finally, pseudotime reconstruction-based lineage analysis reveals that alveolar luminal progenitor cells are the most likely cell of origin for this putative tumor promoting cell population in the breast. Altogether, our integrative approach reveals that B1 heterozygosity in combination with RS leads to accumulation and proliferation of a specific mammary cell population with a unique transcriptomic profile, that contributes to breast tumorigenesis. Identification of such early drivers is critical for the design of effective preventive and therapeutic strategies for women with BRCA1 mutation. Citation Format: Shailja Pathania, Joshua Rivera, Stevension Tran, Carman Man Chung Li, Joan Brugge, Kourosh Zarringhalam. Single cell transcriptomics reveals putative tumor promoting subpopulation in Brca1 mutant breast cancer mouse model [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr A065.

Inhibition of NF-κB signalling pathway by methanol extract of fruit pericarp of Garcinia gummi-gutta in inflammatory breast cancer with triple negative phenotype

Inhibition of NF-κB signalling pathway by methanol extract of fruit pericarp of Garcinia gummi-gutta in inflammatory breast cancer with triple negative phenotype

Clinicopathological features associated with CD44 and CD63 expression in breast cancer.

CD44 is a cell-surface transmembrane glycoprotein that participates in the regulation of many cellular processes, including cell division, adhesion, migration and stem-like characteristics. CD63 is involved in the exocytosis process. To evaluate the relationship between CD44 and CD63 expression and clinicopathological features, including tumor-infiltrating lymphocytes (TILs), phosphoinositide 3-kinase (PIK3CA) mutation and survival. CD44 and CD63 were stained in samples from 101 breast cancer cases from Peruvian women. Median age was 52 years, most were most were grade-3 (68%), estrogen receptor (ER)+ (64%) and stage II-III (92%). Median ki67 was 30%, median stromal TIL was 30% and PIK3CA mutation was found in 49%. Longer survival was associated with earlier stages (p = 0.016), lower ki67 (p = 0.023), ER+ (p = 0.034), luminal phenotype (p = 0.029) and recurrence (p < 0.001). CD44 was classified as high cell density staining in 57% and high intensity in 55%. High CD44 density was associated with younger age (p = 0.043), triple-negative phenotype (p = 0.035) and shorter survival (p = 0.005). High CD44 expression was associated with short survival (p = 0.005). High CD63 cell density was found in 56% of cases and was associated with ER-positive (p = 0.045), low TIL levels (p = 0.007), Luminal-A (p = 0.015) and low CD44 intensity (p = 0.032). CD44 expression was associated with aggressive features and low CD63 density staining.