Invasive Ductal Cancer Research Articles

Long-term outcome of invasive pure micropapillary breast cancer compared with invasive mixed micropapillary and invasive ductal breast cancer: a matched retrospective study.

Data on the prognostic impact of the micropapillary component in breast cancer are limited. The purpose of this study was to investigate the clinicopathological characteristics and long-term outcomes of pure and mixed invasive micropapillary breast cancer (IMPC) patients compared to invasive ductal cancer (IDC) patients. This retrospective study analysed all IMPC and IDC patients treated at the European Institute of Oncology (IEO) between 1997 and 2019. The overall cohort of IMPC patients was divided in two groups, pure and mixed IMPC. Each patient with mixed or pure IMPC was matched with one patient with IDC, based on year of surgery, age, pT, pN, and molecular subtype. A total of 30,115 IDC, 120 pure IMPC and 150 mixed IMPC patients were considered eligible. Compared to IDC, pure and mixed IMPC patients presented a higher rate of locally advanced disease (pT2-T3, pN2-N3), vascular invasion, and Luminal B subtype. After matching, pure and mixed IMPC showed a significant higher rate of vascular invasion compared to IDC patients (p < 0.001). Invasive disease-free survival was better in IDC compared to pure IMPC patients (p = 0.11). Long-term overall survival was significantly worse in pure IMPC group compared to IDC group (p = 0.004), being instead similar between mixed IMPC vs matched IDC (p = 0.07). These real-world data reported the worse prognosis of pure IMPC compared to IDC, highlighting the peculiar prognostic value of the micropapillary subtype itself in the decision-making process of IMPC management. An accurate pre-surgical diagnostic evaluation and a multidisciplinary approach are pivotal to best personalize its treatment.

Preoperative Differentiation of HER2-Zero and HER2-Low from HER2-Positive Invasive Ductal Breast Cancers Using BI-RADS MRI Features and Machine Learning Modeling.

Accurate determination of human epidermal growth factor receptor 2 (HER2) is important for choosing optimal HER2 targeting treatment strategies. HER2-low is currently considered HER2-negative, but patients may be eligible to receive new anti-HER2 drug conjugates. To use breast MRI BI-RADS features for classifying three HER2 levels, first to distinguish HER2-zero from HER2-low/positive (Task-1), and then to distinguish HER2-low from HER2-positive (Task-2). Retrospective. 621 invasive ductal cancer, 245 HER2-zero, 191 HER2-low, and 185 HER2-positive. For Task-1, 488 cases for training and 133 for testing. For Task-2, 294 cases for training and 82 for testing. 3.0 T; 3D T1-weighted DCE, short time inversion recovery T2, and single-shot EPI DWI. Pathological information and BI-RADS features were compared. Random Forest was used to select MRI features, and then four machine learning (ML) algorithms: decision tree (DT), support vector machine (SVM), k-nearest neighbors (k-NN), and artificial neural nets (ANN), were applied to build models. Chi-square test, one-way analysis of variance, and Kruskal-Wallis test were performed. The P values <0.05 were considered statistically significant. For ML models, the generated probability was used to construct the ROC curves. Peritumoral edema, the presence of multiple lesions and non-mass enhancement (NME) showed significant differences. For distinguishing HER2-zero from non-zero (low + positive), multiple lesions, edema, margin, and tumor size were selected, and the k-NN model achieved the highest AUC of 0.86 in the training set and 0.79 in the testing set. For differentiating HER2-low from HER2-positive, multiple lesions, edema, and margin were selected, and the DT model achieved the highest AUC of 0.79 in the training set and 0.69 in the testing set. BI-RADS features read by radiologists from preoperative MRI can be analyzed using more sophisticated feature selection and ML algorithms to build models for the classification of HER2 status and identify HER2-low. Stage 2.

PET/CT with &lt;sup&gt;68&lt;/sup&gt;Ga-FAPI in the Diagnosis of Cancer of Unknown Primary Localization. Clinical Case

Purpose: Analysis of a clinical case of detection the primary focus in a patient with metastatic liver damage from cancer of unknown primary localization using PET/CT with 68Ga-FAPI. Material and methods: A patient with metastatic liver damage from CUP underwent a set of diagnostic methods, according to the results of which the primary focus was not detected. PET/CT with 68Ga-FAPI revealed the primary focus, which was localize in the left breast and did not accumulate 18F-FDG. According to mammography, the formation in the left breast was regard as benign changes (BI-RADS-2). According to the results of histological examination, the node in the left breast is invasive ductal cancer. Conclusion: PET/CT with 68Ga-FAPI can potentially surpass PET/CT with 18F-FDG in the detection of primary tumors in metastases from cancer of unknown primary localization.

Efficacy of Single-Agent Chemotherapy in Endocrine Therapy-Refractory Metastatic Invasive Lobular Carcinoma.

Hormone receptor (HR)-positive, HER2-negative metastatic invasive lobular breast cancer (mILC) is distinct from invasive ductal cancer (IDC) in clinicopathologic and molecular characteristics, impacting its response to systemic therapy. While endocrine therapy (ET) combined with targeted therapies has shown efficacy in ET-sensitive mILC, data on chemotherapy in ET-refractory mILC remain limited. We investigated the efficacy of single-agent capecitabine (CAP) versus taxanes (TAX) in ET-refractory HR+ HER2-negative patients with mILC. Using data from the MD Anderson prospectively collected breast cancer database, we identified patients with HR+ HER2-negative mILC who received prior ET and first-time chemotherapy in the metastatic setting. We compared outcomes between 173 CAP-treated and 96 TAX-treated patients. CAP-treated patients had significantly better median progression-free survival (PFS) than TAX-treated patients (8.8 vs 5.0 months, HR 0.63, P < .001). Overall survival (OS) did not differ significantly between the groups (42.7 vs 36.6 months for CAP vs TAX, respectively, HR 0.84, P = .241). Multivariate analyses for PFS and OS revealed better outcomes in subjects with fewer metastatic sites and those exposed to more lines of ET. Additionally, Black patients showed worse OS outcomes compared to White patients (HR 2.46; P = .001). In ET-refractory HR+ HER2-negative mILC, single-agent CAP demonstrated superior PFS compared to TAX. Our findings highlight the potential benefit of CAP in this patient subset, warranting further investigation through prospective trials.

Osteoid containing breast masses: A rad-path correlation

Objectives: Breast cancer is very common, of which the most common subtype is invasive ductal cancer (IDC). However, there are some rare types that also occur and manifest radiologically in a different manner. Our article aims to emphasize a rare type of breast neoplasm, which shows osteoid matrix on pathology, and to correlate their imaging findings, thus enabling differentiation from usual carcinoma and aiding in further pathology typing. Material and Methods: A retrospective audit of breast masses with osteoid matrix was done from 2008 to 2021. The cases were retrieved from pathology archives. Twenty-five such cases were found with histopathology reports mentioning the osteoid matrix. Eight patients from these 25 had pre-operative mammograms as well as histopathology available for review. We evaluated these with mammograms with multiple parameters. The project was approved by the Institutional Ethics Committee. Waiver of consent was obtained since there was no direct contact between the researcher and the participants. Results: Most cases of eccentric coarse calcification seen on mammography showed type IV matrix, in turn meaning that these cases had mature bone formation with tumor cell rimming type on histopathology. Three tumors produced an osteoid matrix in our study, namely, Metaplastic carcinoma, primary osteosarcoma, and malignant phyllodes tumor. Coarse calcification mostly indicates metaplastic carcinoma with osteosarcoma element. The preoperative diagnosis can guide pathology sampling. Conclusion: When eccentric, large, and coarse calcifications are visible within a mass on a mammogram, it raises suspicion of mature bone formation with tumor cell rimming within the tumor matrix.

Lobular-Like Features and Outcomes of Mixed Invasive Ductolobular Breast Cancer (MIDLC): Insights from 54,403 Stage I-III MIDLC Patients.

Mixed invasive ductolobular breast cancer (MIDLC) is a rare histological subtype of breast cancer (BC), with components of both invasive ductal cancer (IDC) and invasive lobular cancer (ILC). Its clinicopathological features and outcomes have not been well characterized. The National Cancer Database 2010-2017 was reviewed to identify women with stage I-III BCs. Univariate analysis was performed using Chi-square or Wilcoxon rank-sum tests and multivariable analysis with logistic regression to predict surgical decisions. Survival was assessed using multivariable Cox proportional hazards regression analysis. We identified 955,828 women with stage I-III BCs (5.7% MIDLC, 10.3% ILC, and 84.0% IDC). MIDLC was more like ILC than IDC in terms of multicentricity (14.2% MIDLC, 13.0% ILC, 10.0% IDC), hormone receptor positivity (96.6% MIDLC, 98.2% ILC, 81.2% IDC), and use of neoadjuvant chemotherapy (NAC; 5.8% MIDLC, 5.2% ILC, 10.8% IDC). 744,607 women underwent upfront surgery. The mastectomy rates were 42.3% for MIDLC, 46.5% for ILC, and 33.3% for IDC (all p<0.001). With 5.5 years of median follow-up, the adjusted overall survival in the upfront surgery hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) biological subgroup was better in MIDLC (hazard ratio 0.88, p<0.001) and ILC (hazard ratio 0.91, p<0.001) than in IDC. Like ILC, MIDLC also had a lower pathological complete response to NAC than IDC (12.3% MIDLC, 7.3% ILC, 28.6% IDC). MIDLC displays a mixed pattern of characteristics favoring features of ILC compared with IDC, with favorable 5-year overall survival compared with IDC within the HR+/HER2- subtype who underwent upfront surgery.

Prognosis of squamous cell carcinoma of the breast by biological subtypes and the efficacy of radiotherapy: The Japanese Breast Cancer Registry analysis.

561 Background: Primary squamous cell carcinoma (SCC) of the breast is a rare disease, accounting for about 0.1% of all breast cancers. We aimed to determine the clinical features and prognosis of breast SCC, and the effect of radiotherapy by biological subtypes using the Japanese Breast Cancer Registry. Methods: We conducted a matched-pair analysis of 350,977 breast cancer patients with SCC or invasive ductal cancer (IDC) in the Japanese Breast Cancer Registry between 2004 and 2014. Inclusion criteria were female breast cancer patients who underwent surgery with stage I–III diseases, SCC or IDC, and age ≥ 18. Patients who received preoperative radiotherapy were excluded. We performed 1:1 SCC-IDC exact matching analysis by predominant subtypes in SCC: ER(-) and PgR(-)/HER2(-) or ER(+) and/or PgR(+)/HER2(-). Overall survival (OS), breast cancer-specific survival (BCSS), recurrence-free survival (RFS), and first locoregional or distant metastasis recurrence incidence were compared between IDC and SCC by Kaplan-Meier methods and log-rank test. In-field area recurrence was compared between those who received radiotherapy and those who did not. Results: We included 452 SCC and 182,707 IDC patients for the analysis. SCC patients were more likely to present with advanced stage disease compared to those with IDC. Among SCC patients, 59% was ER(-)/PgR(-)/HER2(-), 19% was ER(+)/PgR(+)/HER2(-), 8% was ER(-)/PgR(-)/HER2(+), 2% was ER(+)/PgR(+)/HER2(+), and 12% was data missing. Ten-year OS, BCS, and RFS rates were 70%, 80%, and 66% in SCC, and 88%, 93%, and 81% in IDC, respectively, and SCC carried a significantly worse prognosis than IDC (all P &lt; 0.001). For exact-matched analysis, 10-year BCS of ER(-)/PgR(-)/HER2(-) SCC patients was significantly worse than IDC (P = 0.02), whereas there were no significant differences between SCC and IDC of ER(+)/PgR(+)/HER2(-) patients in OS, BCS, and RFS. Among patients who received radiotherapy, no difference was found in in-field area recurrence between SCC and IDC in either ER(-)/PgR(-)/HER2(-) or ER(+)/PgR(+)/HER2(-) subtype. Conclusions: SCC of the breast was often diagnosed in an advanced stage and had a worse prognosis than IDC. More than half of them were triple-negative subtype. In the triple-negative subtype, SCC was an independent poor prognostic factor. No significant differences in in-field area recurrence after radiotherapy between SCC and IDC suggested that the effect of radiotherapy on local control for SCC was similar to IDC.

Impact of early testing and analysis of germline genetic mutation patterns in patients with breast cancer: A single institution experience.

10613 Background: Approximately 3% of patients with breast cancer have a pathogenic or likely pathogenic variant (mutation) in a high-risk breast cancer gene, such as BRCA1, BRCA2and PALB2, which increases breast cancer risk more than fourfold. Approximately 3% have a germline mutation in a moderate-penetrance breast cancer gene, such as ATM or CHEK2, which confers a two- to threefold increased risk of breast cancer. Methods: In 2020 we started offering germline genetic testing to all newly diagnosed breast cancer patients at the time of diagnosis irrespective of their family history. Our objectives included the following: Prevalence of mutations in breast cancer patients treated at our institution. Germline mutations in patients with Ductal carcinoma in situ (DCIS). To identify if early universal germline testing affected the surgical modality. Results: A total of 525 patients were seen in the oncology clinic from January 2020 to December 2022 with a breast cancer diagnosis. The median age of diagnosis is 66 (32-91) years. Invasive ductal cancer (IDC 66 %) was the most common subtype, followed by DCIS (18%) (Table 1). Most patients had estrogen-positive cancer (82% vs. 18%), and approximately 13% had HER2-positive disease (61% HER2 low). Mutation in CHEK2 (9 patients) was our cohort's most common pathogenic mutation, followed by BRCA1 (6 patients) and MUYTH (6 patients) genes. Predominant germline mutations were identified in patients with IDC, followed by DCIS. One patient with a pure mucinous subtype had a germline pathogenic mutation (RECQL4 gene). We identified a higher percentage of pathogenic breast cancer-related mutations in patients above 60 years (63% vs. 37%) and all CHEK2 mutations were in patients above 60. Out of 41 patients with pathogenic mutations, 17 underwent a partial mastectomy, 12 had a bilateral mastectomy, and two had a unilateral mastectomy. All patients with BRCA1/2 mutation chose bilateral mastectomy, and all patients with a CHEK2 mutation underwent a partial mastectomy. Several variants of unknown significance (VUS) mutations were identified, and they followed a similar pattern, being more common in patients with IDC. VUS mutations in the ATM gene were the most reported abnormality. Conclusions: Pathogenic mutation in the CHEK2 gene is more prevalent, and we hypothesize that this finding could be related to the demographic population treated in our institution. Also, CHEK2 mutation was only identified in patients older than 60, which argues for more testing in patients in this age group. Approximately 9% of all IDC patients had a germline mutation compared to 4.2 % in patients with DCIS. Our review identifies that patients with BRCA1/2 mutations tend to undergo prophylactic mastectomy, and early testing likely impacted this decision. From our study, we believe that germline genetic testing should be offered to all breast cancer patients.

Comparison of breast cancer patients over the age of 70 and under the age of 35

Introduction: Although breast cancer is a type of cancer that is mainly seen in advanced ages, its incidence is increasing in early ages in developing countries. While advanced age may create limitations in treatment due to the person’s functional capacity and low life expectancy, treatments may be exaggerated at a young age due to the long-life expectancy and expectations from life. In this study, we aimed to examine possible differences in approach in two different age groups diagnosed with breast cancer. Materials and Methods: The retrospective study included 123 patients over the age of 70 or under 35 who applied to our hospital’s breast surgery outpatient clinic between 2016 and 2021 and were diagnosed with breast cancer. The patients’ complaints at the outpatient clinic, the histopathological features of the tumor, and the treatments applied were compared. Results: 64 (52%) of the patients included in the study were over 70 years old, and 59 (47%) were under 35 years old. Patients in both groups were applied to the outpatient clinic with a palpable mass. Histopathologically, invasive ductal cancer constituted the majority in both groups. While the elderly patients were lower grade and Estrogen receptor-positive, the younger patients were high grade, Estrogen receptor negative, and mostly triple negative. Conclusions: Regardless of age, breast cancer is a cancer type that can have better results with early diagnosis. While making the treatment decision the decision should be made according to the characteristics of the tumor, comorbidity, and life expectancy, regardless of the patient’s age. Keywords: Breast Neoplasms; Aged; Age Distribution; Therapeutics.

PALB2 germline mutations in a large cohort of Middle Eastern breast-ovarian cancer patients

The PALB2 gene is a breast cancer (BC) and ovarian cancer (OC) predisposition gene involved in the homologous recombination repair pathway. However, the prevalence and clinicopathological association of PALB2 pathogenic/likely pathogenic (PV/LPV) variants in Middle East is still not fully explored. Total 918 BC/OC patients from Saudi Arabia were selected for PALB2 mutations screening using capture sequencing technology. Five heterozygous PVs or LPVs were identified in six cases, accounting for 0.65% (6/918) of entire cohort. Two cases (33.3%) harbored PVs and four cases (66.7%) carried LPVs. Four PVs/LPVs (80%) were frameshift along with one novel splicing LPV (c.2835-2_2835-1delinsTT). One recurrent LPV (c.3425delT: p.L1142fs) was identified in two cases. All six affected carriers have breast cancer diagnosis with median age of 39.5 years (range 34–49 years). Only two cases (33%) have documented family history of cancer. Breast cancer phenotype was invasive ductal unilateral cancer in all cases with 66.7% of hormone receptor positive and 16% of triple negative tumors. Germline PVs/LPVs in the PALB2 gene were observed in low frequency of 0.65% in Saudi BC and/or OC. Our study confirms one recurrent LPV and one novel LPV in Saudi breast cancer patients.

Abstract 6086: PALB2 germline mutations in a large cohort Middle Eastern breast-ovarian cancer patients

Abstract Background: The PALB2 gene encoding protein is involved in the homologous recombination repair pathway and plays an important role in maintaining genomic integrity. PALB2 heterozygous pathological variants (PV) or likely pathogenic variants (LPV) are associated with increased risk of breast and ovarian cancer. However, the prevalence and clinicopathological association of PALB2 germline PV/LPV in Middle Eastern breast and ovarian cancers is not fully identified. Purpose: We retrospectively screened a cohort of 918 cancer patients (791 breast cancer and 127 ovarian cancer) from Saudi Arabia using targeted capture-based next generation sequencing (NGS) method for PALB2 germline variants regardless the family history of these patients or the presence of other hereditary cancer susceptibility genes mutations. Clinicopathological criteria were also fully analyzed. Results: Five heterozygous PVs or LPVs were identified in six cases, accounting for 0.65% (6/918) of entire cohort. Two cases (33.3%) harbored PVs and four cases (66.7%) carried LPVs. Four PVs/LPVs (80%) were frameshift along with one novel splicing LPV (c.2835-1 C&amp;gt;A). One recurrent LPV (c.3425delT) was identified in two cases. All six affected carriers have breast cancer diagnosis with median age of 39.5 years (range 34-49 years). Only two cases (33%) have documented family history of cancer. Breast cancer phenotype was invasive ductal unilateral cancer in all cases with 66.7% of hormone receptor positive and 16% of triple negative tumors. Conclusion: Germline PVs/LPVs in the PALB2 gene were observed in low frequency of 0.65% in Saudi breast and/or ovarian cancer. Our study confirms one recurrent LPV and one novel LPV in Saudi breast cancer patients. Citation Format: Rong Bu, Abdul K. Sira, Sandeep Parvathareddy, Kaleem Iqbal, Saud Azam, Zeeshan Qadri, Maha Al-Rasheed, Wael Haqawi, Mark Diaz, Ingrid G. Victoria, Khawla S. Al-Kuraya. PALB2 germline mutations in a large cohort Middle Eastern breast-ovarian cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6086.

Excellent results of screening for subsequent breast cancers in long-term survivors of childhood Hodgkin's lymphoma-Results of a population-based study.

Subsequent breast cancer (SBC) represents a major complication in childhood cancer survivors and screening for SBC in survivors after incidental irradiation of breasts is recommended. In this article, we report the results and discuss benefits of SBC screening in female pts treated for Hodgkin's lymphoma (HL) in Slovenia in a period of 45 years. Between 1966 and 2010, 117 females were treated for HL under the age of 19 in Slovenia. One hundred five of them survived for 5 years and were included in our study. They were 3-18 (med. 15) years old at diagnosis and followed for 6-52 (med. 28) years. Eighty-three percent of them had chest RT with a median dose of 30 Gy. Ninety-seven (92%) of 105 pts were regularly followed according to the international guidelines including yearly screening mammography/breast MRI in those who received chest RT. We diagnosed 10 SBCs in eight pts 14-39 (med. 24) years after diagnosis at the age of 28-52 (med. 42) years. At 40 years of follow-up, cumulative incidence of SBCs in females who got chest RT was 15.2%. Seven of eight patients (with 9 SBCs) got chest RT with 24-80 (med. 36) Gy at the age of 12 to 18 (median 17) years. Two patients in this group got bilateral SBC. One patient got invasive SBC after being treated with ChT containing high-dose of anthracyclines without chest RT at the age of 13. All eight invasive SBCs were invasive ductal cancers, HER2 receptors negative, all but one with positive hormonal receptors. Six invasive cancers were of stage T1N0, one T1N1mi, only one, diagnosed before era of screening, was of T2N1. None of 8 pts died of SBC. After introduction of regular breast screening in our female patients, who received chest RT in childhood, all SBCs were of early stage and no patients died of SBC. Survivors of pediatric HL should be informed about the risk of late sequelae of treatment for HL, including SBC. Regular follow-up with breast cancer screening and breast self-examination is of vital importance in those treated with chest RT.

Abstract P4-01-24: Targeting receptor tyrosine kinases in overcoming tamoxifen resistance and dormancy in invasive lobular cancer

Abstract Objective: The molecular hallmark of invasive lobular cancer (ILC) is the loss of E-cadherin, resulting in the unique morphology, low mitotic index and unusual metastatic spread to ovaries, gut, and peritoneum. Patients with ILC face delayed, and higher stage at diagnosis, worse disease-free and overall survival1. The most frustrating challenge is the delayed recurrence, likely due to resistance and induction of dormancy2. Despite these unique features, ILC is lumped with hormone receptor-positive invasive ductal cancers (IDC); consequently, management strategies are based on data from IDC. Hence there is an unmet need to address the unique challenges of ILC. We generated Tamoxifen-resistant (TAMR) ILC cell lines with the aim to study the distinct characteristics, dormancy, differentially activated pathways, and response to drugs targeting such pathways in the resistant cells. Methods: We used MDA-MB-134-VI and SUM44-PE cells to study the effect of tamoxifen in combination with multi-targeted receptor tyrosine kinase inhibitor, Lenvatinib. TAMR cells from both MB-134 and SUM44PE cells were generated by growing them in increasing concentrations of 4-hydroxy tamoxifen (4-HT) up to 500nM, for 6 months. Total RNA from parental and TAMR cells were subjected to RNA-seq. Whole cell extracts were analyzed for specific phospho proteins by Western Blot analysis. Growth kinetics and effect of drugs on cell viability was measured using MTT assay (Roche). Cell migration was measured using Transwell migration assay. Novel engineered 2D and 3D cultures were used to study dormancy and the effect of the drug combination. Orthotopic tumor induction in NSG mice is ongoing to determine the effect of drug combination in vivo. Results: The TAMR cell lines show distinct morphological features, small but significant increase in growth rate (p=0.05) and remarkably higher migration (MB-134TAMR:11.5-fold, p&amp;lt; 0.005 and SUM44TAMR:&amp;gt;100-fold, p&amp;lt; 0.005). The IC50 for tamoxifen increased from 8.1M (MB-134) to 16.8M (MB-134TAMR) and from 11.3 M (SUM44) to 26.6 M (SUM44TAMR). RNA seq analysis revealed enrichment of PI3K-AKT, MAPK, cAMP, Rap1 signaling pathways, ECM-receptor interaction, Focal adhesion, and steroid hormone biosynthesis pathways in the TAMR cells. Upon stimulation by endothelial growth factor, the MB-134TAMR but not the parental cells showed dose dependent increase in phospho-AKT and phospho-MAPK levels. Using novel 2D/3D cultures, we show differential morphologies between IDC (MCF7) cells, MB-134TAMR, and the parental cells. MCF7 and MB-134TAMR cells are more adherent to fibronectin (p&amp;lt; 0.0001), whereas the parental ILC cells are more adherent to COL3A1 (p&amp;lt; 0.0001), a feature observed in dormancy3. Further, the administration of 5 M 4-HT induced a cessation of growth in the parental cell line, with a sub-population of apparent dormant cells. The combination of Lenvatinib (5 M) and 4-HT (7.5 M) synergistically inhibited both the parental cell lines by ~60%. Lenvatinib (5 M) and 4-HT (15 M) inhibited the MB-134TAMR and SUM44TAMR cell lines synergistically by 65% and 45% respectively. In vivo, the growth of MB-134 induced tumors were completely suppressed when 5mg sustained release pellet of TAM citrate was injected in the subscapular region of tumor bearing mice (tumor @100cm3). The results of the combination using in vivo models and 2D/3D cultures will be reported. Conclusion and significance: Lenvatinib with tamoxifen is active and synergistic against parental and TAMR ILC cell lines. Our novel 2D/3D cultures show distinct pattern of growth for ILC cells and a possible induction of a dormant subpopulation upon 4-HT treatment. Overcoming resistance to conventional therapies and preventing induction of dormancy will improve long-term outcomes of patients with ILC. 1. PMID:33641217 2. PMID: 34388695 3. PMID: 35121989 Citation Format: Bhuvaneswari Ramaswamy, Nikhil Pramod, Anagh Kulkarni, Xilal Y. Rima, Eduardo Reátegui, Eswar Shankar, Sarmila Majumder. Targeting receptor tyrosine kinases in overcoming tamoxifen resistance and dormancy in invasive lobular cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-01-24.

Abstract GS1-02: Racial disparity in tumor microenvironment and outcomes in residual breast cancer treated with neoadjuvant chemotherapy

Abstract Background: Black, compared to White women with localized breast cancer have higher mortality and worse distant recurrence free survival (DRFS). This has been attributed to social determinants of health and higher prevalence of triple negative breast cancer (TNBC) in Black compared to White women. Recent studies indicate that racial disparity in outcome is present in patients with estrogen receptor-positive (ER+), but not ER- disease, in particular in patients with residual disease after neoadjuvant chemotherapy (NAC). It has been shown that in some patients NAC may induce pro-metastatic changes in tumor microenvironment, such as increased density of tumor associated macrophages and portals for cancer cell dissemination to distant sites called TMEM doorways (TMEM score). TMEM score correlates with metastasis in patients with ER+/HER2- breast cancer. We hypothesized that racial disparity in DRFS in patients with residual ER+/HER2- disease is due to enhanced pro-metastatic components (macrophage and TMEM doorway density) in the tumor microenvironment post-chemotherapy in Black compared to White women. Methods: We performed a retrospective, multi-institutional study of TMEM score and macrophage density in the residual disease after NAC from 196 patients diagnosed with unilateral invasive ductal cancer of breast between 2004 and 2014. 99 patients self-identified as Black and 97 as White. TMEM doorways were visualized by triple immunohistochemistry for macrophages (CD68), tumor cells (panMena), and endothelial cells (CD31). The evaluation of TMEM score and macrophage density was done using automated image analysis. Tumor characteristics and patient survival were compared between Black and White patients. The relationship between TMEM score, macrophage density and DRFS was examined by log-rank test and multivariate Cox regression model. The covariates in Cox model included TMEM score, age (continuous), race (Black vs White), surgery type (mastectomy vs lumpectomy), tumor stage (T3 vs T1; T2 vs T1), lymph node status (positive vs negative), and tumor subtype (triple negative [TN] vs ER+/HER2-; other vs ER+/HER2-). Results: Black compared to White women were more likely to develop distant recurrence (49.5% vs 34%, p=0.04), receive mastectomy (69.7% vs 51.5%, p=0.014), and have higher grade (p=0.001). Tumors from Black patients had more macrophages and a higher TMEM score in the entire cohort (p=0.004; p=0.001 respectively) and in the ER+/HER2- subset (p=0.008; p=0.008 respectively), but not in the TNBC subset. High TMEM score was associated with worse DRFS in all patients (p=0.004) and in the ER+/HER2- (p=0.03), but not in TNBC. In multivariate Cox model, TMEM score was an independent prognostic factor in the entire cohort (HR, 1.92; 95%CI, 1.15-3.22; p=0.01) and trended towards significance in ER+/HER2- disease (HR, 2.13; 95%CI, 0.96-4.71; p=0.06). TN, compared to ER+/HER2- cancers had higher TMEM score (p=0.01), and macrophage density (p=0.001). Conclusion: Racial disparity in outcome in patients with localized breast cancer may be due to a more pronounced pro-metastatic response to chemotherapy in Black, compared to White patients with ER+/HER2- disease. Thus, higher prevalence of TNBC in Black patients may not be the controlling factor in racial disparity. Citation Format: Burcu Karadal, Gina Kim, Ved Sharma, Jessica Pastoriza, Isabelle Oktay, Yu Lin, Xianjun Ye, Jiyue Qin, Esther Cheng, Nurfiza Ladak, John Condeelis, Esther Adler, Paula Ginter, Timothy D’Alfonso, Xiaonan Xue, David Enterberg, Joseph Sparano, Maja Oktay. Racial disparity in tumor microenvironment and outcomes in residual breast cancer treated with neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr GS1-02.

HER2-positive invasive lobular carcinoma: a rare breast cancer which may not necessarily require anti-HER2 therapy. A population-based study.

HER2-positive (HER2 +) invasive lobular breast cancer (ILC) is rare and poorly characterised. In particular, patient outcomes compared to those associated with HER2 + invasive ductal cancer (IDC) and HER2-negative (HER2-) ILC, as well as the benefits of anti-HER2 therapy, are not well established. We analysed the data from the Côte d'Or Registry of Breast and Gynaecological Cancers (France) for all patients diagnosed with early-stage HER2 + ILC (62 cases), HER2 + IDC (833 cases) and HER2- ILC (685 cases) between 1998 and 2015 to compare overall and disease-free survival (OS and DFS) between these groups in correlation with anti-HER2 therapy. ILCs were associated with older age, larger tumours, lower histological grades, higher hormonal receptor positivity rates and multifocality, and more common endocrine therapy. OS and DFS between the three groups did not differ. We found that anti-HER2 therapy was associated with a survival benefit in patients with HER2 + IDC. In contrast, the survival of HER2 + ILC patients was not improved by anti-HER2 treatment, remaining close to that of HER2- ILC patients. HER2 + ILC seems not to be associated with better outcomes than HER2 + IDC but may not differ from HER2- ILC in terms of survival.

Diagnostic Contrast-Enhanced Mammography Performed Immediately Prior to Same-Day Biopsy: An Analysis of Index Lesion Enhancement Compared to Histopathology and Follow-up in Patients With Suspicious Ultrasound Findings.

To measure the diagnostic performance of contrast-enhanced mammography (CEM) for the index lesion when it is performed the same day prior to biopsy in patients with suspicious findings at US. This IRB-approved retrospective study compared radiologist original reports of the presence or absence of index lesion enhancement on CEM to biopsy results and follow-up. The most suspicious lesion or the larger of equally suspicious lesions recommended for biopsy by US after a diagnostic workup including mammography was considered the index lesion. CEM exams were performed the same day, immediately prior to the scheduled biopsy, as requested by the radiologist recommending the biopsy. Numeric variables were summarized with means and standard deviations, or medians and the minimum and maximum, where appropriate. Biopsy demonstrated cancer in 64.7% (200/309) of index lesions. Of these, 197/200 demonstrated enhancement for a sensitivity of 98.5% (95% CI: 95.7%-99.7%) (197/200) and the negative predictive value of CEM for non-enhancing index lesions was 95.1% (58/61; 95% CI: 86.1%-98.4%). The three false negative exams were two grade 1 ER+ HER2- invasive ductal cancers that were 6 mm and 7 mm in size, and a 3-mm grade 2 ductal carcinoma in situ in a complex cystic and solid mass. False positive exams made up 20.6% (51/248) of the positive exams. Diagnostic CEM showed high sensitivity and specificity for cancer in lesions with suspicious US findings. CEM may reduce the need for some biopsies, and negative CEM may support a true negative biopsy result.

Roles of Different Radiations in Treatment of Breast Cancer

The review aimed to describe the role of radiations in treatment of breast cancer. The review also describe that which type of radiation is used to treat different stages of breast cancer i.e, metastatic stage, advance stage and early stage of breast cancer. The radiation therapy plays a significant role in the treatment of breast cancer. The treatment delivery methods are considerably changed in the recent decades. The concept of using radiotherapy for the treatment of breast cancer has remained equally important for oncologists throughout the years still research has been going on to make these radiotherapy sessions more and more convenient for the patients. The combination of breast conservation surgery an APBI can result in survival without having any other health related issues for other nearby organs. Recent findings have reported about incorporation of APBI into clinical usage. APBI should be used for patients with low risk of ductal carcinoma or in case of first stage of invasive ductal cancer which has prominent margins for the excision, and where the estrogen receptor positivity is clear. Radiation therapy is effectively used for the treatment and management of loco regionally advanced and distant metastatic disease. There is research going on to find most appropriate technique in which convenient and protected procedure is used for patients to avoid any side effects. New and advanced techniques are used to limit radiation related toxicity.

The Effect of Dynamic Contrast Magnetic Resonance Imaging (DCE-MRI) in the Diagnosis of Breast Cancer Cases

Aim: The aim of this study is to investigate the effect of dynamic contrast magnetic resonance imaging (DCE-MRI) in the diagnosis of breast cancer (BC) and to compare it with ultrasonography (USG).&#x0D; Materials and Methods: In our study, 78 patients who underwent preoperative DCE-MRI and USG in our diagnosis center in TRNC between 2009 and 2022 and were diagnosed with BC histopathologically were investigated retrospectively.Findings obtained according to the BI-RADS classification in both methods, detection of BC, detection of tumor foci (TF) in multiple tumors (multicentric and multifocal tumors) (MT), correct diagnosis rates(CDR)s in invasive lobular cancers (ILC) and invasive ductal cancers (IDC) were compared and the results were evaluated statistically.&#x0D; Results: The mean age of the ILC and MT cases was found to be significantly lower than the IDC and unifocal tumor(UF) cases (p

Do non-classic invasive lobular carcinomas derive a benefit from neoadjuvant chemotherapy?

Invasive lobular breast cancers (ILCs) respond poorly to neoadjuvant chemotherapy (NAC). The degree of benefit of NAC among non-classic ILC (NC-ILC) variants compared with classic ILCs (C-ILCs) is unknown. Consecutive patients with Stage I-III ILC treated from 2003 to 2019 with NAC and surgery were identified, and grouped as C-ILC or NC-ILC as per the original surgical pathology report, with pathologist (A.G.) review performed if original categorization was unclear. A subset of similarly treated invasive ductal cancers (IDCs) was identified for comparison. Clinicopathologic characteristics and pathologic complete response (pCR) rates were evaluated. Of 145 patients with ILC, 101 (70%) were C-ILC and 44 (30%) were NC-ILC (IDC cohort: 1157 patients). ILC patients were older, more often cT3/T4 and cN2/N3, and less often high-grade compared to IDC patients. Those with NC-ILC were less often ER+/HER2- (55% versus 93%), and more often HER2 + (25% versus 7%) and TN (21% versus 0%, all p < 0.001). Breast pCR was more common among NC-ILC, but most frequent in IDC. Nodal pCR rates were also lowest among C-ILC patients, but similar among NC-ILC and IDC patients. On multivariable analysis, C-ILC (OR 0.09) and LVI (OR 0.51) were predictive of lack of breast pCR; non-ER+/HER2- subtypes and breast pCR were predictive of nodal pCR. When our analysis was repeated with patients stratified by receptor subtype, histology was not independently predictive of either breast or nodal pCR. NC-ILC patients were significantly more likely to achieve breast and nodal pCR compared with C-ILC patients, but when stratified by subtype, histology was not independently predictive of breast or nodal pCR.

A Prospective, Multicenter, Randomized, Double-Arm Trial to Determine the Impact of the Perimeter B-Series Optical Coherence Tomography and Artificial Intelligence System on Positive Margin Rates in Breast Conservation Surgery

Introduction: Optical coherence tomography (OCT) enables high-resolution, real-time tissue-imaging up to 2mm deep. The Perimeter B-Series OCT System combines wide field-OCT (WF-OCT) with artificial intelligence (AI) to help identify areas suspicious for cancer. The objective of this trial is to assess adjunctive use of WF-OCT and standard care (SOC) in identifying unaddressed positive margins (UPMs). Methods: Prospective, multicenter, randomized, double-arm trial in up to 309 adult women undergoing breast conservation surgery (BCS) for biopsy-confirmed Stage 0-III invasive ductal cancer and/or DCIS, including post-neoadjuvant therapy (NCT05113927). After BCS and SOC intraoperative margin assessment participants will be randomized (2:1) to device or SOC arm. Controls may undergo intraoperative pathology or frozen section analysis, per routine. WF-OCT will be done on all device arm specimens, with an opportunity to excise tissue from the cavity post-analysis, up to 6 total shaves and 2 in each orientation. Results: The study hypothesis is that WF-OCT & AI use will reduce the proportion of subjects with UPM. The primary endpoint is occurrence of ≥1 UPM for a subject; the secondary endpoint is the number of UPMs per subject. Safety includes Adverse Events; false-positive shaves/subject; and BREAST-Q Satisfaction with Breasts. Other outcomes are total excised tissue volume, initial and all procedures; and margin-level effectiveness (sensitivity, specificity, NPV and PPV). Conclusion: Primary endpoint was powered assuming a 15% UPM rate, 90% power, 2:1 allocation, and 10% loss of subjects. Both primary and secondary effectiveness endpoints are based on within-subject comparison of the 2 treatments in the device arm (SOC+WF-OCT).