Invasive Ductal Carcinoma Group Research Articles

The Association of Neuroendocrine Differentiation with MicroRNA 21 and MicroRNA let7f Expression and the Clinicopathological Parameters in Primary Invasive Breast Carcinomas with Neuroendocrine Features.

MiRNAs have been reported as biomarkers with diagnostic, prognostic, and predictive value for many different diseases. Therapeutic agents targeting some miRNAs are currently being developed. We aimed to compare BC-NEFs (carcinoma of the breast with neuroendocrine features) with IDC (invasive ductal carcinoma) cases without neuroendocrine features in terms of the level of miRNA expression known to show the oncogenic (miR-21) and tumor-suppressor effects (miR-let7f) and the clinicopathological features. A total of 29 patients with a diagnosis of BC-NEFs (15 cases with neuroendocrine differentiation >50% of the whole section of tumor and 14 cases with neuroendocrine differentiation 10-50% of the tumor) and 30 patients with a diagnosis of IDC (no neuroendocrine differentiation) were retrospectively re-evaluated. Expression levels of miR-21 and miR-let7f were determined by the qRT-PCR method in paraffin tissue blocks. MiR-21 expression was significantly higher in the IDC group than in the group with BC-NEFs. miR-let7f expression was significantly lower in the group with BC-NEFs compared to the IDC group. A high expression level of miR-21 was found to be associated with progesterone receptor (PR) negativity. Our findings show that the presence of NEFs in breast carcinomas makes a significant difference in the expression levels of the investigated oncogenic (miR-21) and tumor-suppressor (miR-let7f) miRNAs. These findings suggest that miRNAs may be a potential biomarker in BC-NEFs and would benefit from targeted therapy.

Abstract PO3-08-11: Association between Histologic Variants and the Results of Multigene Testing in Patients with Hormone Receptor-positive, HER2-negative Invasive Lobular Cancer

Abstract Invasive lobular carcinoma (ILC), which accounts for approximately 5-15% of all breast cancers, can be divided into classic type and various other variants. Multigene testing (MGT) has prognostic value in hormone receptor (HR)-positive, HER2-negative breast cancer. We aimed to investigate the association between the results of MGT and histological variation of ILC. 1582 HR-positive, HER2-negative breast cancer patients treated between January 2014 and December 2022 were reviewed. Patients were divided into three groups; ILC-favorable group, ILC-unfavorable group and invasive ductal carcinoma (IDC) group. The ILC-favorable group consisted of classic and tubulolobular types, while the ILC-unfavorable group included pleomorphic, solid, signet ring cell, florid, and alveolar types according to the reported prognosis of each ILC variant. Among the various types of MGT, the 21-gene assay (OncotypeDX), the 70-gene assay (Mammaprint), and the 12-gene assay (Endopredict) assay were used in clinical setting. The median age of patients was 50 years (range 20-85 years). 75.5% of patients received the 21-gene assay, 12.8% received the 70-gene assay, and 11.6% received the 12-gene assay. The high-risk results in MGT were showed in 7.7% of 155 patients in ILC-favorable group, 26.1% of 23 patients in ILC-unfavorable group, and 20.9% of 1404 patients in IDC group (p-value < 0.001). In the multivariate logistic regression analysis, ILC-favorable group showed significantly lower odds of high-risk results compared to IDC group (OR=0.284, 95% CI; 0.147-0.548), while ILC-unfavorable group did not show any significant difference compared to IDC group (OR=0.797, 95% CI; 0.263-2.411). In comparison to IDC, the variants of ILC with favorable prognosis show lower rates of high-risk results in MGT, while the variants of ILC with poor prognosis do not differ significantly from IDC. For patients who diagnosed the variants of ILC with poor prognosis, MGT could be useful for prognosis prediction or treatment decision-making. Citation Format: Jee Hyun Ahn, Suk Jun Lee, Seung Hye Yang, Jee Ye Kim, Hyung Seok Park, Seung Il Kim, Byeong Woo Park, Seho Park. Association between Histologic Variants and the Results of Multigene Testing in Patients with Hormone Receptor-positive, HER2-negative Invasive Lobular 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 PO3-08-11.

Abstract PO4-08-03: Prognostic Effect of Ductal Carcinoma in Situ in Breast Cancer with BRCA1/2 Mutations

Abstract Abstract Background: Although Breast Cancer Susceptibility Gene (BRCA)-associated invasive breast cancer has been extensively studied, there are few reports on ductal carcinoma in situ (DCIS) in patients with BRCA1/2 mutations. This study aims to evaluate the prognostic effect of DCIS in breast cancer patients with pathologic variants of BRCA1/2 genes. Methods: Retrospective analysis was performed on a prospective cohort of 157 patients who were found positive for BRCA1/2 mutations through genetic testing from August 2003 to January 2022 at Seoul National University Bundang Hospital. Survival outcomes were compared between patients who had both invasive ductal carcinoma (IDC) and DCIS components (IDC-DCIS group, n = 121) and patients who had IDC only (IDC group, n = 36). Cox regression analysis was performed for evaluation of predictive factors for recurrence. Results: Among the 157 patients, 65 (41.4%) patients showed BRCA1 mutations, 90 (57.3%) patients had pathological variants of BRCA2, and 2 (1.3%) patients tested positive for both BRCA1/2 mutations. There was no difference in baseline clinical characteristics between the IDC-DCIS and IDC groups. When pathological features were compared, the IDC-DCIS group was more likely to express positivity in both estrogen receptor (IDC 5 (13.9%) vs. IDC-DCIS 74 (61.2%), P < 0.001) and progesterone receptor status (IDC 5 (13.9%) vs. IDC-DCIS 67 (55.4%), P < 0.001). Tumors in the IDC group were associated with a higher histologic grade (P = 0.004). There was no statistically significant difference in 5-year disease-free survival between the two groups (IDC 83.6% vs. IDC-DCIS 89.3%, P = 0.989). In univariate Cox regression analysis, younger age at diagnosis was a significant predictor for recurrence (hazard ratio (HR) 2.236, P = 0.049); salpingo-oophorectomy showed a risk-reducing effect (HR 0.106, P < 0.001). Further multivariate analysis found only the effect of salpingo-oophorectomy to be prognostic (HR 0.112, P < 0.001). Presence of DCIS was not a risk factor for recurrence in patients with BRCA1/2 mutations (HR 1.006, P = 0.989). Conclusion: BRCA1/2-positive breast cancer with DCIS components is more likely to be hormone receptor-positive and of lower grade compared to patients with IDC only. A tailored approach might be necessary in establishing treatment options for breast cancer patients with BRCA1/2 mutations according to the presence of DCIS. Citation Format: Kyung-Hwak Yoon, Eun-Kyu Kim, Hee-Chul Shin. Prognostic Effect of Ductal Carcinoma in Situ in Breast Cancer with BRCA1/2 Mutations [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 PO4-08-03.

Comparison of long-term outcome between clinically high risk lobular versus ductal breast cancer: a propensity score matched study

Abemaciclib is currently approved for the adjuvant treatment of high-risk, lymph node (LN)-positive, hormone receptor (HR)-positive breast cancer (BC). In a real-world setting the clinicopathologic features of patients potentially eligible for adjuvant abemaciclib remain to be defined. There are conflicting data regarding the biological behavior and long-term outcomes across invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC). In our study we retrospectively assessed the real-world data and long-term outcome of selected high-risk features ILC compared to IDC, according to the MonarchE trial inclusion criteria. We identified 15,071 patients who got surgery at the European Institute of Oncology for a first primary, non-metastatic, HR-positive, HER2-negative BC from 2000 to 2008. 11,981 (79.5%) patients had an IDC and 1524 (10.1%) an ILC. The remaining 1566 patients (10.4%) had either combined ductal and lobular breast cancer or another histological breast cancer subtype. According to the eligibility criteria of the MonarchE study, we identified two high-risk groups, based on high number of positive lymph nodes, large tumor size, or a high cellular proliferation as measured by tumor grade or biomarkers. Patients were matched by propensity score. A total of 2872 (21.3%) patients were selected as clinically high-risk, including 361/1524 ILC (23.7%) and 2511/11,981 IDC (21%). 322 high-risk ILC were matched with similar high-risk IDC. The median follow-up was 13.2 years for survival. In the matched set, invasive disease-free survival (IDFS) (log-rank P=0.09) and overall survival (OS) (log-rank P=0.48) were not statistically significantly different between the two histological groups. For IDC patients, the 5-year and 10-year IDFS rates (95% CI) were 77.7% (72.9-82.2) and 57.3% (51.7-63.1) respectively, compared to the 5-year and 10-year IDFS rates of ILC patients that were 75.5% (70.6-80.2) and 50.7% (45.0-56.6). The 5-year and 10-year distant relapse free survival (DRFS) rates were 80% (75.3-84.2) and65.3% (59.8-70.7) in IDC cohort, compared to the 5-year and the 10-year DRFS rates of 78.7% (74.0-83.1) and 61.5% (55.9-67.1) in the ILC cohort. Such data match the recent outcomes efficacy results of the MonarchE control arm. More patients in the ILC (n=17) than in the IDC group (n=10) developed axillary recurrence. At multivariable analysis, stratified for specific clinical features, age <35 years, pT2-3, axillary involvement with more than 10 positive axillary nodes were found to be predictors of unfavorable IDFS and OS in the overall matched high-risk population. Findings from this matched cohort study reported similar IDFS and DRFS rates for high risk HR positive early BC when compared to the control arm overall IDFS and DRFS rates reported from the MonarchE trial. Our study demonstrated rates of concordant long-term outcome status beyond histologic subtype. These data support an escalation strategy for these two different histological entities when diagnosed with high-risk features. In our dataset approximately 21% rate of high-risk HR positive early BC patients are potentially eligible for adjuvant abemaciclib treatment. Umberto VeronesiFoundation.

A hematological parameter-based model for distinguishing non-puerperal mastitis from invasive ductal carcinoma.

Non-puerperal mastitis (NPM) accounts for approximately 4-5% of all benign breast lesions. Ultrasound is the preferred method for screening breast diseases; however, similarities in imaging results can make it challenging to distinguish NPM from invasive ductal carcinoma (IDC). Our objective was to identify convenient and objective hematological markers to distinguish NPM from IDC. We recruited 89 patients with NPM, 88 with IDC, and 86 with fibroadenoma (FA), and compared their laboratory data at the time of admission. LASSO regression, univariate logistic regression, and multivariate logistic regression were used to screen the parameters for construction of diagnostic models. Receiver operating characteristic curves, calibration curves, and decision curves were constructed to evaluate the accuracy of this model. We found significant differences in routine laboratory data between patients with NPM and IDC, and these indicators were candidate biomarkers for distinguishing between the two diseases. Additionally, we evaluated the ability of some classic hematological markers reported in previous studies to differentiate between NPM and IDC, and the results showed that these indicators are not ideal biomarkers. Furthermore, through rigorous LASSO and logistic regression, we selected age, white blood cell count, and thrombin time to construct a differential diagnostic model that exhibited a high level of discrimination, with an area under the curve of 0.912 in the training set and with 0.851 in the validation set. Furthermore, using the same selection method, we constructed a differential diagnostic model for NPM and FA, which also demonstrated good performance with an area under the curve of 0.862 in the training set and with 0.854 in the validation set. Both of these two models achieved AUCs higher than the AUCs of models built using machine learning methods such as random forest, decision tree, and SVM in both the training and validation sets. Certain laboratory parameters on admission differed significantly between the NPM and IDC groups, and the constructed model was designated as a differential diagnostic marker. Our analysis showed that it has acceptable efficiency in distinguishing NPM from IDC and may be employed as an auxiliary diagnostic tool.

Overexpression of TPL2 may be a predictor of good prognosis in patients with breast invasive ductal carcinoma

The objective of this study was to investigate the clinical significance and roles of tumor progression locus 2 (TPL2) and peptidyl-prolyl cis–trans isomerase 1 (Pin1) in the occurrence and development of breast invasive ductal carcinoma (IDC). Immunohistochemistry was used to detect the expression of TPL2 and Pin1 in human breast tissues, which included normal breast tissues (Normal), tissues with fibrocystic changes (FCC), ductal carcinoma in situ (DCIS), and IDC. The roles of TPL2 and Pin1 in the occurrence and development of IDC, as well as the correlation between their expression levels and clinicopathological parameters, were analyzed. Compared with Normal and FCC groups, the overexpression of TPL2 and Pin1 was significantly increased in DCIS and IDC groups (DCIS vs Normal: P = 0.002/P < 0.001; IDC vs Normal: P = 0.007/P = 0.003; DCIS vs. FCC: P = 0.008/P = 0.004; IDC vs. FCC: P = 0.04/P = 0.043). The expression levels of TPL2 and Pin1 were positively correlated in DCIS and IDC groups (P = 0.001, P = 0.011). In the IDC group, the Ki67 level in the TPL2 overexpression group was significantly lower than that in the TPL2 low expression group (P = 0.02). The TPL2 overexpression rate was significantly higher in IDC with histological grades 1–2 than that in IDC with histological grade 3 (P = 0.029). The TPL2 overexpression rate in IDC with tumor-node-metastasis (TNM) stage I was significantly higher than that in IDC with TNM stages II–III (P = 0.035). We conclude that TPL2 and Pin1 may synergistically promote the occurrence and development of IDC, but TPL2 overexpression may be an early molecular event in IDC development. TPL2 overexpression is significantly related with IDC with lower malignancy or earlier TNM stage, suggesting that the prognosis of IDC patients with TPL2 overexpression may be better and TPL2 overexpression may be a predictor of good prognosis in IDC.

Clinicopathological characteristics and prognosis of triple-negative breast cancer invasive ductal carcinoma with ductal carcinoma in situ.

The purpose of this study is to compare and analyze the clinicopathological characteristics and prognosis of patients with invasive ductal carcinoma coexisting with ductal carcinoma in situ (IDC-DCIS) and invasive ductal carcinoma (IDC) in triple-negative breast cancer (TNBC), and to explore the factors affecting the prognosis, so as to provide new ideas for clinical diagnosis and treatment of these patients. The patients with TNBC underwent surgery in the Department of Breast Surgery of Harbin Medical University Cancer Hospital from October 2012 to December 2018 were retrospectively analyzed and divided into IDC-DCIS group and IDC group. The clinicopathological characteristics and prognosis of the two groups were compared. P < 0.05 was considered statistically significant. A total of 358 patients were enrolled. There were significant differences in age (P = 0.002), family history (P = 0.016), menopausal status (P = 0.003), KI-67% (P < 0.001), lymphovascular invasion (P = 0.010), histologic grade of IDC (P < 0.001) and multifocal (P < 0.001) between the two groups. The disease-free survival (DFS) of the IDC-DCIS group was better than that of the IDC group (the 5-year DFS was 87.9% vs. 82.6%, P = 0.045), but the overall survival (OS) of the two groups was not statistically significant (the 5-year OS was 96.2% vs. 96.0%, P = 0.573). In addition, the coexistence of DCIS (P = 0.030), lymph node pathologic stage (P = 0.001), tumor location (P = 0.011), and adjuvant chemotherapy (P < 0.001) were independent prognostic factors for DFS. In TNBC, the IDC-DCIS group had less invasive biological characteristics. The DFS of the IDC-DCIS group was better than that of the IDC group, but there was no statistical difference in OS between the two groups. In addition, the coexistence of DCIS, lymph node stage, tumor location and adjuvant chemotherapy may be independent prognostic factors for DFS.

Abstract P3-04-08: Comparison Of Cone Beam Breast CT And Breast MRI In Preoperative Assessment Of Primary Breast Cancer Tumor Size

Abstract Comparison Of Cone Beam Breast CT And Breast MRI In Preoperative Assessment Of Primary Breast Cancer Tumor Size Yinan Ji＊1, Geyi Liao＊1, Ningbing Luo2, Yi Jiang1, Xiaoming Liao1, Wei Tang1, Huawei Yang 1. 1Department of Breast Surgery, 2Department of Radiology, Guangxi Medical University Tumor Hospital, Nanning, China Correspondence to: Dr. Huawei Yang, Department of Breast Surgery, Guangxi Medical University Cancer Hospital, 71 Hedi Road, Nanning, Guangxi Zhuang Autonomous Region 530021, P.R. China Email: Lordyhw@163.com ＊Contributed equally Background: Breast cancer is the malignant tumor with the highest incidence among women in China, seriously endangering women’s health. After breast cancer is diagnosed, surgery is one of the primary treatments. Assessing the extent of breast cancer is vitally important to formulate the best surgical option, obtain clear margins while minimizing the volume of removed tissue, and improve the treatment outcome and patient’s quality of life. Currently, breast surgery relies heavily on Breast MRI (bMRI) for preoperative assessment. However, bMRI may overestimate the tumor sizes. bMRI is contraindicated in patients with claustrophobia, metal implants, and allergy to gadolinium contrast medium. In addition, bMRI is generally expensive and time-consuming. Some patients find bMRI less favorable for cost and time concerns. Cone Beam Breast CT (CBBCT) is a new modality using Cone Beam CT technology and iodinated contrast media for true 3D high-resolution imaging of the breast. Our previous studies have proved the feasibility of CBBCT in the preoperative assessment of breast cancer. A large-scale study has been done to further examine the clinical significance of CBBCT in pre-operative assessment compared with bMRI. Methods: 273 female primary breast cancer patients were included in this study. The maximal diameters of the tumors were measured in CBBCT and bMRI images by an experienced radiologist. The differences between the image-measured size and surgical pathology size (gold standard) were calculated as ΔDCT and ΔDMR. ΔD ˃ 5mm was considered an overestimation and ΔD ˂-5mm was considered an underestimation. The absolute values of ΔDCT and ΔDMR were also calculated as ΔDCT_abs and ΔDMR_abs. A Student t-test was used to compare the statistical differences between ΔDCT_abs and ΔDMR_abs. Among ΔDCT_abs and ΔDMR_abs, a 5mm cut-off value was used to determine the concordance between image and pathology. The concordance rates of CBBCT-Pathology and bMRI-Pathology were tested with the χ2 method. Factors that may affect the accuracy of tumor size measurement were analyzed. Results: Overall there were no statistically significant differences between ΔDCT_abs and ΔDMR_abs. (0.58±0.68cm vs. 0.65±0.68cm; t=1.653, P=0.100). Using 5mm as the cut-off value of concordance, there was no significant difference in the CBBCT-Pathology and bMRI-Pathology concordance rates (64.8% vs. 60.1%, χ2 =1.320, P=0.251). The overestimation rate of CBBCT was significantly lower than that of bMRI (11.4% vs. 19.4%, χ2=6.810, P=0.009). But there was no significant difference in the underestimation rates (23.8% vs. 20.5%, χ2=0.860, P=0.354). ΔDCT_abs is significantly smaller than ΔDMR_abs among the invasive ductal carcinoma group (P=0.017), the premenopausal group (P=0.004), and the small tumor size (≤2cm) group (P=0.003). ΔDCT_abs and ΔDMR_abs.have no significant differences among the lymph node metastasis group, multi-lesion group, and enhancement type group (P &amp;gt; 0.05). Conclusions: CBBCT is concordant with surgical pathology in breast tumor size measurement and provides more accurate tumor size estimation compared with bMRI. CBBCT can be used as a valuable modality for pre-operative assessment. Citation Format: YINAN JI, Geyi Liao, Ningbing Luo, Yi Jiang, Xiaoming Liao, Wei Tang, Huawei Yang. Comparison Of Cone Beam Breast CT And Breast MRI In Preoperative Assessment Of Primary Breast Cancer Tumor Size [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 P3-04-08.

Investigation of the miR-637 and miR-523-5p as candidate biomarkers in breast cancer.

The distinction of benign lesions from malign tumors is crucial for the diagnosis and treatment of breast cancers. The aim of this study was to investigate the use of miRNAs as plasma biomarkers for the discrimination of malign and benign breast tumors. Whole blood samples obtained from 40 individuals in 3 groups designated as invasive ductal carcinoma group, fibroadenoma group and healthy controls were included in this study. The expression levels of 372 miRNAs were determined using RT-PCR. Results: The comparison of fibroadenoma group with healthy controls revealed an upregulation of thirty miRNAs and downregulation of twenty-nine miRNAs. The comparison of invasive ductal carcinoma (IDC) group with controls has shown that eight miRNAs were upregulated while eleven miRNAs were downregulated. When comparing IDC and fibroadenoma groups, 15 miRNAs were found to be upregulated, while 10 miRNAs were downregulated. Further analysis of these miRNAs aimed to determine their power in distinguishing IDCs from fibroadenomas. Among the miRNAs analyzed, seven miRNAs have shown sufficient discriminative power, of which three miRNAs, namely miR-637, miR-523-5p and miR-490-3p, have shown a significantly high discriminative power. Circulating miR-637 and miR-523-5p combination maybe used to discriminate between invasive ductal carcinomas and fibroadenomas. (Tab. 9, Fig. 4, Ref. 30).

Ten-Year Survival of Breast Cancer in Iran: A National Study (Retrospective Cohort Study)

Purpose: This study aimed to estimate the 5- and 10-year survival rates of breast cancer in Iran. Methods: This retrospective cohort study was performed in 2019 on breast cancer patients registered in the national cancer registry system of Iran during 2007–2014. The patients were contacted to collect their information and status (alive or dead). Age and pathological type of tumor were categorized into five groups, and the place of residence was divided into 13 regions. The Kaplan-Meier method and the Cox proportional hazards model were used for data analysis. Results: A total of 87,902 patients were diagnosed with breast cancer during the study, 22,307 of whom were followed-up. The 5- and 10-year survival rates of the patients were 80% and 69%, respectively. The mean age of the patients was 50.68 ± 12.76 years (median age, 49 years). About 2.3% of the patients were male. The 5- and 10-year survival rates were 69% and 50% in men, respectively. The highest survival rate was reported in the age group of 40–49 years, and the lowest rate was found in the age group of ≥70 years. Of all pathological types, 88% were found in the invasive ductal carcinoma group; the highest survival rate was reported in the noninvasive carcinoma group. The highest survival rate was reported in the Tehran region and the lowest in the Hamedan region. Based on the results, the Cox proportional hazards model, sex, age group, and pathological type were statistically significant differences. Conclusion: This nationwide study performed on breast cancer patients indicated an improvement in the overall survival rate of these patients over the past years (the 5-year survival rate increased from 71% in 2011 to 80% in the present study), which might be attributed to advances in cancer management.

A high-quality model for predicting the prognosis of breast neuroendocrine carcinoma to help clinicians decide on appropriate treatment methods: A population-based analysis

BackgroundBreast neuroendocrine carcinoma (NEC) is a rare malignancy with unclear treatment options and prognoses. This study aimed to construct a high-quality model to predict overall survival (OS) and breast cancer-specific survival (BCSS) and help clinicians choose appropriate breast NEC treatments. Patients and methodsA total of 378 patients with breast NEC and 349,736 patients with breast invasive ductal carcinoma (IDC) were enrolled in the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2018. Propensity score matching (PSM) was performed to balance the clinical baseline. Prognostic factors determined by multivariate Cox analysis were included in the nomogram. C-index and calibration curves were used to verify the performance of the nomogram. ResultsNomograms were constructed for the breast NEC and breast IDC groups after PSM. The C–index of the nomograms ranged from 0.834 to 0.880 in the internal validation and 0.818–0.876 in the external validation, indicating that the nomogram had good discrimination. The risk stratification system showed that patients with breast NEC had worse prognoses than those with breast IDC in the low-risk and intermediate-risk groups but had a similar prognosis that those in the high-risk group. Moreover, patients with breast NEC may have a better prognosis when undergoing surgery plus chemotherapy than when undergoing surgery alone or chemotherapy alone. ConclusionsWe established nomograms with a risk stratification system to predict OS and BCSS in patients with breast NEC. This model could help clinicians evaluate prognosis and provide individualized treatment recommendations for patients with breast NEC.

Sigmoid model analysis of breast dynamic contrast-enhanced MRI: Distinguishing between benign and malignant breast masses and breast cancer subtype prediction.

Dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) is performed to distinguish between benign and malignant lesions by evaluating the changes in signal intensity of the acquired image (kinetic curve). This study aimed to verify whether the existing breast DCE‐MRI analyzed by the sigmoid model can accurately distinguish between benign and invasive ductal carcinoma (IDC) and predict the subtype.A total of 154 patients who underwent breast MRI for detailed breast mass examinations were included in this study (38 with benign masses and 116 with IDC. The sigmoid model involved the acquisition of images at seven timepoints in 1‐min intervals to determine the change in signal intensity before and after contrast injection. From this curve, the magnitude of the increase in signal intensity in the early phase, the time to reach the maximum increase, and the slopes in the early and late phases were calculated. The Mann–Whitney U‐test was used for the statistical analysis.The IDC group exhibited a significantly larger and faster signal increase in the early phase and a significantly smaller rate of increase in the late phase than the benign group (P < 0.001). The luminal A‐like group demonstrated a significantly longer time to reach the maximum signal increase rate than other IDC subtypes (P < 0.05).The sigmoid model analysis of breast DCE‐MRI can distinguish between benign lesions and IDC and may also help in predicting luminal A‐like breast cancer.

Survival analysis in patients with invasive lobular cancer and invasive ductal cancer according to hormone receptor expression status in the Korean population.

BackgroundWe compared the clinicopathological characteristics and survival outcomes of invasive lobular carcinoma (ILC) cases with those of invasive ductal carcinoma (IDC) cases in various hormone receptor expression subgroups.MethodsWe compared clinicopathological characteristics, overall survival (OS), and breast cancer-specific survival (BCSS) between patients with IDC (n = 95,486) and ILC (n = 3,023). In addition, we analyzed the effects of different hormone receptor expression subgroups on survival.ResultsThe ILC group had more instances of advanced stage and hormonal receptor positivity than did the IDC group (p < 0.001), but the IDC group had higher histological grade and nuclear grade, as well as higher frequency of human epidermal growth factor receptor 2 and Ki67 expression than did the ILC group (p < 0.001). The OS and BCSS were not significantly different between the IDC and ILC groups. The 5-year OS of the IDC group was 88.8%, while that of the ILC group was 90.6% (p = 0.113). The 5-year BCSS of the IDC group was 94.8%, while that of the ILC group was 95.0% (p = 0.552). When analyzing each hormone receptor expression subgroup, there were no significant differences in survival between the IDC and ILC groups. However, the estrogen receptor (ER) negative/progesterone receptor (PR) negative subgroup showed differences in survival between the IDC and ILC groups. Moreover, the hazard ratio of ILC in the ER negative/PR negative subgroup was 1.345 (95% confidence interval: 1.012–1.788; p = 0.041).ConclusionsHormone receptor expression should be considered when determining prognosis and treatment regimen for IDC and ILC. Researchers should further study the ER negative/PR negative population to identify treatment and prognostic models that will facilitate the development of individualized therapy for these patients, which is needed for good outcomes.

Analysis of sentinel lymph node biopsy and non-sentinel lymph node metastasis in invasive ductal and invasive lobular breast cancer: a nationwide cross-sectional study (CSBrS-001).

BackgroundInformation regarding the implementation of sentinel lymph node biopsy (SLNB) in invasive lobular carcinoma (ILC) is scarce, and whether ILC patients with 1–2 positive sentinel lymph nodes (SLNs) can be omitted from axillary lymph node dissection (ALND) remains controversial. This study aimed to compare involvement of SLNs and non-SLNs between patients with invasive ductal carcinoma (IDC) and ILC.MethodsWe retrospectively collected the clinical and pathological data of invasive breast cancer patients from 37 medical centers in China from January 2018 to December 2018. The number of resected SLNs, positive rate of SLNs, and non-SLNs metastasis were compared between patients with IDC and ILC.ResultsA total of 6,922 patients were included, comprising 6,650 with IDC (96.1%) and 272 with ILC (3.9%). No difference was observed in the number of resected SLNs between patients with IDC and ILC (IDC: 4.0±1.9 vs. ILC: 3.9±1.6, P=0.352). The positive rate of SLNs was significantly higher in patients with IDC than that in patients with ILC (19.3% in IDC vs. 12.9% in ILC, P=0.008). The difference in positive rate of SLNs between IDC and ILC was mainly attributed to macro-metastasis. For patients with positive SLNs who received ALND, and those with 1–2 positive SLNs, the metastatic rate of non-SLNs in the ILC group was higher than that in the IDC group (for patients with positive SLNs: 50.0% in ILC vs. 39.9% in IDC, P=0.317; for patients with 1–2 positive SLNs: 45.4% in ILC vs. 34.8% in IDC, P=0.366), but the differences were not statistically significant.ConclusionsPatients with ILC had similar number of resected SLNs and lower positive rate of SLNs compared to those with IDC. In participants with 1–2 positive SLNs, the ILC group had an increased tendency for non-SLNs metastasis compared with the IDC group. Surgeons may need to be more cautious about omitting ALND for ILC patients with 1–2 positive SLNs.

14-3-3ζ promoted invasion and lymph node metastasis of breast invasive ductal carcinoma with HER2 overexpression

BackgroundHER2 was a recognized oncogene that promoted the development and metastasis of breast cancer, but its positive expression rate in invasive ductal carcinoma (IDC) was much lower than that in ductal carcinoma in situ (DCIS). The correlation between the occurrence and development of breast cancer and the amplification and overexpression of HER2 gene alone was still controversial. 14–3–3ζ had a strong protein binding ability and a variety of functions, mainly through the interaction with other proteins to exert its unique biological activities. However, influence and interaction relationship of the two proteins on the development of IDC was not clear. Furthermore, the mutual effect mechanism of synergy effect on lymph node metastasis of IDC was not known well too. MethodsImmunohistochemistry experiment was performed to detect expression status of 14–3–3ζ, HER2, TGF-β, p53 and Gli2 in paraffin-embedded samples respectively, including 30 cases of normal breast tissue, 30 cases of usual ductal hyperplasia (UDH), 30 cases of atypical ductal hyperplasia (ADH), 30 cases of DCIS and 120 cases of IDC. ResultsThe positive expression rates of 14–3–3ζ/HER2 in Normal group, UDH group, ADH group, DCIS group and IDC group were 30%/0.00%, 26.7%/0.00%, 53.3%/33.3%, 46.7%/53.3% and 50%/24.2%, respectively. Compared with Normal group or UDH group, the expression of 14–3–3ζ was significantly increased in ADH, DCIS and IDC groups. 14–3–3ζ was overexpressed in only 4 of the 16 DCIS cases with HER2 overexpression (25.0%, 4/16), but it was overexpressed in 7 of the 9 IDC cases with DCIS (77.8%, 7/9). Among HER2 overexpression cases, 14–3–3ζ overexpression was significantly different between DCIS group and IDC with DCIS group (P = 0.017). In 18 IDC cases with lymph node metastasis and HER2 overexpression, 14–3–3ζ was overexpressed in 15 cases (83.3%, 15/18), while in the 11 IDC cases without lymph node metastasis, 14–3–3ζ and HER2 were overexpressed in only 5 cases (45.5%, 5/11). Co-overexpression of 14–3–3ζ and HER2 was positively correlated with occurrence of lymph node metastasis (P = 0.048). TGF-β was overexpressed in both precancerous lesion group and IDC group compared with normal group. Compared with the IDC group without lymph node metastasis, TGF-β expression was significantly increased in the IDC group with lymph node metastasis (P = 0.015). In IDC cases with 14–3–3ζ and HER2 co-overexpression, the expression of p53 in IDC with lymph node metastasis was significantly decreased (P = 0.010), while the expression of Gli2 was significantly increased compared with IDC cases without lymph node metastasis (P = 0.038). The co-overexpression of 14–3–3ζ and HER2 was positively correlated with ER negative expression (P < 0.001) and PR negative expression (P = 0.038), respectively. Conclusion14–3–3ζ synergistic with HER2 could promote the occurrence and development of breast IDC and induce the lymph node metastasis of IDC, suggesting that combined overexpression of 14–3–3ζ and HER2 would lead to higher invasion and metastasis risk of breast cancer. It was speculated that the combined detection of 14–3–3ζ and HER2 would be one of the key factors affecting the clinical treatment decision and prognosis.

Abstract PS17-27: Molecular evaluation of immunogenicity and genomic alterations in invasive lobular breast cancer

Abstract Background: Invasive lobular carcinoma (ILC) is the second most common type of invasive breast cancer and accounts for 10-15% of all cases. Though ILC has distinct clinical, prognostic and molecular features, studies are limited and include few patients. ILCs show a decreased response to neoadjuvant chemotherapy and an increased resistance to endocrine therapy. Thus, there is a great need to identify alternative therapies, such as immunotherapy, that could improve overall survival. Success of immunotherapy largely depends on tumor immunogenicity which varies with histologic type. Determination of predictive and prognostic biomarkers for ILC will help determine who can benefit the most. Our study investigates canonical markers of immunogenicity - PD-L1 expression and Tumor Mutational Burden (TMB) - in patients with ILC compared to invasive ductal carcinoma (IDC). We further correlate these markers in different subtypes i.e. hormone receptor positive (HR+), HER2 positive (HER2+), and in triple negative breast cancers (TNBC). We also analyze differences in immune cell profiles constituting the tumor microenvironment (TME) and differences in genomic alterations between ILC and IDC. Methods: A retrospective data analysis was performed to identify breast cancer tumors with ILC or IDC histology profiled at Caris Life Sciences (Phoenix, AZ) that were tested for PD-L1 by SP142 assay and had whole transcriptome sequencing data available. ILC and IDC cases were further subtyped as HR+ and HER2+ and TNBC. PD-L1 expression in immune cell was assessed using Ventana PD-L1 (SP142) histochemical assay and PD-L1 expression in tumor cell was assessed by laboratory developed test using SP142 clone with staining higher than 2+ considered positive. TMB was measured by counting somatic non-synonymous missense mutations on the 592 gene panel (Nextseq) next generation sequencing (NGS) assay, and ≥ 10 mutations/megabase (mut/Mb) was considered high. Using the whole transcriptome RNA sequencing (NovaSeq) data we analyzed the difference in immune cell profiles constituting the TME using a computational RNA deconvolution approach. NGS was used to identify significant differences in genomic alterations between ILC and IDC. Results: We identified 1,359 breast cancer patients (ILC: 194 vs IDC: 1,165). Among ILC, 79% were HR +, 11% TNBC, &amp;lt;2% HER2+ and the rest were of unclear subtype, compared to 55% HR +, 31% TNBC, 10% HER2+ in the IDC group. PD-L1 expression in immune cells was lower in ILC (PD-L1≥ 1% ILC: 13% vs. IDC: 35% p &amp;lt;0.0001; PD-L1&amp;gt;10% ILC: 1% vs. IDC: 5% p=0.017). PD-L1 expression in tumor cells was also lower in ILC (ILC 1% vs IDC 5%; p =0.0136). All subtypes of ILC had lower PD-L1 expression in immune and tumor cells when compared to IDC. TMB was similar and comparable in IDC and ILC (median TMB 7 mut/Mb). Assessment of TME showed a significantly increased abundance of cytotoxic lymphocytes and monocytic cells in IDC, and stromal endothelial cells in ILC. Androgen receptor (AR) expression, and mutations in CDH1 (ILC 76% vs IDC 2%) and PIK3CA (ILC 44% vs IDC 30%) were more common in ILC. CDH1 mutation was significantly higher in both TN ILC (ILC 60% vs IDC 1%; p&amp;lt;0.05) and HR+ ILC (77% vs IDC 2%; p&amp;lt;0.05) subtypes of ILC. TP53 mutation was lower in ILC (ILC 26% vs IDC 65%) irrespective of subtype. Conclusion: In summary, PD-L1 expression in immune cells and tumor cells was lower in ILC, however TMB was comparable between ILC and IDC. Immune cell profiling supports a cold or less immunogenic TME for ILC. A composite immune biomarker may be able to better characterize immunogenicity of ILC. Citation Format: Upama Giri, Joanne Xiu, Tatiana Karadimitriou, Sofi Castanon, Foluso Ademuyiwa, Paula Pohlmann, Elias Obeid, Jasgit Sachdev, Elisa Krill-Jackson, Michael Simon, Antoinette Tan, Neelima Denduluri, Lee Schwartzberg, Michael Korn, Evanthia T Roussos Torres. Molecular evaluation of immunogenicity and genomic alterations in invasive lobular breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS17-27.

Expression of Angiogenesis-related Genes in a Group of Iranian Cases of Breast Cancer

Aims: This study aims to design an angiogenesis gene expression profile; to study angiogenesis gene expression profile in breast cancer; and to map angiogenesis gene expression profile in individual participants. Background: In molecular etiology of each disease, there are some important molecules involved in the related pathways. From the viewpoint of precision medicine, molecular etiology of a disease is different person by person because of genetic variations of the genes involved in these pathways. This point of view intends researchers of drug development to design novel drugs for targeted therapy based on the exact etiology. In the case of angiogenesis, there is a drug profile parallel to the molecular profile. Bevacizumab, sunitinib and aflibercept are examples of anti-angiogenic drugs. Objectives: A hallmark of solid tumors is sustained angiogenesis. Vascular endothelial growth factors (VEGF), VEGF receptors (VEGFR) and placental growth factor (PlGF) are involved in angiogenesis. We aimed to study the gene expression profile of angiogenesis including VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGFR-1, VEGFR-2, VEGFR-3 and PlGF in an Iranian group of patients undergoing breast surgery due to breast cancer and breast fibroadenoma. Methods: Tumor tissue samples of a group of patients with invasive ductal carcinoma (IDC) and a group of patients with fibroadenoma (Fib) were used. Gene expression was studied by real-time quantitative polymerase chain reaction (q-PCR) and fold changes (FC) with their 95% confidence intervals (CI) were reported based on calibration with normal breast tissue. Results: All the genes showed significant up-regulation in IDC group. The extensive up-regulation was for VEGFR-2 (FC=52.68; 95% CI=17.96-154.47; P&lt;0.001). In Fib group, PlGF showed a significant upregulation (FC=10.41; 95% CI=5.35-20.26; P=0.002). Comparison of IDC group with Fib group showed significant up-regulation of VEGFR-1, VEGFR-2 and VEGFR-3 in IDC group (P&lt;0.05). Conclusion: Malignancy of breast tumors is associated with overexpression of all the genes of this profile. However, only VEGFRs showed up-regulation in comparison to benign tumors. Individualized targeted therapy, according to this profile, should be studied in the future.

ASSESSMENT OF SURGICAL MANAGEMENT OF FEMALE BREAST CANCER PATIENTS AFTER NEOADJUVANT SYSTEMIC THERAPY FOR INVASIVE DUCTAL VERSUS INVASIVE LOBULAR CARCINOMA (T3 STAGE)

Background: In the treatment of locally advanced breast cancer, neoadjuvant chemotherapy approach has several objectives, including downsizing of irresectable tumor into operable disease. ILC is known to be less responsive to NAC. The reported proportions of ILC patients with a pathologic complete response (pCR) range from 1 to 3 % compared with 9 to 15 % for IDC patients Objectives: To assess surgical decision after using neoadjuvant systemic therapy for locally advanced breast cancer patients with invasive ductal carcinoma (IDC) versus whom with invasive lobular carcinoma (ILC). To determine the impact of neoadjuvant chemotherapy (NAC) on different pathological types of locally advanced breast cancer cases. Patients and Methods: This retrospective study included 50 patients in the period from Jun 2018 to Jun 2019 who were diagnosed as invasive ductal and invasive lobular Carcinoma classified into two equal groups. Each group had received neoadjuvant systemic therapy, at Department of Clinical Oncology and Nuclear Medicine, while surgical treatment, in form of modified radical mastectomy (MRM) or breast conserving surgery (BCS), was done between June 2019 and Mar 2020, at the Surgical Oncology Department in Al-Azhar university hospitals. Results: In our study, we observed a reduction in T stage after NAC in 6 cases (24%) of ILC patients compared to clinical down staging in 20 cases (80%) of IDC group. Conclusion: ILC patients were less responsive to neoadjuvant chemotherapy compared with IDC patients. BCS is less frequently achieved after NAC in patients with lobular histology compared with ductal histology.

Efficacy of breast MRI for surgical decision in patients with breast cancer: ductal carcinoma in situ versus invasive ductal carcinoma

BackgroundPreoperative breast magnetic resonance imaging (MRI) provides more information than mammography and ultrasonography for determining the surgical plan for patients with breast cancer. This study aimed to determine whether breast MRI is more useful for patients with ductal carcinoma in situ (DCIS) lesions than for those with invasive ductal carcinoma (IDC).MethodsA total of 1113 patients with breast cancer underwent mammography, ultrasonography, and additional breast MRI before surgery. The patients were divided into 2 groups: DCIS (n = 199) and IDC (n = 914), and their clinicopathological characteristics and oncological outcomes were compared. Breast surgery was classified as follows: conventional breast-conserving surgery (Group 1), partial mastectomy with volume displacement (Group 2), partial mastectomy with volume replacement (Group 3), and total mastectomy with or without reconstruction (Group 4). The initial surgical plan (based on routine mammography and ultrasonography) and final surgical plan (after additional breast MRI) were compared between the 2 groups. The change in surgical plan was defined as group shifting between the initial and final surgical plans.ResultsChanges (both increasing and decreasing) in surgical plans were more common in the DCIS group than in the IDC group (P < 0.001). These changes may be attributed to the increased extent of suspicious lesions on breast MRI, detection of additional daughter nodules, multifocality or multicentricity, and suspicious findings on mammography or ultrasonography but benign findings on breast MRI. Furthermore, the positive margin incidence in frozen biopsy was not different (P = 0.138).ConclusionsPreoperative breast MRI may provide more information for determining the surgical plan for patients with DCIS than for those with IDC.

The ultrasonographic characteristics of fibrocystic breast change

Objective To investigate the ultrasonographic features of fibrocystic breast change (FBC) and improve the ultrasonographic diagnosis and differential diagnosis of FBC. Methods Fifty-five patients of FBC with 60 lesions and 39 patients of invasive ductal carcinoma (IDC) with 42 lesions, which were confirmed by pathology after operation in the Affiliated Union Hospital of Fujian Medical University from January 2014 to February 2019 were enrolled. The preoperative sonographic findings of FBC and IDC were retrospectively analyzed and compared. Results There was no significant difference between the two groups in the rates of showing irregular shape, which were 86.7% in FBC group and 88.1% in IDC group, respectively (P>0.05), but the rate of showing crab feet or burrs on the edge of lesions in FBC group was lower than that in IDC group(P<0.05). The occurrence rates of posterior echo enhancement and cystic degeneration in FBC group were 81.7% and 71.7% respectively, which were significantly higher than those in IDC group (38.1% and 16.7%)(P<0.001). In addition, the FBC group showed fewer features such as hyperechoic halo and more features such as hypovascular supply than that of IDC group (all P<0.001). Conclusions In terms of ultrasonic features, including irregular shape or even crab feet and burrs, FBC can be easily misdiagnosed as malignant tumors. However, posterior echo enhancement, interior scattered small cysts, lack of blood supply and rare hyperechoic halo may be the characteristics of FBC, which can be differentiated from malignant tumors. Key words: Ultrasonography; Fibrocystic breast change; Invasive ductal carcinoma