Cases Of Invasive Lobular Carcinoma Research Articles

Contrast-Enhanced Digital Mammography for the Diagnosis and Determination of Extent of Disease in Invasive Lobular Carcinoma: Our Experience and Literature Review.

Contrast-enhanced imaging, including magnetic resonance imaging and, more recently, contrast-enhanced digital mammography (CEM), is indicated for the precise diagnosis of invasive lobular carcinoma (ILC). The aim of our study was to further validate the use of CEM for evaluation of extent of disease in ILC cases, with digital breast tomosynthesis (DBT) as an adjunct. A retrospective, institutional review board approved study was conducted in a tertiary medical center. All CEM examinations performed on ILC patients between 2017 and 2023 were reread by 2 dedicated breast radiologists. Clinical data and pathology reports were retrieved from electronic medical records. The longest diameter of the enhancing lesion was correlated to pathology findings. In addition, for each case, the readers provided brief commentary on the added value of DBT. Twenty-four CEM examinations were evaluated. The subjects in the study cohort were on average older than expected for ILC patients (74 vs 63 years) and were unable to undergo breast magnetic resonance imaging due to advanced age and comorbidities. Three subjects were treated with neoadjuvant therapy and thus were excluded from the correlation to pathology analysis. Enhancing lesions, ranging from 4-75 mm, strongly correlated to pathology results, with statistical significance. This was demonstrated for mass and nonmass lesions (r = 0.94, P < 0.001 and r = 0.99, P = 0.002, respectively). For most lesions (17/24, 71%), readers remarked that the addition of DBT allowed for improved characterization of lesion margins, mainly detecting architectural distortion. When compared with the pathology findings, ILC was accurately diagnosed and assessed using CEM. The addition of DBT was reported by the interpreting radiologists as a valuable adjunct for margin analysis.

Insights into E-Cadherin Impairment in CDH1-Unaltered Invasive Lobular Carcinoma: A Comprehensive Bioinformatic Study.

Invasive lobular carcinoma exhibits unique morphological features frequently associated with alterations in CDH1. Although some studies have identified abnormalities in adhesion factors other than E-cadherin, the molecular mechanisms underlying E-cadherin abnormalities in CDH1-unaltered invasive lobular carcinoma remain poorly understood. In this study, we investigated the molecular underpinnings of E-cadherin dysregulation in invasive lobular carcinoma in the absence of CDH1 gene alterations, using comprehensive bioinformatic analyses. We conducted a comparative study of CDH1-mutated and non-mutated invasive lobular carcinoma and evaluated the differences in mRNA levels, reverse-phase protein array, methylation, and miRNAs. We observed that invasive lobular carcinoma cases without CDH1 alterations exhibited a significantly higher incidence of the Claudin-low subtype (p < 0.01). The results of the reverse-phase protein array indicate no significant difference in E-cadherin expression between CDH1-mutated and non-mutated cases. Therefore, abnormalities in E-cadherin production also exist in CDH1 non-mutated invasive lobular carcinoma. Considering that there are no differences in mRNA levels and methylation status, post-translational modifications are the most plausible explanation for the same. Hence, future studies should focus on elucidating the mechanism underlying E-cadherin inactivation via post-translational modifications in CDH1 non-mutated invasive lobular carcinoma.

A histomorphological and immunohistochemical analysis of invasive lobular carcinoma of breast: A case series

Invasive lobular carcinoma (ILC) is the second most common special subtype of invasive breast carcinoma comprising 5–15%. ILC defines as invasive carcinoma comprising non-cohesive single-file linear pattern in fibrous stroma. The aim of the study was to evaluate the histomorphological features and immunohistochemical analysis of ILC. A total of 19 cases were encountered from March 2020 to February 2024 out of 129 breast cancers. The sociodemographic profiles and clinicopathological parameters of the patients were studied with special emphasis on their morphology and hormone receptor status. The mean age of patients is 42.8 years. Out of 19 cases, 84.2% showed feature of classic type, 5.2% of tubule-lobular, and 10.5% of pleomorphic lobular carcinoma. The majority of cases (63.2%) showed histologic Grade 2, and 10.5% showed Grade 3. On immunohistochemistry examination, 79% were estrogen receptor (ER) and progesterone receptor (PR) positive with 10.5% of cases was human epidermal growth factor receptor 2/neu (HER2/neu) positive. Our study showed higher cases of classic type ILC, mostly of histologic Grade 2; higher ER-PR receptor positivity and HER2/neu negativity.

Outcomes in Nonmetastatic Hormone Receptor-Positive HER2-Negative Pure Mucinous Breast Cancer: A Multicenter Cohort Study.

Although considered a favorable subtype, pure mucinous breast cancer (PMBC) can recur, and evidence for adjuvant therapy is limited. We aimed to compare outcomes of nonmetastatic PMBC with invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) to address these uncertainties. Individual patient-level data from 6 centers on stage I-III hormone receptor-positive and HER2-negative PMBC, IDC, and ILC were used to analyze recurrence-free interval (RFI), recurrence-free survival (RFS), and overall survival (OS), and to identify prognostic factors for PMBC. Data from 20,684 IDC cases, 1,475 ILC cases, and 943 PMBC cases were used. Median follow-up was 6.6 years. Five-year RFI, RFS, and OS for PMBC were 96.1%, 94.9%, and 98.1%, respectively. On multivariable Cox regression, PMBC demonstrated superior RFI (hazard ratio [HR], 0.59; 95% CI, 0.43-0.80), RFS (HR, 0.70; 95% CI, 0.56-0.89), and OS (HR, 0.71; 95% CI, 0.53-0.96) compared with IDC. ILC showed comparable outcomes to IDC. Fewer than half (48.7%) of recurrences in PMBC were distant, which was a lower rate than for IDC (67.3%) and ILC (80.6%). In contrast to RFI, RFS events were driven more by non-breast cancer deaths in older patients. Significant prognostic factors for RFI among PMBC included positive lymph node(s) (HR, 2.42; 95% CI, 1.08-5.40), radiotherapy (HR, 0.44; 95% CI, 0.23-0.85), and endocrine therapy (HR, 0.25; 95% CI, 0.09-0.70). No differential chemotherapy associations with outcomes were detected across PMBC subgroups by nodal stage, tumor size, and age. A separate SEER database analysis also did not find any association of improved survival with adjuvant chemotherapy in these subgroups. Compared with IDC, PMBC demonstrated superior RFI, RFS, and OS. Lymph node negativity, adjuvant radiotherapy, and endocrine therapy were associated with superior RFI. Adjuvant chemotherapy was not associated with better outcomes.

CDH1 methylation analysis in invasive lobular breast carcinomas with and without gene mutation

The proposed role of CDH1 (E-cadherin gene) methylation as a mechanism of gene inactivation in invasive lobular carcinoma (ILC) remains inconclusive. For many years, CDH1 promoter hypermethylation has been regarded as a mechanism for gene inactivation in ILC. However, this assumption has primarily relied on non-quantitative assays, which have reported CDH1 methylation frequencies ranging from 26 to 93% at CpG sites within the island region. Few studies employing quantitative methods and covering CpG island shores, regions of relatively low CpG density situated proximal to conventional promoter CpGs, have been conducted, revealing lower percentages of methylation ranging from 0 to 51%. Therefore, using the quantitative pyrosequencing method, we examined CDH1 methylation in the island region and shores in E-cadherin deficient ILC cases (15 with CDH1 mutation and 22 non-mutated), 19 cases of invasive breast carcinomas non-special type (IBC-NSTs), and five cases of usual ductal hyperplasia (UDH). Our analysis revealed CDH1 methylation frequencies ranging from 3 to 64%, with no significant increase in methylation levels in any group of ILCs (median = 12%) compared to IBC-NST (median = 15%). In addition, considering the poorly studied association between the number of tumor-infiltrating lymphocytes (TILs) and CDH1 methylation in breast cancer, we undertook a thorough analysis within our dataset. Our findings revealed a positive correlation between CDH1 methylation and the presence of TILs (r = 0.5; p-value < 0.05), shedding light on an aspect of breast cancer biology warranting further investigation. These findings challenge CDH1 methylation as a CDH1 inactivation mechanism in ILC and highlight TILs as a potential confounding factor in gene methylation.

Correlation between sentinel lymph node biopsy and non-sentinel lymph node metastasis in patients with cN0 breast carcinoma: comparison of invasive ductal carcinoma and invasive lobular carcinoma

BackgroundSome studies have suggested that axillary lymph node dissection (ALND) can be avoided in women with cN0 breast cancer with 1–2 positive sentinel nodes (SLNs). However, these studies included only a few patients with invasive lobular carcinoma (ILC), so the validity of omitting ALDN in these patients remains controversial. This study compared the frequency of non-sentinel lymph nodes (non-SLNs) metastases in ILC and invasive ductal carcinoma (IDC). Materials Methods: Data relating to a total of 2583 patients with infiltrating breast carcinoma operated at our institution between 2012 and 2023 were retrospectively analyzed: 2242 (86.8%) with IDC and 341 (13.2%) with ILC. We compared the incidence of metastasis to SLNs and non-SLNs between the ILC and IDC cohorts and examined factors that influenced non-SLNs metastasis. Results: SLN biopsies were performed in 315 patients with ILC and 2018 patients with IDC. Metastases to the SLNs were found in 78/315 (24.8%) patients with ILC and in 460 (22.8%) patients with IDC (p = 0.31). The incidence of metastases to non-SLNs was significantly higher (p = 0.02) in ILC (52/78–66.7%) compared to IDC (207/460 − 45%). Multivariate analysis showed that ILC was the most influential predictive factor in predicting the presence of metastasis to non-SLNs. Conclusions: ILC cases have more non-SLNs metastases than IDC cases in SLN-positive patients. The ILC is essential for predicting non-SLN positivity in macro-metastases in the SLN. The option of omitting ALND in patients with ILC with 1–2 positive SLNs still requires further investigation.

Differences in Histological Subtypes of Invasive Lobular Breast Carcinoma According to Immunohistochemical Molecular Classification.

The aim of this study was to compare the differences between histological and molecular subtypes of invasive lobular carcinoma (ILC) of the breast, in order to be able to predict the behavior and prognosis of the disease, as well as to effectively determine therapy. This study included 263 cases of breast ILC diagnosed over a seven-year period. The diagnosis of invasive lobular carcinoma is based on the characteristic growth pattern and phenotype of cancer cells with the respective subtypes: classic, alveolar, solid, tubulolobular, pleomorphic and mixed lobular type. The examined cases were divided into five groups according to molecular classification based on the expression of ER, PR, HER2 and Ki67 immunohistochemical markers. It was found that the pleomorphic subtype occurred statistically significantly less often as the luminal A subtype compared to others (p = 0.00027), and the HER2-enriched subtype occurred statistically significantly more often in the pT4 stage (p = 0.024). The results of this study significantly singled out the luminal A subtype, and among them classic ILC, as the subtype with the most favorable expression ratio of the investigated predictive/prognostic immunohistochemical markers.

Expression of PD-L1 in breast invasive lobular carcinoma.

The purpose of this study was to investigate the expression of PD-L1 in invasive lobular carcinoma (ILC) and to determine its implications. Tissue microarrays were constructed for 101 cases of ILC, and immunohistochemical staining for PD-L1 (using 22C3, SP142, and SP263 antibodies) was performed to examine the correlation between staining results and clinicopathologic parameters. The positive cut-off values were defined as tumor cell (TC)≥1%, immune cell (IC)>0%, and IC≥1%. The range of PD-L1 TC positivity was 0.0-2.0%, with PD-L1 SP263 TC showing the highest positivity of 2.0%. The range of PD-L1 IC positivity was 0-21.8% for IC ≥ 1%, with PD-L1 22C3 IC showing the highest positivity. When PD-L1 IC was positive (IC≥1%), the highest antibody agreement was observed between SP263 and SP142 (OA = 93.1%), while the lowest agreement was observed between 22C3 and SP263 (OA = 73.3%, κ = 0.040). PD-L1 22C3 IC positivity (≥1%) was associated with high nuclear grade (p = 0.002), HER-2 positivity (p = 0.019), and pleomorphic type (p = 0.002). PD-L1 expression in ILC shows a low TC positivity rate (0-2%) with various antibody clones and a variable IC positivity rate (0-21.8%). Pleomorphic type ILC exhibits higher PD-L1 IC positivity.

Invasive lobular carcinoma of the breast with colonic metastasis: a case series of three patients

BackgroundAlthough metastatic spread of breast cancer to the gastrointestinal tract is very rare, it is more likely to occur in invasive lobular carcinoma (ILC) than in ductal carcinoma. Colonic metastasis is particularly rare, and the treatment strategies for these cases are not clearly defined. Herein, we report three cases of ILC with various abdominal symptoms associated with colonic metastasis.Case presentationCase 1 A 70-year-old female patient with vomiting and melena was referred to our hospital. Endoscopic examination revealed a Dieulafoy ulcer in the rectum and an elevated lesion in the descending colon. She also had two breast nodules, and was diagnosed as ILC with colonic metastasis. Considering her general condition, the best supportive care (BSC) was offered. The patient died 4 months after confirmation of the diagnosis. Case 2 An 80-year-old female patient presented with diarrhea and vomiting. She was diagnosed with ILC with colonic metastasis, and a coloscopy revealed stenosis of the transverse colon with a metastatic lesion. Ileosigmoid bypass surgery was performed for intestinal obstruction, and systemic treatment for breast cancer was initiated. The patient developed peritoneal carcinomatosis and died 1 year and 2 months after surgery. Case 3 A 56-year-old female patient underwent left total mastectomy for ILC, and laparoscopic transverse colectomy was conducted for a colonic lesion 9 years and 2 months after. The diagnosis as colonic metastasis was not confirmed at that time. Two years and 2 months later, torose lesions were detected in the hepatic flexural and descending colon, and histopathological findings indicated that all colon tumors, including the previously resected tumor, were metastatic spread of ILC. Systemic treatment was continued, but the transverse colonic lesion penetrated the abdominal wall, and an abscess formed 2 years and 11 months after the resection. The fistula improved by continuous suction drainage following ileostomy but recurred, and the patient died 3 years and 8 months after colectomy.ConclusionsColonic metastases from breast cancer can trigger various abdominal symptoms, and the prognosis in these cases is generally poor. In selected cases, surgical treatment for abdominal symptoms and subsequent systemic therapy can contribute to a prolonged prognosis.

Canonical Kaiso target genes define a functional signature that associates with breast cancer survival and the invasive lobular carcinoma histological type.

Invasive lobular carcinoma (ILC) is a low- to intermediate-grade histological breast cancer type caused by mutational inactivation of E-cadherin function, resulting in the acquisition of anchorage independence (anoikis resistance). Most ILC cases express estrogen receptors, but options are limited in relapsed endocrine-refractory disease as ILC tends to be less responsive to standard chemotherapy. Moreover, ILC can relapse after >15 years, an event that currently cannot be predicted. E-cadherin inactivation leads to p120-catenin-dependent relief of the transcriptional repressor Kaiso (ZBTB33) and activation of canonical Kaiso target genes. Here, we examined whether an anchorage-independent and ILC-specific transcriptional program correlated with clinical parameters in breast cancer. Based on the presence of a canonical Kaiso-binding consensus sequence (cKBS) in the promoters of genes that are upregulated under anchorage-independent conditions, we defined an ILC-specific anoikis resistance transcriptome (ART). Converting the ART genes into human orthologs and adding published Kaiso target genes resulted in the Kaiso-specific ART (KART) 33-gene signature, used subsequently to study correlations with histological and clinical variables in primary breast cancer. Using publicly available data for ERPOS Her2NEG breast cancer, we found that expression of KART was positively associated with the histological ILC breast cancer type (p < 2.7E-07). KART expression associated with younger patients in all invasive breast cancers and smaller tumors in invasive ductal carcinoma of no special type (IDC-NST) (<2 cm, p < 6.3E-10). We observed associations with favorable long-term prognosis in both ILC (hazard ratio [HR] = 0.51, 95% CI = 0.29-0.91, p < 3.4E-02) and IDC-NST (HR = 0.79, 95% CI = 0.66-0.93, p < 1.2E-04). Our analysis thus defines a new mRNA expression signature for human breast cancer based on canonical Kaiso target genes that are upregulated in E-cadherin deficient ILC. The KART signature may enable a deeper understanding of ILC biology and etiology. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Quantifying hormone receptor status in lobular breast cancer in an institutional series: the relationship between estrogen and progesterone receptor status and outcomes

PurposeRecent guidelines defined a new reporting category of ER-low-positive breast cancer based on immunohistochemistry (IHC). While low positivity of either hormone receptor is uncommon in invasive lobular carcinoma (ILC), we sought to investigate whether relatively low hormone receptor positivity was associated with tumor characteristics and patient outcomes in a single institutional cohort.MethodsWe searched an institutional database for cases of stage I-III ILC with available IHC reports. Based on prior published categories in ILC, ER was classified as low, medium, or high as defined by ER staining of 10–69%, 70–89%, and ≥ 90% respectively. PR low and high tumors were defined by < 20%, or ≥ 20% staining respectively. We used chi-squared tests, t-tests, and Cox proportional hazards models to evaluate associations between ER/PR categories and tumor characteristics or disease-free survival (DFS).ResultsThe cohort consisted of 707 ILC cases, with 11% of cases categorized as ER low, 15.1% as medium, and 73.8% as high. The majority (67.6%) were PR high. Patients with ER low/medium expression were significantly younger, and more likely to also have PR low and/or HER2 positive tumors compared to those that were ER high. In a Cox proportional hazards model adjusting for age, stage, grade, pleomorphic histology, and treatment, ER category was not prognostic for DFS, but PR negative and PR low status each had significantly worse DFS compared to PR high status (HR 3.5, 95% CI 1.8–6.7, p < 0.001; and HR 2.0, 95% CI 1.1–3.5, p = 0.015, respectively).ConclusionThese findings highlight the relevance of quantifying ER and PR within ILC.

Overdiagnosis of lobular carcinoma of breast- A review of histomorphological features and immunohistochemistry: A case series

: Invasive lobular carcinoma (ILC) accounts for 5%–15% of all invasive breast cancers (BCs) and is the second most common type of BC behind invasive ductal carcinoma (IDC) of no special type. ILC of the breast is characterized morphologically by small, noncohesive cells that infiltrate the stroma in a single-file pattern(Indian file pattern). ILC tumours display features associated with a good prognosis, being low grade, oestrogen receptor positive and is mainly associated with the complete loss of E-cadherin (E-cad) expression.To review the cases of invasive lobular carcinoma and to immunohistochemically categorize IDC and ILC.This is a retrospective study including all the modified radical mastectomy cases of invasive lobular carcinoma of breast reported in the department of Pathology of a tertiary care centre from January 2021 to January 2022. Histopathological and immunohistochemical analysis of those cases were reviewed.We encountered 10 cases of invasive lobular carcinoma of breast from January 2021 to January 2022. The average age of the patients was 55.9 years old (35–72). The classic presentation was a breast lump found in 100% of the cases. On physical examination, breast carcinoma was suspected in all the patients. The average size of the tumours was 4.5 cm (1.4– 9cm). Out of those 10 cases, 4 cases were right sided lesion and modified radical mastectomy was performed in all the 10 cases. All the 10 cases were diagnosed as invasive lobular carcinoma on histopathology and review of those cases showed 7 out of 10 cases to be IDC. Those cases showed pitfalls in histomorphological analysis which were later confirmed by immunohistochemistry. The findings are presented in the study.Our study found that there was a histomorphological pitfall in the diagnosis of IDC. In ambiguous cases with histologically equivocal features, a strong, complete, membranous E-cadherin expression may help in resolving the problem and in aiding in the subclassification of invasive breast carcinoma.

Abstract HER2-14: HER2-14 HER-2 low status in early stage invasive lobular carcinoma of the breast: associated factors and outcomes in an institutional series

Abstract Objectives: The concept of human epidermal growth factor receptor 2 (HER2)-low status has been proposed as a potential treatment target for breast cancers previously considered to be HER2-negative. Defined by an immunohistochemistry (IHC) score of 1+ or 2+ and negative fluorescent in situ hybridization (FISH) for HER2, HER2-low status predicts significant clinical benefit from novel therapeutic compounds in recent clinical trials. The prevalence and clinical implications of HER2-low status in patients with early stage invasive lobular carcinoma (ILC) has not been described. We aimed to describe the clinicopathologic features and prevalence of HER2-low status in ILC, and identify any potential differences in clinical outcome. Methods: We evaluated stage I-III ILC tumors from a prospectively maintained institutional database of patients where both IHC and FISH testing for HER2 status was performed as standard clinical care. Tumors were classified as HER2 negative (IHC=0), HER2-low (IHC=1+ or 2+ and negative FISH), or HER2 positive (IHC=3+ or FISH ratio ⇒2). Data were analyzed in Stata 16.1 using chi-squared tests, t-tests, and Cox proportional hazards models for disease free survival (DFS). Results: 666 ILC tumors with available HER2 status were available for analysis. The mean age at diagnosis was 59.8 years (range 21-91). The majority of patients had stage I disease (63.1%) with an average follow up time of 6.7 years (standard deviation [5.4]). Overall, 184 (27.6%) tumors were HER2 negative, 434 (65.1%) were HER2-low, and 48 (7.2%) were HER2 positive. There were no associations between HER2 status and age, menopausal status, body mass index, tumor stage, grade, presence of lymphovascular invasion, or molecular assay results. Hormone receptor status was significantly associated with HER2 status, with HER2 positive tumors significantly less likely to be estrogen receptor (ER) positive than both HER2 negative and HER2-low tumors (89.6% versus 97.3% and 96.8% respectively, p=0.03). HER2-low tumors were also significantly more likely to have progesterone receptor (PR) positivity (86.6% compared to 79.9% of HER2 negative and 72.9% of HER2 positive tumors, p = 0.01). This difference remained significant when comparing just HER2-low to HER2 negative cases (p=0.034). While there were no differences in use of neoadjuvant or adjuvant chemotherapy by HER2 status, HER2-low patients were significantly more likely to undergo mastectomy versus lumpectomy when compared to HER2 negative and HER2 positive patients (53.7% versus 38.0% and 43.8% respectively, p= 0.001). In a multivariable Cox proportional hazards model adjusting for tumor size, number of positive nodes, ER/PR status, and local therapy received, patients with HER2-low status had worse DFS than those with HER2 negative tumors (hazard ratio 2.0, 95% confidence interval 1.0 - 4.1, p=0.05). Conclusions: In this analysis of 666 early stage ILC cases, we found that most tumors were HER2-low, and that those with HER2-low disease were significantly more likely to have PR positive tumors and to undergo mastectomy. When adjusting for these variables, we identified a difference in DFS between HER2 negative and HER2-low early stage ILC. These findings support the contention that HER2-low and HER2 negative disease represent two different clinical entities. Further investigation of the potential benefit of HER2 targeted therapy in ILC, which predominately lacks HER2-amplified disease, is needed to ensure optimal outcomes in this understudied tumor type. Citation Format: Harriet T. Rothschild, Elle Clelland, Anne Patterson, Julissa Molina-Vega, Mandeep Kaur, Mary Kathryn Abel, W. Fraser Symmans, Christopher J. Schwartz, Rita Mukhtar. HER2-14 HER-2 low status in early stage invasive lobular carcinoma of the breast: associated factors and outcomes in an institutional series [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 HER2-14.

Abstract P6-01-30: PgR levels and Ki67 expression of Lobular Carcinomas of the Breast might indicate OncotypeDX testing to evaluate Chemotherapy benefit

Abstract AIM: The majority of invasive lobular carcinomas (ILC) of the breast are luminal A tumors of good prognosis, having a low or intermediate OncotypeDX Recurrence Score (RS). They are usually treated with hormonal therapy only and some have doubted the relevance of the RS for patients with ILC. However, in a number of ILC cases a high RS can be found, indicating chemotherapy benefit. The aim of the present analysis was to explore in our database of lobular carcinomas analyzed with OncotypeDX, the percentage of tumors with a RS &amp;gt;25 and test the hypothesis if Progesterone Receptor (PgR) and/or Ki-67 expression could be an indicator to have patients evaluated with OncotypeDX. PATIENTS AND METHODS: Among 2.946 patients analyzed with Oncotype DX, we found 397 patients with pure lobular carcinomas (13.47%). Ki-67 expression was obtained from 315 patients and 13 of them (4%) had a high Ki-67 value of &amp;gt;30%. PgR expression was negative in 56 out of 397 patients (14%). We analyzed the possible relationship of RS values with PgR levels and Ki-67 expression. RESULTS: Overall, 94% of patients with ILC had a Recurrence Score ≤25 and only 6% (24/397) had a RS ≥26. There was a wide distribution of RS among patients with different values of PgR; however, there was a negative trend of Recurrence Score values and PgR expression levels. This trend was more obvious in the 56 patients with negative PgR expression. Although there were high RS values across all levels of Ki-67 expression, there was a trend towards high RS with higher Ki-67 expression; 5 out of 13 patients (38%) with ki-67 &amp;gt;30% had a RS ≥26. CONCLUSION: Our analysis shows that the majority of lobular carcinomas of the breast have a low OncotypeDX RS, suggesting that can be treated only with hormonal therapy. However, negative or low PgR levels and high Ki-67 expression might predict a high RS and thus chemotherapy benefit and those two parameters could be used as indicators for OncotypeDX evaluation of lobular carcinomas of the breast. Citation Format: Christos Markopoulos, Mahi Sariyanni, Asimina Karamargiou, Zoi Antonopoulou, Nikolaos Tsoulos. PgR levels and Ki67 expression of Lobular Carcinomas of the Breast might indicate OncotypeDX testing to evaluate Chemotherapy benefit [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 P6-01-30.

Breast biomarkers profile of invasive lobular carcinoma in a cohort of arab women shows no significant differences from carcinoma of no special type.

Invasive lobular carcinoma (ILC) of the breast is known for its common presentation at an older age, and the frequent expression of favourable profile of estrogen and progesterone receptors (ER & PR) positivity, and human epidermal growth factor receptor 2 (HER2) negativity combined with low proliferation rate as measured by Ki67. This study aimed to test these clinicopathological features of ILC in an Arabic cohort. All breast biopsies diagnosed as IDC or ILC were retrospectively reviewed over 2 years period (2017-2018) in an academic centre. Variables were compared using Fisher's exact test for statistical significance. A total of 134 cases were recruited, 12.7% were ILC. The median age was 52 years for both types. Clustering of ILC cases was noticed in luminal A subtype (47.1%), but there was no statistically significant difference in subtyping between the 2 histologic groups. Ki67 was significantly lower in ILC than IDC category. Our study showed that ILC in our cohort lacks the advantage of older age and the common high expression of ER positivity in comparison to IDC. There is, however, significant difference of the value of Ki67 proliferation marker. The prognosis of lobular morphology is questionable in our cohort.

Evaluation of tumor infiltrating lymphocytes in breast carcinomas

Background: Among the parameters that have a prognostic and/or predictive significance to therapeutic response, in the case of breast carcinoma, the study of tumor-infiltrating lymphocytes in breast carcinomas is emerging. The present study aimed to access the clinicopathological profiles of tumor-infiltrating lymphocytes in patients with primary breast carcinoma. Materials and Methods: Information was collected from the archive of the Department of Pathology, about invasive breast cancers diagnosed between April 2019 –March 2020. Hormone receptor status and Ki-67 index were assessed. For tumor-infiltrating lymphocytes, hematoxylin and eosin sections were evaluated following the guidelines of the “International Working Group for tumor-infiltrating lymphocytes in Breast Cancer—2014”. Results: High tumor-infiltrating lymphocytes were seen in 64.2% and 43.8% in ages &lt; 50 and &gt; 50 respectively. All cases of invasive lobular carcinoma had low tumor-infiltrating lymphocytes. 62.5% of T1 tumors were associated with low TILs whereas 80% of low tumor-infiltrating lymphocytes were T3. 71.4% of lymph node-positive tumors had low tumor-infiltrating lymphocytes. All breast cancers showed lymphocytic infiltrate. 40% of the tumors showed intermediate to high tumor-infiltrating lymphocytes. Lymphocyte-predominant breast cancers were 30%. Among the LPBC, 55.5% were triple-negative breast cancers, 33.3% were HR+, and 11.2% were HER2 positive. Conclusions: Low tumor-infiltrating lymphocytes presented at an advanced stage of the disease at the time of diagnosis. tumor-infiltrating lymphocytes in breasts decreased with increasing age. LPBCs were predominantly TNBCs. All breast cancers were immunogenic, stating the necessity to report tumor-infiltrating lymphocytes in all breast carcinomas.

Perivascular infiltration reflects subclinical lymph node metastasis in invasive lobular carcinoma.

Invasive lobular carcinoma (ILC) is characterized by discohesive cells due to irreversible loss of E-cadherin expression and multiple satellites, where individual cell migration is evident without disturbance of the stroma. Neoplastic cells sometimes infiltrate the surrounding vessel in satellites. Here, we aimed to clarify the specific role of perivascular infiltration (PVI) and ameboid migration, characterized by nondisturbance of the background stromal structure, in ILCs. A total of 139 cases with ILC and 122 cases with invasive breast carcinoma of no special type (IBC-NST) were evaluated retrospectively. PVI was significantly more common in ILC than in IBC-NST (50% [70 of 139 cases] vs. 9% [11 of 122 cases], p < 0.001). ILC cases with PVI showed a larger pathological tumour size than clinical tumour size (p < 0.01), a higher frequency of pathological node status pN2-pN3 when limited to clinically node-negative cases (p < 0.01) and lower circularity of tumour morphology on imaging (p < 0.01) than ILC cases without PVI. In the pathological evaluation, the intensity and occupancy of tumour cells expressing phospho-myosin light chain 2, which is a hallmark of ameboid migration, were significantly higher in ILC cases with PVI than in those without PVI at the tumour margins (p < 0.05). ILC with PVI is associated with irregular, poorly defined tumour margins and lymph node metastasis without adenopathy, which is difficult to assess using imaging. PVI may be caused by ameboid migration, as shown by the positive expression of phospho-myosin light chain 2. The presence of PVI may be a predictor for clinically node-negative pN2-pN3 in ILC patients.

Lack of Clinical Value for Immunohistochemistry for Sentinel Lymph Node Assessment in Invasive Lobular Carcinoma.

The distinct histologic appearance of invasive lobular carcinoma (ILC) may pose diagnostic challenges for sentinel lymph node (SLN) analysis. We evaluated the impact of cytokeratin immunohistochemistry (IHC) on SLN assessment in ILC and its contribution to pathologic nodal upstaging. We identified ILC patients treated with SLN surgery at our institution between September 2008 and August 2021. IHC for SLN assessment was employed at the discretion of the pathologist. Differences between groups evaluated with and without IHC were compared using Chi-square tests. Overall, 608 cases of ILC were identified in patients who underwent SLN surgery. IHC was used in 301 cases (49.5%)and was not associated with cT category, pT category, or tumor grade. Use of IHC increased detection of SLN+ disease when isolated tumor cells (ITCs) were included in the analysis (35.9% with IHC vs. 21.2% without IHC; p<0.001). There was no effect on nodal upstaging to micrometastatic disease (pN1mi) or greater (21.9% with IHC vs. 21.2% without IHC; p=0.82). IHC did not increase the number of positive SLNs detected (median 1 with and without IHC) nor did it increase axillary lymph node dissection (ALND) rates (11.6% with IHC vs. 15.3% without IHC; p=0.18). IHC improved detection of pN0(i+) disease among ILC patients undergoing SLN surgery. IHC did not increase upstaging to pN1mi or higher categories of nodal disease, detection of a greater number of positive SLNs, or ALND rates. Our data suggest routine use of IHC for SLN assessment in ILC patients does not add clinical utility.

MRI background parenchymal enhancement in patients with invasive lobular carcinoma: Endocrine hormonal treatment effect.

High background parenchymal enhancement (BPE) levels and asymmetric distribution could cause diagnostic uncertainty due to morphological similarity to breast cancer, especially invasive lobular carcinoma (ILC). We investigated BPE in ILC patients, its association with the tumor hormonal profile, and the effect of endocrine treatment (ET). The analysis included all MRI examinations performed at our institution between 2010 and 2019 for ILC-diagnosed patients. Baseline study and the first follow-up study were reviewed. Digital medical records were reviewed to retrieve demographics/pathology results/treatment information. BPE and fibroglandular tissue were assessed qualitatively on the contralateral breast according to the criteria of the Breast Imaging Reporting and Data System (BI-RADS). The study included 129 patients. Most (91%) had pure ILC. All received ET; 12% also received chemotherapy; 90% had surgery first; 70% by breast conservation. On the baseline MRI, 70% had mild or moderate BPE; whereas, on the follow-up study, the majority (59%) had minimal BPE. Most BPE reductions were by 2 degrees. In the baseline study, additional biopsies were required in 59% of cases, and in 17%, a short-term follow-up was recommended. In the follow-up study, biopsies were recommended in 10%, and a short-term follow-up was requested in 16%. A correlation between progesterone receptor intensity index and baseline BPE level was observed (r =0.3, p =0.004). ILC patients usually exhibit high BPE. ET decreases BPE, and therefore may decrease false-positive interpretations. Additional research is needed to explore whether study can be performed on ET without compromising sensitivity. ∙ High background parenchymal enhancement levels reduces breast MRI sensitivity, yielding high false positive rates especially when reporting cases of invasive lobular carcinoma [ILC].∙Treatment of ILC with endocrine therapy reduces background parenchymal enhancement and thus could decrease these false-positive interpretations.

Discordance of HER2 Positive Classic Invasive Lobular Carcinoma Between IHC/FISH and Oncotype DX: A Case Report and Literature Review

The classical-type of invasive lobular carcinoma (ILC) usually expresses high levels of estrogen receptor (ER) and progesterone receptor (PR) and does not over-express human epidermal growth factor receptor 2 (HER2) and has a low level of expression of the proliferative marker. Their prognosis is comparable with those of histologic grade 1-2 invasive ductal carcinoma (IDC). HER2 status is prognostically significant and has a huge impact on clinical management; thus, its correct testing and evaluation are critical. Discordant results for HER2 between immunohistochemistry (IHC)/fluorescence in situ hybridization (FISH) and Oncotype DX (ODX) testing can be occasionally seen and cause confusion among clinicians. Here, we present a case of classical ILC (cILC), which was HER2 positive by IHC/FISH but negative by ODX. We also review relevant literature and provide a possible explanation for this discordancy and suggestions on how to approach the discordant results and guide the clinical management.