Subtype Of Invasive Breast Carcinoma Research Articles

Associations between BCL-2 expression and different histopathological prognostic factors in different molecular subtypes of invasive breast carcinoma of no special type.

Breast cancer is heterogeneous and the existing prognostic classifiers are limited in accuracy, leading to the unnecessary treatment of numerous women. B-cell lymphoma 2 (BCL-2), an anti-apoptotic protein, has been proposed as a marker of poor prognosis, associated with resistance to therapy in most tumor types expressing BCL-2. In breast cancer, however, BCL-2 expression has been reported to be a favorable prognostic factor. This study aimed to describe the association between BCL-2 and other well-known pathological prognostic markers among different molecular sub-types of invasive breast carcinoma of no special type (IBC; NST). BCL-2 expression, as well as that of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), were immunohistochemically (IHC) evaluated and compared with other pathological factors, including tumor size, grade, tumor-infiltrating lymphocytes (TILs), lymph-vascular invasion (LVI), and lymph node (LNd) metastasis, in 128 breast cancer cases diagnosed with IBC; NST. Moreover, we analyzed the correlation between BCL-2 expression and relapse-free survival (RFS) in all patients over a two-year period. We found that BCL-2 expression had different pathological prognostic factor associations with different molecular subtypes of breast carcinoma. In the luminal A (i.e., hormonal receptor-positive and HER2-negative) and triple-negative subtypes, the expression of BCL-2 in tumor cells was significantly associated with tumor size, tumor grade, and TILs. BCL2-positive expression in luminal IBC; NST patients resulted in a significantly favorable two-year survival. BCL-2 expression in IBC; NST has different prognostic effects depending on the molecular subtype of the cancer. In cancers with a HER2-enriched phenotype, BCL-2 expression was a marker of poor prognosis, while in cancers with a hormone receptor-positive phenotype, BCL-2 expression had a better prognostic impact.

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.

Evaluating the Clinico-Pathological Relationship Between Stromal Tumor-Infiltrating Lymphocytes and Androgen Receptor Expression Across Molecular Subtypes of Invasive Breast Carcinoma

Evaluating the Clinico-Pathological Relationship Between Stromal Tumor-Infiltrating Lymphocytes and Androgen Receptor Expression Across Molecular Subtypes of Invasive Breast Carcinoma

Preliminary exploration of Trop2 ADC in combination with immune checkpoint inhibitors in the different molecular subtypes of invasive breast carcinoma.

e12558 Background: Human trophoblastic cell surface antigen 2 (Trop2) is a transmembrane protein overexpressed in breast cancer tissues. However, it is present at minimal levels in adult somatic tissues, making it an ideal target for treatment with antibody-drug conjugates (ADCs). Sacituzumab govitecan, an anti-Trop2 ADC, has been approved for the treatment of triple-negative breast cancer and urothelial cancer. Recent studies have demonstrated that human cytotoxic T lymphocytes can recognize Trop2. Accordingly, we aimed to assess the role of Trop2 in the tumor immune activity of different subtypes of breast cancer, and laying the foundation for further studies on the efficacy of the combination of Trop2 ADC and immune checkpoint inhibitors in breast cancer. Methods: We retrospectively retrieved tissues from 152 invasive breast carcinoma of no special type and 111 benign breast tumor tissues and undergoing surgical resection at our institution from 2018 to 2023. Immunohistochemistry was used to detect Trop2 and PD-L1 expression and lymphatic invasion in patients, and their correlations with clinicopathological factors were analyzed. Trop2 expression was evaluated using the H-score. The median as the cut-off value, a score of 0–240 indicated low expression, and 240–300 indicated high expression. Cases with CPS ≥ 1% were considered positive for PD-L1. Results: The expression was Trop2 in breast cancer tissues than in benign tumor tissues (P<0.0001). Immune infiltration analysis suggested that Trop2 expression was correlated with immune cell infiltration and the abundance (P<0.001). Kaplan–Meier plotter analysis demonstrated that high Trop2 expression was related to poor prognosis in patients with triple-negative breast cancer (overall survival: HR=1.53, P=0.029; relapse-free survival: HR=1.26, P=0.045). In contrast, Trop2 expression was not significantly associated with prognosis in other breast cancer subtypes. However, there was no statistically significant correlation found between PD-L1 expression and Trop-2 expression in breast cancer. Conclusions: The findings suggest that Trop2 correlates with poor prognosis and immune cell infiltration in breast cancer. This indicates the role of Trop2 as a potential prognostic biomarker, laying the foundation for further research focusing on the immune regulatory role of Trop2. [Table: see text]

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

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

Abstract 4852: High brain relapse rates in stage III triple negative inflammatory breast cancer are independent of systemic therapy

Abstract Background - Inflammatory breast cancer (IBC) is an aggressive subtype of invasive breast carcinoma that confers a comparatively poorer prognosis owing to consistently observed inferior responses to systemic therapies as compared to non-IBC cases. Triple negative (TN) breast cancer which is characterized by lack of estrogen receptor (ER) and progesterone receptor (PR) expression, as well as by lack of HER2 amplification portends particularly poor outcomes including high rates of brain failure. Here we reviewed our prospective IBC registry data for contemporary TNIBC patients to assess current outcomes and brain failure risk in the context of standard neoadjuvant immunotherapy. Methods - Given the change to the inclusion of pembrolizumab in addition to chemotherapy in the neoadjuvant setting in 2020, we reviewed records from 2016-2023 for Stage III TNIBC patients who presented to MD Anderson Cancer Center (MDACC) prior to receiving other therapy. TNIBC was defined as ER <1%, PR <1%, HER2 IHC 0/1+ or ISH-. N = 38. We examined PCR and brain mets as first failure by regimen (KN522, ACT, AC/TC) and compared using descriptive statistics. Log rank statistic was used to compare overall survival (OS) by PCR. Patients with stage III TNIBC who started the KN522 regimen achieved a pCR rate of 35% (N= 20) and pCR was less frequent in postmenopausal KN522 patients (1/7 PCRs. P = 0.016). Among this cohort, 20% of patients experienced relapse in the CNS as a site of first failure including two patients who achieved a PCR, and 25% had any brain failure at a median follow up post-surgery of 8M. Among 9 patients treated with AC/T 22% achieved pCR with 22% brain metastasis relapse rate as site of first failure and 33% overall was observed at a median follow up of 14M post-surgery. In 9 patients receiving AC/TC, the PCR was 44% and any brain relapse rate was 22%, 1/2 was a site of first failure, median follow up 38M. Despite similarities in brain relapse rates, achieving pCR nonetheless correlated with improved overall survival, P < 0.05. For comparison, among 11 stage IV TNIBC patients treated with neoadjuvant systemic therapy pre-KN522, median follow up 22M from initial diagnosis, 6/11 patients developed brain involvement, 5/6 as a site of first failure. Given small numbers it is difficult to compare PCR by regimen, however we note the PCR in KN522 is lower than expected, and the rate of brain metastases particularly as a site of first failure is consistently high across regimens regardless of PCR. It is critical to consider brain penetrance of neoadjuvant systemic therapies, brain staging and even prophylaxis of brain metastasis in patients with non-metastatic and metastatic TNIBC. Current efforts are ongoing to determine molecular signatures which may aid in prognostication and potentially study design to incorporate prophylactic therapies with the overarching goal of improving outcomes in patients with triple negative IBC. Citation Format: Azadeh Nasrazadani, Megumi Kai, Rachel Layman, Vicente Valero, Sadia Saleem, Bisrat G. Debeb, Anthony Lucci, Susie X. Sun, Swetha Bopparaju, Hope E. Murphy, Angela Alexander, Angela N. Marx, Michael C. Stauder, Bora Lim, Wendy A. Woodward. High brain relapse rates in stage III triple negative inflammatory breast cancer are independent of systemic therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4852.

Relationship between Age, Histologic Grade, Tumour Size, Immunohistochemical Biomarkers Expressions and Molecular Subtypes of Invasive Breast Carcinoma in Ilorin, Nigeria

Background: Background: Invasive breast carcinoma causes the most cancer-related death in women, and age is an essential non-modifiable risk factor. This study determined the relationship between age and histopathologic grade, tumor size, immunohistochemical biomarkers (ER, PR, and HER-2) expressions, and subtypes of invasive breast carcinoma. Methods: This was a retrospective hospital-based study of patients with prior histopathological diagnoses of invasive breast carcinoma. Relevant data, including age, histologic type, grade, tumor size, and hormonal receptor status, were retrieved from the archival pathology request forms. Results: The mean age of study subjects was 52.14 ± 12.14 years. The peak age group was in the 5th decade, accounting for 37.0 (32.7%) cases. Nottingham grade III invasive breast carcinoma accounted for 47 (41.6 %) cases and predominated in the 6th decade, accounting for 17 (50.0%) cases. Majority of the study subjects presented with tumor size greater than 5.0 cm (75.9%). The mean tumor size was 6.87 ± 3.20 cm and ranged from 3.2 cm to 16.0 cm. The immunohistochemical expressions of ER, PR, and HER-2 biomarkers were 36.3%, 28.3%, and 41.6%, respectively, particularly in the 5th and 6th decades. Also, Luminal A, Luminal B, Triplenegative, and HER-2 enriched subtypes occurred in 16.8%, 20.4%, 42.4%, and 20.4% cases respectively in the 5th and 6th decades. However, the triple-negative subtype was found in the 4th to 6th decades in equal proportions. Conclusion: This study observed triple-negative invasive breast carcinoma immunohistochemical subtypes with age association from the 4th to 6th decade

Comparative expression of trophoblast cell-surface antigen 2 (TROP2) in the different molecular subtypes of invasive breast carcinoma: An immunohistochemical study of 94 therapy-naive primary breast tumors

BackgroundSacituzumab govitecan, targeting trophoblast cell-surface antigen 2 (TROP2), is approved for the treatment of triple-negative and hormone receptor-positive/HER2-negative breast cancers. However, detailed studies comparing TROP2 protein expression in the different molecular subtypes of breast cancer are limited, and definitive evidence supporting the use of TROP2 as a biomarker for predicting response to this agent in patients with breast cancer is currently lacking. ObjectiveTo compare the expression of TROP2 in the different molecular subtypes of breast cancer. MethodsImmunohistochemical staining for TROP2 was performed on 94 therapy-naive primary invasive breast carcinomas, including 25 luminal A-like, 25 luminal B-like, 19 HER2-like, and 25 triple-negative tumors. ResultsIntermediate to high levels of TROP2 expression were observed in the majority of carcinomas of each molecular subtype, with a wide range of expression in each subtype. Occasional tumors with low or absent TROP2 expression were encountered, including two metaplastic carcinomas which were completely negative for TROP2. ConclusionsOur observations support the continued investigation of the efficacy of sacituzumab govitecan in all molecular subtypes of breast carcinoma. Furthermore, the observed wide range of expression of TROP2 suggests that TROP2 may have potential utility as a biomarker for predicting responsiveness to sacituzumab govitecan. If this proves to be the case, then immunohistochemical staining for TROP2 would be critical for identifying those patients whose tumors are completely negative for TROP2, since these patients may be least likely or unlikely to respond to this agent, and alternative therapies may be more appropriate in such instances.

Immunohistochemical and Clinicopathological Characteristics of Invasive Breast Carcinoma in Nigeria.

We aimed to study the immunohistochemical and clinicopathological characteristics of invasive breast carcinoma among Nigerian women. We conducted a retrospective assessment of female patients diagnosed with breast carcinoma at a tertiary hospital in Nigeria between 2012 and 2019. Archived pathology request forms and processed specimens (tissue blocks and slides) were used as source data in addition to the patients' demographic and other relevant data. Reports pertaining to 113 patients were assessed. Their age range was 30 to 80 years (mean = 52.1±12.1 years). Breast carcinoma was most common in patients aged 40 to 49 years (32.7%), closely followed by those aged 50 to 59 years (30.1%). Invasive ductal carcinoma was the most common histopathological subtype (94.7%). Nottingham grade III and grade II breast carcinoma accounted for 41.6% and 40.7% of the cases, respectively. Mastectomy specimens formed 68.1% of the samples. The most common tumor size (75.9%) was > 5cm (mean = 6.8±3.2cm), consistent with the most common staging of T3 (46.0%). The most common lymph node involvement was N1 (56.6%). Immunohistochemical assessment of these tumors with estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2 (HER-2) biomarkers expressed positivity of 36.3%, 28.3%, and 41.6%, respectively. These tumors were immunohistochemically classified into luminal A (16.8%), luminal B (20.4%), HER-2 enriched (20.4%), and triple-negative (42.5%) subtypes. The most common immunohistochemical subtype of invasive breast carcinoma among this sample of Nigerian women was the triple-negative subtype, similar to the finding among African Americans.

The prognostic significance of non-lymphoid immune cells of the tumor microenvironment, including neutrophils, eosinophils, and mast cells in breast carcinomas

Background and objectiveThe prognostic importance of lymphoid cells in the tumor microenvironment and their effect on treatment response have been demonstrated in many cancer types. However, there are limited studies on non-lymphoid immune cells. Conflicting results have been obtained regarding the effects of these cells on prognosis. Materials and methodsA total of 331 patients who underwent surgery for breast cancer were included. Patients that received neoadjuvant chemotherapy and those with distant metastasis were excluded. CD 15 immunohistochemistry was performed to detect tumor-infiltrating neutrophils (TINs) and eosinophils (TIEs), while Toluidine Blue histochemistry was performed to detect tumor-infiltrating mast cells (TIMs). ResultsHigh TINs were statistically associated with low ER expression (p < 0.001), low PR expression (p = 0.001), high Ki-67 proliferation index (p = 0.008), and HER2/TN molecular subtypes (p = 0.001). High TIEs were associated with low ER expression (p = 0.001), high Ki67 proliferation index (p = 0.005), and HER2/TN molecular subtype (p = 0.002). High TIMs were associated with high PR expression (p = 0.024), low Ki-67 proliferation index (p = 0.003), and high survival rate (p = 0.006). TIMs and TIEs were good prognostic factors for overall survival in Luminal A and Luminal B subtypes, while TINs and TIEs were found to be independent risk factors for disease-free survival. ConclusionThe evaluation of components of the tumor microenvironment including TINs, TIEs, and TIMs is easy and practical. High TIMs and TIEs are independent prognostic factors, especially in luminal molecular subtype of invasive breast carcinoma. However, to use this parameter in routine pathology practice, more studies from different centers and standard evaluation are needed.

A Clinicopathological Analysis of Molecular Subtypes of Breast Cancer using Immunohistochemical Surrogates: A 6-Year Institutional Experience from a Tertiary Cancer Center in North India.

Puneet Kaur SomalObjective Classification of breast cancer into different molecular subtypes has important prognostic and therapeutic implications. The immunohistochemistry surrogate classification has been advocated for this purpose. The primary objective of the present study was to assess the prevalence of the different molecular subtypes of invasive breast carcinoma and study the clinicopathological parameters in a tertiary care cancer center in rural North India. Materials and Methods All female patients diagnosed with invasive breast cancer and registered between January 1, 2015, and December 31, 2020, were included. Patients with bilateral cancer, missing information on HER2/ER/PR receptor status, absence of reflex FISH testing after an equivocal score on Her 2 IHC were excluded. The tumors were classified into different molecular subtypes based on IHC expression as follows-luminal A-like (ER- and PR-positive, Her2-negative, Ki67 < 20%), luminal B-like Her2-negative (ER-positive, Her2-negative and any one of the following Ki67% ≥ 20% or PR-negative/low, luminal B-like Her2-positive (ER- and HER2-positive, any Ki67, any PR), Her2-positive (ER- and PR-negative, Her2-positive) and TNBC (ER, PR, Her2-negative). Chi square test was used to compare the clinicopathological parameters between these subtypes. Results A total of 1,625 cases were included. Luminal B-like subtype was the most common (41.72%). The proportion of each subtype was luminal A (15.69%), luminal B Her2-negative (23.93%), luminal B Her2-positive (17.78%), Her2-positive (15.26%), TNBC (27.32%). Majority of the tumors were Grade 3 (75.81%). Nodal metastases were present in 59%. On subanalysis of the luminal type tumors without Her2 expression (luminal A-like and luminal B-like (Her2-negative), luminal A-like tumors presented significantly with a lower grade ( p < 0.001) and more frequent node-negative disease in comparison to luminal B-like (Her2-negative) tumors. In comparison to other subtypes, TNBC tumors were more frequently seen in the premenopausal age group ( p < 0.001) and presented with node-negative disease ( p < 0.001). Conclusion This is one of the largest studies that enumerates the prevalence of various molecular subtypes of breast cancer in North India. Luminal B-like tumors were the most common followed by TNBC. TNBC tumors presented more commonly in premenopausal age group and with node negative disease in comparison to other subtypes.

Abstract P2-23-11: Quantitative gene expression by RT-PCR in histologic subtypes of invasive breast carcinoma: an update in nearly one million cases

Abstract Background: Invasive ductal carcinoma (IDC) accounts for ~80% of all invasive breast carcinomas (IBC) with several histologic subtypes comprising the remainder of cases. Some histologic subtypes of IDC (such as tubular carcinoma) have been associated with better prognosis, while other subtypes (such as metaplastic and micropapillary) have been associated with poorer prognosis. Prior studies have shown patients with early stage, hormone-receptor positive IBC that have low Recurrence Score® (RS), as measured by the 21-gene Oncotype DX® (ODX) assay, have little benefit from chemotherapy. Here, we report our experience with the histologic subtypes of IDC and associated patterns of observed gene expression using ODX. Methods: All US samples submitted for IBC ODX between 2005 to 2021 were reviewed. Ductal carcinoma NOS (DC), tubular carcinoma (TC), cribriform carcinoma (CC), mucinous carcinoma (MUC), lobular carcinoma classic, solid or alveolar type (ILC), pleomorphic lobular carcinoma (PL), medullary/medullary-like carcinoma (MED), metaplastic carcinoma (MET), micropapillary carcinoma (MP), papillary carcinoma (PC) and solid papillary carcinoma (SPC) were included. Quantitative expression of 16 cancer-related genes was measured on a scale from 2 to 15 (relative to reference genes) where 1 unit increment is associated with ~2-fold change in expression. RS was calculated as published. Descriptive statistics for the RS, individual genes (ER, PR, HER2), and gene groups [invasion gene group (IGG) and proliferation gene group (PGG)] were obtained. Results: A total of 957,624 samples were included in this analysis with 85.4% DC, 9.7% ILC, 2.8% MUC, 0.5% TC, 0.4% PL, 0.4% PC, 0.3% MP, 0.2% CC, 0.2% MED, 0.1% SPC, and 0.02% MET. For all types, a wide continuous range of RS was noted. MET had the highest median RS, followed in decreasing order by MED, PL, DC &amp; ILC, TC, MUC, MP, CC, SPC, and PC. ER and PR were highest among PC and SPC. ER and PR were lowest among MED and MET. HER2 was highest among PC and TC and lowest among MED and MET. IGG was highest in MET and lowest in SPC. PGG was lowest for TC and highest for MED and MET. ER+/PR-/HER2- phenotype occurred more often in MED and PL. ER-/PR+/HER2- phenotype rarely occurred, but was most frequent in MED and MET. ER+/PR+/HER2+ accounted for 0.4% of our total sample. Conclusions: Here, we demonstrate histologic subtypes of IDC have a wide continuous range of RS. ODX assay may be used to further stratify patients with IDC and its histologic subtypes; however, further studies are needed to better understand the predictive capability of ODX in the histologic subtypes. Table 1. Quantitative gene expression by RT-PCR in histologic subtypes of invasive breast carcinoma Table 2. Biomarker profile in histologic subtypes of invasive breast carcinoma Citation Format: Nhu Thuy Can, Cynthia A. Flannery, Jess Hoag, Alekhya Akkunuri, Helen Bailey, Frederick Baehner. Quantitative gene expression by RT-PCR in histologic subtypes of invasive breast carcinoma: an update in nearly one million cases [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 P2-23-11.

Pure Mucinous Carcinoma of the Breast: Radiologic-Pathologic Correlation.

Mucinous carcinoma (MC) of the breast is a rare, specialized subtype of invasive breast carcinoma (IBC) accounting for approximately 1% to 4% of all primary breast malignancies. Mucinous carcinoma occurs predominantly in patients who are postmenopausal or elderly. It is usually detected on screening mammography, but occasionally the patient may present with a palpable mass. The most common mammographic appearance is an equal to high density, oval or round mass with circumscribed or indistinct margins; MC can mimic a benign lesion. Histologically, MC is a well-differentiated cancer characterized by pools of mucin around neoplastic cells. Depending on mucin content, the tumor is classified as pure (≥90% mucin) or mixed (>10% and <90% mucin). Pure MCs (PMCs) are of low or intermediate nuclear grade, and the vast majority are hormone receptor-positive and human epidermal growth factor-2 receptor-negative (luminal A subtype). Pure MCs may be classified as hypocellular (type A) or hypercellular (type B) and have a lower rate of axillary lymph node involvement and more favorable prognosis than IBCs, no special type. The purpose of this article is to review the clinical features, imaging appearances, associated histopathology, and management of PMC.

TROP2, androgen receptor, and PD-L1 status in histological subtypes of high-grade metaplastic breast carcinomas.

High-grade metaplastic breast carcinoma (HG-MBC) is a rare subtype of invasive breast carcinoma, mostly triple-negative. Metaplastic carcinomas are less responsive to neoadjuvant chemotherapy and are associated with a worse outcome than invasive carcinomas of no special type. Clinicopathological characteristics and immunophenotype were retrospectively assessed in a series of 65 patients diagnosed with HG-MBC between 2005 and 2017 at the Curie Institute (antibody panel: oestrogen receptor [ER], progesterone receptor [PR], androgen receptor [AR], human epidermal growth factor receptor 2 [HER2], programmed death ligand-1 [PD-L1], and trophoblast cell surface antigen 2 [TROP2]). The median age at diagnosis was 59.5 years. Six (9%) patients had metastatic disease at diagnosis. Among the nonmetastatic patients receiving neoadjuvant therapy, 26% (5/19) achieved pathological complete response. Most tumours were pT1/pT2 (77%) and 12% were pN+. Histological subtypes (mixed, squamous, mesenchymal, and spindle cell) were 40%, 35.5%, 15.5%, and 9%, respectively. Tumour-infiltrating lymphocytes were low or moderate except when squamous differentiation was present. Most tumours were triple-negative (92%). AR and TROP2 were positive in 34% and 85% of the cases, respectively. PD-L1 was positive in tumour cells in 18% (cutoff: 1% of positive tumour cells) of the cases and in tumour-infiltrating immune cells in 40% (cutoff: 1% of tumour area) of the cases. Notably, spindle cell and mesenchymal metaplastic breast carcinomas were mostly PDL1-negative. Lastly, 21 (32.3%) cases were HER2-low, all being HER2 1+, with no HER2 2+. Metaplastic breast carcinoma could benefit from tailored therapeutic strategies adapted to the phenotypic specificities of histological subtypes.

Acinic Cell Carcinoma of the Breast: A Rare and Diagnostically Challenging Entity

Acinic Cell Carcinoma (AcCC) of the breast is a rare subtype of invasive breast carcinoma that falls under the category of salivary gland-type tumours of the breast. Histologically, it closely resembles AcCC of the salivary gland. Here, the authors report a case of AcCC of the breast in a 51-year-old woman who presented with a palpable lump in her right breast. Radiological investigation revealed a Breast Imaging Reporting and Data System (BIRADS) score V lesion. A core biopsy was performed, and the histopathological examination revealed relatively bland cells arranged in an acinar pattern within a myxoid stroma, closely resembling adenosis rather than a neoplasm. The diagnosis posed a challenge in the core biopsy due to its close resemblance to adenosis. However, the clinical and radiological findings strongly suggested malignancy. Immunostaining with p63 was conducted, which helped demonstrate the absence of myoepithelial cells around the tumour cell nests and supported the neoplastic nature of the lesion. Despite the bland and low-grade morphology, the tumour was found to be triple negative for Oestrogen Receptor (ER), Progesterone Receptor (PR), and Human Epidermal Growth Factor Receptor 2 (HER2), and it exhibited characteristic positivity for SRY-Box Transcription Factor 10 (SOX 10), S100, and CK7, which aided in making the diagnosis. The authors presented the case report to highlight the rarity of this subtype of breast carcinoma and to emphasise the importance of histomorphology and immunoprofile in reaching a diagnosis. To the best of the authors’ knowledge, the present case was the second reported case of AcCC of the breast from India, adding to the novelty of this case.

Model-Free and Model-based Parameters Derived From CAIPIRINHA-Dixon-TWIST-VIBE DCE-MRI: Associations With Prognostic Factors and Molecular Subtypes of Invasive Ductal Breast Cancer.

CAIPIRINHA-Dixon-TWIST-VIBE (CDTV) dynamic contrast-enhanced MRI (DCE-MRI) can be used to characterize breast cancer. However, the influence of the clinicopathologic factors and molecular subtypes of invasive breast carcinoma (IDC) on the model-free and model-based parameters has not been investigated. To compare model-free and model-based parameters of CDTV DCE-MRI with both clinicopathologic factors and molecular subtypes of IDC. Prospective. A total of 152 patients (mean age, 52 years) with IDC including 42 luminal A, 64 luminal B, 22 human epidermal growth factor receptor-2 (HER2) positive, and 24 triple-negative subtypes. A 3 T; turbo-FLASH, Dixon VIBE, and CDTV. Model-free parameters (initial enhancement rate [IER] and maximum slope [MS]) were estimated from the time-intensity curve. The mean, minimum, maximum, and range between the minimum and maximum values of inline model-based parameters (Ktrans , kep , and ve ) were measured to assess intratumoral heterogeneity of IDC lesions. Student's t tests, Mann-Whitney U tests, Kruskal-Wallis tests, post hoc Steel-Dwass tests, and receiver operating characteristic (ROC) curves. P < 0.05 was considered significant. No significant differences in IER and MS values were seen among the clinicopathologic factors and molecular subtypes (Bonferroni-corrected P=0.011-0.862, P=0.145-0.601, respectively). The minimum kep values in HER2-positive IDC were significantly lower than those in HER2-negative IDC. The mean and range kep values were independent predictors for distinguishing the high (grade 3) and low (grade 1 or 2) nuclear grade groups according to multivariable analyses. The post hoc test showed that the kep minimum and kep range values were significantly different between luminal A and HER2-positive tumor subtypes, yielding an area-under-the-curve of 0.820. Compared with the model-free parameters, inline kep related model-based parameters on CDTV DCE-MRI can be applied as a feasible tool to differentiate luminal A from HER2-positive breast cancers. 2. Stage 2.

A comparison of invasive lobular carcinoma with other invasive breast cancers at Tygerberg Academic Hospital.

The second most common histological subtype of invasive breast carcinoma is invasive lobular carcinoma (ILC) occuring with a frequency 10-15% in Western countries and approximately 5%, in Africa, the Middle East and Asia (AMA). Combined hormone replacement therapy (CHRT) is a risk factor for the development of ILC which is infrequently diagnosed at our centre.This study aimed to investigate the incidence and clinicopathological characteristics of ILC as compared to invasive breast carcinoma of no special type (IBC-NST). Clinical and pathological data on breast carcinoma patients attending the breast and endocrine unit at Tygerberg Academic Hospital since 2017 have been recorded on a Stellenbosch University REDCap® database. IBC-NST was the most frequent subtype diagnosed (83.9%) and ILC the second most common subtype (5.2%). Most ILCs were of luminal B intrinsic subtype, and the median size was slightly smaller than IBC-NST. There were significantly more grade 2 ILCs than IBC-NSTs (81.5% vs 50.9%). There was no statistical difference between stage and histological subtype. ILC has clinicopathological differences when compared to IBC-NST, although these were less pronounced in this study. The prevalence of ILC was similar to numbers reported in AMA. We hypothesise that there may be a discrepancy in the prevalence of ILC between public and private healthcare systems in South Africa, and that it may be due to differing trends in prescribing CHRT.

A comparison of invasive lobular carcinoma with other invasive breast cancers at Tygerberg Academic Hospital

BACKGROUND: The second most common histological subtype of invasive breast carcinoma is invasive lobular carcinoma (ILC) occuring with a frequency 10-15% in Western countries and approximately 5%, in Africa, the Middle East and Asia (AMA). Combined hormone replacement therapy (CHRT) is a risk factor for the development of ILC which is infrequently diagnosed at our centre.This study aimed to investigate the incidence and clinicopathological characteristics of ILC as compared to invasive breast carcinoma of no special type (IBC-NST METHODS: Clinical and pathological data on breast carcinoma patients attending the breast and endocrine unit at Tygerberg Academic Hospital since 2017 have been recorded on a Stellenbosch University REDCap® database RESULTS: IBC-NST was the most frequent subtype diagnosed (83.9%) and ILC the second most common subtype (5.2%). Most ILCs were of luminal B intrinsic subtype, and the median size was slightly smaller than IBC-NST. There were significantly more grade 2 ILCs than IBC-NSTs (81.5% vs 50.9%). There was no statistical difference between stage and histological subtype CONCLUSION: ILC has clinicopathological differences when compared to IBC-NST, although these were less pronounced in this study. The prevalence of ILC was similar to numbers reported in AMA. We hypothesise that there may be a discrepancy in the prevalence of ILC between public and private healthcare systems in South Africa, and that it may be due to differing trends in prescribing CHRT

Correlation between tumor to liver SUV ratio and molecular subtypes of invasive breast carcinoma in PET CT

BackgroundBreast cancer is known to be one of the most cancer affecting women around the globe and the second most common cancer in general. In third worlds countries, breast cancer is the most cause of cancer death. Early diagnosis and accurate follow-up of these patients affect the management. There are multiple prognostic factors most important one is the immunohistochemical molecular markers in the specimens including human epidermal growth factor, progesterone, and estrogen receptors (HER2, PR, ER). In breast cancer, the HER2 positive molecular subtype is associated with a bad prognosis and aggressive histological features, yet while following neoadjuvant chemotherapy, it achieves an increased pathological complete response rate. 18F-fluoro-2-deoxy-d-glucose positron emission tomography (FDG PET) has proved to be an effective and accurate imaging technique for lymph node and distant metastasis assessment, tumor staging, restaging of recurrence, treatment response, and follow-up. In breast cancer, tumor molecular subtype, tumor size, proliferation index, and histological grade correlated with 18F-fluoro-2-deoxy-d-glucose (FDG) uptake. This study evaluates the possible correlation between tumor to liver and tumor to spleen (standardized uptake value) SUV max ratio and the four different molecular subtypes in patients with pathologically proven primary breast cancer.ResultsTumor to liver and tumor to spleen SUV max ratio (TLR, TSR) was a significant parameter for HER2 molecular subtype identification (P value = 0.0005 and 0.014 respectively) and luminal A molecular subtype identification (P value = 0.016 and 0.037 respectively). The specificity, sensitivity, and area under the receiver operating-characteristic curve (AUC) of TLR parameters for HER2-positive subtype identification were 89.4%, 83.3%, and 0.89, respectively. The specificity, sensitivity, and AUC of the TSR parameter for HER2-positive subtype identification were 57.9%, 100%, and 0.83, respectively.ConclusionsTLR and TSR appeared to be valuable for HER2- and luminal A molecular subtype detection. thus, 18F-FDG PET/CT could be a beneficial tool for prediction of tumor biological characteristics that help in management of breast cancer patients.

The diffusion MRI signature index is highly correlated with immunohistochemical status and molecular subtype of invasive breast carcinoma.

To evaluate the relationship of the signature index (S-index), an advanced diffusion MRI marker, and the immunohistochemical (IHC) status, proliferation rate, and molecular subtype of invasive breast cancers. A retrospective study of patients with invasive carcinoma was conducted between 2017 and 2021. All patients underwent dynamic contrast-enhanced MRI and DWI using a 3-T system. For DWI, three b values (0, 200, and 1500 s/mm2) were used to derive the S-index. Three-dimensional ROIs were manually placed over the whole tumor on DWI. Mean and 85th percentile S-index values were compared to the IHC status, proliferation rate, and molecular subtypes of lesions. The study included 153 patients (mean age, 60 ± 13 years) with 160 invasive carcinomas. S-index values were significantly higher in estrogen receptor-positive (mean, p = .005; 85th percentile, p < .001) and progesterone receptor-positive (mean, p = .003; 85th percentile, p < .001) tumors, and significantly lower in human epidermal growth factor receptor 2 (HER2) - positive tumors (mean, p = .023; 85th percentile, p < .001). Mean and 85th percentile S-index values were significantly different among breast cancer subtypes (mean, p = .015; 85th percentile, p = .002), and the AUC of these values for the prediction of IHC status were 0.64 and 0.66 for HER2, and 0.70 and 0.74 for hormone receptors, respectively. The DWI S-index showed significantly higher values in invasive carcinomas with immunohistochemical status associated with good prognosis, suggesting its usefulness as a noninvasive imaging biomarker to estimate IHC status and orient treatment. • The signature index, an advanced diffusion MRI marker, showed good discrimination of immunohistochemical status in invasive breast carcinomas. • The signature index has the potential to differentiate noninvasively invasive breast carcinoma subtypes and appears as an imaging biomarker of prognostic factors and molecular phenotypes.