Search

Metastatic spread of tumour cells to tissues and organs around the body is the most frequent cause of death from breast cancer. This has been modelled mainly using mouse models such as syngeneic mammary cancer or human in mouse xenograft models. These have limitations for modelling human disease progression and cannot easily be used for investigation of drug resistance and novel therapy screening. To complement these approaches, advances are being made in ex vivo and 3D in vitro models, which are becoming progressively better at reliably replicating the tumour microenvironment and will in the future facilitate drug development and screening. These approaches include microfluidics, organ-on-a-chip and use of advanced biomaterials. The relevant tissues to be modelled include those that are frequent and clinically important sites of metastasis such as bone, lung, brain, liver for invasive ductal carcinomas and a distinct set of common metastatic sites for lobular breast cancer. These sites all have challenges to model due to their unique cellular compositions, structure and complexity. The models, particularly in vivo, provide key information on the intricate interactions between cancer cells and the native tissue, and will guide us in producing specific therapies that are helpful in different context of metastasis. [ABSTRACT FROM AUTHOR]

Purpose: Accounting for about 15% of invasive lobular carcinomas and 1% of breast carcinomas, pleomorphic lobular carcinoma is known to be a rare histological subtype of invasive lobular carcinoma. Yet, it is more aggressive and produces a worse prognosis than other breast cancers. Ultimately, the present study compares the clinicopathological features of pleomorphic and invasive lobular breast carcinomas. Methods: In the study, we retrospectively evaluated the data of 262 patients with histological subtypes of classical and pleomorphic lobular cancers having been recruited for surgical operations. After resorting to Kolmogorov-Smirnov and Shapiro-Wilk tests to check the normality of distribution, the categorical and continuous variables were compared between the groups using the chi-square test and independent samples t test, respectively. In all analyses, we considered a P -value of <.05 to be statistically significant. Results: Our findings revealed that the groups with lobular and pleomorphic groups significantly differed by Ki-67 value, estrogen receptor negativity, grade, multicentricity, multifocality, surgical margin positivity, completion mastectomy, and metachronous contralateral tumor (P <.05). Conclusion: We discovered that pleomorphic type was associated with higher grades, estrogen receptor negativity, and Ki-67 expression. The incidence of metachronous breast cancer was high in the pleomorphic group, which may be a noteworthy finding to be considered in follow-ups. In addition, the high rates of multicentricity and multifocality of tumors in the pleomorphic group may be associated with increased surgical margin positivity and a higher likelihood of mastectomy. In a nutshell, our findings may guide patients and surgeons regarding the type of intervention and reconstruction options to be adopted in prospective surgeries. [ABSTRACT FROM AUTHOR]

18F-fluoroestradiol (18F-FES) is a Food and Drug Administration-approved radiopharmaceutical used for molecular imaging of the estrogen receptor (ER). When combined with PET, 18F-FES may improve the diagnosis of ER-positive breast cancer in the metastatic setting and provide insights into tumor heterogeneity. In this article, we review data on the use of 18F-FES imaging for treatment selection, staging, imaging lobular breast cancer, and the novel breast specific imaging tool, dedicated breast PET.

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 ERPOSHer2NEG 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. [ABSTRACT FROM AUTHOR]

Gastrointestinal tract breast cancer (BC) metastases represent a rare event and generally originate from the lobular subtype. Duodenal involvement was rarely described in previous case series. Abdominal symptoms are extremely unspecific and misleading. Diagnosis is challenging, and it consists of a few mandatory steps from radiological examinations to histological and immunohistochemical analyses. Here, we presented the clinical case of a 54-year-old postmenopausal woman who was hospitalized for vomiting and jaundice, presenting increased level of liver enzymes and minimal main bile duct and choledocus dilatation at abdominal ultrasonography. She underwent breast-conserving surgery and axillary lymph node dissection for stage IIIB lobular BC, 5 years before. Metastatic infiltration of the duodenal bulb originating from lobular BC was proven histologically, through fine-needle aspiration during endoscopic ultrasonography. Treatment was established after multidisciplinary team evaluation, based on the clinical status and prognosis of the patient. Pancreaticoduodenectomy was performed, and final histological examination confirmed the secondary localization of lobular BC, infiltrating the duodenal and gastric wall, pancreas parenchyma, and surrounding tissues. No metastatic lymph nodes were found. After surgery, the patient underwent first line of adjuvant systemic treatment with fulvestrant and ribociclib. After a follow-up of 21 months, the patient was in good clinical condition, without signs of locoregional or distant recurrence. This report stressed on the importance of a tailored therapeutic approach. Although systemic therapy generally represents the preferred option, surgery should not be excluded if an oncological radical resection can be performed achieving acceptable locoregional disease control.

Introduction: Mutations occurring in the CDH1 gene elevate the susceptibility to the development of hereditary diffuse gastric cancer (HDGC) as well as lobular breast cancer (LBC). LBCs with CDH1 germline mutations are classified as hered- itary breast cancers, devoid of any indication of gastric carcinoma. As prophylactic gastrectomy is a recommended course of treatment for individuals with CDH1 mu- tations, it is advised that genetic testing be conducted for those who meet the criteria established by the National Comprehensive Cancer Network (NCCN). This study aimed to screen patients with HDGC for CDH1 testing and clinical management for the prevention of HDGC. Moreover, patients with LBC are tested for CDH1 mutation. Materials and Methods: In this multicenter study, thirty-one patients with HDGC were selected among 615 patients and admitted for CDH1 mutation testing. PCR for all 16 exons of CDH1 and Sanger sequencing were performed. Patients with LBC who are negative for BRCA1/2 were also included in this study regardless of gastric cancer history. Results: The results showed that 5.04% of patients with DGC were identified as HDGC of which 9.6% of individuals had a pathogenic CDH1 mutation and only 15.38% of cases with a family history carried germline mutation in CDH1. Furthermore, 7.6% of patients with LBC and negative for a family history of gastric cancer have CDH1 mutation. Discussion: All patients who met the NCCN criteria were not CDH1 mutation-positive, indicating other genes should be involved in DGC. Moreover, patients with LBC and negative for BRCA1/2 are recommended for testing the mutation in CDH1. [ABSTRACT FROM AUTHOR]

Gastrointestinal tract breast cancer (BC) metastases represent a rare event and generally originate from the lobular subtype. Duodenal involvement was rarely described in previous case series. Abdominal symptoms are extremely unspecific and misleading. Diagnosis is challenging, and it consists of a few mandatory steps from radiological examinations to histological and immunohistochemical analyses. Here, we presented the clinical case of a 54-year-old postmenopausal woman who was hospitalized for vomiting and jaundice, presenting increased level of liver enzymes and minimal main bile duct and choledocus dilatation at abdominal ultrasonography. She underwent breast-conserving surgery and axillary lymph node dissection for stage IIIB lobular BC, 5 years before. Metastatic infiltration of the duodenal bulb originating from lobular BC was proven histologically, through fine-needle aspiration during endoscopic ultrasonography. Treatment was established after multidisciplinary team evaluation, based on the clinical status and prognosis of the patient. Pancreaticoduodenectomy was performed, and final histological examination confirmed the secondary localization of lobular BC, infiltrating the duodenal and gastric wall, pancreas parenchyma, and surrounding tissues. No metastatic lymph nodes were found. After surgery, the patient underwent first line of adjuvant systemic treatment with fulvestrant and ribociclib. After a follow-up of 21 months, the patient was in good clinical condition, without signs of locoregional or distant recurrence. This report stressed on the importance of a tailored therapeutic approach. Although systemic therapy generally represents the preferred option, surgery should not be excluded if an oncological radical resection can be performed achieving acceptable locoregional disease control. [ABSTRACT FROM AUTHOR]

The thirteenth annual workshop of the European Network for Breast Development and Cancer (ENBDC) Laboratories Annual Workshop took place on the 28–30 April 2022 in Weggis, Switzerland and focused on methods in mammary gland biology and breast cancer. Sixty scientists participated in the ENBDC annual workshop which had not been held in person since 2019 due to the global COVID-19 pandemic. Topics spanned the mammary gland biology field, ranging from lactation biology and embryonic development, single cell sequencing of the human breast, and stunning cutting-edge imaging of the mouse mammary gland and human breast as well as breast cancer research topics including invasive progression of the pre-invasive DCIS stage, metabolic determinants of endocrine therapy resistance, models for lobular breast cancer, and how mutational landscapes of normal breast during age and pregnancy determine cancer risk. The latest findings from participating researchers were presented through oral presentations and poster sessions and included plenty of unpublished work. [ABSTRACT FROM AUTHOR]

Breast cancer incidence has been steadily rising and is the leading cause of cancer death in women due to its high metastatic potential. Individual breast cancer subtypes are classified by both cell type of origin and receptor expression, namely estrogen, progesterone and human epidermal growth factor receptors (ER, PR and HER2). Recently, the importance and context-dependent role of glucocorticoid receptor (GR) expression in the natural history and prognosis of breast cancer subtypes have been uncovered. In ER-positive breast cancer, GR expression is associated with a better prognosis as a result of ER-GR crosstalk. GR appears to modulate ER-mediated gene expression resulting in decreased tumor cell proliferation and a more indolent cancer phenotype. In ER-negative breast cancer, including GR-positive triple-negative breast cancer (TNBC), GR expression enhances migration, chemotherapy resistance and cell survival. In invasive lobular carcinoma, GR function is relatively understudied, and more work is required to determine whether lobular subtypes behave similarly to their invasive ductal carcinoma counterparts. Importantly, understanding GR signaling in individual breast cancer subtypes has potential clinical implications because of the recent development of highly selective GR non-steroidal ligands, which represent a therapeutic approach for modulating GR activity systemically. • Glucocorticoid receptor (GR) is expressed in about 60% of both estrogen receptor positive (ER+) and negative (ER-) breast cancers. • Glucocorticoid receptor transcriptional activity is breast cancer subtype dependent (e.g. luminal versus basal). • GR activation inhibits proliferation in ER+ breast cancer cells. • GR-mediated gene expression pathways (e.g. EMT, cell survival, metastasis) are associated with worse TNBC prognosis. [ABSTRACT FROM AUTHOR]

Introduction: Invasive lobular breast cancer (ILC) is a diagnostic challenge due to the diversity of morphological features. The objective of the study was to investigate the presentation and local extent of ILC using various imaging techniques and to assess the correlation between imaging and molecular profile. Materials and methods: We reviewed 162 consecutive patients with ILC found on vacuum-assisted biopsy, who underwent evaluation of the lesion morphology and extent using ultrasound (US), mammography (MMG), and magnetic resonance imaging (MRI). Radiographic features were compared with ILC intrinsic subtype based on the expression of Ki-67 and estrogen, progesterone, and HER2 receptors. Results: A total of 113 mass lesions and 49 non-mass enhancements (NMEs) were found in MRI. Masses were typically irregular and spiculated, showing heterogeneous contrast enhancement, diffusion restriction, and type III enhancement curve. NMEs presented mainly as the area of focal or multiregional distribution with heterogeneous or clumped contrast enhancement, diffusion restriction, and type III enhancement curve. Lesion extent significantly varied between MRI and MMG/ultrasonography (USG) (P < 0.001) but did not differ between MGF and ultrasonography (USG). The larger the ILC, the higher the disproportion when lesion extent in MRI was compared with MMG (P < 0.001) and ultrasonography (USG) (P < 0.001). In the study group, there were 97 cases of luminal A subtype (59.9%), 54 cases of luminal B HER2-(33.3%), nine cases of luminal B HER2+ (5.5%), and two cases of triple negative (1.2%). The HER2 type was not found in the study group. We did not observe any significant correlation between molecular profile and imaging. Conclusion: MRI is the most effective technique for the assessment of ILC local extent, which is important for optimal treatment planning. Further studies are needed to investigate if the intrinsic subtype of ILC can be predicted by imaging features on MRI. [ABSTRACT FROM AUTHOR]

IntroductionInvasive lobular breast cancer (ILC) is a diagnostic challenge due to the diversity of morphological features. The objective of the study was to investigate the presentation and local extent of ILC using various imaging techniques and to assess the correlation between imaging and molecular profile.Materials and methodsWe reviewed 162 consecutive patients with ILC found on vacuum-assisted biopsy, who underwent evaluation of the lesion morphology and extent using ultrasound (US), mammography (MMG), and magnetic resonance imaging (MRI). Radiographic features were compared with ILC intrinsic subtype based on the expression of Ki-67 and estrogen, progesterone, and HER2 receptors.ResultsA total of 113 mass lesions and 49 non-mass enhancements (NMEs) were found in MRI. Masses were typically irregular and spiculated, showing heterogeneous contrast enhancement, diffusion restriction, and type III enhancement curve. NMEs presented mainly as the area of focal or multiregional distribution with heterogeneous or clumped contrast enhancement, diffusion restriction, and type III enhancement curve. Lesion extent significantly varied between MRI and MMG/ultrasonography (USG) (P < 0.001) but did not differ between MGF and ultrasonography (USG). The larger the ILC, the higher the disproportion when lesion extent in MRI was compared with MMG (P < 0.001) and ultrasonography (USG) (P < 0.001). In the study group, there were 97 cases of luminal A subtype (59.9%), 54 cases of luminal B HER2− (33.3%), nine cases of luminal B HER2+ (5.5%), and two cases of triple negative (1.2%). The HER2 type was not found in the study group. We did not observe any significant correlation between molecular profile and imaging.ConclusionMRI is the most effective technique for the assessment of ILC local extent, which is important for optimal treatment planning. Further studies are needed to investigate if the intrinsic subtype of ILC can be predicted by imaging features on MRI.

The detection of circulating tumor DNA (ctDNA) in the plasma of cancer patients is emerging as a very sensitive and specific prognostic biomarker. Previous studies with ctDNA have focused on the ability of ctDNA detection to predict micrometastatic and eventual clinical metastatic relapse. There are few data on the role of ctDNA in monitoring response to local therapy. The present study reports the case of a patient with early-stage lobular breast cancer, with a detectable ctDNA test which resolved with local radiotherapy to the breast. This case suggests that ctDNA is sensitive enough to detect the response of minimal residual disease, localized in the breast, to radiation therapy, and thus may assist in providing indications for local breast cancer treatment. [ABSTRACT FROM AUTHOR]

Purpose: Lobular breast cancer (LBC) accounts for ~ 15% of breast cancer. Here, we studied the frequency of pathogenic germline variants (PGVs) in an extended panel of genes in women affected with LBC. Methods: 302 women with LBC and 1567 without breast cancer were tested for BRCA1/2 PGVs. A subset of 134 LBC affected women who tested negative for BRCA1/2 PGVs underwent extended screening, including: ATM, CDH1, CHEK2, NBN, PALB2, PTEN, RAD50, RAD51D, and TP53.Results: 35 PGVs were identified in the group with LBC, of which 22 were in BRCA1/2. Ten actionable PGVs were identified in additional genes (ATM(4), CDH1(1), CHEK2(1), PALB2(2) and TP53(2)). Overall, PGVs in three genes conferred a significant increased risk for LBC. Odds ratios (ORs) were: BRCA1: OR = 13.17 (95%CI 2.83–66.38; P = 0.0017), BRCA2: OR = 10.33 (95%CI 4.58–23.95; P < 0.0001); and ATM: OR = 8.01 (95%CI 2.52–29.92; P = 0.0053). We did not detect an increased risk of LBC for PALB2, CDH1 or CHEK2. Conclusion: The overall PGV detection rate was 11.59%, with similar rates of BRCA1/2 (7.28%) PGVs as for other actionable PGVs (7.46%), indicating a benefit for extended panel genetic testing in LBC. We also report a previously unrecognised association of pathogenic variants in ATM with LBC. [ABSTRACT FROM AUTHOR]

Background: Vitamin D (vitD) may be involved in different extraskeletal conditions as well as skeletal muscle diseases. It has been hypothesized that, at least in part, a low level of vitD could contribute to facilitating cancer development. Breast cancer (BC) seems to be associated with low levels of vitD. Materials and methods: This was an observational retrospective evaluation of 87 women (mean age: 54 ± 12 years old) who underwent surgery for the treatment of BC. Our main purpose was to correlate the types of BC and the levels of vitD. Results: A positive significant correlation (R > 0.7) was found between non-invasive carcinoma in situ and 25(OH)D levels and age (R = 0.82, p < 0.05). A positive, but nonsignificant, correlation was reported between invasive ductal carcinoma and 25(OH)D and age (R = 0.45, p > 0.05). A negative but nonsignificant correlation was found between invasive lobular carcinoma and 25(OH)D and age (R = 0.24, p > 0.05). Discussion and Conclusions: We did not find a significant relationship between vitD and BC subtypes. Considering the positive significant correlation between vitD levels and age for in situ BC, although preliminary, our results seem to suggest a possible role of vitD in in situ BC. However, these findings need to be confirmed in larger studies. [ABSTRACT FROM AUTHOR]

Invasive lobular carcinoma (ILC) comprises 8–15 % of all invasive breast cancers and large population-based studies with >10 years of follow-up are rare. Whether ILC has a long-time prognosis different from that of invasive ductal carcinoma, (IDC) remains controversial. To investigate the excess mortality rate ratio (EMRR) of patients with ILC and IDC and to correlate survival with clinical parameters in a large population-based cohort. From 1989 through 2006, we identified 17,481 patients diagnosed with IDC (n = 14,583) or ILC (n = 2898), younger than 76 years from two Swedish Regional Cancer Registries. Relative survival (RS) during 20 years of follow up was analysed. ILC was significantly associated with older age, larger tumours, ER positivity and well differentiated tumours. We noticed an improved survival for patients with ILC during the first five years, excess mortality rate ratio (EMRR) 0.64 (CI 95 % 0.53–0.77). This was shifted to a significant decreased survival 10–15 years after diagnosis (EMRR 1.49, CI 95 % 1.16–1.93). After 20 years the relative survival rates were similar, 0.72 for ILC and 0.73 for IDC. During the first five years after surgery, the EMRR was lower for patients with ILC as compared to patients with IDC, but during the years 10–15 after surgery, we observed an increased EMRR for patients with ILC as compared to IDC. These EMRR between ILC and IDC were statistically significant but the absolute difference in excess mortality between the two groups was small. • This is a large population-based study with more than 17,000 patients with a follow up exciding 20 years. • There is clinically important differences between invasive lobular and ductal carcinoma of the breast. • Lobular carcinoma shows better survival during the first period but significantly worse at the late period of observation. [ABSTRACT FROM AUTHOR]

Invasive lobular carcinoma accounts for 5%–15% of all invasive breast cancers, with a marked increase in incidence rates over the past two decades. Distinctive biological hallmarks of invasive lobular carcinoma include the loss of cell adhesion molecule E-cadherin leading to cells with a discohesive morphology, proliferating into single-file strands and estrogen receptor positivity. These key molecular features can make diagnosis difficult, as invasive lobular carcinoma is challenging to detect both physically and with current standard imaging. Treatment of invasive lobular carcinoma strongly favors endocrine therapy due to low chemosensitivity and lower rates of pathological response as a result. This review will summarize the distinct biological and molecular features of invasive lobular carcinoma, focusing on the diagnostic challenges faced and the subsequent surgical and medical management strategies. Prospective therapeutic options will also be explored, highlighting how furthering our understanding of the unique biology of lobular breast carcinoma is essential in guiding and informing the treatment of patients in the future. [ABSTRACT FROM AUTHOR]

Invasive lobular carcinoma (ILC) is the most common of the breast cancer special types, accounting for up to 15% of all breast cancer cases. ILCs are noted for their lack of E-cadherin function, which underpins their characteristic discohesive growth pattern, with cells arranged in single file and dispersed throughout the stroma. Typically, tumours are luminal in molecular subtype, being oestrogen and progesterone receptor positive, and HER2 negative. Since last reviewing the lobular literature (McCart Reed et al., Breast Cancer Res 17:12, 2015), there has been a considerable increase in research output focused on this tumour type, including studies into the pathology and management of disease, a high-resolution definition of the genomic landscape of tumours as well as the evolution of several potential therapeutic avenues. There abounds a huge amount of new data, which we will review herein. [ABSTRACT FROM AUTHOR]

Background: Invasive lobular breast cancer (BC) is the second most common BC subtype. Prognostic parameters (tumor classification, lymph node status, histologic grade, Oncotype DX recurrence score [RS], progesterone receptor status, and Ki67 index) were retrospectively studied in a large, prospective clinical trial encompassing 2585 patients who had hormone receptor‐positive early BC (the West German Study Group PlanB trial). Methods: BCs were centrally reviewed and classified as lobular (n = 353; 14%) or nonlobular (n = 2232; 86%). The median follow‐up was 60 months. Five‐year disease‐free survival (DFS) estimates were obtained using the Kaplan‐Meier method. Prognostic parameters were evaluated using Cox proportional hazard models. Results: Lobular BC was associated with higher tumor classification, higher lymph node status, lower histologic grade, lower Ki67 index, and low or intermediate RS. The prevalence of high RS (RS range, 26‐100) was 3‐fold lower in patients who had lobular BC compared with those who had nonlobular BC (8% vs 24%; P <.001). However, 5‐year DFS estimates for lobular and nonlobular BC were similar (92.1% and 92.3%, respectively; P =.673). In multivariate analyses, prognostic parameters for DFS in lobular BC included grade 3 (hazard ratio, 5.06; 95% CI, 1.91‐13.39) and a pathologic lymph node status (pN) of pN3 (hazard ratio, 12.16; 95% CI, 3.87‐38.24), but not RS. By contrast, prognostic parameters in nonlobular BC included grade 3 (hazard ratio, 1.65; 95% CI, 1.11‐2.44), pN3 (hazard ratio, 3.68; 95% CI, 1.60‐8.46), and high RS (hazard ratio, 2.49; 95% CI, 1.69‐3.68). Conclusions: Lobular BC is associated with low and intermediate RS, although 5‐year DFS is similar to that of nonlobular BC. The effect of the RS in lobular BC appears to be distinct from that in nonlobular BC. For risk assessment, the RS needs to be complemented by clinicopathologic parameters for therapy decision making. The prognostic impact of the Oncotype DX recurrence score in lobular breast cancer is distinct from that in nonlobular breast cancer. Correct histologic classification is a prerequisite for the adequate clinical utilization of prognostic gene expression profiles. [ABSTRACT FROM AUTHOR]

Invasive lobular carcinoma (ILC) has been reported to be less responsive to neoadjuvant chemotherapy (NAC) than invasive ductal carcinoma (IDC). We sought to determine whether ILC histology indeed predicts poor response to NAC by analyzing tumor characteristics such as protein expression, gene expression, and imaging features, and by comparing NAC response rates to those seen in IDC after adjustment for these factors. We combined datasets from two large prospective NAC trials, including in total 676 patients, of which 75 were of lobular histology. Eligible patients had tumors ≥3 cm in diameter or pathologic documentation of positive nodes, and underwent serial biopsies, expression microarray analysis, and MRI imaging. We compared pathologic complete response (pCR) rates and breast conservation surgery (BCS) rates between ILC and IDC, adjusted for clinicopathologic factors. On univariate analysis, ILCs were significantly less likely to have a pCR after NAC than IDCs (11 vs. 25 %, p = 0.01). However, the known differences in tumor characteristics between the two histologic types, including hormone receptor (HR) status, HER2 status, histological grade, and p53 expression, accounted for this difference with the lowest pCR rates among HR+/HER2- tumors in both ILC and IDC (7 and 5 %, respectively). ILC which were HR- and/or HER2+ had a pCR rate of 25 %. Expression subtyping, particularly the NKI 70-gene signature, was correlated with pCR, although the small numbers of ILC in each group precluded significant associations. BCS rate did not differ between IDC and ILC after adjusting for molecular characteristics. We conclude that ILC represents a heterogeneous group of tumors which are less responsive to NAC than IDC. However, this difference is explained by differences in molecular characteristics, particularly HR and HER2, and independent of lobular histology.

Abstract Background Metastases to the thyroid gland are more frequent than previously thought, although most of them are occult or not clinically relevant. Overall, only 42 cases of metastases to thyroid from breast cancer have been reported thus far. Here we report the case of a patient with breast cancer metastatic to the thyroid. We also review the 42 previously reported cases (published between 1962 and 2012). This is the first review about metastases to thyroid gland from breast cancer. Case presentation A 64-year-old woman of Caucasian origin was diagnosed with a lobular invasive carcinoma of the breast (luminal A, stage II). She received adjuvant chemotherapy, followed by endocrine therapy. During follow-up, fine-needle cytology of a thyroid nodule revealed malignant cells that were estrogen-positive, which suggested a diagnosis of metastases to the thyroid. Imaging did not reveal any other metastatic site and showed only enlargement of the left thyroid lobe and an inhomogeneous pattern of colloid and cystic degeneration and calcifications. The patient underwent left hemithyroidectomy. Histology of thyroid tissue showed a colloid goitre containing dispersed small atypical neoplastic cells with eccentric nuclei. Immunohistochemistry showed cytokeratin-19 and oestrogen receptor, but not tireoglobulin, e-cadherin or cytokeratin-7, thereby confirming metastases from a lobular breast carcinoma. Hormonal treatment is ongoing. Conclusion This case report and first review of the literature on metastases to thyroid from breast cancer highlight the importance of a correct early diagnostic work-up in such cases. Indeed, a primary lesion should be distinguished from metastases given the different treatment protocol related to primary cancer and the clinical impact on prognosis.

Breast cancer is the main site of origin of orbital metastatic disease. Although invasive lobular breast carcinoma accounts for 10–15% of all breast cancer cases, it has been noticed that it metastasizes to the orbit more often compared to breast cancer of no special type (NST). The pathogenesis of this metastasis is not entirely understood; however, it seems that the unique tissue-specific characteristics of orbital microenvironment might contribute to metastatic disease in this particular site. Given the increasing survival of breast cancer patients and the prolonged metastatic potential of invasive lobular breast carcinoma, it is possible that the incidence of this rare metastasis might increase in the future. The purpose of this review is to present clinical manifestations, immunohistochemical characteristics and therapeutic options for orbital metastases from invasive lobular carcinoma. [ABSTRACT FROM AUTHOR]

Background: Pleomorphic invasive lobular cancer (pleomorphic ILC) is a rare variant of ILC that is characterized by a classic ILC-like growth pattern combined with an infiltrative ductal cancer (IDC)-like high nuclear atypicality. There is an ongoing discussion whether pleomorphic ILC is a dedifferentiated form of ILC or in origin an IDC with a secondary loss of cohesion. Since gene promoter hypermethylation is an early event in breast carcinogenesis and thus may provide information on tumor progression, we set out to compare the methylation patterns of pleomorphic ILC, classic ILC and IDC. In addition, we aimed at analyzing the methylation status of pleomorphic ILC. Methods: We performed promoter methylation profiling of 24 established and putative tumor suppressor genes by methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) analysis in 20 classical ILC, 16 pleomorphic ILC and 20 IDC cases. Results: We found that pleomorphic ILC showed relatively low TP73 and MLH1 methylation levels and relatively high RASSF1A methylation levels compared to classic ILC. Compared to IDC, pleomorphic ILC showed relatively low MLH1 and BRCA1 methylation levels. Hierarchical cluster analysis revealed a similar methylation pattern for pleomorphic ILC and IDC, while the methylation pattern of classic ILC was different. Conclusion: This is the first report to identify TP73, RASSF1A, MLH1 and BRCA1 as possible biomarkers to distinguish pleomorphic ILC from classic ILC and IDC. [ABSTRACT FROM AUTHOR]

Metastasis to the periocular soft tissue of the orbit is a rare manifestation of metastatic cancer. Infiltrating lobular breast cancer (ILBC) is a special breast cancer subtype, which accounts for 10-15% of all mammary carcinomas and for ~1% of all malignancies. Here, we report on a high frequency of lobular breast cancer in patients with orbital metastases identified in an original series of metastatic tumor specimens and by a systematic literature review. A series of 14 orbital metastases was compiled from formalin-fixed paraffin-embedded archival tissues. All cases were subjected to histological re-review and detailed immunophenotypical characterization. In addition, we performed a meta-analysis of 68 previously published case reports describing orbital metastases, with special reference to breast cancer subtypes. Based on clinical history, histomorphology, immunophenotype, and/or comparison with matched primary tumors, orbital metastases were derived from breast cancer in 8/14 cases, seven of which were classified as metastatic lobular breast cancer. Other entities included non-small cell lung cancer (4/14), infiltrating ductal breast cancer (1/14), prostate cancer (1/14) and adenocarcinoma of the esophagus (1/14). In line with this original series of orbital metastases, lobular breast cancer was the most common malignancy in 72 patients with orbital metastases described in 68 independent case reports. In conclusion, lobular breast cancer represents the cancer subtype with the highest prevalence among orbital metastases. The high frequency of ILBC in orbital metastases illustrates the special metastatic behavior of this tumor entity and may have implications for the understanding of the organotropism of metastatic lobular breast cancer. [ABSTRACT FROM AUTHOR]

Invasive lobular carcinoma (ILC) is the second most common histological subtype among newly diagnosed breast cancers. The clinical features of ILC are related to the underlying biology of this disease, which is distinguished by loss of the cell adhesion protein e-cadherin. The resulting poorly cohesive growth pattern is responsible for the comparatively poor detection of ILC both on imaging and palpation. Recent genomic and proteomic discoveries have identified other molecular features of ILC which may lead to its future treatment with more targeted therapy. The presentation, treatment, and outcome of ILC is reviewed and future research directions are considered. [ABSTRACT FROM AUTHOR]

Breast cancer is one of the major diseases in women and devote great economic and scientific efforts. The intention of continuing to find ways of better and early diagnosis, and improved prognosis. In the age ranges of increased risk for this disease have been described several triggers such as receptors: estrogen (ER), progesterone (PR), and protein c-erbB-2. Biopses were used ductal and lobular breast cancer diagnostic routine, subjected to immunohistochemical antibodies to ER, PR and specifically anti c-erbB-2.The development was through HRP AEC and DAB commercial kit. Images were captured with Olympus CX31 microscope and digital camera and software built Micrometrics SE Premium 2011. The results allow observed positive reaction in red color in the samples developed with AEC and brown when used DAB in cells expressing the bearing and which are distributed equally at the site of pathology tissue affected. These techniques are protocolized by clinical use in diagnosing breast cancer, so its standardization and visualization are of extreme importance to the histopathology laboratory of integrated units of breast disease. [ABSTRACT FROM AUTHOR]

BACKGROUND: Late age at first full-term birth and nulliparity are known to increase breast cancer risk. The frequency of these risk factors has increased in recent decades. METHODS: The purpose of this population-based case-control study was to examine associations between parity, age at first birth (AFB), and specific histological subtypes of breast cancer. Women with breast cancer were identified from cancer registries in Wisconsin, Massachusetts, and New Hampshire. Control subjects were randomly selected from population lists. Interviews collected information on reproductive histories and other risk factors. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of ductal, lobular, and mixed ductal-lobular breast cancer diagnosis in association with AFB and nulliparity. RESULTS: AFB ≥30 years was associated with a 2.4-fold increase in risk of lobular breast cancer compared with AFB <20 years (OR, 2.4; 95% CI, 1.9-2.9). The association was less pronounced for ductal breast cancer (OR, 1.3; 95% CI, 1.2-1.4). Nulliparity was associated with increased risk for all breast cancer subtypes, compared with women with AFB <20 years, but the association was stronger for lobular (OR, 1.7; 95% CI, 1.3-2.2) than for ductal (OR, 1.2; 95% CI, 1.1-1.3) subtypes (P = .004). The adverse effects of later AFB was stronger with obesity (P = .03) in lobular, but not ductal, breast cancer. CONCLUSIONS: Stronger associations observed for late AFB and nulliparity suggest that these factors preferentially stimulate growth of lobular breast carcinomas. Recent temporal changes in reproductive patterns and rates of obesity may impact the histological presentation of breast cancer. [ABSTRACT FROM AUTHOR]

Hereditary diffuse gastric cancer (HDGC) is an inherited cancer-susceptibility syndrome characterized by autosomal dominance and high penetrance. In 30-50% of cases, a causative germline mutation in CDH1, the E-cadherin gene, may be identified. Female carriers of CDH1 mutations also have an increased (20-40%) risk of lobular breast cancer. Endoscopic surveillance of patients with CDH1 mutations is ineffective because early foci of HDGC are typically small and underlie normal mucosa. CDH1 mutation carriers are therefore offered the option of prophylactic gastrectomy, which commonly reveals early foci of invasive signet-ring cell cancer. We review recommendations for genetic testing, surveillance and prophylactic surgery in HDGC. Areas for future research are discussed, including development of new screening modalities, optimal timing of prophylactic gastrectomy, identification of additional causative mutations in HDGC, management of patients with CDH1 missense mutations and prevention/early detection of lobular breast cancer in CDH1 mutation carriers. [ABSTRACT FROM AUTHOR]

Accumulating evidences indicate that p120 catenin, a member of the E-cadherin (E-CD)/catenin adhesion complex, plays a role in tumor invasion. To establish the expression pattern of p120 in breast cancer, we analysed 326 breast tissue biopsies by tissue microarray. Most of the lobular tumors (88%) showed exclusive cytoplasmic localization, and 6% of them also had p120 nuclear staining. Cytoplasmic p120 strongly associated with complete loss of E-CD and ß-catenin not only in lobular carcinoma and its metastases but also in atypical lobular hyperplasias. In the latter, loss of heterozygosity of E-CD gene was also observed. Complete loss of E-CD and cytoplasmic and nuclear p120 staining was also observed in primary lobular cancer cell cultures generated by us. In ductal tumors, by contrast, reduction of p120 and E-CD in membrane was very common (57 and 53%, respectively), whereas cytoplasmic p120 staining was rarely seen. This simultaneous reduction of membranous E-CD and p120 was not associated with increased Src kinase activity. To demonstrate that cytoplasmic p120 localization was a consequence of the absence of E-CD, the endogenous E-CD was re-expressed in MDA-231 cells by 5-Aza-2'-deoxycytidine (5Aza) treatment. After treatment, p120 shifted from the cytoplasm to the membrane, where it colocalized with endogenous E-CD. Additionally, suppressing E-CD expression in Madin-Darby canine kidney cells by stable transfection of the transcriptional repressors Snail, E47 or Slug, provokes p120 cytoplasmic localization and p120 isoform switching. In conclusion, abnormal cytoplasmic and nuclear localization of p120, which are mediated by the absence of E-CD, characteristically occur in the early stages of lobular breast cancer and are maintained during tumor progression to metastasis. Consequently, p120 may be an important mediator of the oncogenic effects derived from E-CD inactivation, including enhanced motility and invasion, in lobular breast cancer.Oncogene (2004) 23, 3272-3283. doi:10.1038/sj.onc.1207439 Published online 12 April 2004 [ABSTRACT FROM AUTHOR]

We review the case of an elderly woman with invasive lobular breast cancer presenting as malignant ascites. This unusual presentation is discussed, as well as the options for treatment. Most invasive lobular breast cancers are hormone receptor positive and the roles of hormonal and chemotherapy are reviewed. [ABSTRACT FROM AUTHOR]