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Surgical Pathology Clinics Mar 2018Lobular carcinoma in situ (LCIS) is a risk factor and a nonobligate precursor of breast carcinoma. The relative risk of invasive carcinoma after classic LCIS diagnosis... (Review)
Review
Lobular carcinoma in situ (LCIS) is a risk factor and a nonobligate precursor of breast carcinoma. The relative risk of invasive carcinoma after classic LCIS diagnosis is approximately 9 to 10 times that of the general population. Classic LCIS diagnosed on core biopsy with concordant imaging and pathologic findings does not mandate surgical excision, and margin status is not reported. The identification of variant LCIS in a needle core biopsy specimen mandates surgical excision, regardless of radiologic-pathologic concordance. The presence of variant LCIS close to the surgical margin of a resection specimen is reported, and reexcision should be considered.
Topics: Biopsy, Large-Core Needle; Breast Carcinoma In Situ; Carcinoma, Lobular; Disease Management; Female; Humans; Margins of Excision; Mastectomy, Segmental; Precancerous Conditions; Unnecessary Procedures; Watchful Waiting
PubMed: 29413653
DOI: 10.1016/j.path.2017.09.009 -
Breast Cancer Research : BCR Jan 2021Invasive 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... (Review)
Review
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.
Topics: Biomarkers, Tumor; Breast Neoplasms; Carcinoma, Lobular; Diagnosis, Differential; Disease Progression; Disease Susceptibility; Drug Resistance, Neoplasm; Female; Gene Expression; Genomics; Humans; Mutation; Neoplasm Grading; Neoplasm Staging; Phenotype; Prognosis; Tumor Microenvironment
PubMed: 33413533
DOI: 10.1186/s13058-020-01384-6 -
Annals of Oncology : Official Journal... Aug 2022Invasive lobular breast cancer (ILC) is the second most common type of breast cancer after invasive breast cancer of no special type (NST), representing up to 15% of all... (Review)
Review
BACKGROUND
Invasive lobular breast cancer (ILC) is the second most common type of breast cancer after invasive breast cancer of no special type (NST), representing up to 15% of all breast cancers.
DESIGN
Latest data on ILC are presented, focusing on diagnosis, molecular make-up according to the European Society for Medical Oncology Scale for Clinical Actionability of molecular Targets (ESCAT) guidelines, treatment in the early and metastatic setting and ILC-focused clinical trials.
RESULTS
At the imaging level, magnetic resonance imaging-based and novel positron emission tomography/computed tomography-based techniques can overcome the limitations of currently used imaging techniques for diagnosing ILC. At the pathology level, E-cadherin immunohistochemistry could help improving inter-pathologist agreement. The majority of patients with ILC do not seem to benefit as much from (neo-)adjuvant chemotherapy as patients with NST, although chemotherapy might be required in a subset of high-risk patients. No differences in treatment efficacy are seen for anti-human epidermal growth factor receptor 2 (HER2) therapies in the adjuvant setting and cyclin-dependent kinases 4 and 6 inhibitors in the metastatic setting. The clinical utility of the commercially available prognostic gene expression-based tests is unclear for patients with ILC. Several ESCAT alterations differ in frequency between ILC and NST. Germline BRCA1 and PALB2 alterations are less frequent in patients with ILC, while germline CDH1 (gene coding for E-cadherin) alterations are more frequent in patients with ILC. Somatic HER2 mutations are more frequent in ILC, especially in metastases (15% ILC versus 5% NST). A high tumour mutational burden, relevant for immune checkpoint inhibition, is more frequent in ILC metastases (16%) than in NST metastases (5%). Tumours with somatic inactivating CDH1 mutations may be vulnerable for treatment with ROS1 inhibitors, a concept currently investigated in early and metastatic ILC.
CONCLUSION
ILC is a unique malignancy based on its pathological and biological features leading to differences in diagnosis as well as in treatment response, resistance and targets as compared to NST.
Topics: Breast Neoplasms; Cadherins; Carcinoma, Ductal, Breast; Carcinoma, Lobular; Female; Humans; Prognosis; Proto-Oncogene Proteins
PubMed: 35605746
DOI: 10.1016/j.annonc.2022.05.006 -
Cancer Research and Treatment Oct 2022There is a potential risk that lobular carcinoma in situ (LCIS) on preoperative biopsy might be diagnosed as ductal carcinoma in situ (DCIS) or invasive carcinoma in the...
PURPOSE
There is a potential risk that lobular carcinoma in situ (LCIS) on preoperative biopsy might be diagnosed as ductal carcinoma in situ (DCIS) or invasive carcinoma in the final pathology. This study aimed to evaluate the rate of upgrade of LCIS on preoperative biopsy to DCIS or invasive carcinoma.
MATERIALS AND METHODS
Data of 55 patients with LCIS on preoperative biopsy were analyzed. All patients underwent surgery between 1991 and 2016 at Severance Hospital in Seoul, Korea. We analyzed the rate of upgrade of preoperative LCIS to DCIS or invasive cancer in the final pathology. The clinicopathologic features related to the upgrade were evaluated.
RESULTS
The rate of upgrade of LCIS to DCIS or invasive carcinoma was 16.4% (9/55). In multivariate analysis, microcalcification and progesterone receptor expression were significantly associated with the upgrade of LCIS (p=0.023 and p=0.044, respectively).
CONCLUSION
The current study showed a relatively high rate of upgrade of LCIS on preoperative biopsy to DCIS or invasive cancer. The presence of microcalcification and progesterone receptor expression may be potential predictors of upgradation of LCIS on preoperative biopsy. Surgical excision of the LCIS during preoperative biopsy could be a management option to identify the concealed malignancy.
Topics: Biopsy; Breast Carcinoma In Situ; Breast Neoplasms; Calcinosis; Carcinoma in Situ; Carcinoma, Intraductal, Noninfiltrating; Carcinoma, Lobular; Female; Humans; Receptors, Progesterone
PubMed: 34942684
DOI: 10.4143/crt.2021.864 -
The Journal of International Medical... Jun 2021To analyze the characteristics of invasive lobular carcinoma (ILC) compared with invasive ductal carcinoma (IDC) and to investigate the impact of histology on axillary...
OBJECTIVE
To analyze the characteristics of invasive lobular carcinoma (ILC) compared with invasive ductal carcinoma (IDC) and to investigate the impact of histology on axillary lymph node (ALN) involvement in luminal A subtype tumors.
METHODS
We retrospectively analyzed patients diagnosed with ILC or IDC from 2012 to 2016 who underwent surgery. Patients constituted 493 primary early breast cancer cases (82 ILC; 411 IDC).
RESULTS
Compared with IDC, ILC tumors were significantly more likely to be grade 2, estrogen receptor- (ER) positive (+), have a lower proliferation rate (Ki67 <14%), and a higher pathological T stage (pT2-4). The luminal A subtype was significantly more common in ILC compared with IDC. In a multivariate regression model, grade 2, ER+, progesterone receptor-positive, pT2, and pT3 were significantly associated with ILC. Additionally, with the luminal A subtype, ALN involvement (pathological node stage (pN)1-3) was significantly more frequent with ILC versus IDC.
CONCLUSIONS
Our data suggest that grade 2, positive hormone receptor status, and higher pathological T stage are associated with ILC. With the luminal A subtype, ALN involvement was more frequent with ILC versus IDC.
Topics: Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Lobular; Female; Humans; Retrospective Studies
PubMed: 34187216
DOI: 10.1177/03000605211017039 -
Breast Cancer Research : BCR Jan 2015Invasive lobular carcinoma of the breast is the most common 'special' morphological subtype of breast cancer, comprising up to 15% of all cases. Tumours are generally of... (Review)
Review
Invasive lobular carcinoma of the breast is the most common 'special' morphological subtype of breast cancer, comprising up to 15% of all cases. Tumours are generally of a good prognostic phenotype, being low histological grade and low mitotic index, hormone receptor positive and HER2, p53 and basal marker negative, and with a generally good response to endocrine therapy. Despite this, clinicians face countless challenges in the diagnosis and long-term management of patients, as they encounter a tumour that can be difficult to detect through screening, elicits a very invasive nature, a propensity for widespread metastatic colonisation and, consequently, in some studies a worse long-term poor outcome compared with invasive carcinoma of no special type. Here we review the morphological and molecular features that underpin the disparate biological and clinical characteristics of this fascinating tumour type.
Topics: Algorithms; Animals; Biomarkers, Tumor; Breast Neoplasms; Cadherins; Carcinoma, Lobular; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Genomics; Humans; Immunohistochemistry; Immunophenotyping; Neoplasm Invasiveness; Phenotype; Prognosis; Proteomics
PubMed: 25849106
DOI: 10.1186/s13058-015-0519-x -
Breast Cancer Research : BCR Mar 2015While most invasive breast cancers consist of carcinomas of the ductal type, about 10% are invasive lobular carcinomas. Invasive lobular and ductal carcinomas differ... (Review)
Review
While most invasive breast cancers consist of carcinomas of the ductal type, about 10% are invasive lobular carcinomas. Invasive lobular and ductal carcinomas differ with respect to risk factors. Invasive lobular carcinoma is more strongly associated with exposure to female hormones, and therefore its incidence is more subject to variation. This is illustrated by US figures during the 1987 to 2004 period: after 12 years of increases, breast cancer incidence declined steadily from 1999 to 2004, reflecting among other causes the decreasing use of menopausal hormone therapy, and these variations were stronger for invasive lobular than for invasive ductal carcinoma. Similarly, invasive lobular carcinoma is more strongly associated with early menarche, late menopause and late age at first birth. As for genetic risk factors, four high-penetrance genes are tested in clinical practice when genetic susceptibility to breast cancer is suspected, BRCA1, BRCA2, TP53 and CDH1. Germline mutations in BRCA1 and TP53 are predominantly associated with invasive ductal carcinoma, while BRCA2 mutations are associated with both ductal and lobular cancers. CDH1, the gene coding for the E-cadherin adhesion protein, is of special interest as mutations are associated with invasive lobular carcinoma, but never with ductal carcinoma. It was initially known as the main susceptibility gene for gastric cancer of the diffuse type, but the excess of breast cancers of the lobular type in CDH1 families led researchers to identify it also as a susceptibility gene for invasive lobular carcinoma. The risk of invasive lobular carcinoma is high in female mutation carriers, as about 50% are expected to develop the disease. Carriers must therefore undergo intensive breast cancer screening, with, for example, yearly magnetic resonance imaging and mammogram starting at age 30 years.
Topics: Breast Neoplasms; Carcinoma, Lobular; Environment; Female; Gene-Environment Interaction; Genetic Predisposition to Disease; Humans; Incidence; Risk Factors
PubMed: 25848941
DOI: 10.1186/s13058-015-0546-7 -
Molecular Medicine Reports Oct 2021Breast cancer manifests in diverse forms, with particular reference to various cell types harboring different mutations and gene expression profiles. To elucidate the...
Breast cancer manifests in diverse forms, with particular reference to various cell types harboring different mutations and gene expression profiles. To elucidate the clonal relationship between cancer cells in tumors composed of both ductal and lobular phenotypes, two combined lobular and ductal carcinoma (CLDC) cases were analyzed, including one mixed ductal‑lobular carcinoma (MDL) lesion, by direct sequencing of the mitochondrial DNA D‑loop, digital PCR targeting of chromosomes 1q and 16q, as well as next‑generation sequencing. DNA was extracted from formalin‑fixed paraffin‑embedded tissue sections of different histological types, including invasive ductal carcinoma, invasive lobular carcinoma, ductal carcinoma , lobular carcinoma , flat epithelial atypia, non‑neoplastic mammary gland and extramammary organs, using laser‑assisted microdissection. Mutations detected by the comprehensive cancer panel were validated by SYBR green allele‑specific quantitative PCR (RRM1, AKT1, PIK3CA, RALGDS, EGFR, TP53, IL21R, DPYD, SGK1, CDH1, TIMP3 and KMT2C). CLDC, which shared the basic genetic alterations of 1q gain or 16q loss, progresses to invasive lobular or ductual carcinoma with the accumulation of further mutations. Cancer cells contained in an MDL lesion shared closely related genetic alterations, suggesting that these cells have the same origin, despite different histological features, namely 'lobular' or 'ductal'. By contrast, multiple lesions located away from the main tumor, diagnosed as CLDC (excluding an MDL lesion) were not always identical with different genetic alterations, despite being diagnosed as ductal carcinoma . Thus, MDL should be defined as a distinct category separate from CLDC, whose components of 'lobular' and 'ductal' may have the same cellular origin.
Topics: Adult; Breast; Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Intraductal, Noninfiltrating; Carcinoma, Lobular; Female; Genotype; High-Throughput Nucleotide Sequencing; Humans; Male; Middle Aged; Mutation; Phylogeny; Polymorphism, Single Nucleotide
PubMed: 34396426
DOI: 10.3892/mmr.2021.12357 -
Chinese Clinical Oncology Jun 2016The management of in situ lesions ductal carcinoma in situ (DCIS) and lobular carcinoma in situ (LCIS) continues to evolve. These diagnoses now comprise a large burden... (Review)
Review
The management of in situ lesions ductal carcinoma in situ (DCIS) and lobular carcinoma in situ (LCIS) continues to evolve. These diagnoses now comprise a large burden of mammographically diagnosed cancers, and with a global trend towards more population-based screening, the incidence of these lesions will continue to rise. Because outcomes following treatment for DCIS and LCIS are excellent, there is emerging controversy about what extent of treatment is optimal for both diseases. Here we review the current approaches to the diagnosis and treatment of both DCIS and LCIS. In addition, we will consider potential directions for future management of these lesions.
Topics: Breast Neoplasms; Carcinoma in Situ; Carcinoma, Ductal; Carcinoma, Lobular; Disease Management; Female; Humans
PubMed: 27197512
DOI: 10.21037/cco.2016.04.02 -
Breast Cancer Research : BCR Jun 2015Lobular carcinoma in situ (LCIS) is considered to be a risk factor for the development of invasive breast carcinoma, but it may also be a non-obligate precursor to... (Review)
Review
Lobular carcinoma in situ (LCIS) is considered to be a risk factor for the development of invasive breast carcinoma, but it may also be a non-obligate precursor to invasive lobular carcinoma (ILC). Many LCIS lesions do not progress to ILC, and the molecular changes that are necessary for progression from LCIS to ILC are poorly understood. Disruption in the E-cadherin complex is the hallmark of lobular lesions, but other signaling molecules, such as PIK3CA and c-src, are consistently altered in LCIS. This review focuses on the molecular drivers of lobular carcinoma, a more complete understanding of which may give perspective on which LCIS lesions progress, and which will not, thus having immense clinical implications.
Topics: Animals; Breast Neoplasms; Carcinoma in Situ; Carcinoma, Lobular; Cell Transformation, Neoplastic; Disease Progression; Female; Genetic Predisposition to Disease; Humans; Prognosis; Signal Transduction
PubMed: 26041550
DOI: 10.1186/s13058-015-0580-5