Invasive lobular breast cancer: A review of pathogenesis, diagnosis, management, and future directions of early stage disease

Thomas, Mathew; Kelly, Erinn Downs; Abraham, Jame; Kruse, Megan

doi:10.1053/j.seminoncol.2019.03.002

Cited by 114 publications

(93 citation statements)

References 76 publications

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“…[ 16 , 17 , 30 ] Moreover, ILC patients exhibit better disease-free survival and overall survival, especially among those at a high risk. [ 3 , 31 ] Similarly, from our nomogram (Fig. 1 ) it is evident that the prognosis is worse for patients who do not receive chemotherapy, while the probabilities of residual disease and local recurrence decrease after chemotherapy.…”

Section: Discussionsupporting

confidence: 52%

“…[ 2 ] ILC has unique clinical, pathological, and radiographic features that suggest it is a distinct clinical entity. [ 3 ] Over the last 2 decades ILC has accounted for 25,000 to 30,000 new cases of breast cancer in the USA annually, and its incidence is increasing, especially among postmenopausal women. If considered an independent cancer type, ILC would be the sixth-most-common cancer in women, with an occurrence frequency similar to those of non-Hodgkin's lymphoma and melanoma.…”

Section: Introductionmentioning

confidence: 99%

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A nomogram for determining the disease-specific survival in invasive lobular carcinoma of the breast

Yang

Wang

et al. 2020

Medicine

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We aimed to establish and validate a nomogram for predicting the disease-specific survival of invasive lobular carcinoma (ILC) patients. The Surveillance, Epidemiology, and End Results program database was used to identify ILC from 2010 to 2015, in which the data was extracted from 18 registries in the US. Multivariate Cox regression analysis was performed to identify independent prognostic factors and a nomogram was constructed to predict the 3-year and 5-year survival rates of ILC patients based on Cox regression. Predictive values were compared between the new model and the American Joint Committee on Cancer staging system using the concordance index, calibration plots, integrated discrimination improvement, net reclassification improvement, and decision-curve analyses. In total, 4155 patients were identified. After multivariate Cox regression analysis, nomogram was established based on a new model containing the predictive variables of age, the primary tumor site, histology grade, American Joint Committee on Cancer TNM (tumor node metastasis) stages II, III, and IV, breast cancer subtype, therapy modality (surgery and chemotherapy). The concordance index for the training and validation cohorts were higher for the new model (0.781 and 0.832, respectively) than for the old model (0.733 and 0.779). The new model had good performance in the calibration plots. Net reclassification improvement and integrated discrimination improvement were also improved. Finally, decision-curve analyses demonstrated that the nomogram was clinically useful. We have developed a reliable nomogram for determining the prognosis and treatment outcomes of ILC. The new model facilitates the choosing of superior medical examinations and the optimizing of therapeutic regimens with cooperation among oncologists.

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Section: Discussionsupporting

confidence: 52%

Section: Introductionmentioning

confidence: 99%

A nomogram for determining the disease-specific survival in invasive lobular carcinoma of the breast

Yang

Wang

et al. 2020

Medicine

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“…As such, ILC is often difficult to detect via physical exam and mammography, resulting in a delayed diagnosis and more advanced disease at presentation. Additionally, ILC is associated with unique sites of metastasis [ 4 , 5 ] and more challenging surgical management [ 6 , 7 ]. Biomarkers for ILC are consistent with the hormone-dependent “luminal A” molecular subtype (e.g., estrogen receptor alpha (ERα, hereafter ER) and progesterone receptor positive, human epidermal growth factor receptor 2 (HER2) negative)) [ 1 , 3 ].…”

Section: Introductionmentioning

confidence: 99%

Estrogen Regulation of mTOR Signaling and Mitochondrial Function in Invasive Lobular Carcinoma Cell Lines Requires WNT4

Shackleford

Bordeaux

et al. 2020

Cancers

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Invasive lobular carcinoma of the breast (ILC) is strongly estrogen-driven and represents a unique context for estrogen receptor (ER) signaling. In ILC, ER controls the expression of the Wnt ligand WNT4, which is critical for endocrine response and anti-estrogen resistance. However, signaling mediated by WNT4 is cell type- and tissue-specific, and has not been explored in ILC. We utilized reverse phase protein array (RPPA) to characterize ER and WNT4-driven signaling in ILC cells and identified that WNT4 mediates downstream mTOR signaling via phosphorylation of S6 Kinase. Additionally, ER and WNT4 control levels of MCL-1, which is associated with regulation of mitochondrial function. In this context, WNT4 knockdown led to decreased ATP production and increased mitochondrial fragmentation. WNT4 regulation of both mTOR signaling and MCL-1 were also observed in anti-estrogen resistant models of ILC. We identified that high WNT4 expression is associated with similar mTOR pathway activation in ILC and serous ovarian cancer tumors, suggesting that WNT4 signaling is active in multiple tumor types. The identified downstream pathways offer insight into WNT4 signaling and represent potential targets to overcome anti-estrogen resistance for patients with ILC.

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“…Invasive lobular breast cancer (ILC) accounts for around 5-15% of breast cancers and is the second most common histological subtype after invasive breast cancer of no specific type, commonly referred to as invasive ductal carcinoma (IDC). ILC is recognised to exhibit a number of clinico-pathological characteristics distinct from those of IDC [1,2]. It has an increased propensity for multi-centricity, multi-focality and bilaterality, in addition to an unusual pattern of metastatic dissemination having a predilection for spread to the gastro-intestinal tract, peritoneum and ovary [3].…”

Section: Introductionmentioning

confidence: 99%

Identification of stromal genes differentially expressed in lobular breast cancer highlights role for pregnancy-associated-plasma protein-A

Gómez-Cuadrado

Zhao

Souleimanova

et al. 2020

Preprint

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Background: Invasive lobular carcinoma (ILC) is the second most common histological subtype of breast cancer and exhibits a number of clinico-pathological characteristics that are distinct from the more common invasive ductal carcinoma (IDC). Despite these differences, ILC is treated in the same way as IDC. We set out to identify alterations in the tumor microenvironment (TME) of ILC with potential clinical significance. Methods:We used laser-capture microdissection (LCM) to separate tumor epithelium from stroma in 23 ER+ ILC samples. Gene expression analysis was used to identify genes that are enriched in the stroma of ILC, but not IDC or normal breast.Results: 45 genes involved in regulation of the extracellular matrix (ECM) were enriched in the stroma of ILC, but not stroma from ER+ IDC or normal breast. Of these, 10 were expressed in cancer-associated fibroblasts (CAFs) and were increased in ILC compared to IDC in bulk gene expression datasets. PAPPA was the most enriched in the stroma compared to the tumor epithelial compartment in ILC. PAPPA encodes pregnancy-associated plasma protein-A (PAPP-A), a metalloproteinase that cleaves insulin-like binding protein-4 (IGFBP-4) increasing IGF-1 bioavailability and subsequent downstream signaling. Analysis of PAPPA and IGF1 associated genes identified a paracrine signaling pathway and active PAPP-A was shown to be secreted from primary CAFs. Comprehensive survival analysis across 3000 breast cancers identified PAPPA as a potential ILC-specific prognostic marker.Conclusions: This is the first study to demonstrate molecular differences in the TME between ILC and IDC and identifies PAPP-A, a CAF-derived proteinase, as a potential prognostic marker.

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Invasive lobular breast cancer: A review of pathogenesis, diagnosis, management, and future directions of early stage disease

Cited by 114 publications

References 76 publications

A nomogram for determining the disease-specific survival in invasive lobular carcinoma of the breast

A nomogram for determining the disease-specific survival in invasive lobular carcinoma of the breast

Estrogen Regulation of mTOR Signaling and Mitochondrial Function in Invasive Lobular Carcinoma Cell Lines Requires WNT4

Identification of stromal genes differentially expressed in lobular breast cancer highlights role for pregnancy-associated-plasma protein-A

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