Important Studies that Have Advanced Understanding of Lobular Breast Cancer this Century

Invasive lobular carcinoma (ILC) continues to be understudied, but there have been several advances in knowledge these past 20 years. This includes the determination that ILC is a distinct breast cancer subtype. The following are some of the key studies that have contributed to the collective increase in understanding of the basic science, imaging and treatments for ILC since 2000. Click here for a downloadable timeline.

2000

Prevention

Hormone replacement therapy in relation to risk of lobular and ductal breast carcinoma in middle-aged women

This study provided important findings regarding a link between HRT and risk for lobular and ductal breast cancer and laid the ground work for more robust follow-up to determine prevention strategies.

Imaging

Breast imaging with positron emission tomography and fluorine-18 fluorodeoxyglucose: use and limitations

This study demonstrated that primary ILC was harder to detect on FDG PET than IDC.

2003

Epidemiology

Trends in incidence rates of invasive lobular and ductal breast carcinoma

This was one of the first studies to document the rapid increase in the incidence rate of ILC observed in the United States demonstrating that ILC had grown to account for ~20% of all invasive breast cancers. It highlighted the importance of the need for ILC research.

2004

Pathology

Infiltrating lobular carcinoma of the breast: tumor characteristics and clinical outcome

This is a frequently cited analysis that that is still used that showed ILC’s distinct characteristics.

2006

Basic Science

Somatic inactivation of E-cadherin and p53 in mice leads to metastatic lobular mammary carcinoma through induction of anoikis resistance and angiogenesis.

This is the first study demonstrating that E-cadherin loss leads to ILC, rendering the first mouse model of metastatic lobular breast cancer.

2007

Pathology/Diagnosis

Lobular versus ductal breast neoplasms: the diagnostic utility of p120 catenin

This research found that dually staining lesions with both E-cadherin and p120 in analyzing clinical samples created a significantly more accurate process for classifying lesions as ductal or lobular, and was particularly useful in identifying early lesions of lobular neoplasia.

2008

Clinical Pathology

Distinct Clinical and Prognostic Features of Infiltrating Lobular Carcinoma of the Breast: Combined Results of 15 International clinical trials

The results of this large retrospective analysis of 15 international clinical trials concluded that ILC is distinct from IDC in multiple ways, and had prognostic and biologic implications that continue to be important to advance understanding for clinicians and researchers.

2011

Basic Science

Mammary-specific inactivation of E-cadherin and p53 impairs functional gland development and leads to pleomorphic invasive lobular carcinoma in mice

This mouse study corroborated the findings from the Cancer Cell paper from 2006 (above) and pointed to a scenario where a basal progenitor cell type is at the basis of ILC development. It also established a preclinical mouse model of human ILC that can be used for the development of novel interventions to treat ILC.

2015

Systemic Therapy

Relative Effectiveness of Letrozole Compared with Tamoxifen for Patients with Lobular Carcinoma in the BIG 1-98 Trial

This study was important in that it revealed differences in survival rates of patients with ILC and IDC on the same standardly applied therapy, and paved the way for advancing development of more refined treatments and guidelines for more effectively treating ILC.

Imaging

Comparison of 18F-FDG PET/CT for Systemic Staging of Newly Diagnosed Invasive Lobular Carcinoma Versus Invasive Ductal Carcinoma

This study demonstrated that ILC metastases were harder to detect on FDG PET than IDC.

Genetics

Comprehensive Molecular Portraits of Invasive Lobular Breast Cancer

This research was the first comprehensive study describing molecular differences between IDC and ILC using a large number of samples (>100 ILC). It was important to advancing the understanding of ILC as a different breast cancer subtype.

2016

Clinical Pathology

Comparison of clinical outcomes between luminal invasive ductal carcinoma and luminal invasive lobular carcinoma

This study identified the prognosis for early classical, luminal type ILC based on molecular and histological grades. This study showed that luminal ILC and IDC have good early prognosis, however overall ILC carries a worse survival rate compared to IDC, especially over time.

Genetics

Genomic Characterization of Primary Invasive Lobular Breast Cancer

This research was truly important to advance understanding of metastatic ILC.

Basic Science

Cdh1 and Pik3ca Mutations Cooperate to Induce Immune-Related Invasive Lobular Carcinoma of the Breast

ILC research has been hampered by a lack of cellular and animal models. The immune-related ILC mouse models in this study are an important development to aid testing immune-based therapeutics in preclinical settings, developing combination therapies, and for understanding therapy resistance and identifying treatment approaches in metastatic disease.

2017

Metastatic ILC

Distinct Pattern of Metastases in Patients with Invasive Lobular Carcinoma of the Breast

This important study used a prospective metastatic database and showed that ILC often metastasizes to different sites from IDC.

Clinical Pathology

Invasive lobular carcinoma of the breast: A special histological type compared with invasive ductal carcinoma

Analysis of the “Surveillance, Epidemiology, and End Results” (SEER) database showed that metastasis patterns differed between IDC and ILC, and overall long-term outcome was worse for ILC, specifically the ER+/PR-subgroup.  The authors suggest that ILC should be treated as an independent disease, due to different biological behaviors.

2018

Imaging

Breast MR Imaging before Surgery: Outcomes in Patients with Invasive Lobular Carcinoma by Using Propensity Score Matching

It was determined that pre-operative breast MR imaging is beneficial in optimizing surgical planning in ILC and can contribute to a reduction in the rate of repeat surgery without an increase in the initial or final mastectomy rates.

Basic Science

E-Cadherin/ROS1 Inhibitor Synthetic Lethality in Breast Cancer

In a current cancer research approach that exploits tumor features with targeted therapies,  called synthetic lethality screening, research studies whether genetic interactions of two mutations will result in cancer cell death and can be translated into the creation of drug therapies targeting cancer cells. This study demonstrated that licensed ROS1 inhibitors resulted in synthetic lethality of breast cancer cells in conjunction with E-cadherin loss. Because E-cadherin loss of function causes ILC, these findings suggest that ROS1 inhibitors should be considered as candidate drugs for targeted clinical ILC-specific trials.

Basic Science

Immune Infiltration in Invasive Lobular Breast Cancer

This study evaluated tumor-infiltrating lymphocytes and their association with clinic-pathological and outcome variations in ILC and as compared with IDC. Important differences were found in the characterization of immune infiltration of ILC.

Surgery

Breast Conservation and Negative Margins in Invasive Lobular Carcinoma: The Impact of Oncoplastic Surgery and Shave Margins in 358 Patients

This retrospective study of patients undergoing lumpectomy for ILC showed that certain surgical techniques were associated with and important to significantly reducing positive margin rates and the need for more surgeries.

Basic Science

Loss of E-cadherin Enhances IGF1-IGF1R Pathway Activation and Sensitizes Breast Cancers to Anti-IGF-1R/InsR Inhibitors

Studies in cell lines showing that loss of E-cadherin (as seen in lobular tumors) causes increased activation of the insulin like growth factor receptor. Similar observations were made in clinical samples.  Preliminary data show that this activation translates to increased drug sensitivity and reduced proliferation in ILC cultures.

Basic Science

E-cadherin loss induces targetable autocrine activation of growth factor signalling in lobular breast cancer

This study shows that lobular breast cancer cells, because of the loss of E-cadherin may be hyper-responsive to inhibition of Pi3K/AKT independent of activating PI3K mutations. This finding proposed clinical interventions of P13k/Akt in ILC to inhibit ILC cell growth and survival.

2019

Genomics

LobSig is a multigene predictor of outcome in invasive lobular carcinoma

This study has the potential to challenge the status quo standard of care and to provide a clear tool for better treatment of ILC if developed.  It was the first effort to push for other genomic specific tools for ILC.

For a list of more ILC research visit our ILC Research Publication Library.