The 2023 San Antonio Breast Cancer Symposium (SABCS22) included 20 research posters focused on lobular breast cancer. Posters at research conferences are tools used to present new information, often the synopsis and key findings of a research study, in a graphic form. The posters are visual presentations of abstracts that have been submitted for consideration and publication at a conference. These abstracts will be published in a special publication by the American Association of Cancer Research (AACR) in the Spring of 2024.
The following is a collection of lay summaries of many of the lobular breast cancer-specific posters presented at SABCS23. Permission to share the posters and lay summaries have been provided by the authors.
A poster by the Lobular Breast Cancer Alliance (LBCA) sharing the results of our survey on experience with ILC and surgery is also included in the summaries.
List of Posters and Lay Summaries Provided with Author Permission Contained in This Article Include:
(Summaries follow this listing)
- PO1-15-03 Spatially resolved analysis of tumor microenvironment in invasive lobular carcinoma.
- PO2-07-09 Early stage invasive lobular breast cancer is underestimated on conventional imaging including MRI.
- PO2-11-09 European Lobular Breast Cancer Advocates: Bridging the Geographical Gaps in Lobular Breast Cancer Education and Awareness.
- PO2-27-08 Discovery of glucocorticoid receptor-induced EMT and integrin gene expression and increased cell motility in invasive lobular breast cancer.
- PO3-15-09 LobSig4 is a superior and readily implementable ILC-focused prognostic biomarker set.
- PO4-02-03 Distribution of MammaPrint, BluePrint, and Response Predictive Subtypes based on ImPrint and Reprint in ER+/HER2- Invasive Lobular Carcinoma – A FLEX sub study.
- PO4-02-12 MDA iLobular Prognostic Tool: A Novel Approach for Risk Stratification in Invasive Lobular Carcinoma.
- PO4-19-03 FES-PET/MRI for Tailored treatment of luminal A and lobular breast cancer: a prospective cohort study.
- PO4-28-09 Upregulation of the immune checkpoint protein B7-H3 is associated with an immune suppressive microenvironment in progression from in situ to invasive lobular breast cancer.
- PO5-04-12 Comparison of chemotherapy efficacy in metastatic lobular vs. ductal breast cancer.
- PO5-06-14 Genomic Landscape and Clinical Outcomes of Triple-Negative Invasive Lobular Carcinoma.
- PO5-13-12 Personalized circulating tumor DNA testing for recurrence detection and treatment response monitoring in patients with metastatic invasive lobular carcinoma.
- PO5-24-11 An integrated approach for comprehensive molecular and tumor microenvironment characterization of invasive lobular carcinoma.
- PO5-26-07 Surgery for Invasive Lobular Carcinoma: A Patient Experience Survey from the Lobular Breast Cancer Alliance.
Lay Summaries and/or Copies of Posters are Provided Below:
- PO1-15-03 Spatially resolved analysis of tumor microenvironment in invasive lobular carcinoma.
In this study, our goal was to explore the diversity within the tumor microenvironment (the set of normal cells and molecules that surround and feed a tumor cell) of invasive lobular carcinoma (ILC). We used a technique called spatial transcriptomics (ST) on 43 frozen tumor samples from patients with estrogen receptor-positive, HER2-negative ILC. Spatial transcriptomics is a technique that allows us to see how genes are active in different parts of a tissue sample. It’s like creating a map of gene activity, helping us understand how cells function and interact in specific areas of the tissue, thanks to a grid of spots able to capture the RNA of a specific portion of tissue.
For each sample, we carefully analyzed the morphology of the tissue sections and assigned labels to different cell types and structures. We then performed clustering analysis at the individual spot level, identifying groups of spots that shared common gene expression characteristics across all our patients.
Combining the information from spot-level clustering and morphological annotation, we conducted a clustering analysis at the patient level. This revealed four distinct groups of patients within our cohort, each characterized by specific morphological and gene expression patterns. We named these groups: proliferative (P), normal-stroma enriched (NSE), metabolic (M), and metabolic-immune enriched (MIE).
To validate our findings, we examined an external dataset (METABRIC) and found similar biological differences among the four groups. Additionally, we observed variations in disease outcome between these groups, with NSE showing better outcome for relapse-free survival, while M and P were associated with worse outcome. Notably, two of the groups linked to poorer disease outcome (M and MIE) were related to metabolism, emphasizing the significant role of metabolism in the biology of ILC.
- PO2-07-09 Early stage invasive lobular breast cancer is underestimated on conventional imaging including MRI.
The growth pattern of invasive lobular carcinoma (ILC) with loose cells that do not disrupt the architecture of surrounding tissue, makes it difficult to detect on imaging techniques like conventional mammography. Therefore magnetic resonance imaging (MRI) of the breast is needed to better detect multifocality. It is believed that the dimensions of ILC are often underestimated on mammography and overestimated on MRI. In this analysis, we wanted to verify the agreement between imaging findings and findings by the pathologist in our center, University Hospitals Leuven, Belgium.
The data of all patients with stage I-III ILC, diagnosed between 2000 and 2020 and not receiving any neoadjuvant treatment, was used. In total, the data of 1029 patients was included. Statistical analyses were applied to compare the radiological findings with the pathology findings on the surgically removed tumor. MRI of the breast was performed for 709 patients (68.9%). An increase in preoperative use of MRI was seen over the years.
Our findings suggest that ILC is underestimated by all imaging techniques including MRI. Although MRI relates the most with the findings on pathology. The mean difference in largest dimension of the tumor compared to pathology was 14.64 ± 21.15 mm for mammography, 18.19 ± 21.66 mm for ultrasound and 9.93 ± 20.63 mm for MRI. Furthermore, MRI tended to overestimate the number of locations where ILC was present in the breast: in 52.1% of the cases where multiple locations were mentioned on MRI, only 1 focus was found in the surgically removed tissue. We conclude that the local extent of ILC is underestimated by all imaging techniques. It was confirmed that MRI tends to overestimate the number of foci which might lead to additional ultrasounds and biopsies. It is crucial to address these limitations in imaging of ILC and to prioritize the development of better imaging techniques.
- PO2-11-09 European Lobular Breast Cancer Advocates: Bridging the Geographical Gaps in Lobular Breast Cancer Education and Awareness.
I’m Siobhan Freeney a Lobular Breast Cancer Patient Advocate from Ireland, author of the first European Lobular Breast Cancer Advocates (ELBCAdvocates) Poster “Bridging the Geographical Gaps in Lobular Breast Cancer Education and Awareness” and I was delighted to present it at the San Antonio Breast Cancer Conference 2023.
In 2019 European Lobular Advocates were invited to the 3rd European Lobular Breast Cancer Consortium meeting in Leuven, Belgium. We have since developed close collaborative networks of ILC advocates across Europe who work with the ILC research and patient communities to better understand our unique histological subtype.
Up to 30% of ILC tumors are not identified on mammograms, significantly more in Dense Breasts, ultrasound often fails to detect ILC so diagnosis is often delayed. MRI is not routinely offered and there are no standardized diagnostic or standardized treatment protocols for ILC across Europe. We need better imaging for Primary and Metastatic ILC. We aim to INFORM EU policy to recognise ILC as a distinct disease and to enhance education of ILC in the clinical setting.
In 2022 there were 86,500 ILC diagnoses in Europe.
Europe has 24 official languages so it’s an enormous challenge to streamline the translation of clinical, accurate information. To help address this we’ve co-designed the first European ILC Patient Education Leaflet with researchers from the European Lobular Breast Cancer Consortium, it’s now available in 22 European Languages.
We aim to establish a European Charitable Status for ELBC Advocates to ensure ILC is included in Clinical Trials and to lobby for upwards of 5% funding for ILC Research within 3 years.
Our friend and mentor, Leigh Pate taught us that Researchers, Clinicians and Patient Advocates should work together to accelerate research into ILC, that success is grounded in collaboration and as European ILC Advocates we are pivotal to change, and deliverable ILC specific treatments.
Importantly, we want to collaborate with breast cancer organizations to establish a strong EU-based ILC advocacy movement that will help us to achieve our common goal: which is an improved understanding, diagnosis and treatment of Invasive Lobular Carcinoma.”
Huge thanks to all of our esteemed co-authors.
- PO2-27-08 Discovery of glucocorticoid receptor-induced EMT and integrin gene expression and increased cell motility in invasive lobular breast cancer.
Estrogen receptor (ER)-positive, invasive lobular carcinoma (ILC) is the second most common histological subtype of breast cancer. Although the five-year stage-matched survival is improved compared to infiltrating ductal carcinoma (IDC), ILC late metastatic recurrences (>5 years) are more frequent. Understanding the mechanisms of lobular breast cancer’s significantly slow growth yet ultimately metastatic phenotype is important to improve clinical outcomes. ILC growth is primarily driven by estrogen receptor (ER) activity and hormone therapies can effectively decrease primary tumor burden, however, it is still unclear what is driving late metastasis.
Recently, our laboratory has shown that increased activity of the bodies stress response hormone receptor (Glucocorticoid Receptor, GR) which is activated by serum cortisol, reduced cellular proliferation in ER+ IDC, but little is known about this potential effect in ER+ ILC. Therefore, understanding the contribution of other hormone receptors such as the glucocorticoid receptor (GR), integral in stress response, could be of importance in ILC. We hypothesize that activation of the stress hormone, GR, reduces cellular proliferation but enhances migration activities of ILC cells which may contribute to late incidence of metastasis.
Utilizing cell lines derived from patients with metastatic ER+ ILC, we induced the activation of the body’s stress hormone receptor (GR). Interestingly, we observed a reduction in ER-driven cellular proliferation. We also observed that GR increased migratory, and metastasis associated phenotypes in ILC cell lines. Ongoing investigations include in vivo mouse models to test the use of a clinically relevant selective GR modulator which may be beneficial in ILC treatment to slow tumor growth and reduce metastasis.
- PO3-15-09 LobSig4 is a superior and readily implementable ILC-focused prognostic biomarker set.
There are no prognostic tests developed specifically for lobular breast cancers. We previously identified a large panel of genes (‘LobSig’) with the capacity to stratify lobular breast cancers into high- and low-risk of a poor outcome. We have been working to refine the LobSig gene panel and have identified a set of 4 antibodies that has similar prognostic power to LobSig194. The LobSig4 can identify those lobular breast cancers that have a low risk of recurrence, and those with a higher risk of recurrence, and which will need increased clinical follow up. We are working to further validate these antibodies.
- PO4-02-03 Distribution of MammaPrint, BluePrint, and Response Predictive Subtypes based on ImPrint and Reprint in ER+/HER2- Invasive Lobular Carcinoma – A FLEX sub study.
This project utilized data from the FLEX Registry to evaluate genomic signatures in lobular breast cancer cases. The FLEX Registry is a multicenter study collecting information on patients with breast cancer who have tumor profiling with the 70-gene assay, Mammaprint. Mammaprint scores help determine the benefit of chemotherapy for particular tumors, depending on clinical factors as well. Other genomic signatures have recently been developed, including ImPrint and RePrint, which may help identify patients who can benefit from specific treatment types including immunotherapy.
We evaluated over 1000 cases of invasive lobular carcinoma (ILC) in the FLEX Registry to determine the distribution of Mammaprint score, and how often these tumors were ImPrint or RePrint positive. In this study, a very small minority of ILC cases were ImPrint positive (1.4%), which suggests that these tumors would not benefit from immunotherapy. While most ILC cases were Mammaprint low risk, suggesting that most would not benefit from chemotherapy, a substantial proportion (over 20%) were Mammaprint high risk. These findings support the potential utility of chemotherapy in a subset of patients with ILC. Such heterogeneity highlights the role of tumor profiling for tailoring treatment.
- PO4-02-12 MDA iLobular Prognostic Tool: A Novel Approach for Risk Stratification in Invasive Lobular Carcinoma.
Lay summary coming soon.
- PO4-19-03 FES-PET/MRI for Tailored treatment of luminal A and lobular breast cancer: a prospective cohort study.
Name of the Clinical Study: FESTA TRIAL: 18F-FES PET/MRI for tailoring treatment of luminal A and lobular breast cancer: a phase II prospective cohort study evaluating the performance of FES PET/MRI in axillary staging compared with axillary surgery.
ClinicalTrials.gov ID NCT05982496
Eligible patients: Patients with invasive lobular tumors (Lob) showing estrogen receptors (ER) on their surface or luminal A breast cancer (LumA, ER-positive, progesterone receptor-positive, well differentiated, Her2-negative with a low proliferation index).
Summary: This study aims at studying a personalized imaging method for staging LumA and Lob in different settings: upfront surgery, induction endocrine therapy, neoadjuvant chemotherapy, metastatic disease with translational analysis.
Why is this Clinical Study Important: To date, BC staging relies on mammography, breast and axillary ultrasound (US), possible additional magnetic resonance (MRI) for locoregional staging, whilst liver US, thorax X-Ray and bone scan or computed tomography scan (CT) or PET-CT scan are recommended in selected cases for systemic staging. However, the performance of these imaging tools is not equivalent in all tumor subtypes. In particular, the local and systemic staging of LumA and Lob remains complex. On one side, LumA has a worse sensitivity on axillary US, reduced MRI enhancement and low fluorodeoxyglucose-avidity on PET. On the other side, Lob presents a peculiar growth pattern with low metabolic activity harder to distinguish from normal mammary tissue. Although, MRI is very sensitive for Lob, axillary and systemic staging remains difficult due to the frequently low tumor burden in axilla and low fluorodeoxyglucose-avidity.
Background: BC management has become progressively individualized. In this context, as the performance of standard imaging tools is non-homogenous in all BC types, imaging should be tailored as well. In particular, the limited accuracy of standard imaging with LumA and Lob often makes these tumors understaged and, potentially, undertreated. Although they are known as having relatively good prognosis, these subtypes may also recur and spread, and given the high frequency of them (LumA and Lob constitute over 50% of all BCs) final numbers may become larger than other subtypes, especially in the long run. Therefore, improving their detection and staging could allow to ameliorate their prognosis with a measurable impact on the majority of BC patients.
Clinical Study location: IRCCS San Raffaele Scientific Institute, promoted by San Raffaele Vita-Salute University and financed by Associazione Italiana per la Ricerca sul Cancro (AIRC – Next Gen Clinician Scientist Grant ID 28378)
How to learn more about whether participating in this clinical study is right for you: Send inquiries to dimicco.rosa@hsr.it
- PO4-28-09 Upregulation of the immune checkpoint protein B7-H3 is associated with an immune suppressive microenvironment in progression from in situ to invasive lobular breast cancer.
Invasive lobular breast cancer (ILC) is an understudied subtype of breast cancer characterized by late recurrence, metastasis to serosal surfaces including the peritoneum, and poor long-term outcomes. Lobular carcinoma in situ (LCIS) is associated with a 30% increased risk of developing ILC. Therefore, understanding the underlying changes that occur in the invasive lobular cells as well as their tumor microenvironment (TME) during the transition from LCIS to ILC is critical for the development of novel therapeutic targets that could be used in early disease. To address this, we used combined spatial gene expression and a 97-protein expression assay to examine the molecular profiles of coexistent LCIS and ILC. Pan-cytokeratin positive tumor cells and pan-cytokeratin negative stromal cells were analyzed separately for both RNA and protein.
Despite the close spatial proximity of LCIS and ILC, there were notable differences in gene and protein expression in the tumor cells as well as the cells in the TME. Gene expression profiling revealed significant upregulation of genes encoding essential components of the extracellular matrix, including several collagen genes, small leucine-rich proteoglycans byglycan (BGN) and lumican (LUM), periostin (POSTN) and secreted protein acidic and cysteine rich (SPARC). Genes highly expressed in the LCIS tumor compartment were KRT5, KRT14 KRT17 and MYLK which are highly expressed in myoepithelial cells located around the periphery of the LCIS.
One of the most upregulated proteins in ILC cells was B7 homology 3 protein (B7-H3) also known as Cluster of Differentiation 276 (CD276). B7-H3 is an immune checkpoint protein that belongs to the B7 family (that also includes PD-L1 and PD-L2). B7-H3 is overexpressed in many tumors but is mostly absent in normal cells. Overexpression of this protein has been associated with cancer progression and poor prognosis. B7-H3 was also the most upregulated protein in the ILC TME compared to the TME surrounding LCIS. Furthermore, the tumor-promoting macrophage marker CD68 and the regulatory T-cell marker FOXP3 were also higher. The immune cell marker CD45 was downregulated in the TME of ILC, as well as T-cell proteins CD3, CD40 and granzyme B. Moreover, CD27, a protein found on memory B-cells was much more highly expressed in the microenvironment surrounding LCIS compared to ILC. Overall, these molecular profiles support a transition toward a much more suppressed, and hence more “friendly”, immune environment for invasive tumor cells compared to LCIS. Based on these data, our working hypothesis is that upregulation of B7-H3 on lobular tumor cells promotes migration through the basement membrane, allowing interaction with laminins, integrins and other extracellular matrix proteins as LCIS cells acquire invasive properties of ILC. Furthermore, upregulation of B7-H3 on antigen presenting cells may promote a suppressive immune microenvironment by inhibiting T-cell proliferation and downregulating cytokine production.
In sum, these strongly concurrent spatial gene and protein expression data suggest that B7-H3 and the immune suppressive network of ILC may be a promising target for early-stage lobular breast cancer. B7-H3 Inhibitors could be explored in the neoadjuvant setting to evaluate the efficacy of immunotherapy in primary ILC.
- PO5-04-12 Comparison of chemotherapy efficacy in metastatic lobular vs. ductal breast cancer.
Studies in early breast cancer have shown lower rates of pathologic complete response to neoadjuvant chemotherapy for patients with invasive lobular carcinoma compared to invasive ductal carcinoma which has raised the question, what is the efficacy of chemotherapy in metastatic invasive lobular breast cancer? In this study we reviewed all patients with metastatic invasive lobular carcinoma (ILC) treated at our institution from 2000 to 2023 and compared them to a matched cohort of patients with metastatic invasive ductal carcinoma (IDC). We included 122 patients with metastatic ILC and 254 with metastatic IDC and compared the time to starting the next treatment after commencing the first line of chemotherapy. The results showed that while patients with metastatic ILC had a longer median time to starting chemotherapy (5.8 months vs 2 months), there was no difference in efficacy of chemotherapy (as measured by time to next treatment), 8.9 months vs 9.1 months.
Our results support the current ESMO guidelines which state that the standard of care first line therapy for metastatic hormone receptor positive breast cancer is endocrine therapy with a CDK4/6 and on progression sequential endocrine therapy should be offered until endocrine resistance occurs. However, once the patient’s cancer has become endocrine resistant, physicians should have confidence discussing and offering chemotherapy to patients with metastatic invasive lobular breast cancer as they are just as likely to benefit and respond as patients with metastatic IDC.
- PO5-06-14 Genomic Landscape and Clinical Outcomes of Triple-Negative Invasive Lobular Carcinoma.
Roughly 2% of cases of invasive lobular carcinoma (ILC) are triple-negative at initial diagnosis. The disease-related outcomes of patients with triple-negative ILC are worse compared to those with estrogen-receptor (ER+) ILC. Our project’s aims were to share our experience in treating three patients with triple-negative ILC, as well as to investigate the genomic alterations found in the Foundation Medicine, Inc. database of seventeen patients with triple-negative ILC who underwent next-generation sequencing of breast or metastatic tissue as part of routine clinical care. Currently the management of triple-negative ILC is extrapolated from that of triple-negative invasive ductal carcinoma (IDC), however we demonstrated that our three patients with triple-negative ILC had limited or no response to combinations of chemotherapy and immunotherapy which are generally used for triple-negative IDC.
The most common mutations among the triple-negative ILC patients included in this study were in CDH1, TP53, and PIK3CA. The presence of a PIK3CA mutation presents the opportunity for potential research on therapies targeting PIK3CA/AKT1/PTEN alterations in triple-negative ILC. Fourteen of the seventeen patients (82.3%) from the Foundation Medicine, Inc. database would be considered to have HER2-low status (HER2 immunohistochemistry score of 1+ or 2+, with negative fluorescence in situ hybridization [FISH] assessment). Three of the seventeen patients (17.6%) were found to have an ERBB2 mutation, and we demonstrated an example of palliative treatment with neratinib in conjunction with capecitabine for a patient with triple-negative ILC whose tumor had an ERBB2 mutation. The presence of HER2-low status or an ERBB2 mutation may present opportunities for treatment with an anti-HER2 antibody-drug conjugate or tyrosine kinase inhibitor. Studies with larger sample sizes of patients with triple-negative ILC are needed for molecular profiling and assessment of patient outcomes with specific therapies.
- PO5-13-12 Personalized circulating tumor DNA testing for recurrence detection and treatment response monitoring in patients with metastatic invasive lobular carcinoma.
Invasive lobular breast cancer (ILC) is difficult to image, particularly when it moves from the breast to other sites in the body. Better markers are needed for real-time assessment of response to treatment. We examined real world testing results from a liquid biopsy assay performed over time on blood (SignateraTM, Natera Inc.) from patients with metastatic ILC. The SignateraTM assay is a custom-made test which is specific to an individual patient’s tumor and measures the presence of circulating tumor DNA (ctDNA). In this cohort, ctDNA detection and dynamics correlated with clinical status which was determined by conventional monitoring tools. Personalized, longitudinal ctDNA testing may have utility in detecting progression and monitoring treatment response in patients with ILC. Further studies are required to examine the utility of liquid biopsies in ILC.
- PO5-24-11 An integrated approach for comprehensive molecular and tumor microenvironment characterization of invasive lobular carcinoma.
Lay summary coming soon.
- PO5-26-07 Surgery for Invasive Lobular Carcinoma: A Patient Experience Survey from the Lobular Breast Cancer Alliance.
The Lobular Breast Cancer Alliance (LBCA) is a nonprofit, patient advocate organization committed to raising awareness and promoting research on invasive lobular carcinoma (ILC). To understand the surgery and surgical decision-making experience of individuals with ILC, the LBCA conducted an anonymous online survey in late-June, early-July of 2023. Survey respondents were recruited via the LBCA newsletter, social media, and via partner organizations. 1,482 respondents completed the survey, and analyses were restricted to the 1,426 respondents who underwent surgery. While the survey limitations include potential recall and selection bias, the survey demonstrates the experience of a large cohort of women with ILC, reporting high rates of uncertainty about the accuracy of imaging, high rates of repeat surgery, bilateral mastectomies, and positive margins. Patients may have varying degrees of understanding of how surgical choice relates to survival and it was further notes that concerns about how well and whether ILC is detected affects surgical choices. The survey results support the need for improved pre-operative staging and imaging modalities specific to ILC. The authors hope the results will inspire more ILC research to improve imaging. LBCA thanks all respondents for sharing their time and experiences in this survey. LBCA’s poster presentation was dedicated to the memory of LBCA Board Member Dr. Deborah Mueller.
