This year, more than 60 posters on lobular breast cancer research were presented at the 2025 San Antonio Breast Cancer Symposium, up from only 11 just three years ago!
Posters presented at SABCS represent the most recent, unpublished scientific research on breast cancer. Scientists convert the details of their research study’s aims, methods, findings and discussion from written abstracts into six foot long graphic posters to visually and succinctly convey the key points. The abstracts from each poster presented will be published in a special publication by the American Association of Cancer Research (AACR) in the Spring of 2026. After presenting posters, scientists frequently also submit their whole manuscripts for publication in scientific journals.
This year’s group included the 10 abstracts that won the LBCA ILC research merit award and LBCA’s poster with the results from our survey of ILC patients about their experiences and challenges with surveillance. LBCA has created summaries in simple language of these 11 and nearly 20 other ILC- focused poster presentations from SABCS25 to make these promising new studies a little easier to understand. Additional summaries will be added as they are received (last updated 6/25/26).
ILC Research Posters and Lay Summaries
PS1-09-30 Clinical and Genomic Associations of Atypical Metastases in Invasive Lobular Carcinoma (ILC)
Patients with lobular breast cancer have higher rates of metastases to sites like the linings of organs or the ovaries that we rarely see in ductal breast cancer. Because these “atypical” metastases are rarer, they are sometimes found later when they have already grown and caused complications. We do not know what factors make some patients at higher risk of getting these rare metastases and how their development affects outcomes. Our study looks at these questions.
We found that patients with atypical metastases were more likely to be pre-menopausal when they were first diagnosed with early-stage breast cancer and were also more likely to have hormone receptor positive metastatic disease. Certain gene mutations were also more common in these patients. Patients with metastases to organ linings had worse survival than those who did not.
More research needs to be done into why patients with these metastases have worse prognoses. We hope that this study starts to help us identify patients at high risk of developing these metastases so that we can catch them earlier and decide on better imaging and treatment.
PS1-06-11 Fibroblast activation protein (FAP)-targeted dedicated breast PET for primary invasive lobular carcinoma: A pictorial review
Despite the many advances that have been made throughout the years in diagnosing and treating breast cancer, we will not end the disease until we further understand what drives the cancer’s growth and why some cases become metastatic. Our research proposal aims to tackle these big questions by using advanced scanning technology and a new radiotracer.
In this study, we will use a specialized imaging method called dedicated breast positron emission tomography (dbPET) combined with a new radiotracer that targets fibroblast activation protein (FAP). A radiotracer is a tiny amount of radioactive substance that is safely injected into the body, helping to show and measure molecular-level activity within the body. “Dedicated breast” means that it is used specifically on breast tissue in order to get very clear and detailed pictures that enable the tumor to be seen in 3D. “Positron emission tomography (PET)” is a special type of camera that captures pictures of where certain changes in the breast have occurred, such as tumor growth. The “new radiotracer” is a tiny molecule that travels throughout the body, seeking out and attaching to fibroblast activation protein or FAP. “FAP” is mainly found on certain cells called cancer-associated fibroblasts (CAFs), which are located in and around the tumor. CAFs assist the tumor by helping it grow and spread. They do this by releasing substances that help cancer cells multiply and survive, changing the surrounding area to make it easier for the tumor to expand, and by creating a protective environment that shields cancer cells from the body’s defenses.
By taking dbPET pictures that show where the radiotracer has attached to FAP, we can identify the location of CAFs along with tumor cells, enabling accurate diagnosis of breast cancer. Traditional imaging methods such as mammography, ultrasound, and MRI have limitations that cause problems in accurately detecting certain types of breast cancer, such as invasive lobular cancer (ILC). A significant percentage of ILC lesions fail to show up using all of the current imaging techniques. Our early research in patients with ILC shows that targeting FAP with dbPET can overcome these problems, providing a clearer depiction of breast tumor against background normal breast tissue.
This new approach that we are proposing not only provides more accurate pictures of the tumor but also generates valuable information about the tumor’s biological traits without taking out the tumor tissues by surgery or needle biopsy. It shows how the tumor interacts with its neighboring tissues and its potential to become aggressive and spread to other organs in the body.
Our study has two goals. First, we plan to confirm the ability of FAP-dbPET to accurately depict and identify untreated primary breast tumors regardless of the pathological type, by comparing the images to microscopic findings of tissues obtained from surgery or needle biopsies. Second, we will evaluate how the imaging results we capture relate to the cancer’s potential to spread to lymph nodes and other organs. If our research is successful, it could make a breakthrough in breast cancer imaging, offering more accuracy in diagnosis. Moreover, because of the additional information potentially related to tumor growth and spread, it would pave the way for personalized treatment strategies for everyone affected by this disease, including those who have served in the military and their families. Once such potential is proved in this study, we could plan a larger clinical trial to test the results and introduce to clinical practice.
Breast cancer is a serious health issue that affects many people, making early detection and accurate diagnosis very important for effective treatment. Importantly, by conducting this research on innovative dbPET technology and this promising new radiotracer, we aim to obtain evidence that the pictures taken from outside the body can not only locate the tumor but also provide similarly informative or potentially additional data related to tumor growth and spread compared to the data obtained via surgery or needle biopsies. This will accelerate progress toward the Breast Cancer Research Program’s (BCRP) mission of ending breast cancer by providing insights into what drives breast cancer growth and why some cases become metastatic.
PS1-06-21 The impact of 16α-18F-fluoro-17β-estradiol (FES) positron emission tomography (PET) on the staging and management of invasive lobular carcinoma (ILC) of the breast: A Case Series
Invasive lobular breast cancer (ILC) can be difficult to accurately stage at diagnosis because it grows in a diffuse pattern and is often missed or underestimated by standard imaging tests. This can lead to unexpected findings at surgery and changes in treatment plans after the fact. A specialized imaging scan called FES-PET, which highlights estrogen receptor–positive cancer cells, may help doctors better see the true extent of ILC earlier in the care process. This study examined whether FES-PET improved staging and treatment decisions for people newly diagnosed with locally advanced ILC.
The researchers reviewed six patient cases. In three patients who received FES-PET, the scan either detected cancer that standard imaging missed, confirmed the absence of metastatic disease, or clarified where radiation should be directed. These findings directly changed or supported treatment decisions, including radiation planning and the choice to use systemic therapy. In contrast, three patients who did not receive FES-PET were found to have more advanced disease than expected at the time of surgery, despite having standard imaging beforehand.
For patients, these findings suggest that FES-PET may reduce surprises during treatment by providing a clearer picture of where ILC has spread before major decisions are made. Earlier and more accurate staging could help ensure that treatment plans are better tailored from the start, potentially avoiding unnecessary surgery, delays, or changes in therapy and supporting more confident, informed care decisions.
PS1-09-06 Is there misdiagnosis and/or late diagnosis of metastatic ILC? A quantitative and qualitative patient-reported analysis
Invasive lobular breast cancer (ILC) is the second most common type of breast cancer, but it can be difficult to detect because it grows in a diffuse pattern rather than forming a lump. When ILC spreads beyond the breast and becomes metastatic (mILC), it often appears in uncommon locations such as the gastrointestinal tract, abdomen, ovaries, or nervous system. These unusual patterns, combined with limitations of standard imaging tests, can lead to delayed diagnosis or misdiagnosis, sometimes for months or years. This study was designed to better understand how often people with mILC experience delayed or incorrect diagnoses and how this affects their care.
An international patient survey was completed by 520 people, including 321 living with metastatic ILC. More than one quarter reported being misdiagnosed, and nearly one third experienced multiple misdiagnoses before receiving the correct diagnosis. Many waited a year or longer for accurate identification of metastatic disease. Symptoms were often vague, such as back pain, fatigue, or gastrointestinal issues, and were frequently attributed to non-cancer conditions.
For patients, these findings highlight serious gaps in how metastatic ILC is recognized and diagnosed. Improving provider awareness, imaging approaches, and diagnostic pathways is critical to reducing delays, avoiding unnecessary treatments, and ensuring patients receive timely, appropriate care.
PS1-10-18 Genomic analysis of ER+/HER2- metastatic invasive lobular carcinoma (ILC) and clinical outcomes comparison with metastatic invasive carcinoma of no special type (NST)
Invasive lobular breast cancer (ILC) accounts for about 15% of breast cancers and behaves differently from the more common invasive carcinoma of no special type (NST). Despite these differences, people with metastatic ILC are generally treated the same way as those with NST. Studying the genetic changes within metastatic ILC tumors may help explain how this disease behaves and identify opportunities for more tailored treatments. This study examined the genetic features of estrogen receptor–positive, HER2-negative metastatic ILC and compared treatment outcomes with those of metastatic NST .
Researchers analyzed tumor DNA from 533 patients with metastatic breast cancer, including 125 with ILC. Metastatic ILC tumors showed a distinct pattern of genetic alterations, most commonly involving genes such as CDH1, PIK3CA, and ESR1. Certain genetic changes were linked to earlier recurrence or specific metastatic sites, such as liver involvement. However, when treated with standard first-line hormone therapy combined with CDK4/6 inhibitors, patients with ILC had similar time on treatment and overall survival compared with patients with NST.
For patients, these findings are reassuring in that current standard treatments appear to work similarly for metastatic ILC and NST. At the same time, the unique genetic features of metastatic ILC highlight opportunities to develop future therapies that are better tailored to this specific subtype, with the potential to improve precision and personalization of care.
PS2-05-17 Pathologic response in invasive lobular carcinoma versus invasive ductal carcinoma following neoadjuvant therapy: A single institution study
Invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) are two common types of breast cancer. Some patients receive neoadjuvant treatment, such as chemotherapy, HER2-targeted therapy or endocrine therapy, before surgery. However, it is not well understood how well ILC responds to these treatments compared with IDC.
In this study, we reviewed 73 patients with ILC and 587 patients with IDC treated at our institution between 2021 and 2025. All patients received neoadjuvant therapy followed by total or partial mastectomy. We found that patients with ILC were generally older and had lower-grade tumors at the time of biopsy. Among patients with triple-negative breast cancer, neoadjuvant treatment was much less effective for ILC than for IDC. Only 13% of patients with triple-negative ILC had a complete response after neoadjuvant chemotherapy, compared with 52% of those with triple-negative IDC. In contrast, for the other subtypes (ER-positive/HER2-negative and HER2-positive), treatment responses were similar between ILC and IDC.
Overall, our findings show that triple-negative ILC responds poorly to neoadjuvant chemotherapy compared with triple-negative IDC. This suggests that ILC behaves differently at the biological level and highlights the need for further research to optimize treatment strategies for patients with this subtype.
PS2-06-04 Invasive lobular breast cancer: Ten-year follow-up data from a single center
This retrospective single-center study analyzed 372 patients diagnosed with early-stage invasive lobular carcinoma (ILC) between 2003-2008. The median patient age was 62 years, with a median follow-up of 10.7 years. The 5 year and 10 year survival rates for the whole cohort were 85% and 64% respectively. This study compares those treated by breast-conserving surgery (BCS) with mastectomy, with and without follow up Radiotherapy (RT). This study does not highlight the impact of endocrine therapy.
While the loco regional recurrence rates were low overall (8.9%) across the cohort, BCS patients had lower relapse (5.8%) than those who underwent mastectomy (10.7%). Freedom from loco regional recurrence was excellent, reaching 98% at 5 years and 95% at 10 years, indicating strong local disease control regardless of surgical approach. However distant relapse occurred in 22% of patients, with notably higher rate among mastectomy patients compared to those treated with BCS (26.2% vs. 15.3%). Overall survival (os) was significantly better in the BCS group (median 15.1 years vs. 13.4 years).
PS2-06-22 Genomic Insights in Metastatic Invasive Lobular Carcinoma: a Real-world Study
This retrospective study of Metastatic Invasive Lobular Breast Cancer, studied how genomic alterations affect clinical outcomes in these types of patients. Patients in this study underwent genomic profiling between 90 days before metastatic diagnosis and 90 days after starting first-line therapy, and were then followed for at least 6 months to assess treatment outcomes. Patients were tested to determine their genomic alterations. They were classified according to the findings of the tests. All patients in this study were hormone receptor-positive and HER2-negative.
Patients harboring genomic alterations in NF1, RB1, GATA3, and ARID1A demonstrated reduced benefit from standard therapies and it was suggested they may require alternative treatment strategies.
This study shows that there is a need to study ILC targeting these specific pathways of these genomic alterations. Targeting specific abnormalities could reduce the potential for resistance to therapies. This study suggests that genomic screening is essential in mILC patients to help guide treatment decisions and create an individual patient treatment plan that would provide better outcomes for individualized therapy.
PS2-07-22 Serial, multi-omic, multi-analyte, liquid biopsy monitoring of metastatic lobular breast cancer to detect clinically-relevant heterogeneity and evolution
Cancer commonly displays great “molecular heterogeneity” meaning different cells or cell populations of a tumor mass, or even different masses within a patient, have molecular commonalities as well as differences that drive their growing and spreading behavior. This heterogeneity provides fertile ground for cancer to evolve in order to escape the body’s own anti-tumor responses or therapies administered medically. Clones* that are resistant to an anti-cancer mechanism grow preferentially and have made the complete eradication of cancer from the body, especially in metastatic disease, all but impossible. These evolutionary processes span the entire natural life of the disease. Although this aspect of tumor biology is widely recognized, its clinical application is complicated by the inability to obtain multiple informative samples over time.
Different limitations of tumor samples/sampling
- Tissue biopsies are invasive, costly, and only represent one area of one tumor mass.
- Cell free tumor DNA (ctDNA) is non-invasively obtained from a blood sample, and is relatively easy to analyze, but only provides a merged, and DNA-only picture of cancer from all cancer clones releasing DNA.
- Circulating tumor cells (CTCs) are rare, whole tumor cells circulating in blood. They provide a “best of both worlds” scenario, whereby they can be non-invasively obtained, represent all clones that shed cells, yet provide plentiful molecular information from well-defined cancer clones. Their rarity has been an impediment to their clinical use. Remarkably, due to ILC’s E-cadherin (CDH1) loss, the glue that binds cells together, lobular breast cancer patients have several-fold more CTCs than other cancers, supporting their biological and clinical study in ILC.
We and others have pioneered the molecular analysis of CTCs at the individual cell level. Here we analyzed DNA from 180 single CTC, ctDNA, and tissue samples from multiple timepoints in 15 ILC patients, often from the initial breast cancer diagnosis through the course of metastatic disease. We combined these molecular data with the patients’ complete clinical information to look for clinically-relevant disease evolution.
We confirmed that approximately 80% of metastatic ILC patients have elevated CTC numbers. Only about 50% of cancer-driving DNA changes that are targetable by available precision treatments were detected in all 3 sample types together within a patient (tissue, ctDNA, and CTCs). The others were detected in two or only one sample type.
Adding CTC analysis to the process of analyzing tissue and ctDNA provided an additional targetable DNA change in one out of every two patients. Likewise, tumor mutation burden, a known biomarker of immunotherapy, shown to be more elevated in ILC vs IDC, was detected in a non-overlapping manner in the 3 sample types, thus increasing the total number of patients eligible for immunotherapy compared to tissue and/or ctDNA analysis alone. This indicates that using the molecular information contained in all three of the approaches: tissue, ctDNA and CTCs is really important for a full picture to guide clinical treatment decision making.
In our study we also noted within individual patients great clonal heterogeneity and evolution due to therapy, including immunotherapy. Again, it was important to find that there was concordance and discordance between tissue, ctDNA and CTCs. CtDNA appeared to represent clones that responded to therapy and had dying cells, whereas CTCs often appeared to represent non-responding, likely resistant clones that provided live cells in circulation. These data show the unique role monitoring CTCs can have in ILC patients when monitoring tumor evolution with potential clinical implications.
* In the context of the cancer cell cycle, a “clone” refers to a group of cancer cells that are genetically identical to each other because they are all descended from a single, common ancestor cell.
PS2-09-04 Predicting outcomes for patients with mixed ductal/lobular carcinoma of the breast based on circulating tumor DNA positivity patterns
Some breast cancers contain features of both ductal and lobular types—called “mixed” tumors. These account for about 3% of all breast cancers, but it’s been unclear whether their underlying biology—and therefore their expected course—more closely resembles ductal or lobular disease. This study tackled that question using a blood-based test that detects tiny fragments of tumor DNA circulating in the bloodstream.
Working with data from over 11,500 patients with early-stage breast cancer, our research team developed a tool that analyzes the genetic fingerprint of mixed tumors to determine whether they behave more like ductal or lobular cancers. The results were striking: among 316 patients with mixed tumors, about half were classified as “ductal-like,” roughly one-fifth as “lobular-like,” and the remainder fell in between. Importantly, when we tracked how these cancers actually behaved over time—whether and when they recurred—the tumors classified as “lobular-like” followed recurrence patterns similar to pure lobular cancers, while “ductal-like” tumors mirrored pure ductal cancers. This suggests the tool can meaningfully predict a patient’s disease course. With further validation, this approach could help provide more accurate prognostic information for patients with mixed tumors, giving them and their doctors a clearer picture of what to expect based on which subtype their cancer most resembles at the molecular level.
PS2-04-30 Enrollment of Patients with Metastatic Lobular Breast Cancer in Clinical Trials in the Multicenter ESME Cohort
Invasive Lobular Carcinoma (ILC) represents about 15% of breast cancer subtypes, and it is the second most common type of breast cancer. Clinical presentation of ILC differs from Invasive Ductal Carcinoma (IDC) and No Special Type (NST) in the clinical setting due to histological and molecular profiles. ILC is often overlooked in the clinical setting, which creates a gap in representation in clinical trials. ILC often presents with bone involvement, which does not meet the criteria for RECIST 1.1.
This study was conducted using data from 18 French Comprehensive Cancer Centers. The study was created to evaluate different strategies for enrolling more metastatic lobular breast cancer (mILC) patients into clinical trials. Due to the presentation of mILC, patients often do not meet the criteria to be considered for clinical trials. This study also shows that postmenopausal women were the majority of participants, 71% of the 15,950 NST patients had a median age of 62, and about 83% of the 3,868 ILC patients had a median age of 65 years old. There was also a lack of representation for male breast cancer in the clinical trials represented in the ESME MBC (Epidemiological Strategy and Medical Economics Metastatic Breast Cancer) study.
The conclusion of this study is that there are disparities and inequality in representation for mILC patients in clinical trials. The research shows we need to continue to investigate the inclusion and exclusion criteria to create a more balanced representation for ILC and mILC patients in clinical trials. There is also a need to look at the younger population of mILC patients for clinical trials.
PS2-09-27 Patterns of central nervous system (CNS) and leptomeningeal (LM) involvement in advanced breast cancer (BC) with invasive lobular histology: insights from a large multi-center study with a focus on estrogen receptor-positive (ER+)/HER2- disease
Invasive lobular carcinoma (ILC) is the second most common subtype of breast cancer, representing about 10-15% of all cases, and is frequently associated with an estrogen receptor-positive (ER+)/Human Epidermal growth factor Receptor 2-negative (HER2–)profile. This study examined data from 1,710 patients with advanced breast cancer to clarify ILC’s risk for central nervous system (CNS) and leptomeningeal metastases (LM) compared to carcinoma of no special type (NST). Among 1,587 patients with known histology, ILC cases showed strong ER+/HER2- predominance. Overall, CNS occurrence was similar between ILC and NST, but LM involvement occurred significantly more often in patients with ILC. Statistical analyses confirmed that ILC independently predicted a higher risk of LM as the first CNS event.
In ER+/HER2- breast cancer, patients with ILC had an increased hazard of developing LM compared to NST, even after accounting for age, tumor grade, receptor expression, and metastasis patterns. Moreover, outcomes after LM diagnosis were significantly worse for ILC-only; about 6% of patients survived one year post LM compared to 30% for those with NST. These results suggest that ILC has a unique biological behavior that increases its likelihood for LM involvement and worsens survival once LM occurs. All survival analyses presented in the poster refer specifically to the ER-positive/HER2-negative subgroup (n=787 patients). The findings highlight the importance of enhanced CNS monitoring and consideration of tailored surveillance strategies for patients with ER+/HER2- advanced ILC.
PS3-08-22 Uncovering mechanisms of ILC glucocorticoid receptor activity in cell cycle regulation and bone metastasis using in vivo models and human samples.
Researchers from UT Southwestern Medical Center explored the relationship between ILC glucocorticoid receptor (GR) activity, cell cycle regulation, and the development of distant metastasis. The researchers were interested in understanding why estrogen receptor- positive (ER+) ILC so frequently metastasizes to the bone and is relatively slower growing and less aggressive, compared to other types of breast cancer. They studied the impact of GR, a hormone receptor that responds to cortisol and other glucocorticoids and that is involved in stress response, immune regulation, metabolism, and cell survival, on cancer cells in the mammary tumor site as well as in metastatic cells in the bone.
The research provided two main findings. Firstly, when the GR is activated in ER+ ILC cell models, a decrease in mammary tumor cell growth is seen. Secondly, although GR reduces tumor growth in the primary tumor, it appears to increase the expression of genes involved in cell movement, leading to metastasis. It was also noted that the presence of GR activity supports long-term tumor cell survival even under estrogen deprivation. This may explain why ER+ ILC responds well to endocrine therapy but has a higher risk of late recurrences and tends to metastasize to unusual areas such as the bone and peritoneum. This research affirms that ILC is not simply ER+ breast cancer of a different shape but has a distinct hormone-regulated biology. GR activity is a unique part of ILC that has an anti-tumor growth effect in mammary tumors, while it also plays a role in the development of metastasis. Research in this area may eventually identify therapies that target GR signaling in combination with endocrine therapy.
PD9-01 Comprehensive Genomic Landscape of Invasive Lobular Carcinoma Reveals Distinct Molecular Subtypes
We investigated mutations in hormone receptor positive, Her2-negative ILC from 1,370 patients, using Natera’s real-world database. As expected, E-cadherin mutations were the most frequent event (69% of tumors), consistent with E-cadherin loss being the hallmark in ILC. Other frequent alterations included mutations in PIK3CA (47%), TBX3 (11%), FOXA1 (8%), and MAP3K1 (7%). High grade ILC (often pleomorphic ILCs) were associated with higher rates of TP53 and ERBB2 mutations than lower grades, and these mutations were
associated with a worse outcome, and could serve as prognostic markers.
We then used computer algorithms to define specific gene signatures (i.e., unique patterns of mutations) based on the single base substitutions, which means looking at the specific letter mutations in the DNA, such as letters in a different order (“COSMIC SBS signatures”), ie the mutations in the context of neighboring DNA (“flanking DNA sequences.”)
These studies revealed that ILC samples can be grouped into five dominant signature groups. Of those, two signatures called SBS40 and SBS2/13 were associated with worse outcomes of the patients. The SBS40 signature showed an enrichment for BRCA2 mutations, whereas the SBS2/13 signature is reflective of DNA mutations caused by immune system enzymes (APOBEC) that normally fight viruses but
have mistakenly attacked the cell’s own DNA instead.
In summary our study is one of the largest genomic profiling studies of ILC, and it provides insight into mutational changes that ultimately might help to guide precision medicine for patients with ILC
PD9-02 Epigenetic upregulation of TFAP2B expression drives proliferation and survival in Invasive Lobular Carcinoma
Invasive lobular carcinoma (ILC) is responsible for 10%-15% of breast cancers and currently lacks any targeted treatment tailored for ILC patients. Our research focuses on exploring biological molecules that are specifically changed in ILC and studying whether they can be targeted for therapeutic benefit.
Our lab has found that lobular tumors increase the levels of a transcription factor* called AP2β through a unique non-genetic mechanism (called epigenetics). Our data show that this factor is specifically expressed in high levels in the nucleus of ILC cancerous cells where it binds to the DNA and helps in regulation of many genes. We found that reducing the levels of AP2β, by interfering with its mRNA, suppressed the growth of ILC cells, reduced their ability to form colonies, slowed down cell division, and increased cell death which shows the importance of this protein for ILC tumor growth and progression.
Our initial lab sequencing results suggest that this transcription factor plays a role in controlling important processes including how cells divide, how genes are turned on or off, how cells generate and use energy, and cell growth and survival. Studies are ongoing in our lab to identify the genes regulated by AP2β and to explore the therapeutic potential of targeting this factor in ILC tumors to suppress ILC tumor growth.
* A transcription factor (TF) is a protein that controls gene activity by binding to specific DNA sequences, acting as a switch to turn genes “on” or “off” (activating or repressing transcription) to produce RNA and ultimately proteins, ensuring the right genes are expressed in the right cells at the right time for essential functions like growth, development, and response to stimuli.
PD9-03 Comprehensive genomic profiling and clinically targetable mutations of metastatic invasive lobular and no special type breast cancer
Next generation sequencing (NGS) is performed on fragments of DNA circulating in the blood (circulating tumor DNA) and can reveal important genetic information about a patient’s cancer. Genetic alterations found on these tests can impact treatment options. This study evaluated the use of circulating tumor DNA tests in patients with metastatic breast cancer with a focus on differences between invasive lobular and no special type breast cancers.
At the University of Pittsburgh Medical Center and its community practice locations, 1,378 patients (1,797 tests in total) with metastatic breast cancer had circulating tumor DNA blood tests performed between January 2016 and March 2025. 93.5% of patients had genomic alterations detected and 59.4% had mutations detected that are clinically meaningful with potential targets for treatment. The most common actionable mutations were PIK3CA and ESR1. PIK3CA, ERBB2, RB1 and CDH1 mutations were more common in invasive lobular breast cancers. 21.2% of patients had more than one circulating tumor DNA test. Among these patients, the genomic results correlated well with the response of the tumor to treatment in metastatic lobular cancers. Overall, blood tests for circulating tumor DNA have the potential to help guide treatment for patients with metastatic breast cancer and especially in lobular cancers where progression of disease can be more difficult to monitor with current methods.
PD9-04 Context-dependent tumor suppressor role of RHOA in breast cancer through cooperation with CDH1 loss
Invasive lobular carcinoma (ILC) is a distinct type of breast cancer that spreads as single cells due to loss of cell–cell adhesion, most commonly caused by alterations in the CDH1 (E-cadherin) gene. Similar features are seen in diffuse gastric cancer, a subtype of stomach cancer, where mutations in a gene called RHOA are common. RHOA helps control how cells maintain their shape and move. In this study, we examined nearly 9,000 breast cancers and compared them with stomach cancers to understand how often RHOA is altered in breast cancer, which types of tumors are affected, and how these alterations influence cancer behavior.
We found that RHOA mutations are rare overall in breast cancer but occur more frequently in ILC, where they often appear together with CDH1 mutations. Importantly, the types of RHOA mutations seen in breast cancer differ from those in stomach cancer, suggesting that RHOA plays different roles depending on tumor type. Laboratory studies showed that reducing RHOA activity makes breast cancer cells more aggressive—especially when CDH1 is also lost—leading to increased cell movement, survival, and growth. Together, these findings suggest that RHOA normally acts to restrain tumor progression in ILC, and that loss of RHOA function, particularly alongside CDH1 deficiency, contributes to the aggressive behavior in ILC.
PD9-05 Whole transcriptome sequencing reveals diagnostic and molecular complexity of lobular carcinoma associated with CDH1 alteration
Invasive lobular carcinoma (ILC) is a special type of breast cancer that is usually linked to loss of a “cell-cell adhesion” protein called E-cadherin, often caused by changes in the CDH1 gene. But in real practice, some tumors look like lobular tumors yet keep E-cadherin, or look like ductal tumors though they have lost it, which makes diagnosis confusing.
Using an RNA test called “whole-transcriptome sequencing*” on selected cases, we found CDH1 changes even in tumors that didn’t look like classic ILC, and we also uncovered important CDH1 mutations that routine DNA panel tests had missed. This suggests that RNA testing can help clarify difficult “gray-zone” cases and improve diagnostic accuracy for lobular-type breast cancer.
* Note: Whole Transcriptome Sequencing (WTS) is a powerful technique that sequences all RNA molecules (the transcriptome) in a sample, providing a comprehensive snapshot of gene activity, including coding (mRNA) and non-coding (lncRNA, miRNA) RNAs, to understand cellular function, disease mechanisms, and discover biomarkers without needing prior gene annotation. It captures a complete picture of gene expression, including rare events like gene fusions and novel splice variants, offering deeper insights than targeted methods.
PD9-07 The Genomic, Transcriptomic, and Immune Hallmarks of Metastatic Lobular Breast Cancer
In this study, we used a large set of metastatic breast cancer tumor samples tested at Caris Life Sciences to better understand what makes metastatic invasive lobular carcinoma (ILC) biologically distinct. We analyzed DNA changes (mutations), RNA patterns (gene activity), and immune features in tumors from 2,645 patients (605 with ILC and 2,040 with non-lobular breast cancer). Overall, metastatic ILC showed a different molecular “fingerprint,” including frequent alterations in genes commonly seen in lobular tumors (such as CDH1 and PI3K-pathway genes). We also saw differences in immune-related features: some immune cell signals were modestly higher in ILC, and expression of selected immune checkpoint markers (including PD-L1) was slightly higher in ILC, although many immune markers were broadly similar between groups. Taken together, these findings support that metastatic lobular breast cancer has distinct biology across multiple layers, and that understanding these differences may help guide future research into more tailored treatment strategies.
PD9-08 Prevalence of lobular carcinoma in situ in surgical specimens of invasive breast cancer.
Researchers at the Maimonides Medical Center evaluated the prevalence of lobular carcinoma in situ (LCIS), a noninvasive lesion that can be thought of as pre-cancerous and is linked to a higher risk of the development of invasive breast cancer, in a sample of 152 patients. LCIS is typically found in roughly five percent of patients with invasive breast cancer, but is present in approximately 50% of invasive lobular carcinoma (ILC) cases. It is usually found during an evaluation of another breast abnormality.
In this analysis of patients who had surgery to remove breast cancer, the presence of LCIS was found in roughly 30% of all breast cancer cases in the study. LCIS was found in ductal breast cancer (IDC) in 21.4% of the IDC surgical samples (n=140) and in lobular cancer in 92.3% of the ILC surgical samples (n=13). LCIS was more frequently found in ER+ cases (92.7%) but was also found in HER2+ and triple-negative breast cancer samples. These findings suggest that LCIS occurs more frequently than previously reported and may suggest that LCIS has biological significance in the development of breast cancer.
PD9-09 Clinical utility of 18F-fluoroestradiol positron emission tomography (FES PET) in patients (pts) with lobular breast cancer
Lobular breast cancer is usually estrogen receptor-positive (ER+), can metastasize to unusual locations like the abdominal lining (peritoneum), and can be challenging to visualize using standard imaging techniques like mammograms, CT scans, and PET scans. The most common PET scans—FDG PET—use a radiotracer dye that often cannot pick up lobular breast cancer. Therefore, standard FDG PET scans can underestimate the extent of lobular breast cancer involvement and miss unusual metastases. Recently, the National Comprehensive Cancer Network (NCCN) guidelines, which oncologists in the United States use to help make treatment decisions, recommended that oncologists consider using a special type of PET scan, FES PET, to evaluate patients with lobular breast cancer. FES PET utilizes a radiotracer called fluoroestradiol (18F) to identify and map out the locations of ER+ cancer cells throughout the body. In our study, we reviewed clinical information and imaging for 102 Mayo Clinic patients who had undergone FES PET, representing the largest group of patients, to our knowledge, with lobular breast cancer who have undergone FES PET. Our study aimed to find out how FES PET has been used to improve the diagnostic evaluation and treatment of patients with ER+ lobular breast cancer.
We learned that the most common reasons why oncologists ordered FES PET scans were for:
- staging or restaging lobular breast cancer (49%),
- detecting suspected recurrent or metastatic breast cancer (30%), and
- evaluating rising tumor markers like CA 15-3 or CA 27.29 (15%).
Some patients experienced a change in stage based on FES PET. Importantly, FES PET led to a change in the care of 37% of the patients, including decisions related to systemic treatment (19 patients), biopsies (10 patients), additional imaging like MRI scans (4 patients), surgical and/or radiation treatment (3 patients), and referrals to other subspecialists like gastroenterologists to evaluate a suspected metastatic site (2 patients).
We also compared FES PET and standard FDG PET scans for patients who completed both scans. 63 patients had FDG PET prior to FES PET.
- FES PET detected a higher number of metastatic areas in the body than FDG PET in 21 patients, especially in the bones and lymph nodes.
- Only 9 patients had metastases that were seen on the FDG PET but not the FES PET.
When we looked at the group of patients whose FES PET had led to a change in their care, we found that 32% had metastases on their FES PET scan that had not been seen on their FDG PET scan and 8% had metastases on the FDG PET scan that were not seen on the FES PET scan.
Thirteen patients had a special FES PET scan that utilized MRI scanning instead of CT. Two of these patients were found to have metastases in unusual sites (the brain and peritoneum), which were not seen on their FDG PET scan.
In summary, we learned that FES PET scans are useful to evaluate both early-stage and metastatic lobular breast cancer. These scans added useful information beyond what FDG PET scans provided. Approximately one-third of patients whose FES PET scan led to a change in their care had metastases that were detected on their FES PET scan but not on their FDG PET scan. Using MRI with FES PET scanning may be better than using CT scanning with FDG PET for identifying unusual lobular breast cancer metastases.
PD9-10 Factors Associated with Early and Late Mortality in Invasive Lobular Carcinoma
In this study, we looked at a large national database to understand what factors influence survival in people diagnosed with invasive lobular carcinoma (ILC), a common but distinct type of breast cancer. ILC is known to behave differently from the more common ductal breast cancer, particularly because it can come back many years after diagnosis. Our goal was to understand which tumor features and treatments matter most in the early years after diagnosis and which continue to affect outcomes many years later, so care can be better tailored to people with ILC.
We found that overall survival for people with ILC is generally excellent, but certain factors were linked to a higher risk of death, both early and late after diagnosis. Larger tumors, cancer spread to lymph nodes, higher tumor grade, and invasion into blood or lymph vessels were associated with worse outcomes. Treatments such as surgery, radiation, chemotherapy, endocrine (hormonal) therapy, and progesterone receptor positivity were associated with better survival. We also found that patients with a high Oncotype DX recurrence score had worse survival when compared to those with intermediate or low scores.
These findings matter because they highlight that ILC carries ongoing risk even many years after diagnosis, and that some commonly used tools may underestimate long-term risk for certain patients. This suggests that many people with ILC may benefit from more personalized long-term risk assessment and in some cases, extended hormonal therapy or closer follow-up. Our results support the need for ILC-specific research and decision-making tools, so patients and clinicians can make more informed choices about treatment and long-term care.
PD9-11 The association of breast density with clinicopathological characteristics and survival in patients with early stage ER+ HER2- lobular breast cancer
This study looked at the association of breast density and characteristics of ILC and survival outcomes in patients with invasive lobular carcinoma (ILC). ILC differs from invasive breast cancer of no-special type on (IBC-NST) on histological, clinical, and molecular level and these differences might (partially) be explained by different interactions with the environment surrounding the tumor. This makes breast density such an interesting factor to look at. Breast density originates from the field of radiology, where we see fibroglandular tissue of the breast as radio dense and fat tissue as radio lucent.
For this trial, 566 mammograms of patients diagnosed with ILC in the university hospital of Leuven between the years 2000-2020 were re-evaluated by 5 different radiologists. For the analysis described, researchers focused on the estrogen-receptor positive breast cancer (ER+ BC) group. We have found that a higher breast density is associated with younger age, less overweight/obesity, more multifocality, and possibly a lower tumor grade. When looking at survival, we found that a higher breast density at the time of ILC diagnosis is associated with a better survival.
This finding is notable because earlier studies looked at all breast cancer types together and reported mixed results. This is the first study to focus specifically on lobular breast cancer, which behaves biologically differently from other breast cancers.
However, the underlying reasons for these relationships are still unclear. More research is needed to understand the biological mechanisms behind breast density in this specific breast cancer type.
PS3-08-01 Validation of the Modified Preoperative Endocrine Prognostic Index (mPEPI) in a single institution cohort of patients with invasive lobular carcinoma
In this study, we looked at patients with invasive lobular breast cancer (ILC) who received neoadjuvant (i.e. before surgery) endocrine therapy (NET) . We wanted to know whether the Modified Preoperative Endocrine Prognostic Index (mPEPI) score — which is based on features seen in tissue removed during surgery, such as tumor size, whether lymph nodes had cancer, and how actively the cancer cells were growing — could help predict whose cancer was more or less likely to come back. The mPEPI score has been studied in other types of breast cancer, but not specifically in ILC, which behaves differently and currently lacks good tools to measure response to treatment.
The study validated that the mPEPI score was an effective tool for helping separate post-menopausal ILC patients into lower- and higher-risk groups after endocrine therapy and surgery. Patients with low mPEPI scores had fewer recurrences over long-term follow-up, while those with higher scores were more likely to have their cancer return.
If confirmed in larger studies, these results suggest that the mPEPI score could help tailor treatment for patients with ILC. For some patients with very low scores, it may support safely avoiding chemotherapy and relying on endocrine therapy alone. Patients with higher scores may benefit from additional treatments and closer follow-up. Ultimately, improving tools that predict outcomes after treatment may lead to more personalized and effective care for patients with ILC.
PS4-02-01 Differential early response to neoadjuvant endocrine therapy in lobular versus non-lobular breast cancer on the Endocrine Optimization Pilot (EOP) of the I-SPY2 Trial
Invasive lobular breast cancer (ILC) behaves differently from more common ductal breast cancers, especially in how it responds to hormone-based treatments and how response is measured on imaging. This study, conducted as part of the I-SPY2 Endocrine Optimization Pilot trial, examined whether lobular tumors respond differently from non-lobular tumors when treated with endocrine therapy before surgery (referred to as “neoadjuvant”). Researchers focused on early biological changes in the tumor and how much cancer remained visible on MRI after treatment with endocrine therapy over time.
The study included 253 patients with estrogen receptor–positive (ER+), Human Epidermal Growth Factor 2-negative ( HER2-) breast cancer. Lobular tumors had lower levels of tumor growth at the start and showed similar reductions (based on a reading of a growth marker referred to as “Ki67” from a blood test) after three weeks of treatment compared with non-lobular tumors. However, despite these early signs that tumor growth had been reduced, lobular tumors had more remaining tumor volume than non-lobular tumors as determined by MRI scans just before surgery, particularly in cases of tumors with mixed lobular and ductal features.
These findings suggest that standard ways of measuring tumor response to treatment that are not specific for assessing changes in lobular tumors may not fully capture how lobular breast cancer behaves. This highlights the need for lobular-specific tools to guide treatment decisions, avoid overtreatment or undertreatment, and ensure care is tailored to the biology of each person’s cancer.
PS5-10-20 Invasive lobular breast cancer and surveillance: A patient experience survey study.
People diagnosed with invasive lobular breast cancer (ILC) often face unique challenges during follow-up care. Because ILC tends to spread in single cells rather than forming a lump, standard imaging tests may be less reliable for detecting recurrence or disease progression. This study, led by the Lobular Breast Cancer Alliance (LBCA), surveyed people with early-stage ILC and those living with metastatic ILC to better understand real-world surveillance practices, confidence in those plans, and fear of cancer recurrence or progression.
Across 1,706 respondents from more than 30 countries, many reported low confidence that their current surveillance plans would detect recurrence or progression. High fear of recurrence was strongly linked to this lack of confidence. Among people with early-stage ILC, surveillance plans that included imaging beyond standard mammography, such as breast MRI or contrast-enhanced mammography, were associated with greater confidence.
For patients, these findings highlight an urgent need for clearer, more consistent, and ILC-specific surveillance strategies. Improving surveillance approaches may reduce fear, support shared decision-making, and help patients feel safer and more confident during long-term follow-up care.
PS3-12-21 A Novel Spatial Profiling Approach Reveals Distinct Fibroblast and Immune Architectures in Invasive Pleomorphic versus Classic Lobular Carcinomas
This descriptive study aimed to explore the spatial environment* including relationships and distribution patterns of Invasive Classic Lobular Carcinomas (ICLCs) and Invasive Pleomorphic Lobular Carcinomas (IPLCs), addressing the limited knowledge regarding fibroblast and immune cell organization in these histologic subtypes. Understanding the spatial organization of fibroblasts and immune cells in invasive lobular carcinoma (ILC) matters because it directly influences how the cancer grows, spreads, and responds to treatment.
ILC is the second most common subtype of breast cancer, and distinct biology has been described compared to IDC and among its variants. The Tumor microenvironment (TME) components (fibroblasts, immune cells, and extracellular matrix) interact in unique ways that can either suppress or promote tumor growth. The presence and number of cancer-associated fibroblasts (CAFs) vary between ILC subtypes. The spatial arrangement of immune cells (like T cells and macrophages) around tumor cells can determine whether immunotherapies—such as checkpoint inhibitors**—are effective. Studying spatial cell organization helps identify mechanisms of resistance and potential new drug targets.
What was found:
The stroma ( I.e, the connective tissue, blood vessels, lymphatic vessels, and nerves) in IPLCs is dynamic and heterogeneous, marked by complex fibroblast–tumor interactions and heightened immune infiltration, consistent with their aggressive clinical phenotype. In contrast,ICLCs exhibit a more cohesive tumor structure with streamlined, peripheral stroma and limited immune involvement.
Our data reveal profound differences in the spatial microenvironments of IPLC and ICLCs.These findings underscore the importance of spatial context as a novel lens for understanding ILC biology and suggest that stromal and immune characteristics may guide therapeutic approaches, including potential susceptibility of IPLCs to stroma- or immune-directed interventions.
How this might affect patients, care, or future research: By integrating spatial context into ILC biology, we move closer to precision oncology—where treatment decisions are guided not only by tumor genetics but also by the architecture and behavior of the surrounding stroma and immune cells.
* The spatial environment of a cancer cell refers to the specific, three-dimensional physical arrangement, location, and neighboring cellular context within a tumor tissue that directly influences the cell’s behavior, growth, and response to treatment. Unlike traditional analyses that study cells in isolation, the spatial environment emphasizes “location, location, location”—how a cancer cell’s proximity to immune cells, blood vessels, or fibroblasts impacts its malignancy.
**Checkpoint inhibitors are a type of immunotherapy treatment. These drugs block different proteins called checkpoint proteins that stop the immune system from attacking the cancer cells.
PS3-11-06 Long-term prognostic and predictive value of lobular histology in the PALLAS trial
This analysis used data from the PALLAS clinical trial, a large prospective study including people with stage II–III hormone receptor–positive, HER2-negative early breast cancer who received standard endocrine (hormone) therapy with or without 2 years of palbociclib (a CDK4/6 inhibitor). We compared outcomes for patients with invasive lobular carcinoma (ILC) versus the more common non-lobular type and followed patients long term (median follow-up ~7 years). We found that, overall, ILC tended to have later recurrences: differences in outcomes became more apparent after the first few years, highlighting that lobular breast cancer can have a distinct long-term pattern.
When we looked at treatment effect, palbociclib appeared to be associated with more favorable outcomes in ILC than in non-lobular cancers across several endpoints. The findings suggest a potential benefit of palbociclib in ILC that warrants further investigation in other adjuvant trials evaluating CDK4/6 inhibitors.
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