The Lobular Breast Cancer Alliance Inc. (LBCA), powered by Conquer Cancer’s EveryGrant®, has awarded a total of $1M through the LBCA-Shannon Klingman Lobular Breast Cancer Clinical Research Grants to Steffi Oesterreich, PhD and Rita Mukhtar, MD. Each investigator will receive $500,000 over two years to accelerate urgently needed research into invasive lobular carcinoma (ILC), administered through Conquer Cancer’s EveryGrant program. The two-year award term starts in January 2027.
ILC is the second most common histological type of breast cancer, representing 10% to 15% of all breast cancer diagnoses—accounting for up to 48,000 individuals diagnosed each year in the United States alone. Despite its prevalence and rising incidence, ILC remains historically underfunded and understudied, receiving less than 1% of dedicated breast cancer research funding.
Unlike more common forms of breast cancer, ILC exhibits distinct biology and growth patterns. Rather than forming discrete, easily palpated lumps, lobular cancer cells typically spread in single-file strands through surrounding tissue. This characteristic makes ILC notoriously difficult to detect through standard screening mammography—particularly in women with dense breast tissue—and challenging to track when it metastasizes. Consequently, tumors are frequently discovered at later stages, exhibit late recurrences decades after initial diagnosis, and are difficult to measure using standard response criteria. Because measuring response is challenging, ILC patients are frequently excluded from clinical trials, stalling the discovery and validation of lobular-specific therapies.
The grants are named in honor of Dr. Shannon Klingman—board-certified OB-GYN, founder of Lume Deodorant, and dedicated ILC survivor and advocate. Following her own diagnosis with invasive lobular carcinoma in 2025, Dr. Klingman partnered with LBCA to drive philanthropic momentum, raise public awareness, and direct vital resources toward lobular-specific scientific discovery.
“When patients are diagnosed with lobular breast cancer and then hear that it is a peculiar breast cancer type but has no specific treatments yet because of too little research they are horrified. LBCA was founded to raise awareness of lobular breast cancer and the urgent need for more research to change this,” said Laurie Hutcheson, MS, Executive Director of LBCA. “We were able to start funding small lobular breast cancer-focused research grants in 2021. Thanks to the generosity of Dr. Klingman, this grant is by far the largest we have been able to award to-date bringing significant and much needed resources to two excellent lobular breast cancer researchers and a big dose of hope to the lobular breast cancer patient community.”
Funded by the Lobular Breast Cancer Alliance (LBCA), these awards are managed and administered through Conquer Cancer’s EveryGrant program, which partners with organizations worldwide to design, launch, and manage high-impact cancer research grant programs.
Steffi Oesterreich, PhD
Professor, Dept. of Pharmacology and Chemical Biology, Univ. of Pittsburgh School of Medicine, Co-Leader, Cancer Biology Program, UPMC Hillman Cancer Center, Co-Director, Women’s Cancer Research Center at Magee-Womens Research Institute & UPMC Hillman
Project Title: “Identification of therapeutic targets in pleomorphic Invasive Lobular Carcinoma (pILC)”
Research Overview: Affecting nearly 5,000 individuals in the U.S. annually, pleomorphic invasive lobular carcinoma (pLIC) is an aggressive and understudied variant associated with higher recurrence rates and limited targeted therapy options. Dr. Oesterreich’s study utilizes high-resolution genomic and spatial transcriptomic assays to map mutated genes and gene expression pathways to identify key drivers of pILC and uncover prognostic tumor biomarkers for novel therapeutic vulnerabilities.
“This insightful funding from the Lobular Breast Cancer Alliance is critical to enabling high-risk, high-reward research that will, we hope, lead to impactful discoveries in ILC that can be translated from the laboratory into clinical trials and ultimately bring life-saving therapies to thousands of patients,” Dr. Oesterreich said. “It provides me and my fellow scientists with the unique opportunity to think outside the box and find innovative approaches to identify targets on the lobular cancer cells that we can exploit to destroy the cancer with novel therapies.”
Lay Abstract
ILC affects an estimated 46,000 women each year in the United States (U.S.), representing 10–15% of all breast cancers. pILC is a rare and more aggressive form of ILC. About 4,000–5,000 people in the U.S. are diagnosed with pILC each year (roughly 10% of ILC cases), and around 75,000 are currently living with the disease. Even with treatment, many patients face a higher risk that the cancer will return or become fatal.
pILC shares some features with ILC, such as being driven by estrogen and growing in similar patterns. However, pILC cells look more abnormal under the microscope, behave more aggressively, and are linked to worse outcomes. Because pILC is rare, it remains understudied. Early research has found certain genetic changes in pILC, including alterations in the ErbB2 gene.
Our team has collected and verified 40 frozen pILC tumor samples, along with matching normal tissue or blood, from a biobank at the University of Pittsburgh. Surprisingly, nearly one-third of these tumors contain high levels of immune cells, suggesting the immune system may actively respond to the cancer in some cases. This is unexpected, since this type of breast cancer is usually considered “immune cold” and unlikely to respond to immunotherapy. This finding challenges that assumption and opens the door to immune-based treatments for pILC. Preliminary sequencing on these cases also hinted at errors in DNA repair, which could offer opportunities to target the disease with existing drugs.
We believe that thoroughly studying the genetic makeup of pILC tumors can reveal the key genetic changes driving this disease, potentially pointing to new treatments and explaining how these changes shape immune cell activity within tumors. To test this idea, we will:
- Analyze the genetic material (DNA and RNA) from pILC tumor samples to fully characterize what’s happening inside these tumors.
2. Use computer-based analysis to identify genetic changes that could be targeted by existing or new drugs, then confirm findings using over 300 preserved pILC tissue samples.
3. Test candidate genes and pathways in specialized pILC laboratory models to determine whether they could serve as effective drug targets.
This research will help identify new treatment targets and better predict patient outcomes, laying the groundwork for clinical trials toward more effective, personalized treatments for this challenging form of breast cancer.
Rita Mukhtar, MD
Professor of Clinical Surgery, Division of Surgical Oncology, Director, UCSF Lobular Breast Cancer Research Program, University of California, San Francisco
Project Title: “The E-cadherin Complex Spectrum: Utilizing Protein-Based Drug Target Landscape Mapping of the E-cadherin Complex in Invasive Lobular Carcinoma to Personalize Therapy in I-SPY2”
Research Overview: Historically, diagnostic classification has treated E-cadherin expression as a binary biomarker: negative in ILC and positive in invasive ductal carcinoma (IDC). However, emerging evidence indicates that E-cadherin exists along a continuous spectrum. Leveraging clinical data, imaging, and biospecimens from over 700 patients enrolled in the nationwide I-SPY clinical trial, this study evaluates whether shifting from historical histology to a quantitative “E-cadherin high” versus “E-cadherin low” defined identification of ILC subtypes improves prognostic and molecular therapeutic stratification and helps to identify new drug targets in ILC.
“While we have made progress in understanding ILC, there is still a huge need for better diagnostic approaches and appreciation for heterogeneity within ILC,” said Dr. Mukhtar. “This generous funding will allow us to analyze data from a biomarker rich trial, I-SPY2, to improve diagnostic precision, hopefully leading to better clinical trial design and discovery of targeted therapies specifically for those with ILC.”
Lay Abstract
ILC is the second most common type of breast cancer, representing 10-15% of all cases. It has unique features that can lead to challenges with diagnosis and treatment. ILC tends to grow in “single-file lines,” forming a thread-like pattern that makes them hard to see on standard imaging tools. Many ILC tumors do not form a lump and can go undetected. Surgical treatment often requires more extensive procedures compared to other types of breast cancer. Furthermore, ILC often does not respond well to standard chemotherapy and carries a higher risk of late recurrence.
These unique features of ILC are thought to result from the absence of the protein E-cadherin, which is a type of cellular “glue” that normally allows cells to stick together. While ILC is usually E-cadherin negative, and IDC is usually E-cadherin positive, this binary “negative or positive” definition may be an oversimplification. Our preliminary research shows that E-cadherin levels exist on a spectrum, with some IDC tumors having levels of E-cadherin that are just as low as ILC tumors. Similarly, among some mixed ILC/IDC tumors, we see a broad range of E-cadherin levels. This could explain why we see variation within ILC and IDC. For example, some ILC tumors do show up on imaging, form lumps, and respond to chemotherapy. Conversely, some IDC tumors display the same clinical behavior as ILC.
This project aims to change how we classify and treat these cancers by shifting away from the historical diagnostic approach to ILC, which has existed for decades. We will analyze tissue samples to quantitatively measure E cadherin protein levels, imaging patterns, and treatment results from over 700 patients enrolled in the innovative, nationwide I-SPY clinical trial. First, we will map out how E-cadherin protein levels relate to a tumor’s underlying biology. Second, we will evaluate how E-cadherin levels affect tumor appearance on MRI and whether this can help plan successful surgeries. Finally, we will determine if a tumor’s E-cadherin level can predict whether a patient will respond better to certain therapies. By improving the classification of ILC, we will be able to more accurately predict tumor behavior. Ultimately, identifying a new classification system of “E-cadherin low” versus “E-cadherin high” tumors could lead to the discovery of treatment targets unique to each group.