LBCA’s Scientific Advisory Board Is Tackling ILC through Research

The Lobular Breast Cancer Alliance keeps its invasive lobular carcinoma (ILC) information and research cutting edge with the guidance of a Scientific Advisory Board (SAB) of clinicians and scientists spanning the US and Europe who are experts in and committed to ILC research and treatment. Here is a summary of their current work:

SAB Chair: Steffi Oesterreich, PhD

Research in Steffi’s lab at the University of Pittsburgh focuses on understanding why ILC shows resistance to many clinical breast cancer treatments and determining more effective ways to target and treat ILC. One important reason is that a number of drug companies are focusing on developing oral Selective Estrogen Receptor Degraders (SERDs), taken as pills, which have shown to have great potential in the treatment of ER+ breast cancer.

Steffi’s lab has shown that one of these new drugs does not show high efficacy in preclinical models of ILC, while it does work in other breast cancer models. Steffi and her colleagues have been surprised by this and puzzled by the underlying mechanism driving both the resistance of ILC to these drugs, and about what other factors in the tumor environment might contribute to the development of metastases. Steffi believes that these findings are important to understand given the great potential these drugs have for treatment, and they highlight the need for inclusion of ILC models in the development of hormonal treatments to ensure developed drug therapies are effective in treating ILC.

Nancy E. Davidson, MD

As a practicing medical oncologist, Nancy frequently cares or consults for women with lobular breast cancer, and as a clinical researcher, she has been a leader in the development of clinical trials for lobular breast cancer including the current TBCRC trial.

In addition, Nancy’s lab researches how hormones, particularly estrogen, affect gene expression and cell growth in endocrine responsive breast cancer, a type of breast cancer which includes most invasive lobular breast cancers. She is intent on understanding the signaling pathways that might be unique to ILC and collaborates with other researchers in the field including Dr. Steffi Oesterreich on such investigations.

Patrick W.B. Derksen, PhD

The Derksen Lab at University Medical Center Utrecht, Netherlands focuses on all aspects of ILC. Almost two decades ago, Patrick’s work established the causal connection between development of ILC and loss of cell-cell adhesion through a protein called E-cadherin. Patrick’s lab combines a comprehensive collection of scientific techniques that aims to study the biology and resulting clinical presentation and behavior of ILC.

Patrick’s long-standing interest and expertise in ILC has formed the basis for the development of a European conglomerate of ILC researchers, clinicians, and patient advocates. For this, Patrick initiated the European Lobular Breast Cancer Consortium (ELBCC) in 2018 in close collaboration with Christine Desmedt (KU Leuven) and Anne Vincent Salomon (Curie Paris). It is Patrick’s hope that the ongoing interactions among leading clinical ILC experts will yield new biomarkers/drugs and other novel approaches to better manage ILC.

Rachel C. Jankowitz, MD

The current standard is to treat patients with ILC similarly to those with the more common form of breast cancer, invasive ductal cancer (IDC), despite numerous studies suggestive of inherent differences in their tumor types. In 2014, Rachel was awarded a $450,000 Susan G. Komen® Career Catalyst Research (CCR) Award. She used it to open an investigator-initiated clinical trial to study ILC at multiple academic institutions in a highly collaborative way through the Translational Breast Cancer Research Consortium (TBCRC). The TBCRC037 trial was designed to study response to tamoxifen, anastrozole (an aromatase inhibitor, which inhibits the synthesis of estrogen), and a SERD, Fulvestrant, in the tumor tissue of women with newly diagnosed ILC. Rachel and her collaborators are hopeful that findings from this work will help develop more effective future treatments for ILC patients.

Christopher I. Li, MD, PhD

Christopher is a cancer epidemiologist at Fred Hutchinson Cancer Research Center. Cancer epidemiology is the study of the cause, distribution, and control of cancer development. His ILC research focuses on studying the etiology (i.e. cause or causes) of ILC, and the experiences and presence or absence of disease in those living with, through, and beyond cancer diagnosis and treatment.

Christopher led one of the largest observational studies of ILC that identified several unique risk factors for ILC including those related to hormones and lifestyle factors. His lab and collaborators are now following this cohort to identify factors associated with development of ILC and changes in patient disease-free status post-treatment.  More recent work in Christopher’s lab has focused on understanding molecular differences between ILC and IDC with a focus on hormonal pathways.

Otto Metzger, MD

Otto is a clinical investigator focused on the development of therapies for breast cancer treatment. His principal research effort is centered on investigating two subtypes of breast cancer: ILC and HER2+ breast cancer. He also maintains an active clinical practice in the Breast Oncology Center at Dana-Farber/Brigham and Women’s Cancer Center.

Otto’s ILC-focused research seeks to identify predictive biomarkers of sensitivity to specific agents and mechanisms of resistance to endocrine therapy. Most recently he has been focused on studies including clinical trials to test the efficacy of hormone treatment on patients with IDC and ILC prior to surgery (i.e., “neoadjuvant”)  in shrinking tumors and for their potential to identify factors affecting tumor resistance to endocrine therapy, which may ultimately guide treatment decisions for the post-surgical or “adjuvant” time periods. He is also studying the effects of neoadjuvant treatment on the axilla, i.e., the lymph nodes under the arm, which has not yet been studied.

Rita Mukhtar, MD

As a breast cancer surgeon with a particular interest in ILC, Rita’s research aims at improving surgical outcomes for those with this type of tumor.  Women with ILC have the highest rates of positive margins after surgical excision and higher rates of completion mastectomy than those with IDC. Inaccuracy of pre-operative imaging and lack of effective neoadjuvant approaches contribute to these problems.  To this end, Rita’s research focuses on how different surgical techniques (e.g. shave margins, oncoplastic surgery, type of mastectomy, extent of axillary surgery) impact outcomes, as well as the accuracy of pre-operative imaging in the neoadjuvant (pre-surgical) setting. Her lab is studying the ability of dedicated breast PET (positron emission tomography) scanning with tagged estradiol (the most common type of estrogen measured) to accurately measure ILC tumors and show the response to endocrine therapy. Tagged estradiol involves a measurable, identifiable marker attached to estradiol in order to track estrogen binding in a PET scan. She is the site’s primary investigator for the TBCRC037 pre-operative endocrine therapy window trial for women with ILC.  Her group also studies how women with ILC are potentially excluded from clinical trials that require “measurable disease,” with a study currently ongoing to determine how commonly this occurs.

Jorge S. Reis–Filho, MD PhD FRCPath

Jorge’s team focuses on understanding the molecular make up of rare forms of breast cancer through a combined approach bringing together how cancers look under the microscope, the genes that harbor genetic alterations, and how these alterations affect the development and progression of cancers in laboratory models. Jorge’s work on ILC and lobular carcinomas in situ (LCIS – i.e., non-invasive) has demonstrated that LCIS creates the starting point from which ILCs can develop.

Another interest of Jorge’s team is in the identification of therapeutic targets and mechanisms of resistance to hormone treatment in ILCs. He collaborates with numerous LBCA investigators and other leaders in the field to bring cutting-edge technologies to study lobular carcinomas. His vision is that by systematically analyzing these tumors we can understand not only what drives these cancers, but what their weaknesses are, so that we can have a future free from the fear of ILC.

Matthew J. Sikora, PhD

Matt Sikora’s Lab at the University of Colorado Anschutz Medical Campus is focused on understanding the unique functions of the estrogen receptor (ER) in ILC. Nearly all ILC tumors contain ERs, the proteins that allow tumor cells to use the hormone estrogen to grow. For decades, ER+ breast cancers have been treated with anti-estrogen drugs such as Tamoxifen and aromatase inhibitors that block the functions of the ERs. Research has suggested that ILC does not respond to anti-estrogens in the same way as other breast cancers and may develop anti-estrogen drug resistance. Recent research has found that this indicates that patients with ILC have a greater risk of long-term disease recurrence than patients with other breast cancer types.

These recent findings about ILC have led Matt to focus his study on the distinct mechanisms of ILC relative to ER function, anti-estrogen response, and therapy resistance. Matt’s team is currently working to identify and understand other proteins that control ER function and the way ERs respond to anti-estrogens (“co-regulator” proteins) and are working to understand how ER controls ILC cell biology. They hope that in understanding these processes they will be able to identify strategies and potential drugs to undermine ER activity better than commonly used anti-estrogen drugs, for example, drugs that may target other proteins or cell signaling pathways that are specific to and effective with ILC-. Matt’s long-term goal is to develop targeted therapies specifically designed to benefit patients with ILC by targeting biology unique to ILC cancer cells.

Christos Sotiriou, MD, PhD

Christos’ research group has contributed seminal and practice changing results in breast cancer translational research (i.e., research that applies knowledge from basic biology and clinical trials to techniques and tools that address medical needs to improve health outcomes). Recent work from the Sotiriou Lab has focused on identifying mechanisms of cancer progression and endocrine resistance in ILC. This research furthered understanding of how mutations in genes such as ERBB2, ESR1 & AKT1, and CDH1 affect responses to and efficacy of cancer therapies. Additionally, Christos is a former elected member of the Scientific Council of the International Agency for Research on Cancer (World Health Organization).

Gary Ulaner, MD, PhD

Gary’s work has focused on the staging of breast cancer and breast cancer imaging. He notes that staging of breast cancer is critical to determine proper therapy as it helps determine the extent of cancer and how much a cancer has spread from the primary site. Medical imaging (radiology) is the primary method for breast cancer staging.  ILC is more difficult to detect on medical imaging than the more common IDC.  One of the focuses of research in Gary’s lab is the development and application of new methods to image ILC and its metastases.  Gary’s group has demonstrated the utility and limitations of FDG PET/CT imaging for metastatic ILC and has active research projects into novel molecular imaging methods for ILC. The overall goal of Gary’s research is to improve imaging of ILC, leading to better staging and therapy.