LBCA Scientific Advisory Board Member Dr. Rebecca Riggins Discusses the Challenges of ILC-Specific Research and Potential Solutions
In 2004, I was a new postdoctoral fellow studying estrogen receptor-positive (ER+) breast cancer. I had just completed my PhD in microbiology, trained in a lab whose goal was to better understand how individual cells – human and bacteria – sense and respond to their environment.
As I dug through the scientific literature, I learned more about invasive lobular breast cancer (ILC), also known as lobular breast cancer, but that our molecular understanding was limited and based mostly on other, more common breast cancers. In fact, almost everything we knew about ER+ breast cancer in the lab came from one particular model. Every time I looked at those thin streams of cancer cells probing and tunneling through breast tissue, I became more convinced that ILC was unique, and it needed more specific study.
Since then, our knowledge of what drives ILC has grown exponentially (summarized beautifully in a recent review by Dr. McCart Reed and colleagues, ). Still, ILC, the sixth most common cancer diagnosed in women in the US, presents us with several research challenges, both in the clinic and in the lab.
Their relative rarity means that even busy academic medical centers may see only a few cases each year. Their slow growth compared to other types of cancer presents other challenges:
- Neoadjuvant therapy (best at eliminating fast-growing tumor cells) is not as effective in ILC
- ILC is harder to see by standard methods of positron emission tomography (PET) scanning
- We may need decades of follow-up to know whether new drugs (or combinations) prevent distant recurrence in ILC
And when ILC does recur, it can do so in unusual places (e.g. the ovaries, GI tract, and even the eye socket) where a woman and her primary care physician may not immediately think, “This could be breast cancer!”
In the lab, ILC’s relatively slow growth means our work takes longer. Other challenges include:
- There are just a handful of cell line models that have been established from ILC, which means we are not capturing the full range of its genetic diversity in our experiments.
- There are models of ILC-like breast cancer development in mice, but most of these are not ER+, so they don’t accurately reflect how ILC grows in women.
- New methods allow us to grow samples of patient tumors in mice, as “avatars” of their patient, to support drug testing and development. However, ER+ ILC tumors have been hard to establish in these systems, so there are currently only two validated ER+ ILC avatars in regular use.
- Unless we are privileged to research at one of those busy academic medical centers, we struggle to have access to ILC tumor tissue to confirm the new scientific findings we are making with the cell models we do have.
The Lobular Breast Cancer Alliance (LBCA) is dedicated to overcoming these challenges to research in ILC, by partnering with the patient advocacy, clinical, and basic science communities. Some solutions we envision could include:
- Increased education for oncologists and patients regarding the critical need for ILC-focused tissue banking and tumor registries, with strong encouragement of data sharing and ‘living room language’ summaries of findings by investigators who use these resources.
- ILC-specific grant mechanisms, with calls for proposals at multiple levels – from pilot grants to larger awards for multi-national teams – that target some of our critical ‘research infrastructure’ needs, e.g.,:
- building and validating new laboratory models that capture features of ILC missing from our current repertoire
- collaborative testing of new treatment combinations
- Decentralized clinical trials, a current area of intense interest and discussion at the FDA, to increase opportunities and reduce the barriers for women with ILC to participate in clinical trials, no matter where they live.
- Dedicated support for long follow-up required for clinical trials to monitor the true long-term impact of new drugs (or combinations) on distant recurrence in ILC.
We’ve come a long way since 2004, from my struggle to find just one ILC cell model I could study in the lab to ILC featuring prominently in major international breast cancer meetings with its own dedicated sessions. LBCA is eager to continue building on this momentum, supporting research, treatment, education, and patient advocacy to benefit those affected by ILC everywhere.
Rebecca B. Riggins, PhD, is an Associate Professor of Oncology and Associate Director of Education and Training, Georgetown Lombardi Comprehensive Cancer Center (LCCC).
1. McCart Reed AE, Kalinowski L, Simpson PT, Lakhani SR. Invasive lobular carcinoma of the breast: the increasing importance of this special subtype. Breast Cancer Res. 2021;23:6.