Valerie Fraser was the recipient of one of the Lobular Breast Cancer Alliance’s travel grants to attend the 2022 San Antonio Breast Cancer Symposium (SABCS22). Valerie is a trained breast cancer research advocate with experience collaborating with both researchers and breast cancer patient advocates. She is also a seasoned breast cancer research grant peer reviewer. She was eager to attend the symposium and to share her perspective as an inflammatory breast cancer survivor on all she learned about the new research into challenging breast cancer types such as hers and lobular. She was happy to share her experiences and takeaways from SABCS22 with the LBCA community. 

SABCS2022 was chock full of some amazing presentations and follow-up research data that will most surely translate into the clinic and impact many patients. It was certainly a difficult task to pick and choose which sessions to attend over the four days of the conference, and the Year In Review on Saturday was something not to be missed! I know I’m just scratching the surface here with highlights from two sessions from among the many outstanding talks and poster discussions that took place this year. 

On Thursday, December 8, I found of particular interest the session titled “Challenging Types of Breast Cancer.” It was the only formal session other than poster sessions that delved into specific information about invasive lobular carcinoma (ILC). Moderator Dr. Bora Lim and presenters Dr. Jorge S. Reis-Filho and Dr. Sibylle Loibl discussed different aspects of the latest findings and evolving approaches that can help detect and potentially guide treatment for lobular breast cancer. A couple of key points made by presenters in this session were the following: 

• Dr. Bora Lim, Associate Professor of Oncology at Baylor College of Medicine and Director of Translational Research for the Dan L Duncan Comprehensive Cancer Center Breast Cancer Research Program, explained how understanding biological differences in breast cancer can make a real difference in the diagnosis and treatment of that cancer. She discussed how lobular carcinoma when caught early can very often be cured because it is usually of a low-grade and very slow-growing. However, lobular carcinoma that has metastasized can be very challenging because the biological features of the lobular structure of where the tumor originated and the metastases often do not appear on PET scans because of the low metabolic profile of the cancer. She also described the more unusual organs that lobular metastasis can travel to like the peritoneum and/or bowel walls and where it can be missed. She mentioned how important developments in PET platforms are emerging that are more sensitive to the estrogen-specific receptor in lobular carcinoma so as to be able to identify these types of metastases in lobular breast cancer. 
• Dr. Jorge S. Reis-Filho, MD, PhD, Director, Experimental Pathology, MSKCC, and LBCA Scientific Advisory Board member, elaborated on the pathology of ILC. He explained how invasive ductal carcinoma (IDC) is a diagnosis of exclusion, as all of the other 20 histologic breast cancer types must be ruled out first. And some of these histologic types (based on their histology) have important clinical implications and can have a much better outcome than IDC. He described some findings about mutations his group has found in metastatic ILC. I perceived that the overall point of his discussion was that special histologic types of breast cancer, such as in lobular, have distinct features and genotypic-phenotypic correlations, and because of this distinct biology it is most important to determine the subtype, although challenging. 
• Prof. Dr. Sibylle Loibl, Chair of the German Breast Group, Centre for Haematology and Oncology Bethanien, Frankfurt/M, Goethe University Frankfurt/M, Germany, provided a clinical overview of invasive lobular carcinoma that delved into much of the information currently understood about ILC and its subtypes at various stages. She provided an interesting description of the evolution of ILC from normal cells to losing E-cadherin and transitioning through atypical lobular hyperplasia and beyond. She noted that PIK3CA, AKT1 and PTEN mutations account for more than 50% of the mutations in ILC. She conveyed how genomic alterations can arise during any stage of progression and discussed some mutations that are associated with an increased risk of early relapse, such as mutations of Her2 and AKT. She discussed some of the differences among subtypes of ILC and different clinical trials underway attempting to answer the question of whether and how to treat ILC differently.  

The other highlight I would like to share is from the Molecular Tumor Board discussion earlier that day of metastatic and early breast cancer. These kinds of sessions at SABCS22 entail the presentation and discussion of clinical treatment options for cases presented and then discussed.

One interesting case study presented (Case #2 at 16.35 if you have access to the recorded discussion) was about a 71-year-old patient whose lobular breast cancer, which was most likely pleomorphic, had metastasized after 3 1/2 years. The patient’s genomic profile on the primary and bone biopsy had shown mutations in ERBB2 (Her2) and CDH1 (loss of E-cadherin).

The discussion raised the question of whether/when we need germline testing, inhibitors such as abemaciclib and adding endocrine therapy, moving on and targeting the Her2 mutation, or a standard of care approach. Her2 mutations are more common in lobular, and she had a poorly differentiated tumor.

It was proposed that this disease may not be endocrine sensitive and Her2 signaling may be a mechanism of resistance, independent of the ER pathway. It was suggested that this tumor is being driven by something that is not the classic endocrine pathway. In discussing moving on in therapy, they suggested some clinical evidence of activity of the HER kinase inhibitor, Neratinib, in the SUMMIT trial in ERBB2 mutant MBC and updated evidence at SABCS 2021 using Trastuzumab+Neratinib+Fulvestrant as well as some evidence of activity with ADCs in ERBB2 mutant solid tumors like T-DM1 and T-DXd. The consensus of the tumor board was leaning toward targeting Her2 with T-DXd and including Neratinib.

After this discussion, it was revealed that the treating institution’s decision was to do a liquid biopsy to assess for polyclonal resistance and identify other potential resistance mechanisms, enroll her in the SUMMIT Phase 2 Trial (Neratinib+Fulvestrant_Trastuzumab) and offer enrollment in the DESTINY-PanTumor01 Trial, a Phase II Basket Study of T-DXd. 

Additionally, an advocate was included for the patient perspective as part of the tumor board, which was so important. I believe an advocate representative should be a part of all tumor boards in these types of discussion. Nothing about us, without us!

It was also mentioned during the tumor board discussion that this lobular patient wanted to be integral in the decision making process, showing just how important it is to have patient-centricity throughout the process from presentation onward. Perhaps this patient might have had a different perspective on her AI or proposed important questions early on if she had been offered more detailed information about her cancer. 

I felt the discussion in the Molecular Tumor Board and the Education Session covering Challenging Types of Cancers, such as lobular, reinforce just how important it is to move research forward in lobular breast cancer through gaining a deeper understanding of what the drivers are in the various subtypes of this disease, and how important the pathologic features are in determining these subtypes.

Molecular profiling, particularly in advanced disease, could lead to critical information that would have an impact on overall treatment decisions and ultimately outcomes. Challenging types of breast cancer, such as lobular, can surely benefit from more precise detection methods, detailed pathology, and from a more personalized and targeted approach to therapies so as to achieve the best outcomes for patients.