Lobular Breast Cancer Updates from ASCO 2025
The 2025 ASCO Annual Meeting is almost here! This is the largest oncology meeting in the world with over 40,000 people attending. There are over 5,000 abstracts, posters, oral presentations and education sessions happening over 5 days. My goal in the next two weeks is to share as much research with you as I can, focusing on what’s clinically relevant and may be practice changing. The abstracts have been released meaning we have the basic information about the studies but usually will get more information at the meeting as the full data is presented. The late breaking study results don’t get presented until the ASCO meeting itself. I get a lot of questions about new lobular breast cancer research so in this Substack, I’m going to share some of the lobular research being presented at ASCO. Invasive lobular carcinoma is the second most common histologic subtype of breast cancer and represents about 10-15% of cases but is unique in biology, behavior, recurrence and outcomes so it is really important to have lobular cancer specific research. Here we go!
Just a quick note that some of the findings shared here may feel overwhelming or upsetting, especially when it comes to prognosis or recurrence. Please skip this update if it feels like too much right now—your mental and emotional well-being always comes first.
Patient experiences of diagnosis and treatment of invasive lobular carcinoma: A qualitative study from a prospective registry (Abstract 11111, Quirarte A et al).
This study asked 92 patients diagnosed with ILC about their experience with diagnosis and treatment through open-ended questions and patient interviews. This was done at a single institution so it’s hard to know if experiences are similar elsewhere but these experiences are important and I want to share this study. Some key themes that emerged through these interviews:
Participants reported a delay in diagnosis due to disease not showing up on mammogram (and even more pronounced among patients who reported a physical finding related to their breast cancer prior to diagnosis).
Participants felt that their providers dismissed their symptoms
Participants expressed concerns over the impact of dense breasts on imaging sensitivity and the underestimation of ILC tumor size on pre-operative imaging
Participants felt that providers did not recognize ILC as a distinct tumor subtype
After treatment of ILC, participants had concerns about how they would identify a recurrence and desire for improved surveillance methods
This study highlights the unique challenges faced by patients with invasive lobular carcinoma, including delayed diagnoses, dismissed symptoms, and inadequate recognition of ILC as a distinct subtype. We really need greater clinical awareness, improved imaging strategies, and more personalized surveillance approaches to better support patients with ILC.
Outcomes of neoadjuvant endocrine therapy versus neoadjuvant chemotherapy in stage II-III invasive lobular carcinoma (Abstract 603, Mouabbi J et al).
This was a study done at MD Anderson Cancer Center looking at 611 patients with stage II-III ER+/HER2- invasive lobular carcinoma. They looked back (retrospective study) to see what treatment they had and the results. All patients received adjuvant (after surgery) endocrine therapy. 80% (509 patients) received neoadjuvant chemotherapy and 20% (102 patients) received neoadjuvant endocrine therapy.
Median age was 55 (range 30-91), 77% patients were white, 8.5% patients were Hispanic, 8.1% patients were Black. 65% were postmenopausal and all received adjuvant endocrine therapy.
In the neoadjuvant endocrine therapy group, 83% received anastrozole or letrozole and in the neoadjuvant chemotherapy group, 98% received anthracycline containing chemotherapy.
Pathologic complete response rates were very low for both groups (2.5% for neoadjuvant chemotherapy and 1.9% for neoadjuvant endocrine therapy)
Interestingly, axillary downstaging was 11% in NAC vs 5% in NAET (meaning more patients with chemotherapy had their lymph node disease eliminated)
Rates of lumpectomy and axillary lymph node dissection were similar
10 year distant recurrence free survival (alive without a distant recurrence): 55% for neoadjuvant chemotherapy versus 65% for neoadjuvant endocrine therapy and this was not impacted by age, race or stage. The neoadjuvant chemotherapy patients were compared to the neoadjuvant endocrine therapy patients who did not later receive adjuvant chemotherapy.
The authors conclude that this analysis shows limited efficacy from neoadjuvant chemotherapy in ILC with minimal pathologic complete response rates and that neoadjuvant endocrine therapy appears to be a viable and promising neoadjuvant strategy in stage II-III ER+ ILC. This data is likely before the addition of CDK 4/6 inhibitors so it would be interesting to see how that impacts the results. We have already known that chemotherapy is less effective in ILC so this is more data to add to that. This study highlights the need to tailor neoadjuvant treatment strategies in lobular breast cancer.
Treatment patterns, genomic characteristics and outcomes among patients with metastatic lobular breast cancer (Abstract 1119 Shen S et al).
This study looks at outcomes of 654 patients with metastatic ILC at a single center (Memorial Sloan Kettering Cancer Center). 99.8% were female, 89% were white, 96% non-Hispanic. From 307 patients, 45% classic ILC, 21% pleomorphic, 15% mixed and 19% other. 87% were hormone receptor positive, 9.1% were HER2-positive and 9.5% were triple negative. Overall survival did not vary by invasive lobular carcinoma subtype or by HER2, AKT1 or ESR1 status. However, overall survival was worse in patients who had CDH1, PIK3CA, or PTEN mutations. This study really emphasizes the importance of next generation sequencing in metastatic ILC (as it is all in types of metastatic breast cancer) but that it can be helpful with prognosis in ILC…and hopefully will lead the way toward specific clinical trials in ILC targeting these mutations.
Long-term outcomes of patients with HER2-positive invasive lobular carcinoma in the ALTTO Trial (Abstract 542, Marta GN et al).
This is an important study because HER2-positive invasive lobular carcinoma (ILC) is rare and there is limited data on outcomes of patients with HER2+ ILC. The ALTTO study was a study that looked at trastuzumab (Herceptin), lapatinib, or sequence/combo of both in adjuvant therapy for HER2-positive BC. (We no longer use lapatinib for early stage HER2+ BC). For this analysis, the authors looked at patients who were in the trastuzumab arms. The cohort they analyzed had 5,981 HER2-positive patients of no special type (essentially everyone who did not have pure ILC) and 61 patients with pure ILC (excluding patients with mixed IDC and ILC, for example).
What did they find?
Patients with ILC were older (average age 54.8 vs 50.9 years), more likely to be white (95.1% versus 68.8%), and postmenopausal (72.1% vs 56.3%). More of the patients with ILC were hormone receptor positive (80.3% vs 57.4%), Grade 1-2 (51.7% vs 39.3%).
After a median f/u of 9.8 years, there were no significant differences in disease free survival (meaning, alive without disease recurrence), overall survival, or time to distant recurrence between the patients with pure ILC and patients with no special type.
However, relapses in the central nervous system (CNS) (brain and spinal cord) were more frequent in ILC (13.6% at 10 years versus 5%).
The authors concluded that this highlights the unique relapse pattern of ILC and needs further research into the CNS relapses. I think this is important information to be aware of but there are a couple of things to keep in mind - this is a very small number of patients (and 13.6% of 61=8 patients). The ALTTO trial was conducted between June 2007 and July 2011 and this was before we had Perjeta and Kadcyla. Kadcyla is used in the adjuvant setting if pathologic complete response is not achieved so it’s hard to say if/how these statistics would change with current treatment. Would we see the same increase in relapse in the CNS with current therapies? We cannot say. (There’s also neratinib which I won’t get into here but is considered in occasional cases depending on risk and side effects).
I do think that this study provides reassuring information about similar long term outcomes between the two groups, which is great. With the increase in CNS relapse rate, again, it’s ~8/61 patients—- I would want to know more about these patients and the characteristics of their breast cancer (size, stage, lymph nodes, HR status etc) and it’s hard to make conclusions in such a small number of patients. If we end up getting that information at the meeting, I’ll share it here.
To wrap up, these studies highlight and emphasize the unique biology and behavior of invasive lobular carcinoma. They underscore the critical need for more dedicated research, tailored treatment strategies, and increased clinical awareness to improve outcomes for patients with this distinct subtype of breast cancer.
Let me know any questions you have on these studies and what else you want to hear about from ASCO! I’ll be sharing on here and on Instagram as well so follow along!
Thank you for taking the time to compile and share this important information about ILC. We definitely feel like our subtype does not get the focus that it deserves.
Thank you for writing this piece on ILC. I was diagnosed with ILC in 2001. I was also fortunate enough to be treated at the Royal Marsden where ILC was recognised. My oncologist told me it was a sneaky cancer that avoided detection for so long because it grows in lines ie not a lump. On diagnosis via US my tumour measured 5.5cm. I had an MRI using a powerful scanner and that detected cancer up to 8cm from top to bottom. My tumour looked like a multi legged spider. I was placed on a NEO-RT trial which involved giving me RT first followed by 5 months of tamoxifen. This reduced the tumour by 40% cellularity. I then had surgery to remove the tumour. Given the size of the tumour I am very aware of my risk of secondary.
I am so interested to hear from you that the medical profession know which mutations make ILC more likely to spread/give poorer outcomes. I would love to hear that some fabulous research team is choosing to focus their time on how to tackle these mutations and improve outcomes.