Abstract ED4-4: Lobular/pleomorphic Breast Cancer
Authors: Loibl Sibylle 
Published: March 2023

Abstract
Invasive lobular carcinoma (ILC) accounts for up to 15% of all invasive breast cancers. The general marker to identify lobular cancer is the loss or low expression of E-cadherin which is the result of genetic alterations of the E-cadherin gene which accounts for about 95%. The majority of classical ILCs are of low grade and express both hormone receptors strongly and rarely any HER2. Those not expressing the hormone-receptors are categorised as apocrine breast cancers which is a small group.
Recently it has been shown that ILC is a breast cancer type which has unique genomic features. Desmedt and colleagues genomically profiled 430 ILCs, to characterize the genomic alterations present in these tumors compared to invasive ductal carcinoma (now cold unfortunately NST non-specific subtype). The most frequent altered gene was CDH1 which results in a mRNA or protein loss of the cell adhesion molecule E-cadherin. Amongst the genes found to be altered at a high frequency are ESR1 and PIK3CA/PTEN. Currently those have little or no clinical impact in early breast cancer there might be consequences for metastatic breast cancer.
The molecular alterations result in a less cohesive tissue connection and influence imaging as well as surgical procedures and in the end the prognosis in those patients.
The size and extend of ILC is often underestimated by imaging and clinical examination. MRI thought to be the optimal imaging turned out to have no influence on positive margins and is no longer considered standard for all ILCs.
Several data suggest that ILCs have an improved outcome the first 5 years after primary diagnosis but thereafter the survival curves in general lie below those for non lobular breast cancer. ILC has a distinct metastatic pattern and often metastasise into the GI tract and the ovaries and less frequently to the lung.
Breast conserving surgery as well as mastectomy can be used when indicated based on tumor size and patients preference. Because ILC more often presents at higher stage, mastectomy is more frequently performed. But even after neoadjuvant chemotherapy we could demonstrate, despite response even resulting in pCR, mastectomy was more frequently conducted in ILC patients compared to non-ILC. In this analysis 71% of the non-ILC did receive BCS compared to only 59% in ILC (p
Systemic therapy follows the general recommendations based on stage and histopathological profile.
Neoadjuvant chemotherapy results in significantly lower rates of pathological responses. All analyses showed response rate in single digit numbers (far below 10%) but the less classical ILCs with either grade 3 or hormone-receptor negativity have a higher chance of achieving a pCR. Those ILCs with grade 3 and hormone-receptor negativity (apocrine cancer) have a pCR rate comparable to invasive ductal carcinoma (IDC). It is not surprising that lobular breast cancer does not respond as well as IDC to neoadjuvant chemotherapy because their biological features are, as described above, more luminal A like (high hormone receptor positivity, low grade, low proliferation). Because many patients with ILC present with extended diseases, they might still benefit from neoadjuvant chemotherapy even if they do not achieve a pathologic complete response, downstaging is an option and would potentially lead to less mastectomies.
Because of the luminal A like type of the majority of ILCs endocrine therapy seems to be the treatment of choice. Some data even suggested a better outcome for ILC breast cancer when treated with an aromatase inhibitor compared to tamoxifen. But other data are controversial in this regard and did not confirm the data from BIG 1-98.
In conclusion the molecular profile of ILC seems to be distinct but does not result in different treatment paradigms. We should not underestimate the necessity of optimal treatment, including chemotherapy for invasive lobular breast cancer patients.
Citation Format: Sibylle Loibl. Lobular/pleomorphic Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr ED4-4.