Abstract P3-05-04: Absence of Lobular Carcinoma In Situ, a Poor Prognostic Marker in Invasive Lobular Carcinoma
Authors: Mouabbi Jason , Raghavendra Akshara Singareeka , Christgen Matthias , Hassan Amy , Hortobagyi Gabriel N. , Tripathy Debu , Layman Rachel M. 
Published: March 2023

Background: Lobular carcinoma in situ (LCIS) is known to be a risk factor for the development of invasive lobular carcinoma (ILC). Recent genetic analysis indicates that LCIS is a facultative precursor of ILC. It was reported that ~50% of ILC co-occur with LCIS, however it is unclear whether patients with this co-occurrence behave similarly to patients with pure ILC.

Methods: We retrospectively searched for patients treated at MD Anderson Cancer Center with a diagnosis of stage I-III ILC in our prospectively collected electronic database. Patients were divided into 2 groups: those with ILC with co-occurring ipsilateral LCIS (ILC/LCIS) and those with pure ILC without a histologically detected co-occurring ipsilateral in situ lesion (ILC alone). We obtained data on demographics, tumor size (T), lymph nodes (N) involvement, estrogen (ER), progesterone (PR) receptor status, HER2 expression, Ki67, treatment received, distant recurrence and survival status. The Kaplan-Meier product-limit method was used to compare distant recurrence-free survival (DRFS) and overall survival (OS) between the two groups. Multivariate analysis using Cox regression was used to assess association between co-variables and recurrence/survival.

Results: We identified 4,217 patients with stage I-III ILC treated at MDACC between 1966 and 2021. 45% of cases (n = 1,881) had co-existing LCIS. 90% of ILCs were classical and 96% of LCIS were classical. Overall, the median age was 56 years, 95% of cases were ER+, 80% PR+, 5% HER2+. 40% of cases were T1, 60% N0 and 70% of tumors with available Ki67 data had low Ki67 (&lt; 20%). Around 65% underwent mastectomy, 20% received neoadjuvant chemotherapy, and 35% received adjuvant chemotherapy. Statistically and numerically, ILC alone tended to have more T4 and N3 disease (P &lt; 0.001), more ER/PR negative disease (P = 0.0002), more HER2+ disease (P = 0.010), higher Ki67 (P = 0.005), more non-classical ILC subtype (P = 0.04) and more exposure to neoadjuvant chemotherapy (P = 0.0002) than the ILC/LCIS group. The median follow-up time was 6.5 years. Patients with ILC co-existing with LCIS had better DRFS (28.0 vs 14.3 years, Hazard ratio (HR) 0.53, 95% confidence interval (CI) 0.47 – 0.59, P &lt; 0.0001) and better OS (18.9 vs 13.7 years, HR 0.62, 95% CI 0.56 – 0.69; P &lt; 0.0001). Multivariate (MV) analysis showed the absence of LCIS to be a poor prognostic factor along with a higher T and higher N for distant recurrence and overall survival (Table 1).

Conclusion: The findings of this study suggests that the co-existence of LCIS with ILC is a good prognostic factor and that further studies are warranted to understand this phenomenon.

Table 1. Multivariate Analysis between Clinico-Pathological Variables and Distant Recurrence-free Survival/Overall Survival

Citation Format: Jason Mouabbi, Akshara Singareeka Raghavendra, Matthias Christgen, Amy Hassan, Gabriel N. Hortobagyi, Debu Tripathy, Rachel M. Layman. Absence of Lobular Carcinoma In Situ, a Poor Prognostic Marker in Invasive Lobular Carcinoma [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 P3-05-04.