Abstract P6-09-43: Bcl2 as a long-term prognostic factor in invasive lobular carcinoma of the breast
Authors: Narbe U , Forsare C , Bendahl P-O , Rydén L , Ingvar C , Fernö M 
Published: March 2017

Background: B-cell lymphoma 2 (Bcl2) is an anti-apoptotic protein with known tumor suppressor effect in breast cancer. Multiple studies have shown that high Bcl2-expression is associated with a better prognosis in breast cancer, but its clinical usefulness as a prognostic factor is still not fully elucidated. Invasive lobular carcinoma (ILC) of the breast is the second most common histologic subtype and comprises 5 to 15 % of all breast cancers. ILC has distinct clinico-pathological features and a specific pattern of recurrence, but treatment strategies are often similar as for the whole group of breast cancers. ILC´s are typically estrogen receptor positive (ER+), progesterone receptor positive (PgR+), HER2 negative, low proliferative and histological grade 2. According to the St Gallen surrogate definitions of the intrinsic subtypes of breast cancer most ILC´s are classified as 'luminal disease' and predominantly as low-risk 'luminal A-like'. Patients with 'luminal disease' in general and 'luminal A-like' in particular falls into prognostic categories where uncertainty about optimal treatment strategy often arises, as clinicians seek to avoid both over- and under-treatment. Additional prognostic factors are needed in order to further improve risk stratification. The use of multigene assays to better predict recurrence is increasing, but the availability is still limited and the cost is high. Measurement of apoptosis-related factors, such as Bcl2 gene expression is included as a prognosticator in a majority of these tests. The aim of this retrospective study was to evaluate the long-term prognostic effect of Bcl2 in a subset of patients with ILC.

Patients and methods: One hundred and ninety-two well-characterized patients with primary ILC were included in the present study. Bcl2 was evaluated together with ER, PgR, HER2, Ki67, histological grade, tumor size, nodal status and age at diagnosis. Ninety-two percent of the patients were ER and/or PgR positive and 41% were node positive. Forty-one percent of the patients received adjuvant endocrine treatment and 3% received adjuvant chemotherapy. The median follow-up of the 52 patients still alive was 26 years. Bcl2 was analyzed immunohistochemically on whole sections of tumor tissue and Bcl2-positivity (Bcl2+) was defined as more than 10% cells with stained cytoplasma. Eighty-six percent of the patients (165/192) were Bcl2+. The primary endpoint was breast cancer mortality (BCM).

Results: Overall, 32% (61/192) of the patients have died from breast cancer. Bcl2 (positive vs negative) was a significant prognostic factor for BCM in univariable Cox regression analysis (HR 0.44, 95% CI: 0.23-0.85). Essentially the same Bcl2 effect was seen after multivariable adjustment for ER, Ki67, histological grade, tumor size, nodal status, age at diagnosis and adjuvant therapy (HR 0.33, 95% CI: 0.15-0.74).

Conclusions: Bcl2 is an independent long-term prognostic factor in this subset of patients with ILC. Bcl2 might add new prognostic information based on apoptotic tumor features that could be useful in the clinical treatment decision-making.

Citation Format: Narbe U, Forsare C, Bendahl P-O, Rydén L, Ingvar C, Fernö M. Bcl2 as a long-term prognostic factor in invasive lobular carcinoma of the breast [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-09-43.