AIB1 is a new putative prognostic biomarker in the luminal A and B-like (HER2-negative) classification of invasive lobular carcinoma

Body: Background: Estrogen receptor (ER) positive HER2-negative breast cancer comprises 75–80% of all breast cancer. This
fraction is even higher (>90%) in invasive lobular carcinoma (ILC). According to the St Gallen surrogate definitions of the intrinsic
subtypes, Ki67 and progesterone receptor (PgR) are used to classify these tumors as luminal A- and luminal B-like
(HER2-negative). These guidelines are based on information derived from patient materials with mixed histological types, where
the vast majority of the patients have invasive ductal carcinoma. The `luminal-like classification´ together with histological grade,
tumor size and lymph node status is widely used in the clinic for prognostication. The aim of the present study was to investigate
if the same markers are applicable for ILC, and furthermore, if additional biomarkers involved in the endocrine signaling system,
e.g. Amplified in breast cancer 1 (AIB1) and the putative G protein-coupled estrogen receptor (GPER), might provide
complementary prognostic information.
Patients: Two hundred and thirty-three (N = 233) well-characterized patients with primary ILC, diagnosed between 1980 and
1991 were included. Forty-two percent of the patients received adjuvant endocrine treatment and 2 % received adjuvant
chemotherapy. All biomarkers were analyzed immunohistochemically on tissue microarray, whereas histological grade was
evaluated on whole sections according to Elston and Ellis (NHG). The primary endpoint was breast cancer mortality (BCM).
Results: In univariable analyses with 10-year follow-up, Ki67 (high vs. low), NHG (3 vs. 1+2) and AIB1 (high vs. low) were
significantly associated to BCM (Hazard Ratio: 4.7, 95% CI: 2.1–10.4, p 95% CI: 1.4–7.2, p = 0.005 respectively), whereas PgR (respectively). Essentially the same effect was seen after multivariable adjustment for lymph node status (+ vs. -), tumor size (>20
mm vs. according to St Gallen surrogate definitions did not show significant prognostic differences between the two groups (p = 0.12).
Patients with AIB1) had a 10-year BCM of 4.2% (95% CI: 1.4–12%). This group constituted 34% of the patients included in the present study.
Conclusions: In contrast to other previous studies, where breast cancers of mixed histological types were included, PgR was not
significantly associated to prognosis in the ER-positive HER2-negative subgroup in the present study, consisting only of ILC. The
prognostic role of PgR and the clinical usefulness of the luminal A and B-like (HER2-negative) classification (using only Ki67 and
PgR) in ILC is still to be further investigated. The prognostic importance of Ki67 and NHG in this subgroup was, however,
confirmed also in ILC, and AIB1 might be a new putative prognostic factor. By combining Ki67, NHG, and AIB1, together with
lymph node status and tumor size, a group of patients with an excellent prognosis could be identified.