Differential impact of prognostic parameters in hormone receptor–positive lobular breast cancer

Abstract

BACKGROUND: Invasive lobular breast cancer (BC) is the second most common BC subtype. Prognostic parameters (tumor classification, lymph node status, histologic grade, Oncotype DX recurrence score [RS], progesterone receptor status, and Ki67 index) were retrospectively studied in a large, prospective clinical trial encompassing 2585 patients who had hormone receptor-positive early BC (the West German Study Group PlanB trial). METHODS: BCs were centrally reviewed and classified as lobular (n = 353; 14%) or nonlobular (n = 2232; 86%). The median follow-up was 60 months. Five-year disease-free survival (DFS) estimates were obtained using the Kaplan-Meier method. Prognostic parameters were evaluated using Cox proportional hazard models. RESULTS: Lobular BC was associated with higher tumor classification, higher lymph node status, lower histologic grade, lower Ki67 index, and low or intermediate RS. The prevalence of high RS (RS range, 26-100) was 3-fold lower in patients who had lobular BC compared with those who had nonlobular BC (8% vs 24%; P < .001). However, 5-year DFS estimates for lobular and nonlobular BC were similar (92.1% and 92.3%, respectively; P = .673). In multivariate analyses, prognostic parameters for DFS in lobular BC included grade 3 (hazard ratio, 5.06; 95% CI, 1.91-13.39) and a pathologic lymph node status (pN) of pN3 (

Invasive lobular carcinoma of the breast: the increasing importance of this special subtype

“…A comparison of patients with HER2+ ILC and HER2+ IBC-NST provided further evidence that HER2+ ILC has different clinical and biological characteristics [54]: relative to HER2+ IBC-NST, HER2+ ILCs were more often multicentric or multifocal, with a lower histological grade and proliferative index, and show more frequent nodal metastases (i.e. these are similar features observed when ILC is compared to IBC-NST, regardless of HER2 status [15,47,55,56]). Whilst HER2+ ILC and IBC-NST have differing characteristics, both groups appear to benefit similarly from adjuvant treatment with Figure 2 in Sokol et al [40] trastuzumab, with similar recurrence rates, indicating HER2+ ILC patients do benefit from anti-HER2 therapy [54,57].…”

“…The clinical utility in ILC of the 21-gene OncotypeDx®, remains unclear; two studies show classification of 42% [102] and 35.5% [103] of patients into the intermediate-risk group, which is considered challenging to manage clinically [104]. However, a multivariate analysis of the SEER dataset showed that the OncotypeDx recurrence score was an independent prognostic indicator in ILC [96], and a recent analysis of the PlanB trial data determined that OncotypeDx® classed 72% of ILC as intermediate risk, and 20% and 8% as low and high risk, respectively, amounting to a threefold lower rate of high-risk results compared to non-lobular cancers [55]. These low rates of high-risk ILC are similar to those observed elsewhere [97,98].…”

Lobular Breast Cancer: Histomorphology and Different Concepts of a Special Spectrum of Tumors

“…The current WHO classification defines ILC as BC composed of dyscohesive cells that are mostly individually dispersed or arranged in single files [19]. However, a large proportion of ILCs does not show this classic growth pattern [43,46,[61][62][63][64][65][66]. In 1975, Fechner reported an ILC variant with solid growth and description of further variants followed [66].…”

“…Furthermore, ILC and BCs of NST constitute a morphological continuum with a proportion of indefinite cases termed mixed BC (NST/ILC) [67]. Mixed BC (NST/ILC) accounts for up to 18% of BC cases (Appendix A, Table A1) [42,61,[67][68][69][70][71]. According to the traditional WHO definition, this term was applicable for BCs showing a mixture of 11-50% ductal and 50-89% lobular growth pattern [72].…”

“…Two large clinical trials (MINDACT and WSG PlanB trials) have recently reported the results of central pathology review of thousands of BC specimens, which confirmed ILC in 60% (395/654) and in 66% (253/385) of cases classified as ILC by local assessment. Conversely, central review changed the diagnosis of NST to ILC in only 2% (37/1763) of cases [61,78]. Hence, ILC might be slightly over-diagnosed in current practice and according to the concept of a special growth pattern.…”