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Review
. 2020 Jun;8(1):1-11.
doi: 10.1007/s40487-019-00105-0. Epub 2019 Dec 24.

Invasive Lobular Breast Cancer as a Distinct Disease: Implications for Therapeutic Strategy

Jocelyn Luveta  1   2 , Ruth M Parks  3 , David M Heery  2 , Kwok-Leung Cheung  3 , Simon J Johnston  4   5
Affiliations
Review

Invasive Lobular Breast Cancer as a Distinct Disease: Implications for Therapeutic Strategy

Jocelyn Luveta et al. Oncol Ther. 2020 Jun.

Abstract

Invasive lobular carcinoma comprises 10-15% of all breast cancers and is increasingly recognised as a distinct and understudied disease compared with the predominant histological subtype, invasive ductal carcinoma. Hallmarks of invasive lobular carcinoma include E-cadherin loss, leading to discohesive morphology with cells proliferating in single-file strands and oestrogen receptor positivity, with favourable response to endocrine therapy. This review summarises the distinct histological and molecular features of invasive lobular carcinoma with focus on diagnostic challenges and the impact on surgical management and medical therapy. Emphasis is placed on recent advances in our understanding of the unique molecular biology of lobular breast cancer and how this is optimising our therapy approach in the clinic.

Keywords: Aromatase inhibitors; Breast cancer; Endocrine therapy; Histology; Immunotherapy; Invasive lobular carcinoma; Molecular biology; Surgical management; Tamoxifen; Targeted therapy.

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Figures

Fig. 1
Fig. 1
Comparison of key molecular and histological features of ILC and IDC and the implications for treatment of ILC. E2 = oestradiol; PTEN/Akt refers to PTEN loss and Akt activation; ER programme refers to the distinct ER-mediated gene expression programme in ILC. Adapted with permission from Ciriello et al. [12]
Fig. 2
Fig. 2
Retrospective clinical evidence of a differential response to different classes of endocrine therapy in ILC. These data formed the basis of in vitro functional and early clinical studies of the differences between ILC and IDC. Kaplan-Meier plots show a disease-free survival and b overall survival stratified by histology (ductal/lobular) and endocrine therapy agent (letrozole, L/tamoxifen, T); N = 2923. Reproduced with permission from Metzger Filho et al. [60]
Fig. 3
Fig. 3
PELOPS trial of neoadjuvant palbociclib, including a window-of-opportunity phase to provide prospective evidence on endocrine therapy of choice in ILC [78]. Study population is enriched for ILC. Treatment with palbociclib is randomly allocated. Primary outcome measure is complete pathological response
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