title: Lobular breast cancer: Clinical, molecular and morphological characteristics.
abstract: Infiltrating lobular breast cancer (ILBC) is the most common special breast cancer subtype. This review provides a comprehensive description of ILBC characteristics, including epidemiology, clinical features, molecular genetics and histomorphology. Twenty detailed supplemental data tables guide through primary data of more than 200 original studies. Meta-analyses indicate that ILBC is at least twice as common in the Western world as it is in other geographic regions. ILBC is over-represented in so-called interval carcinomas and in primary metastatic breast cancer. ILBC is also associated higher age, higher pT stage and hormone receptor (ER/PR) positivity. Pathological complete response rates after neoadjuvant chemotherapy are low, ranging between 0% and 11%. Positive resection margins after breast-conserving surgery are comparatively frequent and 17% to 65% of patients undergo a second surgical intervention. Depending on the morphological stringency in the diagnosis of ILBC, lack of E-cadherin expression is observed in 55% to 100% of cases. CDH1/E-cadherin mutation detection rates vary between 12% and 83%. Various additional molecular factors, including PIK3CA, TP53, FOXA1, FGFR1, ZNF703 and BCAR4, have been implicated in ILBC or progression of lobular carcinoma in situ (LCIS) to invasive cancer and are discussed in detail. Eight instructive figure plates recapitulate the histomorphology of ILBC and its variants. Furthermore, we draw attention to rarely addressed histological details, such as two-sided nuclear compression and fat-avoiding growth at the invasion front. Last but not least, we discuss future translational research directions and emphasize the concept of synthetic lethality, which promises new options for targeted ILBC therapy.
authors.affiliation: Institute of Pathology, Hannover Medical School, Hannover, Germany. Electronic address: Christgen.Matthias@MH-Hannover.de.
authors.forename: Matthias
authors.initials: M
authors.lastname: Christgen
authors.affiliation: Institute of Human Genetics, Hannover Medical School, Hannover, Germany.
authors.forename: Doris
authors.initials: D
authors.lastname: Steinemann
authors.affiliation: Department of Gynecology and Obstetrics, Hannover Medical School, Hannover, Germany.
authors.forename: Elna
authors.initials: E
authors.lastname: Kühnle
authors.affiliation: Institute of Pathology, Hannover Medical School, Hannover, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Länger
authors.affiliation: Evangelic Bethesda Hospital, Breast Center Niederrhein, Moenchengladbach, Germany; West German Study Group, Moenchengladbach, Germany.
authors.forename: Oleg
authors.initials: O
authors.lastname: Gluz
authors.affiliation: West German Study Group, Moenchengladbach, Germany; Breast Center, University of Munich (LMU), Munich, Germany.
authors.forename: Nadia
authors.initials: N
authors.lastname: Harbeck
authors.affiliation: Institute of Pathology, Hannover Medical School, Hannover, Germany.
authors.forename: Hans
authors.initials: H
authors.lastname: Kreipe
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D015820:Cadherins / Q000378:metabolism*; D018275:Carcinoma, Lobular / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D005260:Female; D006801:Humans; D008408:Mastectomy; D012086:Reoperation
chemical_list: D014408:Biomarkers, Tumor; D015820:Cadherins
keywords: Anti-hormone therapy; CDH1; E-cadherin; Lobular breast cancer; Molecular profiling; Resection margins; Screening