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.

Lobular breast cancer: Clinical, molecular and morphological characteristics

Invasive lobular breast cancer (ILC) is the most common special histological type of breast cancer (BC). This review recapitulates developments in the histomorphologic assessment of ILC from its beginnings with the seminal work of Foote and Stewart, which was published in 1941, until today. We discuss different concepts of ILC and their implications. These concepts include (i) BC arising from mammary lobules, (ii) BC growing in dissociated cells and single files, and (iii) BC defined as a morpho-molecular spectrum of tumors with distinct histological and molecular characteristics related to impaired cell adhesion. This review also provides a comprehensive overview of ILC variants, their histomorphology, and differential diagnosis. Furthermore, this review highlights recent advances which have contributed to a better understanding of the histomorphology of ILC, such as the role of the basal lamina component laminin, the molecular specificities of triple-negative ILC, and E-cadherin to P-cadherin expression switching as the molecular determinant of tubular elements in CDH1-deficient ILC. Last but not least, we provide a detailed account of the tumor microenvironment in ILC, including tumor infiltrating lymphocyte (TIL) levels, which are comparatively low in ILC compared to other BCs, but correlate with clinical outcome. The distinct histomorphology of ILC clearly reflects a special tumor biology. In the clinic, special treatment strategies have been established for triple-negative, HER2-positive, and ER-positive BC. Treatment specialization for patients diagnosed with ILC is just in its beginnings. Accordingly, ILC deserves greater attention as a special tumor entity in BC diagnostics, patient care, and cancer research.

https://www.mdpi.com/2072-6694/13/15/3695/pdf

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

Atypical hyperplasia and lobular carcinoma in situ are rare proliferative breast lesions, growing inside ducts and terminal ducto-lobular units. They represent a marker of increased risk for breast cancer and a non-obligate precursor of malignancy. Evidence available on diagnosis and management is scarce. They are frequently found incidentally associated with other lesions, but can be visible through mammography, ultrasound or magnetic resonance. Due to the risk of underestimation, surgical excision is often performed. The analysis of imaging and histopathological characteristics could help identifying low-risk cases, for which surgery is not necessary. Chemopreventive agents can be used for risk reduction. Careful imaging follow up is mandatory; the role of breast MRI as screening modality is under discussion.

Management of atypical lobular hyperplasia, atypical ductal hyperplasia, and lobular carcinoma in situ

Historically, lobular carcinoma in situ (LCIS) has been poorly understood in terms of its biologic behavior and natural history. There is considerable debate as to whether LCIS represents a breast cancer risk factor or a precursor lesion for invasive carcinoma. LCIS has been shown to convey heightened breast cancer risk both in the breast in which it was identified and also in the contralateral breast where it is not known to be present. However, evidence including genotypically and phenotypically similar invasive carcinomas developing at prior LCIS biopsy sites suggests that LCIS may also act as a precursor lesion for invasive cancer in some cases. The primary purpose of this chapter is to detail the evidence in support of the current view, LCIS as both a risk factor, conferring increased risk of both ipsilateral and contralateral invasive carcinoma, and a non-obligate precursor lesion at or near the site of the index lesion.

Lobular Carcinoma In Situ: Risk Factor or Cancer Precursor?

Invasive Lobular Carcinoma

Aim Lobular carcinoma in situ (LCIS) is a known risk factor for invasive breast carcinoma, but there is increasing data indicating a possible precursor relationship. This study investigates the incidence of lobular carcinoma in situ that occurs with invasive lobular carcinoma (ILC). Methods Women diagnosed with ILC or LCIS from 2000 to 2010 were retrospectively identified and reviewed after institutional review board approval. This group was divided into two cohorts: ILC alone, and LCIS and ILC (ILC/LCIS). Patient demographics, disease characteristics, and treatment modalities were captured. p Results A total of 148 patients with ILC or LCIS were identified. Forty-four (54%) patients with only ILC, and 37 (46%) patients with ILC/LCIS were identified. Median age at diagnosis was 62 for ILC and 64 years for ILC/LCIS ( p  = 0.8). In patients with ILC, total mastectomy was the predominant treatment modality in 28 of 44 (64%) patients, while 18 of 37 (49%) patients with ILC/LCIS underwent breast conservation therapy ( p  = 0.3). Median largest tumor diameter was 35 mm (range 1–110) for ILC, and 15 mm (range 5–85) for ILC/LCIS ( p  = 0.03). Nodal status was positive in 17 of 39 (44%) ILC and 13 of 34 (38%) ILC/LCIS ( p  = 0.6). Conclusions The 46% incidence of LCIS associated with ILC in our cohort study is similar to that reported for ductal carcinoma in situ identified with invasive ductal carcinoma at ∼40%. The association of pre-invasive and invasive lobular lesions should be further studied in a large scale prospective study to assess for a precursor relationship.

Synchronous lobular carcinoma in situ and invasive lobular cancer: Marker or precursor for invasive lobular carcinoma

Primary focal cryotherapy for non-metastatic prostate cancer: Update from the UK ICE registry

A0624 – Outcomes of focal HIFU for localised prostate cancer determined by modern risk stratification strategies

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Synchronous lobular carcinoma in situ and invasive lobular cancer: Marker or precursor for invasive lobular carcinoma

Primary focal cryotherapy for non-metastatic prostate cancer: Update from the UK ICE registry

A0624 – Outcomes of focal HIFU for localised prostate cancer determined by modern risk stratification strategies