Germline cancer predisposition gene mutations and upgrade rate to breast cancer among patients with pleomorphic and florid lobular carcinoma in situ.

Ijaz K, Arun B, Weber DM, Bevers TB, Yi M, Hunt KK, Middleton LP.

Journal ArticleAbstract only — full text under license

AI summary — for doctors, generated from the abstract only

In a study of patients with pleomorphic or florid lobular carcinoma in situ (high-risk breast lesions), those who also carried a hereditary cancer-predisposing gene mutation were significantly more likely to have invasive cancer found at surgery and more likely to later develop a new breast cancer in the same breast.

What was studied

A 24-year retrospective study of 46 patients with pleomorphic lobular carcinoma in situ (PLCIS) or florid lobular carcinoma in situ (FLCIS) as the most significant biopsy finding, assessing germline genetic testing results, rate of upgrade to invasive cancer at surgery, and subsequent ipsilateral breast cancer recurrence.

Key findings

Among patients with genetic testing, most (82.6%) had no germline pathogenic variant; those with a variant had mutations in CHEK2 (4.3%), CDH1 (2.2%), BRCA2 (2.2%), or VHL (2.2%).
Overall, 24% of PLCIS patients (11 of 46) had an upgrade to invasive carcinoma on surgical excision, and upgrades were significantly more common in patients with a germline pathogenic variant (p=0.0198); 5 of the 11 upgraded cases (36%) had a pathogenic variant.
Six patients (13%) developed ipsilateral breast cancer recurrence, and half of these (3 of 6) had a known germline pathogenic variant, with a median time to recurrence of 83.8 months.

Clinical relevance

The findings suggest that in patients with pleomorphic or florid lobular carcinoma in situ, the presence of a germline cancer-predisposition gene mutation may be an additional risk factor for finding invasive cancer at excision and for later ipsilateral recurrence, which could help refine individualized risk assessment, surveillance, and treatment planning.

Who should care

Pathology

Limitations

This was a retrospective, single-institution study over a long (24-year) period, with a modest sample size (46 patients) and genetic testing performed in only a subset, which may limit the precision of the reported associations.

Patients with pleomorphic or florid lobular carcinoma in situ who also carry a hereditary cancer gene mutation appear to be at higher risk of having invasive cancer found at surgery and of later cancer recurrence in the same breast.

This is an AI-generated summary of the published abstract, not a clinical recommendation. It may not reflect the full text or subsequent updates — verify against the original source before acting on it.

Abstract

Background

Pleomorphic lobular carcinoma in situ (PLCIS) and florid lobular carcinoma in situ (FLCIS) are uncommon entities with variable rates of upgrades. Germline pathogenic variant cancer predisposition genes (PVs) are associated with increased breast cancer risk and influences management recommendations.

Design

Patients diagnosed with PLCIS and FLCIS over a 24-year period were identified. Clinical, radiologic, pathologic, treatment, and genetic testing was extracted from the electronic health record. The immediate rate of upgrade to invasive breast cancer and subsequent recurrence rates were calculated.

Results

Forty-six patients with PLCIS and FLCIS as the most significant lesion on biopsy were identified. Of those with genetic testing, the majority had no germline PV (82.6%). Of those with PV, germline mutations in CHEK2 (4.3%), CDH1 (2.2%), BRCA2(2.2%), and VHL (2.2%) were identified. Forty-six patients underwent surgery to include wide local excision in (84.7%) and mastectomy in (15.2%). Twenty-four percent of patients with PLCIS (n = 11) had an upgrade to invasive carcinoma on excision, of which five had PV (36%). Upgrades to cancer were more common in patients with PV (p = 0.0198). Six patients (13%), developed ipsilateral breast cancer recurrences, of which 3 (50%) had known PV with a median time to recurrence of 83.8 months.

Conclusion

In patients with PLCIS and PV, the presence of PV may represent an additive risk factor for the presence of invasive carcinoma on excision and ipsilateral breast cancer recurrence. Knowledge of the oncogenic drivers of tumors in these patients may help to improve risk assessment, surveillance and treatment recommendations.

DOI

10.1016/j.humpath.2026.106262

PMID

42759617

Research metadata (titles, abstracts, authors, publication dates) is sourced from Europe PMC, which aggregates content from PubMed/MEDLINE, PubMed Central, and other providers under the U.S. National Library of Medicine (NLM/NCBI). NLM does not claim copyright on abstracts; the original journal publishers or authors may hold rights to the full articles. AI-generated summaries are derived only from the abstract, never the full text, and are always labeled as AI-generated.

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