Pure Florid and Pleomorphic Lobular Carcinoma in Situ of the Breast: Towards an Increasingly Uniform Management

March 27, 2026 updated by: Ferrucci Massimo, Istituto Oncologico Veneto IRCCS

Pure Florid and Pleomorphic Lobular Carcinoma in Situ of the Breast: Towards an Increasingly Uniform Management. A Multicenter Observational Retrospective Study.

The goal of this retrospective multicenter observational study is to understand and evaluate the diagnostic and therapeutic management of pure forms of Florid Lobular Carcinoma In Situ (FLCIS) and Pleomorphic Lobular Carcinoma In Situ (PLCIS) of the breast. It addresses the significant challenges and controversies surrounding their clinical management, due to a lack of consensus or approved international guidelines.

The main questions this study aims to answer are:

  • How is the diagnostic process for pure FLCIS and PLCIS currently managed?
  • What are the primary therapeutic approaches for these specific breast conditions?
  • How are positive and "close" surgical excision margins handled?
  • Is adjuvant treatment, such as hormone therapy and radiotherapy, necessary?
  • What factors are associated with recurrences?
  • What are the rates of recurrences and/or upgrade to invasive carcinoma?

Participants will retrospectively collect all cases of pure FLCIS and PLCIS, reporting detailed data about their diagnostic and therapeutic management, as well as clinical and survival outcomes.

Methodology:

This international multicenter retrospective study will collect cases involving the pure forms of FLCIS and PLCIS of the breast. The study aims to provide insights into the current diagnostic and therapeutic approaches, along with the identification of opportunities to enhance clinical management, ultimately providing evidence-based recommendations and addressing the current lack of scientific literature regarding their treatment.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Classical lobular carcinoma in situ (CLCIS) of the breast is considered a non-obligate precursor of invasive carcinoma. Histologically, it is categorized as a lesion with uncertain malignancy potential, and clinical management often parallels that of benign neoplastic conditions.

In contrast, its two variants, florid LCIS (FLCIS) and pleomorphic LCIS (PLCIS), have distinct morphological and genetic characteristics and a higher probability of being obligatory precursors to invasive carcinoma.

PLCIS shows marked cellular-nuclear pleomorphism, resembling high-grade ductal carcinoma in situ (often initially misdiagnosed as such).

FLCIS, on the other hand, displays a complete architectural subversion of lobular structure due to the increased rate of cell replication.

Both variants may show foci of comedonecrosis, a distinctive but not specific diagnostic feature.

A significant difference from CLCIS is their breast distribution; CLCIS tends to be multifocal, while the two variants typically present as unifocal.

Genetically, the two variants differ from CLCIS, with higher genetic instability, and increased alterations in genes coding for tumor suppressors and proteins involved in cell growth regulation and replication.

Immunohistochemically, both FLCIS and PLCIS regularly express estrogen and progesterone receptors, and they may present higher HER2 (Human Epidermal growth factor Receptor 2 - ERBB2 gene) over-expression compared to CLCIS.

Many controversies persist in the clinical management of these variants, largely due to their rarity in pure, isolated forms. Often, they are associated with an invasive carcinoma, which becomes the primary therapeutic focus, according to well established treatment protocols. Dedicated studies, both prospective and retrospective, are completely lacking in the literature, especially for pure FLCIS. Consequently, there is no consensus or approved international guidelines for accurate diagnostic-therapeutic strategies. Even the histological categorization of biopsy tests still remains a subject of debate.

Presently, there is unanimous consensus on the indication for surgical excision of these lesions to improve histological definition and exclude the presence of an invasive neoplastic focus. However, there is no consensus on the need of surgical margins cavity shaving and the management of resection margins when they are proved to be close or involved at the final specimen pathological report. Furthermore, there is a lack of evidence-based recommendations for adjuvant therapies like radiotherapy or endocrine therapy. Some scientific international associations, such as ESMO (European Society of Medical Oncology), suggest a similar approach to pleomorphic variants as for ductal carcinoma in situ due to their morphological similarity; yet, in the absence of robust evidence, this stance does not definitively support the benefit of adjuvant therapeutic strategies and poses a relative risk of overtreatment.

To address these challenges, the investigators propose international multicenter retrospective collection of cases involving the pure forms of FLCIS and PLCIS. Our goal is to comprehensively analyze the diagnostic and therapeutic management of this specific patient group and, notably, to fill the gap in the scientific literature regarding their treatment.

Study Type

Observational

Enrollment (Actual)

1063

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
    • Padova
      • Padua, Padova, Italy, 35168
        • Istituto Oncologico Veneto IRCCS

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Probability Sample

Study Population

Patients diagnosed with pure variant pleomorphic and/or florid lobular carcinoma in situ of the breast

Description

Inclusion Criteria:

  • Histologic diagnosis of PLCIS and/or FLCIS of the breast on both core-biopsy and/or on final specimen histology;
  • Aged 18 years or older.

Exclusion Criteria:

  • Histologic diagnosis of CLCIS;
  • Histologic diagnosis of LCIS (any type) associated with invasive carcinoma

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Pleomorphic Lobular Carcinoma in Situ (PLCIS) of the breast
Patients with diagnosis of pure pleomorphic lobular carcinoma in situ of the breast
Procedure: Surgical wide local excision
Surgical excision of breast carcinoma
Procedure: Cavity shaving
Cavity shaving of resection margins to guarantee oncological safety
Procedure: Excision margin surgical clearance
Surgical clearance of involved and/or closed excision margins
Radiation: Adjuvant Radiotherapy
Adjuvant radiotherapy
Biological: Adjuvant Hormone Therapy
Adjuvant hormone therapy
Florid Lobular Carcinoma in Situ (FLCIS) of the breast
Patients with diagnosis of pure florid lobular carcinoma in situ of the breast
Procedure: Surgical wide local excision
Surgical excision of breast carcinoma
Procedure: Cavity shaving
Cavity shaving of resection margins to guarantee oncological safety
Procedure: Excision margin surgical clearance
Surgical clearance of involved and/or closed excision margins
Radiation: Adjuvant Radiotherapy
Adjuvant radiotherapy
Biological: Adjuvant Hormone Therapy
Adjuvant hormone therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Recurrence rate
Time Frame: From date of surgery until the date of first documented recurrence, assessed up to 120 months
Recurrence rate (both invasive and LCIS, any type)
From date of surgery until the date of first documented recurrence, assessed up to 120 months
Upgrade rate to invasive carcinoma
Time Frame: From date of diagnostic core biopsy until the date of final pathology report after surgery, assessed up to 6 months
Upgrade rate from PLCIS and/or FLCIS to invasive carcinoma from diagnostic core-biopsy to final specimen histology
From date of diagnostic core biopsy until the date of final pathology report after surgery, assessed up to 6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival (OS)
Time Frame: From date of surgery until the date of last follow-up or date of death from any cause, whichever came first, assessed up to 120 months
From date of surgery until the date of last follow-up or date of death from any cause, whichever came first, assessed up to 120 months
Disease-free survival (DFS)
Time Frame: From date of surgery until the date of first recurrence, whenever occurred, assessed up to 120 months
From date of surgery until the date of first recurrence, whenever occurred, assessed up to 120 months
Postoperative complications
Time Frame: From date of surgery until any post-operative complications are resolved, assessed up to 3 months
Incidence and management of post-operative complications
From date of surgery until any post-operative complications are resolved, assessed up to 3 months
Rate of re-operation and/or radiotherapy boost and/or clinical follow-up after "close" or involved resection margins being reported
Time Frame: From date of surgery until the date of surgical margins management completion (any potential clinical follow-up included), assessed up to 72 months
Management of involved and/or closed surgical resection margins
From date of surgery until the date of surgical margins management completion (any potential clinical follow-up included), assessed up to 72 months
Rate of adjuvant therapies utilization
Time Frame: From date of surgery until the date of adjuvant therapies completion, assessed up to 120 months
Adjuvant therapies and associated side effects
From date of surgery until the date of adjuvant therapies completion, assessed up to 120 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Istituto Oncologico Veneto IRCCS

Investigators

  • Principal Investigator: Massimo Ferrucci, MD PhD, Istituto Oncologico Veneto IRCCS

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 15, 2023

Primary Completion (Actual)

December 31, 2024

Study Completion (Actual)

January 31, 2025

Study Registration Dates

First Submitted

November 2, 2023

First Submitted That Met QC Criteria

November 9, 2023

First Posted (Actual)

November 15, 2023

Study Record Updates

Last Update Posted (Actual)

April 1, 2026

Last Update Submitted That Met QC Criteria

March 27, 2026

Last Verified

November 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 22171

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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