Trial Title:
Pure Florid and Pleomorphic Lobular Carcinoma in Situ of the Breast: Towards an Increasingly Uniform Management
NCT ID:
NCT06133465
Condition:
Pleomorphic Lobular Breast Carcinoma in Situ
Breast Florid Lobular Carcinoma in Situ
Conditions: Official terms:
Carcinoma
Breast Neoplasms
Carcinoma in Situ
Breast Carcinoma In Situ
Carcinoma, Lobular
Hormones
Study type:
Observational
Overall status:
Recruiting
Study design:
Time perspective:
Retrospective
Intervention:
Intervention type:
Procedure
Intervention name:
Surgical wide local excision
Description:
Surgical excision of breast carcinoma
Arm group label:
Florid Lobular Carcinoma in Situ (FLCIS) of the breast
Arm group label:
Pleomorphic Lobular Carcinoma in Situ (PLCIS) of the breast
Intervention type:
Procedure
Intervention name:
Cavity shaving
Description:
Cavity shaving of resection margins to guarantee oncological safety
Arm group label:
Florid Lobular Carcinoma in Situ (FLCIS) of the breast
Arm group label:
Pleomorphic Lobular Carcinoma in Situ (PLCIS) of the breast
Intervention type:
Procedure
Intervention name:
Excision margin surgical clearance
Description:
Surgical clearance of involved and/or closed excision margins
Arm group label:
Florid Lobular Carcinoma in Situ (FLCIS) of the breast
Arm group label:
Pleomorphic Lobular Carcinoma in Situ (PLCIS) of the breast
Intervention type:
Radiation
Intervention name:
Adjuvant Radiotherapy
Description:
Adjuvant radiotherapy
Arm group label:
Florid Lobular Carcinoma in Situ (FLCIS) of the breast
Arm group label:
Pleomorphic Lobular Carcinoma in Situ (PLCIS) of the breast
Intervention type:
Biological
Intervention name:
Adjuvant Hormone Therapy
Description:
Adjuvant hormone therapy
Arm group label:
Florid Lobular Carcinoma in Situ (FLCIS) of the breast
Arm group label:
Pleomorphic Lobular Carcinoma in Situ (PLCIS) of the breast
Summary:
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.
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.
Criteria for eligibility:
Study pop:
Patients diagnosed with pure variant pleomorphic and/or florid lobular carcinoma in situ
of the breast
Sampling method:
Probability Sample
Criteria:
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
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Istituto Oncologico Veneto IRCCS
Address:
City:
Padova
Zip:
35168
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Massimo Ferrucci, MD PhD
Phone:
00393331779209
Email:
massimoferrucci@gmail.com
Contact backup:
Last name:
Daniele Passeri, MD
Phone:
00393333839397
Email:
daniele.passeri.1995@gmail.com
Start date:
October 15, 2023
Completion date:
July 31, 2024
Lead sponsor:
Agency:
Istituto Oncologico Veneto IRCCS
Agency class:
Other
Source:
Istituto Oncologico Veneto IRCCS
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06133465
http://www.nccn.org
http://www.cancerscreening.nhs.uk/breastscreen/
http://www.esmo.org
