Negative/Low Hormone Receptor And/or HER2 POsitive Lobular Invasive Breast Carcinoma - A Real-World International Cohort Study

NCT07613151 | Recruiting

• 1 other identifier: CESC IOV 2023-61
• Study Type: observational
• Target: 250
• Locations: 1 country
• Sites: 1

Brief Summary

The NAPOLI Study is a retrospective multicenter observational study designed to characterize hormone receptor-negative/low invasive lobular carcinoma of the breast. The study will collect real-world clinicopathological, molecular, therapeutic and outcome data from patients diagnosed and treated at participating centers. The aim is to describe the clinical behavior, pathological features, receptor profile, treatments received and oncologic outcomes of this rare breast cancer subtype.

Conditions

Lobular Breast Carcinoma

Keywords

Breast; Cancer; Lobular Neoplasia

Outcome Measures

Primary Outcomes (1)

• Invasive disease-free survival (iDFS)

  Time from definitive surgery to first invasive event (ipsilateral invasive, locoregional invasive, or distant recurrence, contralateral invasive BC)

  Through study completion, an average of 5 years

Secondary Outcomes (5)

• Overall survival (OS)

  Through study completion, an average of 5 years

• Distant disease-free survival (DDFS)

  Through study completion, an average of 5 years

• Breast cancer-specific survival (BCSS)

  Through study completion, an average of 5 years

• Locoregional recurrence-free survival (LRRFS)

  Through study completion, an average of 5 years

• Recurrence rate and patterns

  Through study completion, an average of 5 years

Other Outcomes (4)

• Pathologic complete response (pCR) - ypT0/Tis ypN0, with residual cancer burden (RCB) class distribution; in the neoadjuvant cohort, event-free survival (EFS) from treatment initiation where data permit

  Through study completion, an average of 5 years

• Multidisciplinary treatment patterns and treatment-related outcomes according to therapeutic strategy (upfront surgery versus neoadjuvant treatment), surgical management (including reconstruction/oncoplastic approaches), systemic and radiation therapy

  Through study completion, an average of 5 years

• Prognostic, predictive and potential therapeutic relevance of clinicopathologic, molecular, and biologic features

  Through study completion, an average of 5 years

Study Arms (4)

Triple-negative ILC

ER \<1%, PR \<1% and HER2-negative (IHC 0, 1+, or 2+ with negative ISH). Within this cohort, HER2 expression will be further categorized, where assessable, as HER2 null (IHC 0, no staining), HER2-ultralow (IHC 0+ with faint/incomplete staining in ≤10% of tumor cells) and HER2-low (IHC 1+, or 2+/ISH-negative).

Procedure: Upfront Breast Surgery; Radiation: Adjuvant Radiotherapy; Drug: Endocrine Therapy; Drug: Chemotherapy

HER2-positive ILC

HER2-positive disease, defined as IHC 3+ or IHC 2+ ISH-positive. Subgroups within this cohort will include HR-negative ILC (ER and PR both \<1%) and HR-positive (ER\>10%) HER2-positive ILC.

Procedure: Upfront Breast Surgery; Radiation: Adjuvant Radiotherapy; Drug: Endocrine Therapy; Drug: Chemotherapy

HR-low ILC (cross-cutting category)

ER and/or PR 1-10%, with neither receptor \>10%, analyzed separately as a distinct group and also within the HER2-defined groups.

Procedure: Upfront Breast Surgery; Radiation: Adjuvant Radiotherapy; Drug: Endocrine Therapy; Drug: Chemotherapy

Exploratory Subgroups (cross-cutting category)

Apocrine and/or LAR-featured ILC, and non-classic lobular variants (pleomorphic, histiocytoid and other rare histologic variants).

Procedure: Upfront Breast Surgery; Radiation: Adjuvant Radiotherapy; Drug: Endocrine Therapy; Drug: Chemotherapy

Interventions

Upfront Breast Surgery PROCEDURE

Upfront Conservative or Demolitive Breast Surgery

Exploratory Subgroups (cross-cutting category); HER2-positive ILC; HR-low ILC (cross-cutting category); Triple-negative ILC

Adjuvant Radiotherapy RADIATION

Adjuvant Breast or Chest Wall Radiotherapy after Breast Surgery

Exploratory Subgroups (cross-cutting category); HER2-positive ILC; HR-low ILC (cross-cutting category); Triple-negative ILC

Endocrine Therapy DRUG

Adjuvant or Neoadjuvant Endocrine Therapy

Exploratory Subgroups (cross-cutting category); HER2-positive ILC; HR-low ILC (cross-cutting category); Triple-negative ILC

Chemotherapy DRUG

Adjuvant or Neoadjuvant Chemotherapy

Exploratory Subgroups (cross-cutting category); HER2-positive ILC; HR-low ILC (cross-cutting category); Triple-negative ILC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients diagnosed between January 1, 2010 and December 31, 2025 will be included. Follow-up will be collected until the most recent available clinical update.

You may qualify if:

• Female or male patients aged ≥18 years;
• Histologically confirmed ILC, confirmed by E-cadherin loss/aberrant expression and/or p120 cytoplasmic relocalization and/or CDH1 alteration;
• HR-negative (ER \<1% and PR \<1%) or HR-low (ER and/or PR 1-10%) disease, as defined by ASCO/CAP guidelines, is eligible regardless of HER2 status (assessed according to 2025 ASCO/CAP criteria, with HER2-low and HER2-ultralow status recorded where assessable);
• HR-positive (ER\>10% according to the ASCO/CAP guidelines) ILC is eligible only if HER2 status is positive;
• Mixed ductal-lobular carcinomas are eligible provided that a clearly identified invasive lobular component is present and predominant (\>50% lobular) and HR-negative/low criteria are met;
• Stage I-III disease at diagnosis; Patients with de novo stage IV disease who underwent surgery of the primary tumor will not be included in the main study cohort but may be captured in a separate exploratory cohort for dedicated analysis;
• Patients who underwent surgery of the primary tumor at the participating institution, either upfront or after neoadjuvant systemic treatment;
• Diagnosis occurred between 1 January 2000 and 31 December 2025;
• Minimum follow-up of 12 months for patients without an event, unless recurrence or death occurred earlier;
• Local review by a dedicated breast pathologist to confirm the diagnosis and the related molecular features, with particular attention to the confirmation of apocrine morphology.

You may not qualify if:

• Pure IC NST without any lobular invasive component;
• ER or PR expression \>10% in the invasive component, in cases with negative HER2 status;
• In situ lobular neoplasia (lobular carcinoma in situ) without an invasive component;
• De novo stage IV disease (such patients, if they underwent surgery of the primary tumor, will be captured in a separate exploratory cohort for a dedicated analysis)
• Synchronous invasive BC of another dominant histology requiring systemic treatment that precludes attribution of outcomes to HR-negative/low ILC;
• Prior invasive BC under active systemic treatment at the time of diagnosis, unless clearly documented as unrelated and not expected to confound outcomes;
• Insufficient data or follow up

Sponsors & Collaborators

• Istituto Oncologico Veneto IRCCS: lead

Study Sites (1)

Veneto Institute of Oncology

Padova, Italy

RECRUITING

Related Publications (17)

• Van Baelen K, Nguyen HL, Richard F, Zels G, Karsten MM, Nader-Marta G, Vermeulen P, Dirix L, Dordevic AD, de Azambuja E, Larsimont D, Maetens M, Biganzoli E, Wildiers H, Smeets A, Nevelsteen I, Neven P, Floris G, Desmedt C. Association of HER2-low with clinicopathological features in patients with early invasive lobular breast cancer: an international multicentric study. Breast Cancer Res. 2025 Jun 13;27(1):106. doi: 10.1186/s13058-025-02058-x.

  PMID: 40514709 BACKGROUND

• Lehmann BD, Bauer JA, Schafer JM, Pendleton CS, Tang L, Johnson KC, Chen X, Balko JM, Gomez H, Arteaga CL, Mills GB, Sanders ME, Pietenpol JA. PIK3CA mutations in androgen receptor-positive triple negative breast cancer confer sensitivity to the combination of PI3K and androgen receptor inhibitors. Breast Cancer Res. 2014 Aug 8;16(4):406. doi: 10.1186/s13058-014-0406-x.

  PMID: 25103565 BACKGROUND

• Aktas A, Gurleyik MG, Akkus D, Ucur Z, Aker F. Invasive lobular breast carcinoma variants; clinicopathological features and patient outcomes. Breast Cancer Res Treat. 2025 Jul;212(2):347-359. doi: 10.1007/s10549-025-07729-z. Epub 2025 May 21.

  PMID: 40397321 BACKGROUND

• Borella F, Gallio N, Giurdanella M, Capella G, Cassoni P, Castellano I. Triple-negative lobular breast cancer: focus on pathology and clinical challenges. Hum Pathol. 2025 Aug;162:105871. doi: 10.1016/j.humpath.2025.105871. Epub 2025 Jul 8.

  PMID: 40639624 BACKGROUND

• Allison KH, Hammond MEH, Dowsett M, McKernin SE, Carey LA, Fitzgibbons PL, Hayes DF, Lakhani SR, Chavez-MacGregor M, Perlmutter J, Perou CM, Regan MM, Rimm DL, Symmans WF, Torlakovic EE, Varella L, Viale G, Weisberg TF, McShane LM, Wolff AC. Estrogen and Progesterone Receptor Testing in Breast Cancer: ASCO/CAP Guideline Update. J Clin Oncol. 2020 Apr 20;38(12):1346-1366. doi: 10.1200/JCO.19.02309. Epub 2020 Jan 13.

  PMID: 31928404 BACKGROUND

• Conforti F, Pala L, Pagan E, Rocco EG, Bagnardi V, Montagna E, Peruzzotti G, De Pas T, Fumagalli C, Pileggi S, Pesenti C, Marchini S, Corso G, Marchio' C, Sapino A, Graffeo R, Collet L, Aftimos P, Sotiriou C, Piccart M, Gelber RD, Viale G, Colleoni M, Goldhirsch A. Biological and clinical features of triple negative Invasive Lobular Carcinomas of the breast. Clinical outcome and actionable molecular alterations. Breast. 2021 Oct;59:94-101. doi: 10.1016/j.breast.2021.06.011. Epub 2021 Jun 26.

  PMID: 34217971 BACKGROUND

• Taniguchi K, Takada S, Omori M, Igawa T, Nishimura MF, Morito T, Ichimura K, Yoshino T. Triple-negative pleomorphic lobular carcinoma and expression of androgen receptor: Personal case series and review of the literature. PLoS One. 2020 Jul 22;15(7):e0235790. doi: 10.1371/journal.pone.0235790. eCollection 2020.

  PMID: 32697770 BACKGROUND

• He L, Araj E, Peng Y. HER2 Positive and HER2 Negative Classical Type Invasive Lobular Carcinomas: Comparison of Clinicopathologic Features. Curr Oncol. 2021 Apr 24;28(3):1608-1617. doi: 10.3390/curroncol28030150.

  PMID: 33923191 BACKGROUND

• Sidhu S, Kaur G, Singh A, et al. Androgen receptor expression in estrogen receptor and progesterone receptor negative breast cancers and its clinicopathological significance. J Lab Physicians. 2023;15(4):573-579.

  BACKGROUND

• Anjum S, Ahmad F, Islam N, et al. Apocrine lesions of breast and invasive carcinoma with apocrine differentiation: a brief review. Egypt J Radiol Nucl Med. 2023;54:164.

  BACKGROUND

• Niemeier LA, Dabbs DJ, Beriwal S, Striebel JM, Bhargava R. Androgen receptor in breast cancer: expression in estrogen receptor-positive tumors and in estrogen receptor-negative tumors with apocrine differentiation. Mod Pathol. 2010 Feb;23(2):205-12. doi: 10.1038/modpathol.2009.159. Epub 2009 Nov 6.

  PMID: 19898421 BACKGROUND

• Vranic S, Feldman R, Gatalica Z. Apocrine carcinoma of the breast: A brief update on the molecular features and targetable biomarkers. Bosn J Basic Med Sci. 2017 Feb 21;17(1):9-11. doi: 10.17305/bjbms.2016.1811.

  PMID: 28027454 BACKGROUND

• Corso G, Shen S, Criscitiello C, Mukhtar R, Gamble L, Rocco EG, Pesapane F, Nicosia L, Jhaveri K, Salimbeni BT, Massari G, Meduri E, De Scalzi AM, Concardi A, Magnoni F, Mamtani A, Pareja F, Leonardi MC, Sacchini V, Bogani G, Vecchia C, Presti D, Colleoni MA, Veronesi P, Robson ME. Invasive lobular carcinoma: Strategies and perspectives from the lobular breast cancer research group. Cancer Treat Rev. 2025 Nov;140:103001. doi: 10.1016/j.ctrv.2025.103001. Epub 2025 Aug 7.

  PMID: 40815983 BACKGROUND

• Oesterreich S, Nasrazadani A, Zou J, Carleton N, Onger T, Wright MD, Li Y, Demanelis K, Ramaswamy B, Tseng G, Lee AV, Williams N, Kruse M. Clinicopathological Features and Outcomes Comparing Patients With Invasive Ductal and Lobular Breast Cancer. J Natl Cancer Inst. 2022 Nov 14;114(11):1511-1522. doi: 10.1093/jnci/djac157.

  PMID: 36239760 BACKGROUND

• Bergeron A, MacGrogan G, Bertaut A, Ladoire S, Arveux P, Desmoulins I, Bonnefoi H, Loustalot C, Auriol S, Beltjens F, Degrolard-Courcet E, Charon-Barra C, Richard C, Boidot R, Arnould L. Triple-negative breast lobular carcinoma: a luminal androgen receptor carcinoma with specific ESRRA mutations. Mod Pathol. 2021 Jul;34(7):1282-1296. doi: 10.1038/s41379-021-00742-9. Epub 2021 Mar 22.

  PMID: 33753865 BACKGROUND

• Batra H, Mouabbi JA, Ding Q, Sahin AA, Raso MG. Lobular Carcinoma of the Breast: A Comprehensive Review with Translational Insights. Cancers (Basel). 2023 Nov 20;15(22):5491. doi: 10.3390/cancers15225491.

  PMID: 38001750 BACKGROUND

• Barroso-Sousa R, Metzger-Filho O. Differences between invasive lobular and invasive ductal carcinoma of the breast: results and therapeutic implications. Ther Adv Med Oncol. 2016 Jul;8(4):261-6. doi: 10.1177/1758834016644156. Epub 2016 Apr 25.

  PMID: 27482285 BACKGROUND

Related Links

• Related Info

MeSH Terms

Conditions

Carcinoma, Lobular; Neoplasms

Interventions

Radiotherapy, Adjuvant; Drug Therapy

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Ductal, Lobular, and Medullary; Breast Neoplasms; Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics; Radiotherapy

Study Officials

• Francesco Milardi, MD

  Veneto Institute of Oncology IRCCS

  STUDY CHAIR

Central Study Contacts

Massimo Ferrucci, MD PhD

CONTACT

049 821 5500; massimoferrucci@gmail.com

Daniele Passeri, MD

CONTACT

+39 333 383 9397; daniele.passeri.1995@gmail.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD PhD

Study Record Dates

• First Submitted: May 19, 2026
• First Posted: May 29, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: September 2, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will share

Locations

IT (1)