Early-stage Invasive Lobular Breast CarcinomaNCT07842055
AI-based Prognostic Factors Identification in Early-stage Invasive Lobular Breast Carcinoma
An observational study of Early-stage Invasive Lobular Breast Carcinoma, run by Hellenic Cooperative Oncology Group at 1 site in Greece.
Trial summary
Invasive lobular breast carcinoma (ILC), the second most common breast cancer type, represents approximately 15% of all breast cancer cases. Improvement in diagnostic modalities as well as growing evidence that hormone replacement therapy is associated with higher risk of both invasive lobular carcinoma (ILC) and… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Early-stage Invasive Lobular Breast Carcinoma
- How many people
- 3,648 participants
- Where
- 1 siteGreece
- Study dates
- 10 Dec 1996to 13 Jul 2026
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Study population: patients with operable breast cancer treated with dds-CT including taxanes and anthracyclines. Adjuvant hormonal and radiation treatment were administered, as indicated
Who may be able to join
- Age 18 and above
- Histologically confirmed BC
- All treated with adjuvant dose-dense sequential chemotherapy (dds-CT)
- Tumor tissue specimen (FFPE) availability
Who cannot join
- not adequate, and unsuitable tissue for IHC, FISH, NGS analysis
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Identification of Prognostic Factors in Patients With Early-stage Invasive Lobular Breast Carcinoma (ILC) With AI - Assisted Pathology
Invasive lobular breast carcinoma (ILC), the second most common breast cancer type, represents approximately 15% of all breast cancer cases. Improvement in diagnostic modalities as well as growing evidence that hormone replacement therapy is associated with higher risk of both invasive lobular carcinoma (ILC) and invasive ductal-lobular mixed carcinoma (IDLC) have increased ILC incidence during last years.
Most risk factors for ILC, which is more frequently diagnosed in women over the age of 50, are related to increased hormone exposure, including earlier menarche, late menopause, late age at first birth, oral contraceptives, menopausal hormone therapy. Lifestyle factors, like alcohol intake, Western diet and postmenopausal obesity are also associated with lobular breast cancer.
Read more
Along with environment and lifestyle factors, genetic predisposition with germline mutations commonly found in CDH1 and FOXA1 are significant in ILC development. Other implicated genes include PIK3CA, PTEN, AKT1, and GATA3, while more than 50% of ILC harbor mutations in ERBB2, ESR1, FGF, or NF1, conferring endocrine therapy resistance. Interestingly, BRCA1 mutations are less frequent in ILC than in IDC, with similar frequencies of BRCA2, TP53, and CHEK2.
The predominant genetic mutation in CDH1 results in loss of expression of the cell-cell adhesion molecule E-cadherin, leading to a "discohesive" morphology of lobular cells. E-cadherin loss is commonly accompanied by abnormal expression of other parts of the cadherin-catenin complex, like membranous B-catenin and cytoplasmic p120-catenin. The characteristic "Indianfile" pattern of infiltration allows tumor cells to move through the extracellular matrix while causing a very little disruption of the underlying anatomic structures which frequently makes ILC difficult to detect through physical examination or imaging studies, like standard mammograms.
Patients with lobular carcinomas are generally diagnosed at a more advanced stage compared with invasive ductal carcinomas, with larger tumor sizes and more frequent lymph node invasion. Because these tumors are more likely hormone receptor positive and HER2 negative, endocrine therapy is the widely preferred therapeutic approach. Combining endocrine treatments with CDK4/6 inhibitors have shown promising results in HR+ breast cancer, in early as well as in a metastatic setting. However, since endocrine resistance is common in estrogen receptor-positive breast cancer, new therapeutic approaches are needed.
Recent studies have found bromodomain and extraterminal (BET) inhibition as well as FGFR inhibition, since ILC is known to have also FGFR-1 mutations causing resistance to BET inhibition, to be a potential therapeutic strategy for endocrine-resistant ILC cases.
Other promising potential therapies rely on the role of mTOR inhibitors since mutations in the PI3K/Akt signaling pathway are the second most common in ILC and acquired resistance to hormonal therapies is linked to PI3K/AKT/mTOR activation. Targeted immune checkpoint inhibitors therapy is also being investigated in a subset of ILC with higher tumor-infiltrating lymphocytes (TILs) and PD-L1 expression. Finaly, since ILCs seem to have a significant number of cases which are now classified as HER2-low the use of antibody drug conjugates needs to be studied in these cases, preferably by designing multicentric randomized control trials.
There is an urgent need to enhance our understanding of the clinicopathological and molecular features of invasive lobular breast cancer subtype with the goal of refining existing classifications and/or identifying potential biomarkers that could ultimately help improve therapeutic outcomes with established and novel therapies.
Conclusively, the ILC less aggressive biological profile (strong hormone receptor positivity, low proliferative activity, lower histological grade) does not reflect a better long-term outcome. ILC overall biological and clinical features entail a cautious diagnostic and therapeutic approach and as mentioned before, the fact that ILC cells spread in single-file patterns rather than forming distinct masses make them difficult to detect.
Digitalization and deep learning (DL) could definitely enhance ILC management. We intend to use a DL model in digitalized pathology slides and genomic data to improve ILC detection, predict recurrence risk, identify novel biomarkers and guide personalized treatments. Indeed, AI-driven models have been applied to whole-slide digital pathology images (WSIs) to predict CDH1 mutations from H\&E-stained slides. Moreover, a novel AI-derived tumour microenvironment risk score has been tested for long-term risk assessment supporting consideration of extended endocrine therapy in patients with ER+/HER2-, node-negative ILC.
Read the detailed description
From 1996 until 2022, 6,918 eligible patients with operable breast cancer of intermediate or high risk of relapse, according to St.Gallen criteria, were treated, within the context of 3 randomized and 5 observational clinical studies with dose-dense sequential adjuvant chemotherapy with epirubicin, cyclophosphamide, taxane (only one arm in HE_10/97 did not include a taxane) and "intensified" CMF. Adjuvant hormonal and radiation treatment were administered, as indicated.
IHC and FiSH data from patients enrolled in three randomized phase III trials conducted by the Hellenic Cooperative Oncology Group (HeCOG) (HE 10/97, HE 10/00, HE 10/05), a feasibility study (HE 10/04) and in four observational studies (HE 10/08, HE 10/10, HE10/13, HE10A/13) will be retrospectively reviewed.
All patients have signed a study-specific written informed consent before randomization, consenting for the trial and permitting the use of their biological material for future research purposes. All studies were conducted in accordance with the Declaration of Helsinki.
Tumor material is examined mainly on tissue microarrays (TMA). Although, there is a HER2 assessment from local pathology laboratories, all tumors are re-evaluated centrally for ER, PgR and HER2 in the laboratory of Molecular Oncology according to ASCO/CAP guidelines. Tumors are subtyped with immunohistochemistry (IHC4) for ER, PgR, HER2 and Ki67. FISH is performed for the assessment of HER2 gene status. IHC for EGFR and CK5 is used for the classification of basal-like tumors; the expression of CD8 on TILs is also evaluated. Moreover, we investigate the mutational profile of Greek women with breast cancer, via the application of DNA Next Generation Sequencing (NGS) technologies, relative also to patient outcome. All H\&E and IHC-stained slides will be digitalized for the investigation of the potential of a deep learning-based system for automated biomarker prediction.
Patient demographic, clinicopathological and treatment data are available in all cases.
- Keywords
- ILC, AI
- Medical subject headings
- Carcinoma, Lobular
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival (OS)
Correlation of genetic and molecular biomarkers with OS. OS is defined as the time from diagnosis or surgery to death from any cause.
Measured: Time from study entry to death from any cause, assessed up to 120 months
Progression-free survival (PFS)
Correlation of genetic and molecular biomarkers with PFS, with PFS defined as the time from enrollment to disease progression or death
Measured: Time from study entry to first recurrence (local, regional, distant) or death from any cause, whichever comes first, assessed up to 120 months
Secondary outcomes (1)
Evaluation of AI-predictive algorithm
Evaluation of the efficiency of the AI-predictive algorithm, by determining key metrics such as sensitivity and specificity
Measured: Through study completion, 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2026
- Study start10 Dec 1996
- Primary completion13 Jul 2026
- Study completion13 Jul 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (14)Papers the sponsor has linked to this study.
- Other trials for Early-stage Invasive Lobular Breast CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 3,648 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hellenic Cooperative Oncology Group
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07842055
- Sponsor's protocol ID
- HE_10ILC/26
- Status last verified
- Sep 2026
- First submitted
- 21 Sep 2026
- Last updated
- 25 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Zagouri F, Koliou GA, Dimitrakopoulos F, Papadimitriou C, Binas I, Koutras A, Papakostas P, Markopoulos C, Venizelos V, Xepapadakis G, Andrikopoulou Alpha, Karanikiotis C, Psyrri A, Bafaloukos D, Kosmidis P, Aravantinos G, Res E, Mauri D, Koumarianou A, Petraki K, Tsipoura A, Pectasides D, Gogas H, Fountzilas G. Dose-dense sequential adjuvant chemotherapy in the trastuzumab era: final long-term results of the Hellenic Cooperative Oncology Group Phase III HE10/05 Trial. Br J Cancer. 2022 Sep;127(4):695-703. doi: 10.1038/s41416-022-01846-y. Epub 2022 May 24.
PubMed 35610366Yu B, Yan L, Wang H, Yang J, Yang J. Invasive lobular carcinoma of the breast: metastatic patterns and treatment modalities-a review. Front Oncol. 2025 Sep 26;15:1631670. doi: 10.3389/fonc.2025.1631670. eCollection 2025.
PubMed 41079065Walsh L, Haley KE, Moran B, Mooney B, Tarrant F, Madden SF, Di Grande A, Fan Y, Das S, Rueda OM, Dowling CM, Vareslija D, Chin SF, Linn S, Young LS, Jirstrom K, Crown JP, Bernards R, Caldas C, Gallagher WM, O'Connor DP, Ni Chonghaile T. BET Inhibition as a Rational Therapeutic Strategy for Invasive Lobular Breast Cancer. Clin Cancer Res. 2019 Dec 1;25(23):7139-7150. doi: 10.1158/1078-0432.CCR-19-0713. Epub 2019 Aug 13.
PubMed 31409615Pareja F, Dopeso H, Wang YK, Gazzo AM, Brown DN, Banerjee M, Selenica P, Bernhard JH, Derakhshan F, da Silva EM, Colon-Cartagena L, Basili T, Marra A, Sue J, Ye Q, Da Cruz Paula A, Yeni Yildirim S, Pei X, Safonov A, Green H, Gill KY, Zhu Y, Lee MCH, Godrich RA, Casson A, Weigelt B, Riaz N, Wen HY, Brogi E, Mandelker DL, Hanna MG, Kunz JD, Rothrock B, Chandarlapaty S, Kanan C, Oakley J, Klimstra DS, Fuchs TJ, Reis-Filho JS. A Genomics-Driven Artificial Intelligence-Based Model Classifies Breast Invasive Lobular Carcinoma and Discovers CDH1 Inactivating Mechanisms. Cancer Res. 2024 Oct 15;84(20):3478-3489. doi: 10.1158/0008-5472.CAN-24-1322.
PubMed 39106449Dossus L, Benusiglio PR. Lobular breast cancer: incidence and genetic and non-genetic risk factors. Breast Cancer Res. 2015 Mar 13;17:37. doi: 10.1186/s13058-015-0546-7.
PubMed 25848941Biglia N, Mariani L, Sgro L, Mininanni P, Moggio G, Sismondi P. Increased incidence of lobular breast cancer in women treated with hormone replacement therapy: implications for diagnosis, surgical and medical treatment. Endocr Relat Cancer. 2007 Sep;14(3):549-67. doi: 10.1677/ERC-06-0060.
PubMed 17914088Batra 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.
PubMed 38001750Spathas N, Goussia AC, Koliou GA, Gogas H, Zagouri F, Batistatou A, Charchanti AV, Papoudou-Bai A, Bobos M, Chrisafi S, Chatzopoulos K, Kostopoulos I, Koletsa T, Arapantoni P, Pectasides D, Galani E, Koutras A, Zarkavelis G, Saloustros E, Bafaloukos D, Karanikiotis C, Bompolaki I, Aravantinos G, Psyrri A, Razis E, Koumarianou A, Res E, Linardou H, Fountzilas G. Association between CD8+ Tumor Infiltrating Lymphocytes and the Clinical Outcome of Patients with Operable Breast Cancer Treated with Adjuvant Dose-Dense Chemotherapy-A 10 Year Follow-Up Report of a Hellenic Cooperative Oncology Group Observational Study. Cancers (Basel). 2022 Nov 16;14(22):5635. doi: 10.3390/cancers14225635.
PubMed 36428728Papadimitriou CA, Papakostas P, Timotheadou E, Aravantinos G, Bamias A, Fountzilas G. Adjuvant dose-dense sequential chemotherapy with epirubicin, CMF and weekly paclitaxel in patients with resected high-risk breast cancer: a Hellenic Cooperative Oncology Group (HeCOG) study. Cancer Invest. 2008 Jun;26(5):491-8. doi: 10.1080/07357900701829785.
PubMed 18568771Gogas H, Dafni U, Karina M, Papadimitriou C, Batistatou A, Bobos M, Kalofonos HP, Eleftheraki AG, Timotheadou E, Bafaloukos D, Christodoulou C, Markopoulos C, Briasoulis E, Papakostas P, Samantas E, Kosmidis P, Stathopoulos GP, Karanikiotis C, Pectasides D, Dimopoulos MA, Fountzilas G. Postoperative dose-dense sequential versus concomitant administration of epirubicin and paclitaxel in patients with node-positive breast cancer: 5-year results of the Hellenic Cooperative Oncology Group HE 10/00 phase III Trial. Breast Cancer Res Treat. 2012 Apr;132(2):609-19. doi: 10.1007/s10549-011-1913-4. Epub 2011 Dec 21.
PubMed 22187126Fountzilas G, Pectasides D, Christodoulou C, Timotheadou E, Economopoulos T, Papakostas P, Papadimitriou C, Gogas H, Efstratiou I, Skarlos D. Adjuvant dose-dense sequential chemotherapy with epirubicin, CMF, and weekly docetaxel is feasible and safe in patients with operable breast cancer. Med Oncol. 2006;23(4):479-88. doi: 10.1385/MO:23:4:479.
PubMed 17303906Fountzilas G, Dafni U, Papadimitriou C, Timotheadou E, Gogas H, Eleftheraki AG, Xanthakis I, Christodoulou C, Koutras A, Papandreou CN, Papakostas P, Miliaras S, Markopoulos C, Dimitrakakis C, Korantzopoulos P, Karanikiotis C, Bafaloukos D, Kosmidis P, Samantas E, Varthalitis I, Pavlidis N, Pectasides D, Dimopoulos MA. Dose-dense sequential adjuvant chemotherapy followed, as indicated, by trastuzumab for one year in patients with early breast cancer: first report at 5-year median follow-up of a Hellenic Cooperative Oncology Group randomized phase III trial. BMC Cancer. 2014 Jul 15;14:515. doi: 10.1186/1471-2407-14-515.
PubMed 25026897Fountzilas G, Skarlos D, Dafni U, Gogas H, Briasoulis E, Pectasides D, Papadimitriou C, Markopoulos C, Polychronis A, Kalofonos HP, Siafaka V, Kosmidis P, Timotheadou E, Tsavdaridis D, Bafaloukos D, Papakostas P, Razis E, Makrantonakis P, Aravantinos G, Christodoulou C, Dimopoulos AM. Postoperative dose-dense sequential chemotherapy with epirubicin, followed by CMF with or without paclitaxel, in patients with high-risk operable breast cancer: a randomized phase III study conducted by the Hellenic Cooperative Oncology Group. Ann Oncol. 2005 Nov;16(11):1762-71. doi: 10.1093/annonc/mdi366. Epub 2005 Sep 7.
PubMed 16148021Dimitrakopoulos FI, Goussia A, Koliou GA, Dadouli K, Batistatou A, Kourea HP, Bobos M, Arapantoni-Dadioti P, Tzaida O, Koletsa T, Chrisafi S, Sotiropoulou M, Papoudou-Bai A, Nicolaou I, Charchanti A, Mauri D, Aravantinos G, Binas I, Res E, Psyrri A, Pectasides D, Bafaloukos D, Koumarianou A, Bompolaki I, Rigakos G, Karanikiotis C, Koutras A, Zagouri F, Gogas H, Fountzilas G. Ten-year clinical outcome, toxicity and compliance of dose-dense sequential adjuvant administration of cyclophosphamide & epirubicin followed by docetaxel in patients with early breast cancer: A hellenic cooperative oncology group observational study (HE 10/10) with concurrent investigation of significance of tumor infiltrating lymphocytes. Breast. 2024 Feb;73:103668. doi: 10.1016/j.breast.2023.103668. Epub 2023 Dec 25.
PubMed 38176305
Study at a glance
From the registry record, last updated by the sponsor on 25 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Identification of Prognostic Factors in Patients With Early-stage Invasive Lobular Breast Carcinoma (ILC) With AI - Assisted Pathology
- ClinicalTrials.gov ID
- NCT07842055
- Acronym / sponsor ID
- HE_10ILC/26
- Keywords
- ILC, AI
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 3,648 participants (actual)
- Lead sponsor
- Hellenic Cooperative Oncology GroupUniversity, hospital or other
- Study start
- 10 Dec 1996 (actual)
- Primary completion
- 13 Jul 2026 (actual)
- Study completion
- 13 Jul 2026 (actual)
- First posted
- 25 Sep 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Invasive lobular breast carcinoma (ILC), the second most common breast cancer type, represents approximately 15% of all breast cancer cases. Improvement in diagnostic modalities as well as growing evidence that hormone replacement therapy is associated with higher risk of both invasive lobular carcinoma (ILC) and invasive ductal-lobular mixed carcinoma (IDLC) have increased ILC incidence during last years.
Most risk factors for ILC, which is more frequently diagnosed in women over the age of 50, are related to increased hormone exposure, including earlier menarche, late menopause, late age at first birth, oral contraceptives, menopausal hormone therapy. Lifestyle factors, like alcohol intake, Western diet and postmenopausal obesity are also associated with lobular breast cancer.
Along with environment and lifestyle factors, genetic predisposition with germline mutations commonly found in CDH1 and FOXA1 are significant in ILC development. Other implicated genes include PIK3CA, PTEN, AKT1, and GATA3, while more than 50% of ILC harbor mutations in ERBB2, ESR1, FGF, or NF1, conferring endocrine therapy resistance. Interestingly, BRCA1 mutations are less frequent in ILC than in IDC, with similar frequencies of BRCA2, TP53, and CHEK2.
The predominant genetic mutation in CDH1 results in loss of expression of the cell-cell adhesion molecule E-cadherin, leading to a "discohesive" morphology of lobular cells. E-cadherin loss is commonly accompanied by abnormal expression of other parts of the cadherin-catenin complex, like membranous B-catenin and cytoplasmic p120-catenin. The characteristic "Indianfile" pattern of infiltration allows tumor cells to move through the extracellular matrix while causing a very little disruption of the underlying anatomic structures which frequently makes ILC difficult to detect through physical examination or imaging studies, like standard mammograms.
Patients with lobular carcinomas are generally diagnosed at a more advanced stage compared with invasive ductal carcinomas, with larger tumor sizes and more frequent lymph node invasion. Because these tumors are more likely hormone receptor positive and HER2 negative, endocrine therapy is the widely preferred therapeutic approach. Combining endocrine treatments with CDK4/6 inhibitors have shown promising results in HR+ breast cancer, in early as well as in a metastatic setting. However, since endocrine resistance is common in estrogen receptor-positive breast cancer, new therapeutic approaches are needed.
Recent studies have found bromodomain and extraterminal (BET) inhibition as well as FGFR inhibition, since ILC is known to have also FGFR-1 mutations causing resistance to BET inhibition, to be a potential therapeutic strategy for endocrine-resistant ILC cases.
Other promising potential therapies rely on the role of mTOR inhibitors since mutations in the PI3K/Akt signaling pathway are the second most common in ILC and acquired resistance to hormonal therapies is linked to PI3K/AKT/mTOR activation. Targeted immune checkpoint inhibitors therapy is also being investigated in a subset of ILC with higher tumor-infiltrating lymphocytes (TILs) and PD-L1 expression. Finaly, since ILCs seem to have a significant number of cases which are now classified as HER2-low the use of antibody drug conjugates needs to be studied in these cases, preferably by designing multicentric randomized control trials.
There is an urgent need to enhance our understanding of the clinicopathological and molecular features of invasive lobular breast cancer subtype with the goal of refining existing classifications and/or identifying potential biomarkers that could ultimately help improve therapeutic outcomes with established and novel therapies.
Conclusively, the ILC less aggressive biological profile (strong hormone receptor positivity, low proliferative activity, lower histological grade) does not reflect a better long-term outcome. ILC overall biological and clinical features entail a cautious diagnostic and therapeutic approach and as mentioned before, the fact that ILC cells spread in single-file patterns rather than forming distinct masses make them difficult to detect.
Digitalization and deep learning (DL) could definitely enhance ILC management. We intend to use a DL model in digitalized pathology slides and genomic data to improve ILC detection, predict recurrence risk, identify novel biomarkers and guide personalized treatments. Indeed, AI-driven models have been applied to whole-slide digital pathology images (WSIs) to predict CDH1 mutations from H\&E-stained slides. Moreover, a novel AI-derived tumour microenvironment risk score has been tested for long-term risk assessment supporting consideration of extended endocrine therapy in patients with ER+/HER2-, node-negative ILC.
Detailed description
From 1996 until 2022, 6,918 eligible patients with operable breast cancer of intermediate or high risk of relapse, according to St.Gallen criteria, were treated, within the context of 3 randomized and 5 observational clinical studies with dose-dense sequential adjuvant chemotherapy with epirubicin, cyclophosphamide, taxane (only one arm in HE_10/97 did not include a taxane) and "intensified" CMF. Adjuvant hormonal and radiation treatment were administered, as indicated.
IHC and FiSH data from patients enrolled in three randomized phase III trials conducted by the Hellenic Cooperative Oncology Group (HeCOG) (HE 10/97, HE 10/00, HE 10/05), a feasibility study (HE 10/04) and in four observational studies (HE 10/08, HE 10/10, HE10/13, HE10A/13) will be retrospectively reviewed.
All patients have signed a study-specific written informed consent before randomization, consenting for the trial and permitting the use of their biological material for future research purposes. All studies were conducted in accordance with the Declaration of Helsinki.
Tumor material is examined mainly on tissue microarrays (TMA). Although, there is a HER2 assessment from local pathology laboratories, all tumors are re-evaluated centrally for ER, PgR and HER2 in the laboratory of Molecular Oncology according to ASCO/CAP guidelines. Tumors are subtyped with immunohistochemistry (IHC4) for ER, PgR, HER2 and Ki67. FISH is performed for the assessment of HER2 gene status. IHC for EGFR and CK5 is used for the classification of basal-like tumors; the expression of CD8 on TILs is also evaluated. Moreover, we investigate the mutational profile of Greek women with breast cancer, via the application of DNA Next Generation Sequencing (NGS) technologies, relative also to patient outcome. All H\&E and IHC-stained slides will be digitalized for the investigation of the potential of a deep learning-based system for automated biomarker prediction.
Patient demographic, clinicopathological and treatment data are available in all cases.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- patients with operable breast cancer treated with dds-CT including taxanes and anthracyclines. Adjuvant hormonal and radiation treatment were administered, as indicated
Key inclusion criteria (4 listed)
- Age 18 and above
- Histologically confirmed BC
- All treated with adjuvant dose-dense sequential chemotherapy (dds-CT)
- Tumor tissue specimen (FFPE) availability
Key exclusion criteria (1 listed)
- not adequate, and unsuitable tissue for IHC, FISH, NGS analysis
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Overall Survival (OS)
Time frame: Time from study entry to death from any cause, assessed up to 120 months
Correlation of genetic and molecular biomarkers with OS. OS is defined as the time from diagnosis or surgery to death from any cause.
Progression-free survival (PFS)
Time frame: Time from study entry to first recurrence (local, regional, distant) or death from any cause, whichever comes first, assessed up to 120 months
Correlation of genetic and molecular biomarkers with PFS, with PFS defined as the time from enrollment to disease progression or death
1 secondary outcome
Evaluation of AI-predictive algorithm
Time frame: Through study completion, 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Sep 2026.
- Background: PubMed 35610366Zagouri F, Koliou GA, Dimitrakopoulos F, Papadimitriou C, Binas I, Koutras A, Papakostas P, Markopoulos C, Venizelos V, Xepapadakis G, Andrikopoulou Alpha, Karanikiotis C, Psyrri A, Bafaloukos D, Kosmidis P, Aravantinos G, Res E, Mauri D, Koumarianou A, Petraki K, Tsipoura A, Pectasides D, Gogas H, Fountzilas G. Dose-dense sequential adjuvant chemotherapy in the trastuzumab era: final long-term results of the Hellenic Cooperative Oncology Group Phase III HE10/05 Trial. Br J Cancer. 2022 Sep;127(4):695-703. doi: 10.1038/s41416-022-01846-y. Epub 2022 May 24.
- Background: PubMed 41079065Yu B, Yan L, Wang H, Yang J, Yang J. Invasive lobular carcinoma of the breast: metastatic patterns and treatment modalities-a review. Front Oncol. 2025 Sep 26;15:1631670. doi: 10.3389/fonc.2025.1631670. eCollection 2025.
- Background: PubMed 31409615Walsh L, Haley KE, Moran B, Mooney B, Tarrant F, Madden SF, Di Grande A, Fan Y, Das S, Rueda OM, Dowling CM, Vareslija D, Chin SF, Linn S, Young LS, Jirstrom K, Crown JP, Bernards R, Caldas C, Gallagher WM, O'Connor DP, Ni Chonghaile T. BET Inhibition as a Rational Therapeutic Strategy for Invasive Lobular Breast Cancer. Clin Cancer Res. 2019 Dec 1;25(23):7139-7150. doi: 10.1158/1078-0432.CCR-19-0713. Epub 2019 Aug 13.
- Background: PubMed 39106449Pareja F, Dopeso H, Wang YK, Gazzo AM, Brown DN, Banerjee M, Selenica P, Bernhard JH, Derakhshan F, da Silva EM, Colon-Cartagena L, Basili T, Marra A, Sue J, Ye Q, Da Cruz Paula A, Yeni Yildirim S, Pei X, Safonov A, Green H, Gill KY, Zhu Y, Lee MCH, Godrich RA, Casson A, Weigelt B, Riaz N, Wen HY, Brogi E, Mandelker DL, Hanna MG, Kunz JD, Rothrock B, Chandarlapaty S, Kanan C, Oakley J, Klimstra DS, Fuchs TJ, Reis-Filho JS. A Genomics-Driven Artificial Intelligence-Based Model Classifies Breast Invasive Lobular Carcinoma and Discovers CDH1 Inactivating Mechanisms. Cancer Res. 2024 Oct 15;84(20):3478-3489. doi: 10.1158/0008-5472.CAN-24-1322.
- Background: PubMed 25848941Dossus L, Benusiglio PR. Lobular breast cancer: incidence and genetic and non-genetic risk factors. Breast Cancer Res. 2015 Mar 13;17:37. doi: 10.1186/s13058-015-0546-7.
- Background: PubMed 17914088Biglia N, Mariani L, Sgro L, Mininanni P, Moggio G, Sismondi P. Increased incidence of lobular breast cancer in women treated with hormone replacement therapy: implications for diagnosis, surgical and medical treatment. Endocr Relat Cancer. 2007 Sep;14(3):549-67. doi: 10.1677/ERC-06-0060.
- Background: PubMed 38001750Batra 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.
- Results publication: PubMed 36428728Spathas N, Goussia AC, Koliou GA, Gogas H, Zagouri F, Batistatou A, Charchanti AV, Papoudou-Bai A, Bobos M, Chrisafi S, Chatzopoulos K, Kostopoulos I, Koletsa T, Arapantoni P, Pectasides D, Galani E, Koutras A, Zarkavelis G, Saloustros E, Bafaloukos D, Karanikiotis C, Bompolaki I, Aravantinos G, Psyrri A, Razis E, Koumarianou A, Res E, Linardou H, Fountzilas G. Association between CD8+ Tumor Infiltrating Lymphocytes and the Clinical Outcome of Patients with Operable Breast Cancer Treated with Adjuvant Dose-Dense Chemotherapy-A 10 Year Follow-Up Report of a Hellenic Cooperative Oncology Group Observational Study. Cancers (Basel). 2022 Nov 16;14(22):5635. doi: 10.3390/cancers14225635.
- Results publication: PubMed 18568771Papadimitriou CA, Papakostas P, Timotheadou E, Aravantinos G, Bamias A, Fountzilas G. Adjuvant dose-dense sequential chemotherapy with epirubicin, CMF and weekly paclitaxel in patients with resected high-risk breast cancer: a Hellenic Cooperative Oncology Group (HeCOG) study. Cancer Invest. 2008 Jun;26(5):491-8. doi: 10.1080/07357900701829785.
- Results publication: PubMed 22187126Gogas H, Dafni U, Karina M, Papadimitriou C, Batistatou A, Bobos M, Kalofonos HP, Eleftheraki AG, Timotheadou E, Bafaloukos D, Christodoulou C, Markopoulos C, Briasoulis E, Papakostas P, Samantas E, Kosmidis P, Stathopoulos GP, Karanikiotis C, Pectasides D, Dimopoulos MA, Fountzilas G. Postoperative dose-dense sequential versus concomitant administration of epirubicin and paclitaxel in patients with node-positive breast cancer: 5-year results of the Hellenic Cooperative Oncology Group HE 10/00 phase III Trial. Breast Cancer Res Treat. 2012 Apr;132(2):609-19. doi: 10.1007/s10549-011-1913-4. Epub 2011 Dec 21.
- Results publication: PubMed 17303906Fountzilas G, Pectasides D, Christodoulou C, Timotheadou E, Economopoulos T, Papakostas P, Papadimitriou C, Gogas H, Efstratiou I, Skarlos D. Adjuvant dose-dense sequential chemotherapy with epirubicin, CMF, and weekly docetaxel is feasible and safe in patients with operable breast cancer. Med Oncol. 2006;23(4):479-88. doi: 10.1385/MO:23:4:479.
- Results publication: PubMed 25026897Fountzilas G, Dafni U, Papadimitriou C, Timotheadou E, Gogas H, Eleftheraki AG, Xanthakis I, Christodoulou C, Koutras A, Papandreou CN, Papakostas P, Miliaras S, Markopoulos C, Dimitrakakis C, Korantzopoulos P, Karanikiotis C, Bafaloukos D, Kosmidis P, Samantas E, Varthalitis I, Pavlidis N, Pectasides D, Dimopoulos MA. Dose-dense sequential adjuvant chemotherapy followed, as indicated, by trastuzumab for one year in patients with early breast cancer: first report at 5-year median follow-up of a Hellenic Cooperative Oncology Group randomized phase III trial. BMC Cancer. 2014 Jul 15;14:515. doi: 10.1186/1471-2407-14-515.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Early-stage Invasive Lobular Breast Carcinoma, run by Hellenic Cooperative Oncology Group at 1 site in Greece.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Greece. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Survival (OS) (time frame: Time from study entry to death from any cause, assessed up to 120 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07842055, which also lists 14 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Sep 2026.