DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for invasive lobular carcinoma — screening already-approved drugs against its 3-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleInvasive lobular carcinoma maps to a 3-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for invasive lobular carcinoma is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
BRCA2 DNA repair associated (BRCA2) — BRCA2 is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet atpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8PBC · 2.61 Å · ligand ADENOSINE-5'-TRIPHOSPHATE (ATP). Experimental structure, not a prediction.
What the evidence adds up to
Invasive lobular carcinoma (ILC) is the second most common breast cancer histology, and its infiltrative, often discontinuous growth pattern makes preoperative assessment of disease extent difficult with conventional mammography or ultrasonography. A 2005 analysis of 21,596 patients from the National Cancer Data Base (1989–2001) found that local recurrence rates were very low and 5-year disease-free survival rates correspondingly high for both breast conservation therapy and mastectomy across all tumour sizes and lymph node statuses. Over that period, use of breast-conserving surgery increased almost threefold, and sentinel lymph node biopsy use rose from 23% to 57% in the breast-conservation group (1998–2001). The authors concluded that less invasive treatment yields outcomes equivalent to more aggressive surgery.
A 2005 review noted that the risk of contralateral carcinoma and of multifocality is higher for ILC than for invasive ductal carcinoma, and that the response to preoperative chemotherapy is worse for ILC, with a greater need for rescue mastectomy. Dynamic contrast-enhanced magnetic resonance imaging may be useful for detection and preoperative staging, but its value was not yet established. A 2021 case series of 122 patients with lobular neoplasia (atypical lobular hyperplasia, lobular carcinoma in situ, or high-grade lobular neoplasia) reported a 28.3% upgrade rate at definitive surgery (28/99 patients). Age ≥54 years, BI-RADS categories 4–5, and high-grade lobular neoplasia on biopsy were associated with upgrade. Among 23 patients managed without surgery, 17% (4/23) developed an ipsilateral malignant lesion during a median follow-up of 9.5 years.
A 2025 retrospective Brazilian cohort of 153 patients with stage I–III ILC (2015–2020) reported that 50% received adjuvant chemotherapy, 10% neoadjuvant chemotherapy, and 40% no chemotherapy. Median disease-free survival was 11 years for adjuvant, 1.4 years for neoadjuvant, and 9.4 years for omitted chemotherapy (p=0.0001). Median overall survival was 13.3 years, 5.5 years, and 7.5 years respectively (p=0.0395). For stage I and II disease, overall survival was longer with adjuvant chemotherapy than with neoadjuvant or omission; for stage III, median overall survival did not differ significantly between groups (6.2, 5.9, and 4.6 years; p=0.56). In multivariable analysis, age, stage, and HER2 3+ were independent risk factors for shorter overall survival (hazard ratios 1.07, 4.2, and 8.9 respectively). The authors noted that guidelines recommend chemotherapy for ILC based on criteria developed for ductal/no special type tumours, but the benefit may not be the same.
What remains missing is prospective, randomised evidence comparing chemotherapy strategies specifically in ILC, and validated tools to predict which patients with lobular neoplasia or early ILC will progress. The role of MRI in surgical planning and the optimal duration and type of endocrine therapy for ILC are not settled. No drug repurposing data were presented in these abstracts.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Annals of Surgery · 2005 · 85 citations · open access
Treatment Trends in Early-Stage Invasive Lobular Carcinoma
AbstractIn Brief Objective: To examine treatment trends in invasive lobular carcinoma (ILC) over the last 15 years and, in particular, to compare rates of recurrence and disease-free survival associated with breast conservation therapy compared with mastectomy. Summary Background Data: The biologic characteristics of ILC make it difficult to estimate the extent of the disease by either clinical examination or mammography, and can also make it difficult to detect axillary lymph node metastases. Because of this, there has been a bias toward treating ILC with aggressive therapy. Methods: Patients with ILC were selected from the National Cancer Data Base (1989–2001) using an extensive set of inclusion and exclusion criteria. A total of 21,596 patients were selected, including 8108 who received breast conservation therapy and 13,488 who received mastectomy. Analysis included demographic characteristics, trends in usage of sentinel lymph node biopsy, rates of local and distant recurrence, and 5-year disease-free survival rates. Results: The use of breast conversation therapy increased almost threefold during the study period. From 1998 to 2001, the use of sentinel node biopsy increased more than twofold in the breast conservation group (an average of 23% in 1998 versus 57% in 2001), compared with limited usage in the mastectomy group (an average of 10% in 1998 versus 23% in 2001). Local recurrence rates were very low and disease-free survival rates were correspondingly high in both treatment groups for all diagnosis years and across all pathologic tumor size/lymph node status designations. Conclusions: Less invasive treatment options are becoming widely used for invasive lobular carcinoma, yielding outcomes equivalent to those seen with more aggressive treatment. Because of the infiltrative growth pattern and frequent discontinuity seen in invasive lobular carcinoma, there has been a bias toward treating patients with more aggressive surgery, including mastectomy and standard axillary lymph node dissection. Date from the National Cancer Data Base indicate a growing trend toward less invasive treatment, with good treatment outcomes obtained using breast conserving surgery and sentinel lymph node biopsy.
AbstractInfiltrating plcomorphic lobular careinoma is a recently recognized, aggressive variant of lobular carcinoma that has the invasive pattern of classical infiltrating lobular carcinoma but that also has large plcomorphic nuclei and abundant cosinophilic, slightly granular cytoplasm. The authors described an infiltrating pleomorphic lobular carcinoma accompanied by an extensive in situ carcinoma that involved lobular units primarily. The in situ carcinoma was cytologically identical to the infiltrating carcinoma and was interpreted as the in situ counterpart of infiltrating pleomorphic lobular carcinoma.
Current Opinion in Obstetrics & Gynecology · 2005 · 47 citations
Lobular carcinoma in situ and invasive lobular cancer of the breast
AbstractPurpose of review The incidence of lobular carcinoma in situ and invasive lobular carcinoma of the breast is increasing. Recent data suggest that lobular carcinoma in situ is an indolent precursor for breast cancer, rather than a pure risk factor. This could imply free surgical margins become important. The risk of contralateral carcinoma and of multifocality of invasive lobular carcinoma is higher than for invasive ductal carcinoma. Therefore, the need for mastectomy, or even for preventative contralateral mastectomy is questioned. Conventional mammography or ultrasonography cannot always give useful preoperative information about the extent of lobular cancers. The value of dynamic contrast-enhanced magnetic resonance imaging needs to be established for these patients. Recent findings The risk of invasive carcinoma after lobular carcinoma in situ is increased. Invasive carcinoma is usually located at the index point of lobular carcinoma in situ and is of lobular histology. Dynamic contrast-enhanced magnetic resonance imaging can be useful in the detection and preoperative staging of invasive lobular carcinoma. The risk of local recurrence is high in patients with invasive lobular carcinoma. Mastectomy and breast reconstruction could be an option in selected patients. The response to preoperative chemotherapy is worse for invasive lobular carcinoma compared with invasive ductal carcinoma, with a greater need for rescue mastectomy. Summary Lobular carcinoma in situ and invasive lobular carcinoma are different entities from ductal carcinoma in situ and invasive lobular carcinoma. Their biological profile should be studied further in order to make the fine tuning of treatment possible. Abbreviations ALH: atypical lobular hyperplasia; BCS: breast-conservative surgery; DCE-MRI: dynamic contrast-enhanced magnetic resonance imaging; DCIS: ductal carcinoma in situ; IBTR: ipsilateral breast tumour recurrence; IDC: invasive ductal carcinoma; ILC: invasive lobular carcinoma; LCIS: lobular carcinoma in situ; MRI: magnetic resonance imaging; PCT: preoperative chemotherapy; VEGF: vascular endothelial growth factor.
Abstract P2-10-03: Real world outcomes of adjuvant chemotherapy in invasive lobular carcinoma of the breast: a retrospective cohort from a reference center in Brazil
AbstractAbstract Background: Invasive lobular carcinoma is the second most common breast cancer histology and has lower response rate to chemotherapy (CT) compared to ductal/no special type (NST) tumors. In the adjuvant setting, many guidelines recommend CT based on the criteria used for NST. However, the benefit of CT is not necessarily the same. Here, we present survival outcomes of patients with invasive lobular carcinoma from a retrospective cohort. Methods: This study has included patients seen at Instituto do Cancer do Estado de São Paulo, Brazil, between 2015 and 2020. Only patients with invasive lobular carcinoma in stages I-III have been enrolled. Results: After screening, 153 records from patients were included to review, divided in stages I (22%), II (47%) , and III (31%). Mean of age at diagnosis was 62y (range: 28 - 91 years). Received chemotherapy as adjuvant, neoadjuvant and omitted in 76 (50%), 16 (10%), and 61 (40%) respectively. The median of disease-free survival in adjuvant, neoadjuvant and omitted were respectively 11y, 1.4y and 9.4y (p=0.0001); and median of overall survival (mOS) were 13.3y, 5.5y and 7.5y (p = 0.0395). Analyzed by staging, for stage I mOS was not raged among groups (p=0.011), stage II 13y, 5.5y and 7.2y (p=0.006), and stage III: 6.2y, 5.9y, and 4.6y (p=0.56). In a multivariable Cox proportional regression, the hazard ratio (HR) for age, staging and HER2 3+ were 1.07 (p=0.001), 4.2 (p= 0.0001), and 8.9 (p=0.001) respectively. Conclusion: In our study, disease-free survival and overall survival were longer for adjuvant chemotherapy than neoadjuvant, specially for stage I and II. Although age, staging and HER2 3+ were independent risk factors for shorter overall survival. Citation Format: Raelson Miranda, Thamires Haick Martins da Silveira, Douglas Tozzo, Leticia de Mello Graziano, Laura Testa. Real world outcomes of adjuvant chemotherapy in invasive lobular carcinoma of the breast: a retrospective cohort from a reference center in Brazil [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P2-10-03.
The lobular neoplasia enigma: management and prognosis in a long follow-up case series
AbstractAbstract Background Many oncologists debate if lobular neoplasia (LN) is a risk factor or an obligatory precursor of more aggressive disease. This study has three aims: (i) describe the different treatment options (surgical resection vs observation), (ii) investigate the upgrade rate in surgically treated patients, and (iii) evaluate the long-term occurrences of aggressive disease in both operated and unoperated patients. Methods A series of 122 patients with LN bioptic diagnosis and follow-up information were selected. Clinical, radiological, and pathological data were collected from medical charts. At definitive histology, either invasive or ductal carcinoma in situ was considered upgraded lesions. Results Atypical lobular hyperplasia (ALH), lobular carcinoma in situ (LCIS), and high-grade LN (HG-LN) were diagnosed in 44, 63, and 15 patients, respectively. The median follow-up was 9.5 years. Ninety-nine patients were surgically treated, while 23 underwent clinical-radiological follow-up. An upgrade was observed in 28/99 (28.3%). Age ≥ 54 years (OR 4.01, CI 1.42–11.29, p = 0.009), Breast Imaging-Reporting and Data System (BI-RADS) categories 4–5 (OR 3.76, CI 1.37–10.1, p = 0.010), and preoperatory HG-LN diagnosis (OR 8.76, 1.82–42.27, p = 0.007) were related to upgraded/aggressive disease. During follow-up, 8 patients developed an ipsilateral malignant lesion, four of whom were not initially operated (4/23, 17%). Conclusions BI-RADS categories 4–5, HG-LN diagnosis, and age ≥ 54 years were features associated with an upgrade at definitive surgery. Moreover, 17% of unoperated cases developed an aggressive disease, emphasizing that LN patients need close surveillance due to the long-term risk of breast cancer.
The lobular neoplasia enigma: management and prognosis in a long follow-up case series
AbstractAbstract Background Many oncologists debate if lobular neoplasia (LN) is a risk factor or an obligatory precursor of more aggressive disease. This study has three aims: (i) describe the different treatment options (surgical resection vs observation), (ii) investigate the upgrade rate in surgically treated patients, and (iii) evaluate the long-term occurrences of aggressive disease in both operated and unoperated patients. Methods A series of 122 patients with LN bioptic diagnosis and follow-up information were selected. Clinical, radiological, and pathological data were collected from medical charts. At definitive histology, either invasive or ductal carcinoma in situ was considered upgraded lesions. Results Atypical lobular hyperplasia (ALH), lobular carcinoma in situ (LCIS), and high-grade LN (HG-LN) were diagnosed in 44, 63, and 15 patients, respectively. The median follow-up was 9.5 years. Ninety-nine patients were surgically treated, while 23 underwent clinical-radiological follow-up. An upgrade was observed in 28/99 (28.3%). Age ≥ 54 years (OR 4.01, CI 1.42–11.29, p = 0.009), Breast Imaging-Reporting and Data System (BI-RADS) categories 4–5 (OR 3.76, CI 1.37–10.1, p = 0.010), and preoperatory HG-LN diagnosis (OR 8.76, 1.82–42.27, p = 0.007) were related to upgraded/aggressive disease. During follow-up, 8 patients developed an ipsilateral malignant lesion, four of whom were not initially operated (4/23, 17%). Conclusions BI-RADS categories 4–5, HG-LN diagnosis, and age ≥ 54 years were features associated with an upgrade at definitive surgery. Moreover, 17% of unoperated cases developed an aggressive disease, emphasizing that LN patients need close surveillance due to the long-term risk of breast cancer.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
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