Tubular Breast Carcinoma
Tubular breast carcinoma is a rare and unique subtype of invasive ductal carcinoma, accounting for less than 2% of all breast cancer cases. As a leading preclinical CRO, Alfa Cytology has dedicated extensive research efforts to understanding the intricacies of this disease and developing innovative therapeutic approaches.
Introduction to Tubular Breast Carcinoma
Originating from the breast duct cells, tubular carcinoma is characterized by its distinct tubular architectural pattern and typically less aggressive behavior compared to other invasive breast cancers. Despite its rarity, this subtype presents distinct challenges in terms of accurate diagnosis and optimal treatment strategies.
Fig.1 A case of tubular breast carcinoma. (Metovic J., et al. 2021)
Therapy Development for Tubular Breast Carcinoma
Tubular breast carcinoma is characterized by its heterogeneous nature, with diverse molecular profiles and varying responses to individual therapeutic agents. By combining targeted agents, immunotherapies, and traditional chemotherapeutics, researchers aim to target multiple signaling pathways and cellular processes simultaneously.
| Category | Therapeutics | Phase | NCT |
| Combination Therapies | Paclitaxel + Cisplatin + Epirubicin | NCT02879513 | |
| Paclitaxel + Cisplatin + EC to docetaxel or paclitaxel | NCT03201861 | ||
| Non-pegylated liposomal doxorubicin + Carboplatin + Paclitaxel | NCT02125344 | ||
| Nanoparticle-based Therapy | nab-Paclitaxel | NCT01583426 |
Our Services
Tubular breast carcinoma is a relatively rare disease but malignant. Multiple factors influence prognosis and therapy options. Therefore, Alfa Cytology is working on providing one-stop solutions for tubular breast carcinoma, including but not limited to the following.
Therapy Development
Case Study
Modeling Tamoxifen Resistance in DNA Damage-Exposed MCF-7 Cells
- Model Introduction
The MCF-7 cell model serves as a fundamental in vitro tool for studying hormone-responsive breast cancer, including the highly differentiated and prognostically favorable tubular breast carcinoma. As a representative Luminal A subtype model, MCF-7 recapitulates key molecular features of ERα-positive, low-aggressiveness tumors, making it highly relevant for investigating therapeutic resistance mechanisms in this clinical context.
- Model Information
- Model: MCF-7 Cell Line (In Vitro)
- Cancer Type: Breast Cancer (Luminal A Subtype; Modeling Tubular Carcinoma Features)
- Key Applications: Investigation of DNA damage-induced hormonal resistance, evaluation of endocrine therapy efficacy, and analysis of ERα signaling pathway dynamics.
- Cell Line Origin: Pleural effusion from a metastatic breast cancer patient.
- Molecular Profile: ERα-positive, PgR-positive, HER2-negative.
- Model Construction
The experimental model was constructed using standard in vitro culture of MCF-7 cells. To investigate DNA damage-induced hormonal resistance, which is a clinically relevant scenario for tubular breast carcinoma patients receiving adjuvant chemotherapy, two distinct treatment regimens were implemented:
- Acute DNA Damage: Cells were exposed to a single dose of compound A, a DNA damage agent, for 3 days.
- Chronic DNA Damage & Resistant Subline Generation: Cells were subjected to long-term exposure of escalating compound A over 2 months, followed by maintenance in drug-free medium for 1 month to establish the compound A-resistant subline (MCF-7/Compound A).
- In Vivo Efficacy Evaluation
This study utilized the established MCF-7 cellular models to systematically evaluate the impact of DNA-damaging agent compound A on ERα signaling functionality and sensitivity to the anti-estrogen tamoxifen (TAM).
- Transient Hormonal Resistance Induction: Acute compound A treatment induced significant DNA fragmentation, leading to reversible suppression of ERα transcriptional activity and reduced sensitivity to estrogen receptor modulator tamoxifen. All effects were reversed within 10 days after drug withdrawal.
- Irreversible Hormonal Resistance Development: Chronic compound A exposure selected for a resistant cell population that exhibited irreversible suppression of ERα transcriptional activity and sustained partial resistance to estrogen receptor modulator tamoxifen, despite cessation of the DNA-damaging agent compound A.
Fig. 2 The response of MCF-7 cells to compound A and the established sensitivity of MCF-7/Compound A cells to tamoxifen. (A and B) A percentage of 100% was set as the viability of MCF7 cells treated with vehicle control. **p<0.01 and ***p <0.0001. (C) The survival rate of untreated cells was set at 100%. *p < 0.05 compared to the untreated group. (Source: Alfa Cytology)
At Alfa Cytology, our comprehensive suite of oncology services and deep disease-specific expertise provide a powerful platform for accelerating the development of novel tubular breast carcinoma therapies. From molecular profiling and biomarker discovery to the establishment of robust preclinical models and the systematic evaluation of therapeutic candidates, our team of cancer experts is well-equipped to support researchers and clinicians at every stage of the drug development process. If you are interested in our service, please contact us.
Reference
- Metovic J., Bragoni A., and et al. Clinical Relevance of Tubular Breast Carcinoma: Large Retrospective Study and Meta-Analysis. Front Oncol. 2021, 11: 653388.