RARE DISEASE
Rare malignant breast tumor
Rare malignant breast tumor
Rare malignant breast tumor
Synonyms: Rare breast cancer
Synonyms: Rare breast cancer
Synonyms: Rare breast cancer
Drug discovery
2
drugs
With orphan designations
Overview
Rare malignant breast tumors (<5% of cases) encompass diverse epithelial (tubular, mucinous, medullary) and non-epithelial (angiosarcoma, adenoid cystic, phyllodes) subtypes with distinct histopathological features [1][3][6][11]. Prognosis varies widely: mucinous and cribriform carcinomas often show >90% 10-year survival, while metaplastic and angiosarcomas have poorer outcomes [1][6][9]. Diagnostic and therapeutic challenges arise from low incidence, limited trial data, and frequent triple-negative biology [3][11][15].
Therapies
Primary therapy involves wide surgical excision ± adjuvant radiotherapy [1][3][11]. Chemotherapy follows IDC protocols for high-risk cases (e.g., tumor >3cm, lymphovascular invasion) [3][5]. Emerging targeted therapies (PARP inhibitors, HER2-directed agents) show promise in molecularly selected cases [8][17].
Categories: rare gynecological and obstetric diseases, rare neoplastic diseases
Research Papers
104 drug discovery papers about Rare malignant breast tumor, with 1 next-in-class emerging drug candidate forecasted to outperform the average preclinical success rate. Recent publications:
104 drug discovery papers about Rare malignant breast tumor, with 1 next-in-class emerging drug candidate forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-05-28 | Outcomes and clinicopathological characteristics of patients with metaplastic breast cancer at the National Cancer Institute Mexico between 2016-2020.
e12747 Background: Metaplastic breast cancer is a rare histological subtype (< 1%) with dismissal prognosis and few studies regarding patient outcomes and characteristics. Information in Latin America is scarce, therefore our primary objective was to determine Survival Outcomes and Clinicopathological characteristics in a Tertiary Cancer Center in Mexico. Methods: This was a prospective cohort of metaplastic breast cancer patients between 2016-2020 at the National Cancer Institute in Mexico City whether they went to primary systemic therapy or not. For descriptive statistics we used frequencies and proportions. A Kaplan-Meier analysis was performed for Overall Survival, Progression-Free Survival and Recurrence-Free Survival outcomes. Results: The most relevant clinicopathological characteristics are presented in Table 1. Median tumor size was 4.3cm (1-30); 48% underwent neoadjuvant chemotherapy of which 8% (1) had ypT0, 58% (7) ypN0. In upfront surgery patients, 63% (7) were pT1-pT2, and 55% (6) were pN1-pN2. 67% (28) had mastectomy and 48% (13) had axillary dissection. Median follow-up was 67 months (51-82), there were 8 deaths (median survival not reached), 2 recurrences (median recurrence 28 months) and 1 progression. Conclusions: Metaplastic breast cancer in this population consisted of high grade tumors, advanced stages, predominantly triple negative breast cancers and no HER2+ subtypes. 70% of patients had a ductal component, with 52% of nodal disease at presentation. This is an interesting finding since nodal disease in these tumors is not usually reported. Median survival was not reached with a follow-up of more than 5 years, which gives insight on the prognosis of a rare breast cancer subtype in the largest cohort reported in Mexico so far. Clinicopathological characteristics of patients with metaplastic breast cancer. % (n) Age 52 (39-79)* Clinical StageIIIIIIIV 12 (3)19 (5)54 (14)15 (4) T Stage1234 19 (5)26 (7)18 (5)37 (10) Nodal StagecN 0cN 1cN 2cN 3 48 (13)19 (5)26 (7)7 (2) Subtype HR+HER2-HR-HER2-HER2+ 33 (9)67 (18)0 (0) GradeIIIIIIN/A 4 (1)11 (3)56 (15)30 (8) Ductal componentYesNoN/A 70 (19)26 (7)4 (1) Neoadjuvant ChemotherapyYesNoN/A 48 (13)48 (13)4 (1) Adjuvant ChemotherapyYesNoN/A 70 (19)26 (7)4 (1) *Median (range).
2026-02-27 | Genomic Landscape and Therapeutic Implications of Metaplastic Breast Carcinoma: Insights from a Nationwide Database Including Diagnostic Mimickers.
Background/Objectives: Metaplastic breast carcinoma (MpBC) is a rare and aggressive malignancy characterized by significant histological heterogeneity and limited response to standard chemotherapy. Due to its morphological diversity, MpBC often presents diagnostic challenges and can overlap with other mesenchymal tumors. This study aimed to characterize the genomic landscape of MpBC using a nationwide Japanese database and to explore the molecular basis of its diagnostic ambiguities and therapeutic responses. Methods: We retrospectively analyzed genomic and clinical data from 123 MpBC cases registered in the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database. To evaluate diagnostic boundaries, genomic profiles of histological mimickers, including 19 cases of angiosarcoma and eight cases of myoepithelial carcinoma, were also examined. Furthermore, an exploratory single-cell RNA-sequencing analysis was performed on 3274 cells from independent MpBC datasets to investigate cellular heterogeneity and potential lineage plasticity. Results: TP53 (73.2%) and PIK3CA (46.0%) were the most prevalent genomic alterations in the MpBC cohort. Exploratory analysis suggested that PIK3CA mutations may be associated with an improved disease control rate in patients receiving taxane-based therapy (p = 0.028). Comparisons with mimickers identified distinctive molecular signatures, such as MED12 and HRAS hotspot mutations, across entities. Single-cell transcriptomics identified a distinct subpopulation (7.02% of malignant cells) co-expressing epithelial and phyllodes-like signatures. Conclusions: These findings suggest that MpBC harbors hybrid malignant cell populations that may contribute to its complex morphological diversity. While the therapeutic associations are based on a limited cohort and require prospective validation, the integration of comprehensive genomic and single-cell profiling provides an exploratory framework that may potentially enhance diagnostic accuracy in the future. However, these associations remain preliminary and require prospective validation to confirm their clinical utility.
2025-11-21 | Mammary small cell neuroendocrine carcinomas that showed excellent pathologic response following etoposide-based neoadjuvant chemotherapy.
Small cell neuroendocrine carcinoma (SCNEC) is a very rare, highly aggressive subtype of breast cancer. There are no standard recommendations for the management of mammary SCNEC, and the use and response to neoadjuvant chemotherapy are not well studied. Etoposide is an agent not included in guidelines for the management of breast cancer but traditionally used in the treatment of small cell carcinoma of the lung. We searched for institutional and consultation cases of breast SCNEC and identified those treated with neoadjuvant chemotherapy. Clinical, pathologic, and genetic findings of two patients with SCNEC of the breast treated with etoposide are described. Additionally, we performed a literature review of all known cases of mammary SCNEC treated with neoadjuvant chemotherapy to date. These two women were the sole patients who underwent neoadjuvant etoposide-based chemotherapy followed by surgery for breast SCNEC at our institution in the past 25 years. Both patients achieved excellent imaging and pathologic responses, with no evidence of residual carcinoma in the subsequent breast excisions. Etoposide may be considered as a therapeutic option in the neoadjuvant setting of breast SCNEC. More reports on this very rare breast cancer subtype and response to treatment are needed.
2025-10-01 | S3845 Unveiling the Unlikely: Stercoral Colitis Masking Rare Breast Metastasis: A Case Report
Introduction: A patient with rare breast cancer metastasis to the colon was initially diagnosed with stercoral colitis due to symptoms like abdominal cramping and altered bowel habits. However, further investigation revealed the true cause as breast cancer metastasis. This case underscores the challenges in distinguishing between primary gastrointestinal issues and metastatic disease in breast cancer patients. Case Description/Methods: An 84-year-old woman with a history of coronary artery disease, currently on clopidogrel and aspirin, also had stage II invasive ductal carcinoma with extensive lymph node involvement. She underwent right mastectomy and axillary dissection, followed by adjuvant chemotherapy (AC-T) 19 years ago. After poorly tolerating hormonal treatment, she faced a recurrence of cancer in the neck, treated with CyberKnife therapy, radiotherapy, and brief Ixempra chemotherapy until 2012. She was hospitalized for weakness and shortness of breath, she was found to have severe anemia (hemoglobin 6.8) without gross bleeding. An EGD showed congestive gastropathy with no source of anemia. A colonoscopy revealed a 4 mm polyp and a 10 mm ulcer, with the latter biopsied as metastatic breast cancer (ER+/PR-/Her2neu-). A bone marrow biopsy confirmed the diagnosis leading towards a focus on goals of care as surgical intervention is inadvisable. Discussion: Breast cancer is the most prevalent cancer in women in the U.S., comprising 32% of newly diagnosed cancers annually. Metastatic spread primarily targets the bone, lung, and brain, while gastrointestinal (GI) involvement is rare, occurring in only 0.5% of cases. Among GI metastases, the colon and rectum (45%) are most frequently affected, followed by the stomach (28%), small intestine (19%), and esophagus (8%), although some studies claim the stomach as the predominant site (60%). Symptoms of GI metastasis align with the affected region, with epigastric pain and weight loss common in gastric involvement, and abdominal cramping and occult bleeding in colonic cases. Diagnosis hinges on immunohistochemical markers: breast cancer cells typically express mammaglobin and GATA3, while primary GI malignancies showcase CDX2 and CK20. Given the poor prognosis associated with GI metastasis, treatment strategies focus on palliative care, including hormonal therapy for receptor-positive cases and interventions to alleviate obstruction. Overall survival after diagnosis ranges from 4.7 to 33 months, with a median survival of 33 months observed in a specific cohort.
2025-09-13 | Chondroid Differentiated Metaplastic Carcinoma of the Breast: A Case Report and Review of the Literature
Metaplastic carcinoma of the breast is an uncommon and heterogeneous malignancy, accounting for less than 1% of invasive breast cancers. It is defined by the coexistence of epithelial and mesenchymal elements, occasionally with chondroid differentiation, which makes diagnosis challenging. We report the case of a 66 year old postmenopausal woman presenting with a firm right breast mass and mild nipple retraction. Imaging revealed a BI RADS 5 lesion. Core biopsy showed invasive carcinoma with a chondroid component, consistent with metaplastic carcinoma. Immunohistochemistry demonstrated strong positivity for estrogen (80%) and progesterone (70%) receptors, HER2 negativity, and a Ki 67 index of 30%. This hormone receptor–positive profile is rare in metaplastic carcinoma, which is usually triple negative, but may offer a therapeutic advantage with endocrine therapy. The absence of distant metastases at diagnosis further supports a favorable outlook. This case emphasizes the importance of accurate histopathological evaluation and a multidisciplinary, individualized management strategy for this rare breast cancer subtype.
antibodies
2026-06-29 | Triple-Negative Metaplastic Breast Carcinoma With Squamous and Glandular Differentiation Treated With Neoadjuvant Chemoimmunotherapy: A Case Report
Metaplastic breast carcinoma with squamous and glandular differentiation is a rare and aggressive subtype of breast cancer that frequently exhibits a triple-negative phenotype and lacks standardized treatment guidelines. We report the case of a 69-year-old female who presented with a progressively enlarging left breast mass and a palpable axillary lymph node. Imaging demonstrated a suspicious 4 cm breast mass and an enlarged axillary lymph node with cortical thickening. Core needle biopsy revealed a high-grade invasive carcinoma with squamous and focal glandular differentiation, consistent with metaplastic breast carcinoma. Immunohistochemistry demonstrated a triple-negative phenotype with expression of CK5/6 and p63, supporting squamous differentiation and the diagnosis of metaplastic breast carcinoma. Axillary lymph node biopsy was negative for metastatic disease. The patient was initiated on neoadjuvant chemoimmunotherapy according to the KEYNOTE-522 regimen, with plans for breast-conserving surgery. This case highlights the diagnostic challenges and evolving treatment strategies for this rare breast cancer subtype.
2026-05-28 | Treatment outcomes with pembrolizumab and chemotherapy in metastatic metaplastic triple-negative breast cancer: Data from a central European cohort.
e13119 Background: Metaplastic triple-negative breast cancer (MpTNBC) is a rare and clinically aggressive subtype of breast cancer associated with poor prognosis. Although immunotherapy combined with chemotherapy has demonstrated clinical benefit in patients with metastatic triple-negative breast cancer (mTNBC), data specific to MpTNBC remain limited. This study aimed to evaluate the real-world efficacy and safety of pembrolizumab in combination with chemotherapy in patients with metastatic MpTNBC. Methods: Within the CEBCC-101 real-world evidence program, a multinational, multicenter retrospective study collecting data from 20 oncology centers across Central Europe, we performed a predefined subanalysis restricted to patients with histologically confirmed metaplastic MpTNBC treated with first-line pembrolizumab plus chemotherapy in routine practice (outside clinical trials). Among 178 women with mTNBC included in CEBCC-101, 14 MpTNBC cases (7.9%) were identified across 9 oncology centers and constituted the study population for the present analysis. Treatment was initiated in Poland, the Czech Republic and Slovakia between September 2022 and June 2025. Safety was assessed as the incidence and severity of treatment-emergent adverse events (AEs), graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Results: The median age at treatment initiation was 59.7 years (range, 33.1–81.0). The median follow-up was 14.0 months (range, 7.5–20.4). At data cutoff, 13 patients had discontinued treatment due to disease progression (n = 11) or treatment-related toxicity (n = 2), while one patient remained on therapy; 11 patients had died. Objective response rate (ORR) was observed in 7 of 14 patients (50.0%), and disease control rate (DCR) was achieved in 11 patients (78.6%). Median overall survival (mOS) was 14.1 months, with 6-, 12-, and 18-month OS rates of 100.0%, 64.3%, and 40.2%, respectively. Median progression-free survival (mPFS) was 6.0 months, with corresponding PFS rates of 50.0%, 14.3%, and 7.1%. Grade ≥2 AEs occurred in 12 patients (85.7%). Grade 3 toxicity was observed in 6 (42.9%), with no grade 4–5 events reported. The most frequent AEs were chemotherapy-related, predominantly neutropenia and peripheral neuropathy. Conclusions: This first international real-world series evaluates pembrolizumab in combination with chemotherapy in patients with metastatic MpTNBC. mPFS and mOS observed in this real-world cohort were markedly shorter than those reported in the phase III KEYNOTE-355 trial, most likely reflecting the exceptionally aggressive clinical course of MpTNBC. The safety profile of treatment was acceptable. These findings underscore the need for further prospective studies and international collaboration in rare breast cancer subtypes.
2026-04-09 | Chemotherapy is associated with differential survival outcomes in apocrine carcinoma: A nationwide cohort study from the Japanese National Clinical Database-Breast Cancer Registry.
Apocrine carcinoma (AC) is a rare breast cancer subtype, and the benefit of adjuvant chemotherapy for early-stage disease remains uncertain. Prior studies suggest limited chemotherapy responsiveness in triple-negative AC (TNAC), whereas evidence in pure HER2-positive AC is scarce. This study described outcomes in AC using a national registry and examined outcomes by systemic treatment across subtypes. Using the Japanese National Clinical Database-Breast Cancer Registry, we identified 2817 patients with AC from 2004 to 2019. Patients were categorized as pure HER2 AC or TNAC. The primary endpoint was distant metastasis-free survival (DMFS); overall survival (OS) was also assessed. Survival outcomes were analyzed using Kaplan-Meier and Cox models. Adjuvant chemotherapy was associated with longer DMFS in the overall cohort (hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.51-0.96). Subtype-specific analyses showed significantly longer DMFS (HR, 0.26; 95%CI, 0.12-0.57) and OS (HR, 0.18; 95%CI, 0.06-0.57) in patients who received chemotherapy in the pure HER2 AC group; 5-year DMFS was 96.1% with chemotherapy versus 86.8% without. In contrast, no significant association between chemotherapy and DMFS (HR, 0.84; 95%CI, 0.60-1.18) or OS (HR, 0.84; 95%CI, 0.55-1.28) was observed in TNAC, with similar 5-year DMFS with and without chemotherapy (91.1% vs. 89.2%). In this large population-based cohort of early-stage AC, the association between adjuvant chemotherapy and outcomes differed by subtype. Chemotherapy was associated with better outcomes in pure HER2 AC, whereas no clear association was observed in TNAC. These findings suggest that treatment strategies for AC may need to consider subtype-specific differences.
2026-03-11 | Mucinous Micropapillary Carcinoma of Breast in a Developing World Setting: Case Series With Clinicopathological Insights and Survival Analysis From a Tertiary Care Hospital.
Mucinous micropapillary carcinoma breast (MMPC) is one of the rarest subtypes of breast cancer (BC) with clinicopathologic features correlated with poor prognosis. We are aimed at identifying MMPC cases and correlate them with histopathological features, overall survival (OS), and recurrence-free survival (RFS). We retrospectively identified cases of MMPC from our institutional repository from 2017 to 2022. Data were collected regarding age, stage of BC at the time of diagnosis, tumor size, lymphovascular invasion (LVI), extranodal extension (ENE), lymph node (LN) metastasis, tumor biology, recurrence, and OS. Quantitative variables are calculated as median with range (IQR), whereas qualitative variables are presented in percentages. Nine MMPC cases were reported in the last 6 years, with a median age at diagnosis of 49 years. At diagnosis, 66.67% (6/9) were Stage III followed by Stage II; the average tumor size was 4.5 cm and the majority of tumors were Grade II (77.78%) followed by Grade III. LVI was seen in 66.67%, ENE in 33.33%, and LN metastases in 66.67%. Estrogen receptor (ER)/progesterone receptor (PR) was positive in 77.78%. The OS was 7/9 (77.78%) at the median follow-up of 3.5 years; recurrence was reported in two patients with an RFS of 77.78% (7/9). Our results demonstrate that MMPC is a rare entity that presented at a younger age with more advanced disease. Patients presented with larger tumor size, intermediate- to high-grade tumor morphology, LVI, ENE, and LN metastasis. These tumors also overexpressed ER and PR. Despite this, clinical outcomes in our cohort were relatively favorable, which is also reflected in OS (77.78%) and RFS (77.78%) at a median follow-up of 3.5 years.
2025-08-21 | Immunotherapy in rare histologies of breast cancer: challenges, opportunities, and future perspectives.
Immunotherapy has transformed the management of several malignancies, yet its role in rare breast cancer histologies remains poorly defined due to limited research and few dedicated clinical trials. This review critically assesses current knowledge and emerging opportunities for immunotherapy in these uncommon breast cancer subtypes. Rare breast cancer histologies exhibit heterogeneous immunogenicity, including variable expression of programmed death-ligand 1 (PD-L1), differing levels of tumor-infiltrating lymphocytes (TILs), and distinct mutational burdens. Recent studies highlight potential immunotherapy responsiveness in metaplastic, invasive lobular, apocrine, and other rare breast cancer types, though predictive biomarkers like PD-L1 and tumor mutational burden (TMB) alone appear insufficient. Currently, only two clinical trials specifically target rare breast cancer histologies, emphasizing significant knowledge gaps. The effectiveness of immunotherapy in rare breast cancer histologies remains limited, likely due to inadequate patient selection using current biomarkers such as PD-L1 and TMB. Further research must focus on refining predictive biomarkers to better identify patients likely to from immunotherapy and enhance outcomes in these challenging clinical settings.
cell therapies
2023-03-31 | Data from Patient-Derived Triple-Negative Breast Cancer Organoids Provide Robust Model Systems That Recapitulate Tumor Intrinsic Characteristics
<div>Abstract<p>Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer with poor patient outcomes, highlighting the unmet clinical need for targeted therapies and better model systems. Here, we developed and comprehensively characterized a diverse biobank of normal and breast cancer patient-derived organoids (PDO) with a focus on TNBCs. PDOs recapitulated patient tumor intrinsic properties and a subset of PDOs can be propagated for long-term culture (LT-TNBC). Single cell profiling of PDOs identified cell types and gene candidates affiliated with different aspects of cancer progression. The LT-TNBC organoids exhibit signatures of aggressive MYC-driven, basal-like breast cancers and are largely comprised of luminal progenitor (LP)-like cells. The TNBC LP-like cells are distinct from normal LPs and exhibit hyperactivation of NOTCH and MYC signaling. Overall, this study validates TNBC PDOs as robust models for understanding breast cancer biology and progression, paving the way for personalized medicine and tailored treatment options.</p>Significance:<p>A comprehensive analysis of patient-derived organoids of TNBC provides insights into cellular heterogeneity and mechanisms of tumorigenesis at the single-cell level.</p></div>
small molecules
2026-05-28 | Outcomes and clinicopathological characteristics of patients with metaplastic breast cancer at the National Cancer Institute Mexico between 2016-2020.
e12747 Background: Metaplastic breast cancer is a rare histological subtype (< 1%) with dismissal prognosis and few studies regarding patient outcomes and characteristics. Information in Latin America is scarce, therefore our primary objective was to determine Survival Outcomes and Clinicopathological characteristics in a Tertiary Cancer Center in Mexico. Methods: This was a prospective cohort of metaplastic breast cancer patients between 2016-2020 at the National Cancer Institute in Mexico City whether they went to primary systemic therapy or not. For descriptive statistics we used frequencies and proportions. A Kaplan-Meier analysis was performed for Overall Survival, Progression-Free Survival and Recurrence-Free Survival outcomes. Results: The most relevant clinicopathological characteristics are presented in Table 1. Median tumor size was 4.3cm (1-30); 48% underwent neoadjuvant chemotherapy of which 8% (1) had ypT0, 58% (7) ypN0. In upfront surgery patients, 63% (7) were pT1-pT2, and 55% (6) were pN1-pN2. 67% (28) had mastectomy and 48% (13) had axillary dissection. Median follow-up was 67 months (51-82), there were 8 deaths (median survival not reached), 2 recurrences (median recurrence 28 months) and 1 progression. Conclusions: Metaplastic breast cancer in this population consisted of high grade tumors, advanced stages, predominantly triple negative breast cancers and no HER2+ subtypes. 70% of patients had a ductal component, with 52% of nodal disease at presentation. This is an interesting finding since nodal disease in these tumors is not usually reported. Median survival was not reached with a follow-up of more than 5 years, which gives insight on the prognosis of a rare breast cancer subtype in the largest cohort reported in Mexico so far. Clinicopathological characteristics of patients with metaplastic breast cancer. % (n) Age 52 (39-79)* Clinical StageIIIIIIIV 12 (3)19 (5)54 (14)15 (4) T Stage1234 19 (5)26 (7)18 (5)37 (10) Nodal StagecN 0cN 1cN 2cN 3 48 (13)19 (5)26 (7)7 (2) Subtype HR+HER2-HR-HER2-HER2+ 33 (9)67 (18)0 (0) GradeIIIIIIN/A 4 (1)11 (3)56 (15)30 (8) Ductal componentYesNoN/A 70 (19)26 (7)4 (1) Neoadjuvant ChemotherapyYesNoN/A 48 (13)48 (13)4 (1) Adjuvant ChemotherapyYesNoN/A 70 (19)26 (7)4 (1) *Median (range).
2026-02-27 | Genomic Landscape and Therapeutic Implications of Metaplastic Breast Carcinoma: Insights from a Nationwide Database Including Diagnostic Mimickers.
Background/Objectives: Metaplastic breast carcinoma (MpBC) is a rare and aggressive malignancy characterized by significant histological heterogeneity and limited response to standard chemotherapy. Due to its morphological diversity, MpBC often presents diagnostic challenges and can overlap with other mesenchymal tumors. This study aimed to characterize the genomic landscape of MpBC using a nationwide Japanese database and to explore the molecular basis of its diagnostic ambiguities and therapeutic responses. Methods: We retrospectively analyzed genomic and clinical data from 123 MpBC cases registered in the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database. To evaluate diagnostic boundaries, genomic profiles of histological mimickers, including 19 cases of angiosarcoma and eight cases of myoepithelial carcinoma, were also examined. Furthermore, an exploratory single-cell RNA-sequencing analysis was performed on 3274 cells from independent MpBC datasets to investigate cellular heterogeneity and potential lineage plasticity. Results: TP53 (73.2%) and PIK3CA (46.0%) were the most prevalent genomic alterations in the MpBC cohort. Exploratory analysis suggested that PIK3CA mutations may be associated with an improved disease control rate in patients receiving taxane-based therapy (p = 0.028). Comparisons with mimickers identified distinctive molecular signatures, such as MED12 and HRAS hotspot mutations, across entities. Single-cell transcriptomics identified a distinct subpopulation (7.02% of malignant cells) co-expressing epithelial and phyllodes-like signatures. Conclusions: These findings suggest that MpBC harbors hybrid malignant cell populations that may contribute to its complex morphological diversity. While the therapeutic associations are based on a limited cohort and require prospective validation, the integration of comprehensive genomic and single-cell profiling provides an exploratory framework that may potentially enhance diagnostic accuracy in the future. However, these associations remain preliminary and require prospective validation to confirm their clinical utility.
2025-11-21 | Mammary small cell neuroendocrine carcinomas that showed excellent pathologic response following etoposide-based neoadjuvant chemotherapy.
Small cell neuroendocrine carcinoma (SCNEC) is a very rare, highly aggressive subtype of breast cancer. There are no standard recommendations for the management of mammary SCNEC, and the use and response to neoadjuvant chemotherapy are not well studied. Etoposide is an agent not included in guidelines for the management of breast cancer but traditionally used in the treatment of small cell carcinoma of the lung. We searched for institutional and consultation cases of breast SCNEC and identified those treated with neoadjuvant chemotherapy. Clinical, pathologic, and genetic findings of two patients with SCNEC of the breast treated with etoposide are described. Additionally, we performed a literature review of all known cases of mammary SCNEC treated with neoadjuvant chemotherapy to date. These two women were the sole patients who underwent neoadjuvant etoposide-based chemotherapy followed by surgery for breast SCNEC at our institution in the past 25 years. Both patients achieved excellent imaging and pathologic responses, with no evidence of residual carcinoma in the subsequent breast excisions. Etoposide may be considered as a therapeutic option in the neoadjuvant setting of breast SCNEC. More reports on this very rare breast cancer subtype and response to treatment are needed.
2025-10-01 | S3845 Unveiling the Unlikely: Stercoral Colitis Masking Rare Breast Metastasis: A Case Report
Introduction: A patient with rare breast cancer metastasis to the colon was initially diagnosed with stercoral colitis due to symptoms like abdominal cramping and altered bowel habits. However, further investigation revealed the true cause as breast cancer metastasis. This case underscores the challenges in distinguishing between primary gastrointestinal issues and metastatic disease in breast cancer patients. Case Description/Methods: An 84-year-old woman with a history of coronary artery disease, currently on clopidogrel and aspirin, also had stage II invasive ductal carcinoma with extensive lymph node involvement. She underwent right mastectomy and axillary dissection, followed by adjuvant chemotherapy (AC-T) 19 years ago. After poorly tolerating hormonal treatment, she faced a recurrence of cancer in the neck, treated with CyberKnife therapy, radiotherapy, and brief Ixempra chemotherapy until 2012. She was hospitalized for weakness and shortness of breath, she was found to have severe anemia (hemoglobin 6.8) without gross bleeding. An EGD showed congestive gastropathy with no source of anemia. A colonoscopy revealed a 4 mm polyp and a 10 mm ulcer, with the latter biopsied as metastatic breast cancer (ER+/PR-/Her2neu-). A bone marrow biopsy confirmed the diagnosis leading towards a focus on goals of care as surgical intervention is inadvisable. Discussion: Breast cancer is the most prevalent cancer in women in the U.S., comprising 32% of newly diagnosed cancers annually. Metastatic spread primarily targets the bone, lung, and brain, while gastrointestinal (GI) involvement is rare, occurring in only 0.5% of cases. Among GI metastases, the colon and rectum (45%) are most frequently affected, followed by the stomach (28%), small intestine (19%), and esophagus (8%), although some studies claim the stomach as the predominant site (60%). Symptoms of GI metastasis align with the affected region, with epigastric pain and weight loss common in gastric involvement, and abdominal cramping and occult bleeding in colonic cases. Diagnosis hinges on immunohistochemical markers: breast cancer cells typically express mammaglobin and GATA3, while primary GI malignancies showcase CDX2 and CK20. Given the poor prognosis associated with GI metastasis, treatment strategies focus on palliative care, including hormonal therapy for receptor-positive cases and interventions to alleviate obstruction. Overall survival after diagnosis ranges from 4.7 to 33 months, with a median survival of 33 months observed in a specific cohort.
2025-09-13 | Chondroid Differentiated Metaplastic Carcinoma of the Breast: A Case Report and Review of the Literature
Metaplastic carcinoma of the breast is an uncommon and heterogeneous malignancy, accounting for less than 1% of invasive breast cancers. It is defined by the coexistence of epithelial and mesenchymal elements, occasionally with chondroid differentiation, which makes diagnosis challenging. We report the case of a 66 year old postmenopausal woman presenting with a firm right breast mass and mild nipple retraction. Imaging revealed a BI RADS 5 lesion. Core biopsy showed invasive carcinoma with a chondroid component, consistent with metaplastic carcinoma. Immunohistochemistry demonstrated strong positivity for estrogen (80%) and progesterone (70%) receptors, HER2 negativity, and a Ki 67 index of 30%. This hormone receptor–positive profile is rare in metaplastic carcinoma, which is usually triple negative, but may offer a therapeutic advantage with endocrine therapy. The absence of distant metastases at diagnosis further supports a favorable outlook. This case emphasizes the importance of accurate histopathological evaluation and a multidisciplinary, individualized management strategy for this rare breast cancer subtype.
antibodies
2026-06-29 | Triple-Negative Metaplastic Breast Carcinoma With Squamous and Glandular Differentiation Treated With Neoadjuvant Chemoimmunotherapy: A Case Report
Metaplastic breast carcinoma with squamous and glandular differentiation is a rare and aggressive subtype of breast cancer that frequently exhibits a triple-negative phenotype and lacks standardized treatment guidelines. We report the case of a 69-year-old female who presented with a progressively enlarging left breast mass and a palpable axillary lymph node. Imaging demonstrated a suspicious 4 cm breast mass and an enlarged axillary lymph node with cortical thickening. Core needle biopsy revealed a high-grade invasive carcinoma with squamous and focal glandular differentiation, consistent with metaplastic breast carcinoma. Immunohistochemistry demonstrated a triple-negative phenotype with expression of CK5/6 and p63, supporting squamous differentiation and the diagnosis of metaplastic breast carcinoma. Axillary lymph node biopsy was negative for metastatic disease. The patient was initiated on neoadjuvant chemoimmunotherapy according to the KEYNOTE-522 regimen, with plans for breast-conserving surgery. This case highlights the diagnostic challenges and evolving treatment strategies for this rare breast cancer subtype.
2026-05-28 | Treatment outcomes with pembrolizumab and chemotherapy in metastatic metaplastic triple-negative breast cancer: Data from a central European cohort.
e13119 Background: Metaplastic triple-negative breast cancer (MpTNBC) is a rare and clinically aggressive subtype of breast cancer associated with poor prognosis. Although immunotherapy combined with chemotherapy has demonstrated clinical benefit in patients with metastatic triple-negative breast cancer (mTNBC), data specific to MpTNBC remain limited. This study aimed to evaluate the real-world efficacy and safety of pembrolizumab in combination with chemotherapy in patients with metastatic MpTNBC. Methods: Within the CEBCC-101 real-world evidence program, a multinational, multicenter retrospective study collecting data from 20 oncology centers across Central Europe, we performed a predefined subanalysis restricted to patients with histologically confirmed metaplastic MpTNBC treated with first-line pembrolizumab plus chemotherapy in routine practice (outside clinical trials). Among 178 women with mTNBC included in CEBCC-101, 14 MpTNBC cases (7.9%) were identified across 9 oncology centers and constituted the study population for the present analysis. Treatment was initiated in Poland, the Czech Republic and Slovakia between September 2022 and June 2025. Safety was assessed as the incidence and severity of treatment-emergent adverse events (AEs), graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Results: The median age at treatment initiation was 59.7 years (range, 33.1–81.0). The median follow-up was 14.0 months (range, 7.5–20.4). At data cutoff, 13 patients had discontinued treatment due to disease progression (n = 11) or treatment-related toxicity (n = 2), while one patient remained on therapy; 11 patients had died. Objective response rate (ORR) was observed in 7 of 14 patients (50.0%), and disease control rate (DCR) was achieved in 11 patients (78.6%). Median overall survival (mOS) was 14.1 months, with 6-, 12-, and 18-month OS rates of 100.0%, 64.3%, and 40.2%, respectively. Median progression-free survival (mPFS) was 6.0 months, with corresponding PFS rates of 50.0%, 14.3%, and 7.1%. Grade ≥2 AEs occurred in 12 patients (85.7%). Grade 3 toxicity was observed in 6 (42.9%), with no grade 4–5 events reported. The most frequent AEs were chemotherapy-related, predominantly neutropenia and peripheral neuropathy. Conclusions: This first international real-world series evaluates pembrolizumab in combination with chemotherapy in patients with metastatic MpTNBC. mPFS and mOS observed in this real-world cohort were markedly shorter than those reported in the phase III KEYNOTE-355 trial, most likely reflecting the exceptionally aggressive clinical course of MpTNBC. The safety profile of treatment was acceptable. These findings underscore the need for further prospective studies and international collaboration in rare breast cancer subtypes.
2026-04-09 | Chemotherapy is associated with differential survival outcomes in apocrine carcinoma: A nationwide cohort study from the Japanese National Clinical Database-Breast Cancer Registry.
Apocrine carcinoma (AC) is a rare breast cancer subtype, and the benefit of adjuvant chemotherapy for early-stage disease remains uncertain. Prior studies suggest limited chemotherapy responsiveness in triple-negative AC (TNAC), whereas evidence in pure HER2-positive AC is scarce. This study described outcomes in AC using a national registry and examined outcomes by systemic treatment across subtypes. Using the Japanese National Clinical Database-Breast Cancer Registry, we identified 2817 patients with AC from 2004 to 2019. Patients were categorized as pure HER2 AC or TNAC. The primary endpoint was distant metastasis-free survival (DMFS); overall survival (OS) was also assessed. Survival outcomes were analyzed using Kaplan-Meier and Cox models. Adjuvant chemotherapy was associated with longer DMFS in the overall cohort (hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.51-0.96). Subtype-specific analyses showed significantly longer DMFS (HR, 0.26; 95%CI, 0.12-0.57) and OS (HR, 0.18; 95%CI, 0.06-0.57) in patients who received chemotherapy in the pure HER2 AC group; 5-year DMFS was 96.1% with chemotherapy versus 86.8% without. In contrast, no significant association between chemotherapy and DMFS (HR, 0.84; 95%CI, 0.60-1.18) or OS (HR, 0.84; 95%CI, 0.55-1.28) was observed in TNAC, with similar 5-year DMFS with and without chemotherapy (91.1% vs. 89.2%). In this large population-based cohort of early-stage AC, the association between adjuvant chemotherapy and outcomes differed by subtype. Chemotherapy was associated with better outcomes in pure HER2 AC, whereas no clear association was observed in TNAC. These findings suggest that treatment strategies for AC may need to consider subtype-specific differences.
2026-03-11 | Mucinous Micropapillary Carcinoma of Breast in a Developing World Setting: Case Series With Clinicopathological Insights and Survival Analysis From a Tertiary Care Hospital.
Mucinous micropapillary carcinoma breast (MMPC) is one of the rarest subtypes of breast cancer (BC) with clinicopathologic features correlated with poor prognosis. We are aimed at identifying MMPC cases and correlate them with histopathological features, overall survival (OS), and recurrence-free survival (RFS). We retrospectively identified cases of MMPC from our institutional repository from 2017 to 2022. Data were collected regarding age, stage of BC at the time of diagnosis, tumor size, lymphovascular invasion (LVI), extranodal extension (ENE), lymph node (LN) metastasis, tumor biology, recurrence, and OS. Quantitative variables are calculated as median with range (IQR), whereas qualitative variables are presented in percentages. Nine MMPC cases were reported in the last 6 years, with a median age at diagnosis of 49 years. At diagnosis, 66.67% (6/9) were Stage III followed by Stage II; the average tumor size was 4.5 cm and the majority of tumors were Grade II (77.78%) followed by Grade III. LVI was seen in 66.67%, ENE in 33.33%, and LN metastases in 66.67%. Estrogen receptor (ER)/progesterone receptor (PR) was positive in 77.78%. The OS was 7/9 (77.78%) at the median follow-up of 3.5 years; recurrence was reported in two patients with an RFS of 77.78% (7/9). Our results demonstrate that MMPC is a rare entity that presented at a younger age with more advanced disease. Patients presented with larger tumor size, intermediate- to high-grade tumor morphology, LVI, ENE, and LN metastasis. These tumors also overexpressed ER and PR. Despite this, clinical outcomes in our cohort were relatively favorable, which is also reflected in OS (77.78%) and RFS (77.78%) at a median follow-up of 3.5 years.
2025-08-21 | Immunotherapy in rare histologies of breast cancer: challenges, opportunities, and future perspectives.
Immunotherapy has transformed the management of several malignancies, yet its role in rare breast cancer histologies remains poorly defined due to limited research and few dedicated clinical trials. This review critically assesses current knowledge and emerging opportunities for immunotherapy in these uncommon breast cancer subtypes. Rare breast cancer histologies exhibit heterogeneous immunogenicity, including variable expression of programmed death-ligand 1 (PD-L1), differing levels of tumor-infiltrating lymphocytes (TILs), and distinct mutational burdens. Recent studies highlight potential immunotherapy responsiveness in metaplastic, invasive lobular, apocrine, and other rare breast cancer types, though predictive biomarkers like PD-L1 and tumor mutational burden (TMB) alone appear insufficient. Currently, only two clinical trials specifically target rare breast cancer histologies, emphasizing significant knowledge gaps. The effectiveness of immunotherapy in rare breast cancer histologies remains limited, likely due to inadequate patient selection using current biomarkers such as PD-L1 and TMB. Further research must focus on refining predictive biomarkers to better identify patients likely to from immunotherapy and enhance outcomes in these challenging clinical settings.
cell therapies
2023-03-31 | Data from Patient-Derived Triple-Negative Breast Cancer Organoids Provide Robust Model Systems That Recapitulate Tumor Intrinsic Characteristics
<div>Abstract<p>Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer with poor patient outcomes, highlighting the unmet clinical need for targeted therapies and better model systems. Here, we developed and comprehensively characterized a diverse biobank of normal and breast cancer patient-derived organoids (PDO) with a focus on TNBCs. PDOs recapitulated patient tumor intrinsic properties and a subset of PDOs can be propagated for long-term culture (LT-TNBC). Single cell profiling of PDOs identified cell types and gene candidates affiliated with different aspects of cancer progression. The LT-TNBC organoids exhibit signatures of aggressive MYC-driven, basal-like breast cancers and are largely comprised of luminal progenitor (LP)-like cells. The TNBC LP-like cells are distinct from normal LPs and exhibit hyperactivation of NOTCH and MYC signaling. Overall, this study validates TNBC PDOs as robust models for understanding breast cancer biology and progression, paving the way for personalized medicine and tailored treatment options.</p>Significance:<p>A comprehensive analysis of patient-derived organoids of TNBC provides insights into cellular heterogeneity and mechanisms of tumorigenesis at the single-cell level.</p></div>
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Drug Discovery Landscape
2 orphan drug designations for Rare malignant breast tumor, including 2 approved therapies.
2 orphan drug designations for Rare malignant breast tumor, including 2 approved therapies.
Drug | Therapy type | Orphan designation | Clinical trial status | Sponsor |
|---|---|---|---|---|
Epirubicin [Ellence] | small molecules | FDA | Approved | Pharmacia & Upjohn Company |
Exemestane [Aromasin] | small molecules | FDA | Approved | Pharmacia & Upjohn |
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