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Background Metaplastic breast cancer remains poorly characterized given its rarity and heterogeneity. The majority of metaplastic breast cancers demonstrate a phenotype of triple-negative breast cancer; however, differences in clinical outcomes between metaplastic breast cancer and triple-negative breast cancer in the era of third-generation chemotherapy remain unclear. Methods We compared the clinical outcomes between women with metaplastic breast cancer and women with triple-negative breast cancer diagnosed between 1994 and 2014. Metaplastic breast cancer patients were matched 1:3 to triple-negative breast cancer patients by stage and age at diagnosis. Distant disease-free survival (DDFS) and overall survival (OS) were estimated using Kaplan Meier methods and Cox proportional hazard regression models. Immune checkpoint markers were characterized by immunohistochemistry in a subset of samples. Results Forty-four metaplastic breast cancer patients (stage I 14%; stage II 73%; stage III 11%; stage IV 2%) with an average age of 55.4 (± 13.9) years at diagnosis. Median follow-up for the included metaplastic breast cancer and triple-negative breast cancer patients (n = 174) was 2.8 (0.1–19.0) years. The DDFS and OS between matched metaplastic breast cancer and triple-negative breast cancer patients were similar, even when adjusting for clinical covariates (DDFS: HR = 1.64, p = 0.22; OS: HR = 1.64, p = 0.26). Metaplastic breast cancer samples (n = 27) demonstrated greater amount of CD163 in the stroma (p = 0.05) and PD-L1 in the tumor (p = 0.01) than triple-negative breast cancer samples (n = 119), although more triple-negative breast cancer samples were positive for CD8 in the tumor than metaplastic breast cancer samples (p = 0.02). Conclusions Patients with metaplastic breast cancer had similar outcomes to those with triple-negative breast cancer based on DDFS and OS. The immune checkpoint marker profile of metaplastic breast cancers in this study may prove useful in future studies attempting to demonstrate an association between immune profile and survival.

Highlights • The role of radiotherapy (RT) in prognosis of metaplastic breast cancer remains controversial. • The effect of molecular subtype on treatment and prognosis is unclear. • Our study took the variables with difference in multivariate model into adjusted kaplan–Meier analysis. • Adjusted model showed that triple-negative but not HER2-positive or HR-positive patients receiving RT had a superior prognosis ., Background Metaplastic breast cancer (MBC) is a rare and aggressive subtype of breast. However, the effect of molecular subtype on treatment and prognosis of MBC remains unclear. Patients and methods The Surveillance, Epidemiology, and End Results database was used to analyze patients with MBC between 2010 and 2016. Molecular subtype was stratified to TN group (ER and PR-/HER2-), HER2 group (ER and PR-/HER2+, ER/PR+ and HER2+), and HR group (ER/PR+ and HER2-). The breast cancer-specific survival (BCSS) differences were estimated using multivariate Cox regression model and Kaplan-Meier curves. Results We included 1665 patients with median follow-up time of 27 months (range 0–83 months). 1154 (69.3%), 65 (3.9%), and 446 (26.8%) patients presented in TN group, HER2 group, and HR group, respectively. On multivariate Cox analysis, the prognosis was related to age, tumor size, regional node metastasis, and surgery. Molecular subtype remained no impact on BCSS. Radiotherapy (RT) was associated with better prognosis. Patients cannot benefit from chemotherapy. In Kaplan-Meier curve, triple-negative (P = 0.047) and HR-positive (P = 0.006) patients receiving RT had a superior BCSS than that not RT. HER2-positive patients cannot benefit from RT. However, adjusted Kaplan-Meier survival model showed that triple-negative (P = 0.019) but not HER2-positive (P = 0.575) or HR-positive (P = 0.574) patients receiving RT had a superior BCSS than that not RT. Conclusions Molecular subtype is not associated with the better prognosis of MBC. Patients could benefit from RT. However, triple-negative but not HR-positive or HER2-positive patients have superior survival after receiving RT.

Background: Metaplastic breast cancer (MetBC) represents a therapeutic challenge. We evaluated the impact of clinicopathological characteristics and treatment modalities on outcomes among MetBC patients treated at our center. Methods: Women with stage I-III MetBC were reviewed from our database from 2005-2018. Kaplan-Meier method was used to calculate locoregional-failure-free survival (LRFFS), overall-survival (OS) and distant-metastases-free survival (DMFS). We assessed associations with survival outcomes by log-rank tests. Multivariate Cox proportional-hazards models were used to identify independent predictors of LRFFS, OS and DMFS. Results: 81 patients were eligible for the study. Median age at diagnosis was 48 years. 90.1% had G-III tumors, 64.2% were pathologically node negative and lympho-vascular invasion (LVI) was absent in 72.8%. 67.8% were triple negative, and 7.4% were HER2-neu positive. Most (66.7%) patients underwent mastectomy. Free margins were achieved in the entire cohort, however, 17.3% had close margin (5 cm, nodal involvement and LVI correlated with worse OS, ( P = .019, P = .021, P = .028, respectively). There were no survival differences with respect to age, triple negativity, and morphologic subtype. Conclusion: We report the largest single institutional series on MetBC in the Middle East region. MetBC confers worse survival outcomes, and more aggressive local and systemic treatment strategies should be investigated.

Triple-negative breast cancer is a heterogeneous disease with different molecular and histological subtypes. The Androgen receptor is expressed in a portion of triple-negative breast cancer cases and the activation of the androgen receptor pathway is thought to be a molecular subtyping signature as well as a therapeutic target for triple-negative breast cancer. Thus, identification of the androgen receptor pathway status is important for both molecular characterization andclinical management. In this study, we investigate the expression of the androgen receptor pathway in metaplastic breast cancer and luminal androgen receptor subtypes of triple-negative breast cancer and found that the androgen receptor pathway was downregulated in metaplastic breast cancer compared to luminal androgen receptor subtype. Using random forest, we found that the two subtypes of breast cancer can be molecularly classified with the gene expression of the androgen receptor pathway.

RESUMEN El carcinoma metaplásico de mama es un tipo de cáncer infiltrante que asemeja un carcinoma de alto grado histológico, pero cuya incidencia es muy baja (< 1%). Desde el punto de vista anatomopatológico presenta un componente mixto epitelial y mesenquimal; siendo lo más característico su comportamiento clínico altamente agresivo junto con unas características anatomopatológicas, inmunohistoquímicas concordantes, como son el HER2/neu negativo, los receptores hormonales negativos, el tamaño tumoral grande y el alto grado histológico. Por todo ello, resulta de especial interés conocer esta entidad, con la finalidad de realizar un diagnóstico preciso y llevar a cabo un tratamiento adecuado en estas pacientes. En el presente artículo se presenta la revisión de dos casos clínicos de cáncer de mama metaplásico, diagnosticados y tratados en nuestro Hospital durante el año 2015 y 2018. ABSTRACT The metaplastic breast cancer is a subtype of an infiltranting breast cancer and it's usually high grade. However it is a rare subtype of cancer (incidence

Highlights • LGASC is an uncommon form of triple-negative metaplastic breast carcinoma. • Imaging, FNAC, & CNBx are usually indeterminate with no pathognomonic features. • Histopathology is the gold standard for definitive diagnosis. • Relationship between LGASC and benign mimickers (SAN, CSL) continues to evolve. • LGASC is likely multicentric, thus mastectomy is the recommended management., Introduction Low-grade adenosquamous carcinoma (LGASC) is a rare, unique variant of metaplastic breast carcinoma, characterized by clinical indolence and low-grade cytomorphology. Being clinically asymptomatic with indefinite imaging characteristics, diagnosis is solely dependent on histopathology. Presentation of Case A 68-year-old woman presented to the Breast Health Center with mammogram-detected left-sided retroareolar calcifications. She had a three-year history of non-progressive bilateral nipple inversion, and was otherwise asymptomatic. Left breast biopsy revealed atypical metaplastic squamous epithelial cells. Subsequently a wire-guided lumpectomy diagnosed a syringomatous adenoma of the nipple. A surveillance MRI identified a contralateral breast lesion, which on core biopsy showed an atypical adenosquamous lesion. Bilateral central mastectomies with bilateral sentinel node biopsies were undertaken. Histopathological review of both breast specimens confirmed the unique features of adenosquamous carcinoma identified by an infiltrative pattern of small rounded compressed angulated glands with squamous differentiation and low-grade cytomorphology. The tumors were triple negative [ER, PR, HER2]. The sentinel lymph nodes were negative. Conclusion Bilateral synchronous LGASC of the breasts is exceedingly uncommon and remains a diagnostic and therapeutic challenge. Despite being triple negative, due to its indolent behavior, recognition of this unusual primary breast malignancy is important as it has a more favorable prognosis. Yet, due to its rarity, there are no guidelines for best practice management regarding the role of adjuvant therapy.

Breast cancer encompasses a collection of different diseases characterized by different biological and pathological features, clinical presentation, response to treatments, clinical behavior, and outcome. On the basis of cell morphology, growth, and architecture patterns, breast cancer can be classified in up to 21 distinct histological types. Breast cancer special types, including the classic lobular invasive carcinoma, represent 25% of all breast cancers. The histological diversity of breast carcinomas has relevant prognostic implications. Indeed, the rare breast cancer group includes subtypes with very different prognoses, ranging from the tubular carcinoma, associated with an indolent clinical course, to metaplastic cancer, whose outcome is generally unfavorable. New approaches based on gene expression profiling allow the identification of molecularly defined breast cancer classes, with distinct biological features and clinical behavior. In clinical practice, immunohistochemical classification based on the expression of human epidermal growth factor receptor 2 and Ki67 is applied as a surrogate of the intrinsic molecular subtypes. However, the identification of intrinsic molecular subtypes were almost completely limited to the study of ductal invasive breast cancer. Moreover, some good-prognosis triple-negative histotypes, on the basis of gene expression profiling, can be classified among the poor-prognosis group. Therefore, histopathological classification remains a crucial component of breast cancer diagnosis. Special histologies can be very rare, and the majority of information on outcome and treatments derives from small series and case reports. As a consequence, clear recommendations about clinical management are still lacking. In this review, we summarize current knowledge about rare breast cancer histologies.

Aim of the study: Metaplastic breast carcinomas (MBC) are a rare group of cancers, accounting for about 1% of all breast cancers. The study presents a case series of MBC patients diagnosed, treated and followed up in one healthcare center. Material and methods: The study group comprised 18 women at the median age of 63 years. The most common carcinoma type in the study group was MBC with squamous epithelial differentiation (56%). Estrogen receptor expression was identified in one patient. No steroid or HER2 receptor expression was found in the remaining patients. We analyzed recurrence and survival rates in relation to clinical and therapeutic factors by using the Kaplan-Meier method. Results: A significantly longer overall survival time was noted among patients treated with adjuvant radiation therapy, p = 0.018. No other factors had a significant influence on survival. Because of the small size of the study group, results obtained in the study should be treated with caution.

Little is known about mutational landscape of rare breast cancer (BC) subtypes. The aim of the study was to apply next generation sequencing to three different subtypes of rare BCs in order to identify new genes related to cancer progression. We performed whole exome and targeted sequencing of 29 micropapillary, 23 metaplastic, and 27 pleomorphic lobular BCs. Micropapillary BCs exhibit a profile comparable to common BCs: PIK3CA, TP53, GATA3, and MAP2K4 were the most frequently mutated genes. Metaplastic BCs presented a high frequency of TP53 (78 %) and PIK3CA (48 %) mutations and were recurrently mutated on KDM6A (13 %), a gene involved in histone demethylation. Pleomorphic lobular carcinoma exhibited high mutation rate of PIK3CA (30 %), TP53 (22 %), and CDH1 (41 %) and also presented mutations in PYGM, a gene involved in glycogen metabolism, in 8 out of 27 samples (30 %). Further analyses of publicly available datasets showed that PYGM is dramatically underexpressed in common cancers as compared to normal tissues and that low expression in tumors is correlated with poor relapse-free survival. Immunohistochemical staining on formalin-fixed paraffin-embedded tissues available in our cohort of patients confirmed higher PYGM expression in normal breast tissue compared to equivalent tumoral zone. Next generation sequencing methods applied on rare cancer subtypes can serve as a useful tool in order to uncover new potential therapeutic targets. Sequencing of pleomorphic lobular carcinoma identified a high rate of alterations in PYGM. These findings emphasize the role of glycogen metabolism in cancer progression.

Metaplastic carcinoma of the breast is an uncommon type of malignancy that is aggressive but can mimic other benign breast neoplastic processes on imaging. We present a case of a young female patient who presented with a rapidly progressing metaplastic carcinoma with osteoclastic giant cells subtype. There have been only very rare published reports of this pathologic subtype of metaplastic carcinoma containing osteoclastic giant cells.

Rationale: Low-grade adenosquamous carcinoma (LGASC) is a rare subtype of metaplastic breast carcinoma which is generally recognized as a characteristic subgroup of triple-negative breast cancers previously. However, in this study, we reported for the first time a case of LGASC with hormone receptors expression. Patient concerns: Pathological analysis of breast tumor specimen obtained by a 42-year-old female patient was performed. Morphologically, it composed of glandular structures with scattered squamous differentiation accompanied by haphazard arrangement of spindle cell stroma. Immunohistochemically, all myoepithelial and squamous differentiation markers showed typical LGASC positive or negative staining pattern. Interestingly, we found that normally aberrant hormone receptors were reactivated in this case. To our knowledge, this is the first report of a hormone receptor-positive LGASC. Apart from this, in the extended resection sample, we found scattered squamous metaplasia and florid adenosquamous proliferation (ASP). Meanwhile, it was positive for CD44 variant isoforms (CD44v), which is a breast cancer stem cell (CSC) marker, and expressed in LGASC, squamous metaplasia, and ASP. Diagnosis: LGASC with hormone receptors expression. Interventions: The breast-extended local excision and axillary lymph node dissection were performed. Outcomes: The patient was free of local recurrence and distant metastasis 6 months after surgical resection. Lessons: We herein report the first case of LGASC with immunoreactivity for hormone receptors, expanding its profile of immunophenotypes. CD44v may play an important role in the transition of LGASC precursor lesions into malignant processes, which may serve as a therapeutic target in LGASC.

Metaplastic carcinoma of the breast is a rare, aggressive form of cancer occurring in less than 1% of all breast cancers. Spindle cell carcinoma is a rare variant of the metaplastic carcinoma seen in less than 10% of such cases. The prognosis of spindle cell breast cancers is poor, hence aggressive treatment with surgery, chemotherapy and/or radiation is required. Here we report a case of a 62-year-old female with metastatic metaplastic breast cancer to the lungs.

Carcinosarcoma of the breast represents a ductal carcinoma which consists sarcoma like component. Both malign epithelial and malign mesenchymal elements exist together in the breast carcinosarcoma. Glandular epithelium differentiates into non-glandular mesenchymal tissue, a process called metaplasia. Metaplastic breast malignancy is a rare type of the breast cancer, moreover carcinosarcoma is the rarest subtype which is less than 1% of the whole breast cancers. There are limited studies and case reports of carcinosarcoma in literature. Fourty-four aged woman applied to breast diseases polyclinic with palpable mass on her left breast. We evaluated the findings of the physical examination, mammography and ultrasound. On radiological evaluation we determined a lobulated complex mass with solid and cystic components. Histopathological examination resulted as carcinosarcoma. Lumpectomy and axillary dissection were performed. One axillary lymph node was metastatic out of 16 lymph nodes. There were no distant metastases. Our purpose is to define the radiologic findings about this rare tumour and to review the literature., Meme karsinosarkomu, sarkom benzeri bileşeni bulunan duktal tip karsinomayı ifade eden, malin epitelyal vemalin mezenkimal elemanların bir arada bulunduğu bir malinitedir. Glandüler epitelin glandüler olmayanmezenşimal dokuya farklanmasıyla ortaya çıkan ve seyrek görülen metaplastik meme kanserlerinin en seyrekgörülen alt tipidir. Tüm meme malinitelerinin %1'inden azını oluşturur. Literatürde karsinosarkomun radyolojiközelliklerinin değerlendirildiği sınırlı sayıda çalışma bulunmaktadır. Hastanemiz meme hastalıkları polikliniğinesol memede ele gelen kitle yakınmasıyla başvuran 44 yaşında kadın hastada fizik bakı, mamografi veultrasonografi bulguları değerlendirildi. Mamografi ve ultrasonografide lobüle, karma solid ve kistik alanlariçeren kitle izlendi. Histopatolojik olarak karsinosarkom tanısı alan olguda parsiyel mastektomi ve aksillerdiseksiyon yapıldı. Aksilladan çıkartılan 16 lenf nodunun biri metastatikti ve uzak metastaz saptanmadı. Bizimamacımız, nadir görülen bu tümörlerde radyolojik bulguları tanımlamak ve literatürü gözden geçirmektir

Metaplastic breast carcinoma (MBC) is an uncommon malignancy characterized by the co-existence of two or more cellular types, commonly a mixture of epithelial and mesenchymal components. A case of a female patient aged 46 years with MBC (carcinosarcoma) is presented, including mammographic, ultrasonic, gross examination, and pathological findings. After undergoing modified radical mastectomy of the left breast and subsequent six courses of adjuvant chemotherapy and endocrine therapy, the patient is now doing well with no recurrence and metastasis. Conventional treatments for invasive ductal carcinoma (IDC) may appear to be less effective. Patients with MBC would be appropriate candidates for innovative or targeted therapy regimens.

Background Epidemiologic data indicates that Asian diets, which are high in soy protein, reduce a women’s risk of developing breast cancer. However, it has been difficult to dissociate the benefits of soy from other variables including environmental and lifestyle factors. Since prospective studies in humans would take decades to complete, rodent models provide a valuable research alternative. Methods In this study, MTB-IGFIR transgenic mice, which develop mammary tumors resulting from overexpression of the type I insulin-like growth factor receptor (IGF-IR), were utilized. MTB-IGFIR mice were fed a soy-based or casein-based diet throughout all stages of development to reflect soy exposure in Asian cultures. Mammary tumors were initiated at 2 different developmental stages by commencing IGF-IR transgene expression either during puberty or in adult mice. Results MTB-IGFIR mice fed a soy-based diet displayed increased tumor incidence and accelerated tumor onset compared to MTB-IGFIR mice fed a casein diet. Two markers of estrogen receptor signaling, Pgr and Areg, were elevated in mammary tissue from mice fed the soy diet compared to mice fed the casein diet suggesting that high levels of soy may promote mammary tumor development through acting as an estrogen receptor agonist. Mammary tumors from mice fed a soy diet more frequently expressed metaplastic markers such as cytokeratins 5 and 14 as well as p63 and displayed reduced lung metastases compared to mammary tumors from mice fed a casein diet. Conclusions Diets consisting of very high levels of soy protein promote mammary tumor development and decrease tumor latency possibly through activating estrogen receptor signaling. Additional studies are required to determine whether a more moderate amount of dietary soy can inhibit oncogene-induced mammary tumorigenesis. Electronic supplementary material The online version of this article (doi:10.1186/s12885-015-1037-z) contains supplementary material, which is available to authorized users.