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Genes & Diseases Jun 2018As the most commonly occurring cancer in women worldwide, breast cancer poses a formidable public health challenge on a global scale. Breast cancer consists of a group... (Review)
Review
As the most commonly occurring cancer in women worldwide, breast cancer poses a formidable public health challenge on a global scale. Breast cancer consists of a group of biologically and molecularly heterogeneous diseases originated from the breast. While the risk factors associated with this cancer varies with respect to other cancers, genetic predisposition, most notably mutations in or gene, is an important causative factor for this malignancy. Breast cancers can begin in different areas of the breast, such as the ducts, the lobules, or the tissue in between. Within the large group of diverse breast carcinomas, there are various denoted types of breast cancer based on their invasiveness relative to the primary tumor sites. It is important to distinguish between the various subtypes because they have different prognoses and treatment implications. As there are remarkable parallels between normal development and breast cancer progression at the molecular level, it has been postulated that breast cancer may be derived from mammary cancer stem cells. Normal breast development and mammary stem cells are regulated by several signaling pathways, such as estrogen receptors (ERs), HER2, and Wnt/β-catenin signaling pathways, which control stem cell proliferation, cell death, cell differentiation, and cell motility. Furthermore, emerging evidence indicates that epigenetic regulations and noncoding RNAs may play important roles in breast cancer development and may contribute to the heterogeneity and metastatic aspects of breast cancer, especially for triple-negative breast cancer. This review provides a comprehensive survey of the molecular, cellular and genetic aspects of breast cancer.
PubMed: 30258937
DOI: 10.1016/j.gendis.2018.05.001 -
Clinical Breast Cancer Feb 2021Immune cells are present in normal breast tissue and in breast carcinoma. The nature and distribution of the immune cell subtypes in these tissues are reviewed to... (Review)
Review
Immune cells are present in normal breast tissue and in breast carcinoma. The nature and distribution of the immune cell subtypes in these tissues are reviewed to promote a better understanding of their important role in breast cancer prevention and treatment. We conducted a review of the literature to define the type, location, distribution, and role of immune cells in normal breast tissue and in in situ and invasive breast cancer. Immune cells in normal breast tissue are located predominantly within the epithelial component in breast ductal lobules. Immune cell subtypes representing innate immunity (NK, CD68, and CD11c cells) and adaptive immunity (most commonly CD8, but CD4 and CD20 as well) are present; CD8 cells are the most common subtype and are primarily effector memory cells. Immune cells may recognize neoantigens and endogenous and exogenous ligands and may serve in chronic inflammation and immunosurveillance. Progression to breast cancer is characterized by increased immune cell infiltrates in tumor parenchyma and stroma, including CD4 and CD8 granzyme B cytotoxic T cells, B cells, macrophages and dendritic cells. Tumor-infiltrating lymphocytes in breast cancer may serve as prognostic indicators for response to chemotherapy and for survival. Experimental strategies of adoptive transfer of breast tumor-infiltrating lymphocyte may allow regression of metastatic breast cancer and encourage development of innovative T-cell strategies for the immunotherapy of breast cancer. In conclusion, immune cells in breast tissues play an important role throughout breast carcinogenesis. An understanding of these roles has important implications for the prevention and the treatment of breast cancer.
Topics: Breast; Breast Neoplasms; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Carcinoma, Ductal, Breast; Female; Humans; Lymphocytes, Tumor-Infiltrating; Tumor Microenvironment
PubMed: 32893093
DOI: 10.1016/j.clbc.2020.06.011 -
BioRxiv : the Preprint Server For... Apr 2023The adult human breast comprises an intricate network of epithelial ducts and lobules that are embedded in connective and adipose tissue. While previous studies have...
The adult human breast comprises an intricate network of epithelial ducts and lobules that are embedded in connective and adipose tissue. While previous studies have mainly focused on the breast epithelial system, many of the non-epithelial cell types remain understudied. Here, we constructed a comprehensive Human Breast Cell Atlas (HBCA) at single-cell and spatial resolution. Our single-cell transcriptomics data profiled 535,941 cells from 62 women, and 120,024 nuclei from 20 women, identifying 11 major cell types and 53 cell states. These data revealed abundant pericyte, endothelial and immune cell populations, and highly diverse luminal epithelial cell states. Our spatial mapping using three technologies revealed an unexpectedly rich ecosystem of tissue-resident immune cells in the ducts and lobules, as well as distinct molecular differences between ductal and lobular regions. Collectively, these data provide an unprecedented reference of adult normal breast tissue for studying mammary biology and disease states such as breast cancer.
PubMed: 37163043
DOI: 10.1101/2023.04.22.537946 -
Chronic Diseases and Translational... Mar 2016Granulomatous lobular mastitis is an unusual breast benign inflammatory disorder with unknown aetiology. It is generally emerged with the clinical symptoms of breast... (Review)
Review
Granulomatous lobular mastitis is an unusual breast benign inflammatory disorder with unknown aetiology. It is generally emerged with the clinical symptoms of breast mass, abscess, inflammation and mammary duct fistula. The diagnosis is made by histopathology with a chronic non-necrotizing granulomatous inflammation in lobules of the breast tissue as the microscopic feature. Therapy of granulomatous lobular mastitis consists of surgical, medication treatment or combination of both, but now researches suggest that observational management is an acceptable treatment.
PubMed: 29063020
DOI: 10.1016/j.cdtm.2016.02.004 -
Cancers Dec 2022Transgender women experience gender dysphoria due to a gender assignment at birth that is incongruent with their gender identity. Transgender people undergo different... (Review)
Review
Transgender women experience gender dysphoria due to a gender assignment at birth that is incongruent with their gender identity. Transgender people undergo different surgical procedures and receive sex steroids hormones to reduce psychological distress and to induce and maintain desired physical changes. These persons on feminizing hormones represent a unique population to study the hormonal effects on breast development, to evaluate the risk of breast cancer and perhaps to better understand the precise role played by different hormonal components. In MTF (male to female) patients, hormonal treatment usually consists of antiandrogens and estrogens. Exogenous hormones induce breast development with the formation of ducts and lobules and an increase in the deposition of fat. A search of the existing literature dedicated to hormone regimens for MTF patients, their impact on breast tissue (incidence and type of breast lesions) and breast cancer risk provided the available information for this review. The evaluation of breast cancer risk is currently complicated by the heterogeneity of administered treatments and a lack of long-term follow-up in the great majority of studies. Large studies with longer follow-up are required to better evaluate the breast cancer risk and to understand the precise mechanisms on breast development of each exogenous hormone.
PubMed: 36612241
DOI: 10.3390/cancers15010245 -
Journal of Experimental & Clinical... Apr 2023Despite overall improvement in breast cancer patient outcomes from earlier diagnosis and personalised treatment approaches, some patients continue to experience...
BACKGROUND
Despite overall improvement in breast cancer patient outcomes from earlier diagnosis and personalised treatment approaches, some patients continue to experience recurrence and incurable metastases. It is therefore imperative to understand the molecular changes that allow transition from a non-aggressive state to a more aggressive phenotype. This transition is governed by a number of factors.
METHODS
As crosstalk with extracellular matrix (ECM) is critical for tumour cell growth and survival, we applied high throughput shRNA screening on a validated '3D on-top cellular assay' to identify novel growth suppressive mechanisms.
RESULTS
A number of novel candidate genes were identified. We focused on COMMD3, a previously poorly characterised gene that suppressed invasive growth of ER + breast cancer cells in the cellular assay. Analysis of published expression data suggested that COMMD3 is normally expressed in the mammary ducts and lobules, that expression is lost in some tumours and that loss is associated with lower survival probability. We performed immunohistochemical analysis of an independent tumour cohort to investigate relationships between COMMD3 protein expression, phenotypic markers and disease-specific survival. This revealed an association between COMMD3 loss and shorter survival in hormone-dependent breast cancers and in particularly luminal-A-like tumours (ER/Ki67-low; 10-year survival probability 0.83 vs. 0.73 for COMMD3-positive and -negative cases, respectively). Expression of COMMD3 in luminal-A-like tumours was directly associated with markers of luminal differentiation: c-KIT, ELF5, androgen receptor and tubule formation (the extent of normal glandular architecture; p < 0.05). Consistent with this, depletion of COMMD3 induced invasive spheroid growth in ER + breast cancer cell lines in vitro, while Commd3 depletion in the relatively indolent 4T07 TNBC mouse cell line promoted tumour expansion in syngeneic Balb/c hosts. Notably, RNA sequencing revealed a role for COMMD3 in copper signalling, via regulation of the Na/K-ATPase subunit, ATP1B1. Treatment of COMMD3-depleted cells with the copper chelator, tetrathiomolybdate, significantly reduced invasive spheroid growth via induction of apoptosis.
CONCLUSION
Overall, we found that COMMD3 loss promoted aggressive behaviour in breast cancer cells.
Topics: Animals; Mice; Cell Differentiation; Cell Proliferation; Copper; Gene Expression Regulation, Neoplastic; Neoplasms; Signal Transduction
PubMed: 37072858
DOI: 10.1186/s13046-023-02663-8 -
Cancers Feb 2023Breast cancer (BC) is the world's second most frequent malignancy and the leading cause of mortality among women. All in situ or invasive breast cancer derives from... (Review)
Review
Breast cancer (BC) is the world's second most frequent malignancy and the leading cause of mortality among women. All in situ or invasive breast cancer derives from terminal tubulobular units; when the tumor is present only in the ducts or lobules in situ, it is called ductal carcinoma in situ (DCIS)/lobular carcinoma in situ (LCIS). The biggest risk factors are age, mutations in breast cancer genes 1 or 2 (BRCA1 or BRCA2), and dense breast tissue. Current treatments are associated with various side effects, recurrence, and poor quality of life. The critical role of the immune system in breast cancer progression/regression should always be considered. Several immunotherapy techniques for BC have been studied, including tumor-targeted antibodies (bispecific antibodies), adoptive T cell therapy, vaccinations, and immune checkpoint inhibition with anti-PD-1 antibodies. In the last decade, significant breakthroughs have been made in breast cancer immunotherapy. This advancement was principally prompted by cancer cells' escape of immune regulation and the tumor's subsequent resistance to traditional therapy. Photodynamic therapy (PDT) has shown potential as a cancer treatment. It is less intrusive, more focused, and less damaging to normal cells and tissues. It entails the employment of a photosensitizer (PS) and a specific wavelength of light to create reactive oxygen species. Recently, an increasing number of studies have shown that PDT combined with immunotherapy improves the effect of tumor drugs and reduces tumor immune escape, improving the prognosis of breast cancer patients. Therefore, we objectively evaluate strategies for their limitations and benefits, which are critical to improving outcomes for breast cancer patients. In conclusion, we offer many avenues for further study on tailored immunotherapy, such as oxygen-enhanced PDT and nanoparticles.
PubMed: 36900322
DOI: 10.3390/cancers15051532 -
Autopsy & Case Reports Apr 2021Lactating adenoma is a rare benign breast lesion that most often presents as a small (up to 3 cm), solid, well-circumscribed, solitary, painless, mobile, lobulated mass....
Lactating adenoma is a rare benign breast lesion that most often presents as a small (up to 3 cm), solid, well-circumscribed, solitary, painless, mobile, lobulated mass. The highest incidence occurs in primiparous women (20 to 40 years old) during the third trimester of pregnancy. However, in the rare case presented herein, in addition to its giant size (more than 10 centimeters on palpation), this lactating adenoma is distinctive due to the presence of multiple nodules, poorly defined ultrasonographic margins, worrisome radiologic features, growth since early pregnancy, presence of infarction and association with chronic mastitis. From the clinical-radiologic perspective, the differential diagnoses included abscess associated with puerperal mastitis, phyllodes tumor, and galactocele. Biopsy was performed, and pathologic examination revealed the classic characteristics of lactating adenoma with multiple infarcted areas, leading to an unexpected confirmed case of giant lactating adenoma.
PubMed: 33968827
DOI: 10.4322/acr.2021.252