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Critical Reviews in Oncology/hematology May 2024Breast cancer is potentially a lethal disease and a leading cause of death in women. Chemotherapy and radiotherapy are the most frequently used treatment options. Drug... (Review)
Review
Breast cancer is potentially a lethal disease and a leading cause of death in women. Chemotherapy and radiotherapy are the most frequently used treatment options. Drug resistance in advanced breast cancer limits the therapeutic output of treatment. The leading cause of resistance in breast cancer is endocrine and hormonal imbalance, particularly in triple negative and HER2 positive breast cancers. The efflux of drugs due to p-gp's activity is another leading cause of resistance. Breast cancer resistant protein also contributes significantly. Strategies used to combat resistance include the use of nanoparticles to target drug delivery by co-delivery of chemotherapeutic drugs and genes (siRNA and miRNA) that help to down-regulate genes causing resistance. The siRNA is specific and effectively silences p-gp and other proteins causing resistance. The use of chemosensitizers is also effective in overcoming resistance. Chemo-sensitizers sensitize cancer cells to the effects of chemotherapeutic drugs. Novel anti-neoplastic agents such as antibody-drug conjugates and mesenchymal stem cells are also effective tools used to improve the therapeutic response in breast cancer. Similarly, combination of photo/thermal ablation with chemotherapy can act to overcome breast cancer resistance. In this review, we focus on the mechanism of breast cancer resistance and the nanoparticle-based strategies used to combat resistance in breast cancer.
Topics: Humans; Drug Resistance, Neoplasm; Breast Neoplasms; Female; Antineoplastic Agents; Nanoparticles; Drug Delivery Systems; Animals
PubMed: 38615873
DOI: 10.1016/j.critrevonc.2024.104351 -
Cold Spring Harbor Perspectives in... Feb 2011It is now accepted that breast cancer is not a single disease, but instead it is composed of a spectrum of tumor subtypes with distinct cellular origins, somatic... (Review)
Review
It is now accepted that breast cancer is not a single disease, but instead it is composed of a spectrum of tumor subtypes with distinct cellular origins, somatic changes, and etiologies. Gene expression profiling using DNA microarrays has contributed significantly to our understanding of the molecular heterogeneity of breast tumor formation, progression, and recurrence. For example, at least two clinical diagnostic assays exist (i.e., OncotypeDX RS and Mammaprint®) that are able to predict outcome in patients using patterns of gene expression and predetermined mathematical algorithms. In addition, a new molecular taxonomy based upon the inherent, or "intrinsic," biology of breast tumors has been developed; this taxonomy is called the "intrinsic subtypes of breast cancer," which now identifies five distinct tumor types and a normal breast-like group. Importantly, the intrinsic subtypes of breast cancer predict patient relapse, overall survival, and response to endocrine and chemotherapy regimens. Thus, most of the clinical behavior of a breast tumor is already written in its subtype profile. Here, we describe the discovery and basic biology of the intrinsic subtypes of breast cancer, and detail how this interacts with underlying genetic alternations, response to therapy, and the metastatic process.
Topics: Breast Neoplasms; Female; Gene Expression Profiling; Genomics; Humans; Neoplasm Metastasis; Oligonucleotide Array Sequence Analysis; Systems Biology
PubMed: 21047916
DOI: 10.1101/cshperspect.a003293 -
Critical Reviews in Oncogenesis 2013Despite many recent advances, breast cancer remains a clinical challenge. Current issues include improving prognostic evaluation and increasing therapeutic options for... (Review)
Review
Despite many recent advances, breast cancer remains a clinical challenge. Current issues include improving prognostic evaluation and increasing therapeutic options for women whose tumors are refractory to current frontline therapies. Iron metabolism is frequently disrupted in breast cancer, and may offer an opportunity to address these challenges. Iron enhances breast tumor initiation, growth and metastases. Iron may contribute to breast tumor initiation by promoting redox cycling of estrogen metabolites. Up-regulation of iron import and down-regulation of iron export may enable breast cancer cells to acquire and retain excess iron. Alterations in iron metabolism in macrophages and other cells of the tumor microenvironment may also foster breast tumor growth. Expression of iron metabolic genes in breast tumors is predictive of breast cancer prognosis. Iron chelators and other strategies designed to limit iron may have therapeutic value in breast cancer. The dependence of breast cancer on iron presents rich opportunities for improved prognostic evaluation and therapeutic intervention.
Topics: Animals; Breast Neoplasms; Female; Humans; Iron; Neoplasm Staging; Prognosis
PubMed: 23879588
DOI: 10.1615/critrevoncog.2013007784 -
Cancer Metastasis Reviews Jun 2013Cancer is a systemic disease encompassing multiple components of both tumor cells themselves and host stromal cells. It is now clear that stromal cells in the tumor... (Review)
Review
Cancer is a systemic disease encompassing multiple components of both tumor cells themselves and host stromal cells. It is now clear that stromal cells in the tumor microenvironment play an important role in cancer development. Molecular events through which reactive stromal cells affect cancer cells can be defined so that biomarkers and therapeutic targets can be identified. Cancer-associated fibroblasts (CAFs) make up the bulk of cancer stroma and affect the tumor microenvironment such that they promote cancer initiation, angiogenesis, invasion, and metastasis. In breast cancer, CAFs not only promote tumor progression but also induce therapeutic resistance. Accordingly, targeting CAFs provides a novel way to control tumors with therapeutic resistance. This review summarizes the current understandings of tumor stroma in breast cancer with a particular emphasis on the role of CAFs and the therapeutic implications of CAFs. In addition, the effects of other stromal components such as endothelial cells, macrophages, and adipocytes in breast cancer are also discussed. Finally, we describe the biologic markers to categorize patients into a specific and confirmed subtype for personalized treatment.
Topics: Breast Neoplasms; Drug Resistance, Neoplasm; Epigenesis, Genetic; Female; Fibroblasts; Humans; Neoplasm Staging; Prognosis; Stromal Cells; Tumor Microenvironment
PubMed: 23114846
DOI: 10.1007/s10555-012-9415-3 -
Sultan Qaboos University Medical Journal Aug 2020Dermatofibrosarcoma protuberans (DFSP) is a rare, slow-growing mesenchymal neoplasm of the dermis and subcutaneous tissues that has a low-to intermediate-grade... (Review)
Review
Dermatofibrosarcoma protuberans (DFSP) is a rare, slow-growing mesenchymal neoplasm of the dermis and subcutaneous tissues that has a low-to intermediate-grade malignancy. DFSP commonly involves the trunk and extremities, and very rarely the breast skin, mimicking a primary breast neoplasm with few reported cases in the literature. We report a 35-year old female patient who was referred to the Royal Hospital, Muscat, Oman in 2017, with a two-year history of a slow growing left breast lump. Assessment of the breasts with mammography revealed a lobulated lesion in the left-upper-inner quadrant with neither microcalcification nor architectural distortion, mimicking a benign lesion. However, on ultrasound, the lesion had suspicious features with increased vascularity and hence, it was categorised as breast imaging reporting and data system (BIRAD) IV. The patient underwent left breast wide local excision and the histopathological diagnosis was dermatofibrosarcoma protuberans.
Topics: Adult; Biological Mimicry; Breast; Breast Neoplasms; Dermatofibrosarcoma; Female; Humans; Mammography; Oman; Ultrasonography
PubMed: 33110655
DOI: 10.18295/squmj.2020.20.03.019 -
Oncology (Williston Park, N.Y.) Jun 2015Ductal carcinoma in situ (DCIS) is a breast neoplasm with potential for progression to invasive cancer. Management commonly involves excision, radiotherapy, and hormonal... (Review)
Review
Ductal carcinoma in situ (DCIS) is a breast neoplasm with potential for progression to invasive cancer. Management commonly involves excision, radiotherapy, and hormonal therapy. Surgical assessment of regional lymph nodes is rarely indicated except in cases of microinvasion or mastectomy. Radiotherapy is employed for local control in breast conservation, although it may be omitted for select low-risk situations. Several radiotherapy techniques exist beyond standard whole-breast irradiation (ie, partial-breast irradiation [PBI], hypofractionated whole-breast radiation); evidence for these is evolving. We present an update of the American College of Radiology (ACR) Appropriateness Criteria® for the management of DCIS. The ACR Appropriateness Criteria® are evidence-based guidelines for specific clinical conditions, which are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review includes an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi technique) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.
Topics: Antineoplastic Agents, Hormonal; Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Carcinoma, Lobular; Female; Humans; Magnetic Resonance Imaging; Mammography; Mastectomy; Mastectomy, Segmental; Neoplasm Invasiveness; Radiotherapy Dosage; Radiotherapy, Adjuvant; Sentinel Lymph Node Biopsy; Tamoxifen
PubMed: 26089220
DOI: No ID Found -
Current Oncology Reports Feb 2020Oligometastatic breast cancer (OMBC) remains a poorly understood entity for which no standard of care exists at this time. This review will focus on our biologic... (Review)
Review
PURPOSE OF REVIEW
Oligometastatic breast cancer (OMBC) remains a poorly understood entity for which no standard of care exists at this time. This review will focus on our biologic understanding of OMBC and provide an update on current treatment strategies.
RECENT FINDINGS
The introduction of micro RNA expression profiling has advanced our understanding of the biologic underpinnings of OMBC. Although most of the data regarding treatment have come from retrospective studies, there are now prospective randomized trials reporting progression-free survival and overall survival improvements with stereotactic ablative radiotherapy (SABR). Ongoing studies designed to evaluate addition of SABR as well as other novel agents will further develop this field and provide new treatment options. A "cure" for OMBC remains elusive. With further basic research coupled with novel prospective trials, patients will hopefully enjoy increased progression-free survival and overall survival, and ideally a delay to more toxic systemic therapy.
Topics: Antineoplastic Agents; Breast Neoplasms; Female; Humans; Mastectomy; Metastasectomy; MicroRNAs; RNA, Neoplasm; Radiosurgery; Transcriptome
PubMed: 32025905
DOI: 10.1007/s11912-020-0867-2 -
Women's Health (London, England) Jan 2015
Topics: Biomarkers, Tumor; Cooperative Behavior; Drug Discovery; Female; Humans; Molecular Targeted Therapy; Triple Negative Breast Neoplasms
PubMed: 25581048
DOI: 10.2217/whe.14.67 -
BMC Cancer Apr 2018This study aimed to systematically review and to meta-analyse the accuracy of digital breast tomosynthesis (DBT) versus digital mammography (DM) in women with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This study aimed to systematically review and to meta-analyse the accuracy of digital breast tomosynthesis (DBT) versus digital mammography (DM) in women with mammographically dense breasts in screening and diagnosis.
METHODS
Two independent reviewers identified screening or diagnostic studies reporting at least one of four outcomes (cancer detection rate-CDR, recall rate, sensitivity and specificity) for DBT and DM in women with mammographically dense breasts. Study quality was assessed using QUADAS-2. Meta-analysis of CDR and recall rate used a random effects model. Summary ROC curve summarized sensitivity and specificity.
RESULTS
Sixteen studies were included (five diagnostic; eleven screening). In diagnosis, DBT increased sensitivity (84%-90%) versus DM alone (69%-86%) but not specificity. DBT improved CDR versus DM alone (RR: 1.16, 95% CI 1.02-1.31). In screening, DBT + DM increased CDR versus DM alone (RR: 1.33, 95% CI 1.20-1.47 for retrospective studies; RR: 1.52, 95% CI 1.08-2.11 for prospective studies). Recall rate was significantly reduced by DBT + DM in retrospective studies (RR: 0.72, 95% CI 0.64-0.80) but not in two prospective studies (RR: 1.12, 95% CI 0.76-1.63).
CONCLUSION
In women with mammographically dense breasts, DBT+/-DM increased CDR significantly (versus DM) in screening and diagnosis. In diagnosis, DBT+/-DM increased sensitivity but not specificity. The effect of DBT + DM on recall rate in screening dense breasts varied between studies.
Topics: Breast Density; Breast Neoplasms; Early Detection of Cancer; Female; Humans; Mammography; Mass Screening; Odds Ratio; Publication Bias; Quality Assurance, Health Care
PubMed: 29615072
DOI: 10.1186/s12885-018-4263-3 -
American Society of Clinical Oncology... May 2018Metastatic breast cancer continues to be a life-threatening diagnosis that impacts hundreds of thousands of patients around the world. Targeted therapies are usually... (Review)
Review
Metastatic breast cancer continues to be a life-threatening diagnosis that impacts hundreds of thousands of patients around the world. Targeted therapies are usually associated with less toxicity compared with cytotoxic chemotherapies and often induce response or durable disease control in estrogen receptor (ER) and/or HER2+ breast cancers. Drugs that target CDK 4/6 either alone or in combination with endocrine therapy have demonstrated substantial improvements in progression-free survival (PFS) compared with endocrine monotherapy. Most recently, PARP inhibitors have shown longer PFS compared with physician's choice of chemotherapy in BRCA-associated cancers, leading to the first U.S. Food and Drug Administration (FDA) approval of a targeted therapy with the potential to benefit a subgroup of patients with triple-negative breast cancer (TNBC). Finally, newer drug delivery strategies using antibody drug conjugates have also allowed a "targeted approach" to deliver moderate to extremely potent cytotoxins directly to sites of metastatic disease, with less toxicity.
Topics: Antibody-Dependent Cell Cytotoxicity; Antineoplastic Agents; Biomarkers, Tumor; Breast Neoplasms; Combined Modality Therapy; Drug Resistance, Neoplasm; Female; Humans; Immunomodulation; Molecular Targeted Therapy; Mutation; Neoplasm Metastasis; Neoplasm Staging; Polymorphism, Genetic; Protein Kinase Inhibitors; Signal Transduction; Triple Negative Breast Neoplasms
PubMed: 30231328
DOI: 10.1200/EDBK_200715