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lördag 6 januari 2024

Onkologian alueelta: Ductal Ca Mammae Therapy : PubMed haku

 

1,945 results

The Great Immune Escape: Understanding the Divergent Immune Response in Breast Cancer Subtypes.
Onkar SS, Carleton NM, Lucas PC, Bruno TC, Lee AV, Vignali DAA, Oesterreich S. Cancer Discov. 2023 Jan 9;13(1):23-40. doi: 10.1158/2159-8290.CD-22-0475. PMID: 36620880 Free PMC article. Review.Abstract
Breast cancer, the most common type of cancer affecting women, encompasses a collection of histologic (mainly ductal and lobular) and molecular subtypes exhibiting diverse clinical presentation, disease trajectories, treatment options, and outcomes.
 Immunotherapy has revolutionized treatment for some solid tumors but has shown limited promise for breast cancers. In this review, we summarize recent advances in our understanding of the complex interactions between tumor and immune cells in subtypes of breast cancer at the cellular and microenvironmental levels. We aim to provide a perspective on opportunities for future immunotherapy agents tailored to specific features of each subtype of breast cancer. Significance: Although there are currently over 200 ongoing clinical trials testing immunotherapeutics, such as immune-checkpoint blockade agents, these are largely restricted to the triple-negative and HER2+ subtypes and primarily focus on T cells. With the rapid expansion of new in vitro, in vivo, and clinical data, it is critical to identify and highlight the challenges and opportunities unique for each breast cancer subtype to drive the next generation of treatments that harness the immune system.
Fibrosis and cancer: A strained relationship.
Piersma B, Hayward MK, Weaver VM. Biochim Biophys Acta Rev Cancer. 2020 Apr;1873(2):188356. doi: 10.1016/j.bbcan.2020.188356. Epub 2020 Mar 5. PMID: 32147542 Free PMC article. Review.

Abstract
Tumors are characterized by extracellular matrix (ECM) deposition, remodeling, and cross-linking that drive fibrosis to stiffen the stroma and promote malignancy. The stiffened stroma enhances tumor cell growth, survival and migration and drives a mesenchymal transition. A stiff ECM also induces angiogenesis, hypoxia and compromises anti-tumor immunity. Not surprisingly, tumor aggression and poor patient prognosis correlate with degree of tissue fibrosis and level of stromal stiffness. In this review, we discuss the reciprocal interplay between tumor cells, cancer associated fibroblasts (CAF), immune cells and ECM stiffness in malignant transformation and cancer aggression. We discuss CAF heterogeneity and describe its impact on tumor development and aggression focusing on the role of CAFs in engineering the fibrotic tumor stroma and tuning tumor cell tension and modulating the immune response. To illustrate the role of mechanoreciprocity in tumor evolution we summarize data from breast cancer and pancreatic ductal carcinoma (PDAC) studies, and finish by discussing emerging anti-fibrotic strategies aimed at treating cancer. Keywords: CAF; Cancer; ECM; Fibrosis; Mechanoreciprocity.
Mammary gland development.
Macias H, Hinck L. Wiley Interdiscip Rev Dev Biol. 2012 Jul-Aug;1(4):533-57. doi: 10.1002/wdev.35. PMID: 22844349 Free PMC article. Review.
Abstract
The mammary gland develops through several distinct stages. The first transpires in the embryo as the ectoderm forms a mammary line that resolves into placodes. Regulated by epithelial–mesenchymal interactions, the placodes descend into the underlying mesenchyme and produce the rudimentary ductal structure of the gland present at birth. Subsequent stages of development—pubertal growth, pregnancy, lactation, and involution—occur postnatally under the regulation of hormones. Puberty initiates branching morphogenesis, which requires growth hormone (GH) and estrogen, as well as insulin-like growth factor 1 (IGF1), to create a ductal tree that fills the fat pad. Upon pregnancy, the combined actions of progesterone and prolactin generate alveoli, which secrete milk during lactation. Lack of demand for milk at weaning initiates the process of involution whereby the gland is remodeled back to its prepregnancy state. These processes require numerous signaling pathways that have distinct regulatory functions at different stages of gland development. Signaling pathways also regulate a specialized subpopulation of mammary stem cells that fuel the dramatic changes in the gland occurring with each pregnancy. Our knowledge of mammary gland development and mammary stem cell biology has significantly contributed to our understanding of breast cancer and has advanced the discovery of therapies to treat this disease.
Nipple-sparing and skin-sparing mastectomy: Review of aims, oncological safety and contraindications.
Galimberti V, Vicini E, Corso G, Morigi C, Fontana S, Sacchini V, Veronesi P. Breast. 2017 Aug;34 Suppl 1(Suppl 1):S82-S84. doi: 10.1016/j.breast.2017.06.034. Epub 2017 Jun 30. PMID: 28673535 Free PMC article. Review.
Abstract
Skin-sparing (SSM) and nipple-sparing (NSM) mastectomies are relatively new conservative surgical approaches to breast cancer. In SSM most of the breast skin is conserved to create a pocket that facilitates immediate breast reconstruction with implant or autologous graft to achieve a quality cosmetic outcome. NSM is closely similar except that the nipple-areola complex (NAC) is also conserved. Meta-analyses indicate that outcomes for SSM and NSM do not differ from those for non-conservative mastectomies. Recurrence rates in the NAC after NSM are acceptably low (0-3.7%). Other studies indicate that NSM is associated with high patient satisfaction and good psychological adjustment. Indications are carcinoma or DCIS that require mastectomy (including after neoadjuvant chemotherapy). NSM is also suitable for women undergoing risk-reducing bilateral mastectomy. Tumor not less than 2 cm from the NAC is recommended, but may be less important than no evidence of nipple involvement on mandatory intraoperative nipple margin assessment. A positive margin is an absolute contraindication for nipple preservation. Other contraindications are microcalcifications close to the subareolar region and a positive nipple discharge. Complication rates are similar to those for other types of post-mastectomy reconstructions. The main complication of NSM is NAC necrosis, however as surgeon experience matures, frequency declines. Factors associated with complications are voluminous breast, ptosis, smoking, obesity, and radiotherapy. Since the access incision is small, breast tissue may be left behind, so only experienced breast surgeons should do these operations in close collaboration with the plastic surgeon. For breast cancer patients requiring mastectomy, NSM should be the option of choice.
Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis.
Cortazar P, Zhang L et al. Lancet. 2014 Jul 12;384(9938):164-72. doi: 10.1016/S0140-6736(13)62422-8. Epub 2014 Feb 14. PMID: 24529560 Review.
METHODS Abstract Background: Pathological complete response has been proposed as a surrogate endpoint for prediction of long-term clinical benefit, such as disease-free survival, event-free survival (EFS), and overall survival (OS). We had four key objectives: to establish the association between pathological complete response and EFS and OS, to establish the definition of pathological complete response that correlates best with long-term outcome, to identify the breast cancer subtypes in which pathological complete response is best correlated with long-term outcome, and to assess whether an increase in frequency of pathological complete response between treatment groups predicts improved EFS and OS.Methods: We searched PubMed, Embase, and Medline for clinical trials of neoadjuvant treatment of breast cancer. To be eligible, studies had to meet three inclusion criteria: include at least 200 patients with primary breast cancer treated with preoperative chemotherapy followed by surgery; have available data for pathological complete response, EFS, and OS; and have a median follow-up of at least 3 years. We compared the three most commonly used definitions of pathological complete response--ypT0 ypN0, ypT0/is ypN0, and ypT0/is--for their association with EFS and OS in a responder analysis. We assessed the association between pathological complete response and EFS and OS in various subgroups. Finally, we did a trial-level analysis to assess whether pathological complete response could be used as a surrogate endpoint for EFS or OS.Findings: We obtained data from 12 identified international trials and 11 955 patients were included in our responder analysis. Eradication of tumour from both breast and lymph nodes (ypT0 ypN0 or ypT0/is ypN0) was better associated with improved EFS (ypT0 ypN0: hazard ratio [HR] 0·44, 95% CI 0·39-0·51; ypT0/is ypN0: 0·48, 0·43-0·54) and OS (0·36, 0·30-0·44; 0·36, 0·31-0·42) than was tumour eradication from the breast alone (ypT0/is; EFS: HR 0·60, 95% CI 0·55-0·66; OS 0·51, 0·45-0·58). We used the ypT0/is ypN0 definition for all subsequent analyses. The association between pathological complete response and long-term outcomes was strongest in patients with triple-negative breast cancer (EFS: HR 0·24, 95% CI 0·18-0·33; OS: 0·16, 0·11-0·25) and in those with HER2-positive, hormone-receptor-negative tumours who received trastuzumab (EFS: 0·15, 0·09-0·27; OS: 0·08, 0·03, 0·22). In the trial-level analysis, we recorded little association between increases in frequency of pathological complete response and EFS (R(2)=0·03, 95% CI 0·00-0·25) and OS (R(2)=0·24, 0·00-0·70).Interpretation: Patients who attain pathological complete response defined as ypT0 ypN0 or ypT0/is ypN0 have improved survival. The prognostic value is greatest in aggressive tumour subtypes. Our pooled analysis could not validate pathological complete response as a surrogate endpoint for improved EFS and OS.
Breast brachytherapy.
Strnad V, Yashar C. Brachytherapy. 2021 Sep-Oct;20(5):976-983. doi: 10.1016/j.brachy.2020.10.011. Epub 2021 Jan 19. PMID: 33353845 Review.
Abstract
Accelerated partial breast irradiation with brachytherapy is a treatment method with a very low risk profile. In fact, accelerated partial breast irradiation brachytherapy has been proven in randomized trials to have fewer late side effects than whole-breast irradiation. Notably, Grade 3 late side effects are extremely rare, and excellent to good cosmetic results are observed in well over 90% of patients. In this article, published side effects of breast brachytherapy are reviewed and appropriate management discussed.
Tailoring therapies--improving the management of early breast cancer: St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2015.
Coates AS, Winer EP, Goldhirsch A, Gelber RD, Gnant M, Piccart-Gebhart M, Thürlimann B, Senn HJ; Panel Members. Ann Oncol. 2015 Aug;26(8):1533-46. doi: 10.1093/annonc/mdv221. Epub 2015 May 4. PMID: 25939896 Free PMC article.Abstract
The 14th St Gallen International Breast Cancer Conference (2015) reviewed substantial new evidence on locoregional and systemic therapies for early breast cancer. Further experience has supported the adequacy of tumor margins defined as 'no ink on invasive tumor or DCIS' and the safety of omitting axillary dissection in specific cohorts. Radiotherapy trials support irradiation of regional nodes in node-positive disease. Considering subdivisions within luminal disease, the Panel was more concerned with indications for the use of specific therapies, rather than surrogate identification of intrinsic subtypes as measured by multiparameter molecular tests. For the treatment of HER2-positive disease in patients with node-negative cancers up to 1 cm, the Panel endorsed a simplified regimen comprising paclitaxel and trastuzumab without anthracycline as adjuvant therapy. For premenopausal patients with endocrine responsive disease, the Panel endorsed the role of ovarian function suppression with either tamoxifen or exemestane for patients at higher risk. The Panel noted the value of an LHRH agonist given during chemotherapy for premenopausal women with ER-negative disease in protecting against premature ovarian failure and preserving fertility. The Panel noted increasing evidence for the prognostic value of commonly used multiparameter molecular markers, some of which also carried prognostic information for late relapse. The Panel noted that the results of such tests, where available, were frequently used to assist decisions about the inclusion of cytotoxic chemotherapy in the treatment of patients with luminal disease, but noted that threshold values had not been established for this purpose for any of these tests. Multiparameter molecular assays are expensive and therefore unavailable in much of the world. The majority of new breast cancer cases and breast cancer deaths now occur in less developed regions of the world. In these areas, less expensive pathology tests may provide valuable information. The Panel recommendations on treatment are not intended to apply to all patients, but rather to establish norms appropriate for the majority. Again, economic considerations may require that less expensive and only marginally less effective therapies may be necessary in less resourced areas. Panel recommendations do not imply unanimous agreement among Panel members. Indeed, very few of the 200 questions received 100% agreement from the Panel. In the text below, wording is intended to convey the strength of Panel support for each recommendation, while details of Panel voting on each question are available in supplementary Appendix S2, available at Annals of Oncology online.

How to Navigate the Treatment Spectrum from Multimodality Therapy to Observation Alone for ductal carcinoma in situ.DCIS 
Record SM, Hwang ES, Chiba A. Surg Oncol Clin N Am. 2023 Oct;32(4):663-673. doi: 10.1016/j.soc.2023.05.011. Epub 2023 Jun 15. PMID: 37714635 Review.
Current guidance concordant care recommends surgical intervention for all patients with DCIS, followed by radiation and/or endocrine therapy for some. Adjuvant therapies after surgical excision have reduced recurrence rates but not breast cancer mortality. .. …Abstract
DCIS detection has increased dramatically since the introduction of screening mammography. Current guidance concordant care recommends surgical intervention for all patients with DCIS, followed by radiation and/or endocrine therapy for some. Adjuvant therapies after surgical excision have reduced recurrence rates but not breast cancer mortality. Given the lack of evidence of current treatment regimens and the morbidity associated with these treatments, there is concern that DCIS is over-treated. Active surveillance may be a favorable alternative for selected patients and is currently being investigated through four international clinical trials.
Strategies for subtypes--dealing with the diversity of breast cancer: highlights of the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011.
Goldhirsch A, Wood WC, Coates AS, Gelber RD, Thürlimann B, Senn HJ; Panel members. Ann Oncol. 2011 Aug;22(8):1736-47. doi: 10.1093/annonc/mdr304. Epub 2011 Jun 27. PMID: 21709140 Free PMC article.
Abstract
The 12th St Gallen International Breast Cancer Conference (2011) Expert Panel adopted a new approach to the classification of patients for therapeutic purposes based on the recognition of intrinsic biological subtypes within the breast cancer spectrum. For practical purposes, these subtypes may be approximated using clinicopathological rather than gene expression array criteria. In general, systemic therapy recommendations follow the subtype classification. Thus, 'Luminal A' disease generally requires only endocrine therapy, which also forms part of the treatment of the 'Luminal B' subtype. Chemotherapy is considered indicated for most patients with 'Luminal B', 'Human Epidermal growth factor Receptor 2 (HER2) positive', and 'Triple negative (ductal)' disease, with the addition of trastuzumab in 'HER2 positive' disease. Progress was also noted in defining better tolerated local therapies in selected cases without loss of efficacy, such as accelerated radiation therapy and the omission of axillary dissection under defined circumstances. Broad treatment recommendations are presented, recognizing that detailed treatment decisions need to consider disease extent, host factors, patient preferences, and social and economic constraints.
Precision surgery and avoiding over-treatment.
Hosseini A, Khoury AL, Esserman LJ. Eur J Surg Oncol. 2017 May;43(5):938-943. doi: 10.1016/j.ejso.2017.02.003. Epub 2017 Feb 11. PMID: 28238520 Review.
Abstract
Over-diagnosis and over-treatment are consequences of greater awareness about breast cancer, more intensive screening, and the resultant identification of more cases of breast cancer that are low or ultralow risk. This area represents an important opportunity to optimize the delivery of appropriate targeted therapy for breast cancer patients. Despite the evolution of breast cancer care over the last few decades and our ability to tailor treatment to biology, a one-size fits all approach is still prevalent in the local and regional management of and screening for breast cancer, failing to reflect the unique biology and tumor characteristics of each patient. In this review, we explore how we can use new tools to better define tumor biology and also how we can change current clinical practices based on already available data. Every surgeon should be knowledgeable about how to craft personalized breast cancer care in the areas of systemic therapy, adjuvant radiation therapy, management of ductal carcinoma in situ (DCIS), precision surgery, and breast cancer screening.
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