Topical transdermal chemoprevention of breast cancer: where will nanomedical approaches deliver us?

Nanomedicine ◽  
2021 ◽  
Author(s):  
Gabriela Mojeiko ◽  
Julia Sapienza Passos ◽  
Alexsandra Conceição Apolinário ◽  
Luciana Biagini Lopes
Keyword(s):  
Breast Cancer ◽  
Drug Repurposing ◽  
Preventive Therapy ◽  
Mammary Tissue ◽  
High Risk Population ◽  
Prevention Strategies ◽  
New Agents ◽  
Pharmacological Prevention ◽  
High Incidence ◽  
Transdermal Route

Despite the high incidence of breast cancer, there are few pharmacological prevention strategies for the high-risk population and those that are available have low adherence. Strategies that deliver drugs directly to the breasts may increase drug local concentrations, improving efficacy, safety and acceptance. The skin of the breast has been proposed as an administration route for local transdermal therapy, which may improve drug levels in the mammary tissue, due to both deep local penetration and percutaneous absorption. In this review, we discuss the application of nanotechnology-based strategies for the delivery of well established and new agents as well as drug repurposing using the topical transdermal route to improve the outcomes of preventive therapy for breast cancer.

scholarly journals Cisplatin +/− rucaparib after preoperative chemotherapy in patients with triple-negative or BRCA mutated breast cancer

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Maitri Kalra ◽  
Yan Tong ◽  
David R. Jones ◽  
Tom Walsh ◽  
Michael A. Danso ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Neoadjuvant Therapy ◽  
Triple Negative ◽  
Residual Disease ◽  
Disease Free Survival ◽  
Parp Inhibition ◽  
High Risk Population ◽  
Risk Population ◽  
The Impact

AbstractPatients with triple-negative breast cancer (TNBC) who have residual disease after neoadjuvant therapy have a high risk of recurrence. We tested the impact of DNA-damaging chemotherapy alone or with PARP inhibition in this high-risk population. Patients with TNBC or deleterious BRCA mutation (TNBC/BRCAmut) who had >2 cm of invasive disease in the breast or persistent lymph node (LN) involvement after neoadjuvant therapy were assigned 1:1 to cisplatin alone or with rucaparib. Germline mutations were identified with BROCA analysis. The primary endpoint was 2-year disease-free survival (DFS) with 80% power to detect an HR 0.5. From Feb 2010 to May 2013, 128 patients were enrolled. Median tumor size at surgery was 1.9 cm (0–11.5 cm) with 1 (0–38) involved LN; median Residual Cancer Burden (RCB) score was 2.6. Six patients had known deleterious BRCA1 or BRCA2 mutations at study entry, but BROCA identified deleterious mutations in 22% of patients with available samples. Toxicity was similar in both arms. Despite frequent dose reductions (21% of patients) and delays (43.8% of patients), 73% of patients completed planned cisplatin. Rucaparib exposure was limited with median concentration 275 (82–4694) ng/mL post-infusion on day 3. The addition of rucaparib to cisplatin did not increase 2-year DFS (54.2% cisplatin vs. 64.1% cisplatin + rucaparib; P = 0.29). In the high-risk post preoperative TNBC/BRCAmut setting, the addition of low-dose rucaparib did not improve 2-year DFS or increase the toxicity of cisplatin. Genetic testing was underutilized in this high-risk population.

scholarly journals Collagen molecular phenotypic switch between non-neoplastic and neoplastic canine mammary tissues

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Masahiko Terajima ◽  
Yuki Taga ◽  
Becky K. Brisson ◽  
Amy C. Durham ◽  
Kotaro Sato ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mammary Gland ◽  
Mammary Carcinoma ◽  
Cancer Biology ◽  
Type I Collagen ◽  
Critical Role ◽  
Premature Death ◽  
Mammary Tissue ◽  
Type I ◽  
Cross Links

AbstractIn spite of major advances over the past several decades in diagnosis and treatment, breast cancer remains a global cause of morbidity and premature death for both human and veterinary patients. Due to multiple shared clinicopathological features, dogs provide an excellent model of human breast cancer, thus, a comparative oncology approach may advance our understanding of breast cancer biology and improve patient outcomes. Despite an increasing awareness of the critical role of fibrillar collagens in breast cancer biology, tumor-permissive collagen features are still ill-defined. Here, we characterize the molecular and morphological phenotypes of type I collagen in canine mammary gland tumors. Canine mammary carcinoma samples contained longer collagen fibers as well as a greater population of wider fibers compared to non-neoplastic and adenoma samples. Furthermore, the total number of collagen cross-links enriched in the stable hydroxylysine-aldehyde derived cross-links was significantly increased in neoplastic mammary gland samples compared to non-neoplastic mammary gland tissue. The mass spectrometric analyses of type I collagen revealed that in malignant mammary tumor samples, lysine residues, in particular those in the telopeptides, were markedly over-hydroxylated in comparison to non-neoplastic mammary tissue. The extent of glycosylation of hydroxylysine residues was comparable among the groups. Consistent with these data, expression levels of genes encoding lysyl hydroxylase 2 (LH2) and its molecular chaperone FK506-binding protein 65 were both significantly increased in neoplastic samples. These alterations likely lead to an increase in the LH2-mediated stable collagen cross-links in mammary carcinoma that may promote tumor cell metastasis in these patients.

Microemulsion for Prolonged Release of Fenretinide in the Mammary Tissue and Prevention of Breast Cancer Development

2021 ◽  
Author(s):  
Giovanna Cassone Salata ◽  
Isabella D. Malagó ◽  
Vanessa F. M. Carvalho Dartora ◽  
Ana Flávia Marçal Pessoa ◽  
Márcia Carvalho de Abreu Fantini ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Development ◽  
Mammary Tissue ◽  
Prolonged Release ◽  
Breast Cancer Development ◽  
Prevention Of Breast Cancer

scholarly journals Deciphering the temporal heterogeneity of cancer-associated fibroblast subpopulations in breast cancer

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Freja Albjerg Venning ◽  
Kamilla Westarp Zornhagen ◽  
Lena Wullkopf ◽  
Jonas Sjölund ◽  
Carmen Rodriguez-Cupello ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Flow Cytometry ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Ex Vivo ◽  
Smooth Muscle Actin ◽  
Mammary Tissue ◽  
Temporal Heterogeneity ◽  
Alpha Smooth Muscle Actin ◽  
Murine Tumours

Abstract Background Cancer-associated fibroblasts (CAFs) comprise a heterogeneous population of stromal cells within the tumour microenvironment. CAFs exhibit both tumour-promoting and tumour-suppressing functions, making them exciting targets for improving cancer treatments. Careful isolation, identification, and characterisation of CAF heterogeneity is thus necessary for ex vivo validation and future implementation of CAF-targeted strategies in cancer. Methods Murine 4T1 (metastatic) and 4T07 (poorly/non-metastatic) orthotopic triple negative breast cancer tumours were collected after 7, 14, or 21 days. The tumours were analysed via flow cytometry for the simultaneous expression of six CAF markers: alpha smooth muscle actin (αSMA), fibroblast activation protein alpha (FAPα), platelet derived growth factor receptor alpha and beta (PDGFRα and PDGFRβ), CD26/DPP4 and podoplanin (PDPN). All non-CAFs were excluded from the analysis using a lineage marker cocktail (CD24, CD31, CD45, CD49f, EpCAM, LYVE-1, and TER-119). In total 128 murine tumours and 12 healthy mammary fat pads were analysed. Results We have developed a multicolour flow cytometry strategy based on exclusion of non-CAFs and successfully employed this to explore the temporal heterogeneity of freshly isolated CAFs in the 4T1 and 4T07 mouse models of triple-negative breast cancer. Analysing 128 murine tumours, we identified 5–6 main CAF populations and numerous minor ones based on the analysis of αSMA, FAPα, PDGFRα, PDGFRβ, CD26, and PDPN. All markers showed temporal changes with a distinct switch from primarily PDGFRα+ fibroblasts in healthy mammary tissue to predominantly PDGFRβ+ CAFs in tumours. CD26+ CAFs emerged as a large novel subpopulation, only matched by FAPα+ CAFs in abundance. Conclusion We demonstrate that multiple subpopulations of CAFs co-exist in murine triple negative breast cancer, and that the abundance and dynamics for each marker differ depending on tumour type and time. Our results form the foundation needed to isolate and characterise specific CAF populations, and ultimately provide an opportunity to therapeutically target specific CAF subpopulations.

Epstein-Barr virus and breast cancer: Serological study in a high-incidence area of nasopharyngeal carcinoma

2011 ◽  
Vol 309 (2) ◽  
pp. 128-136 ◽  
Author(s):  
Jian-Rong He ◽  
Lu-Ying Tang ◽  
Dan-Dan Yu ◽  
Feng-Xi Su ◽  
Er-Wei Song ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Nasopharyngeal Carcinoma ◽  
Epstein Barr Virus ◽  
Serological Study ◽  
Barr Virus ◽  
High Incidence ◽  
Epstein Barr ◽  
High Incidence Area

scholarly journals Breast cancer prevention strategies in lobular carcinoma in situ: A decision analysis

Cancer ◽  
2017 ◽  
Vol 123 (14) ◽  
pp. 2609-2617 ◽  
Author(s):  
Stephanie M. Wong ◽  
Natasha K. Stout ◽  
Rinaa S. Punglia ◽  
Ipshita Prakash ◽  
Yasuaki Sagara ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Decision Analysis ◽  
Cancer Prevention ◽  
Carcinoma In Situ ◽  
Lobular Carcinoma ◽  
Breast Cancer Prevention ◽  
Prevention Strategies ◽  
Lobular Carcinoma In Situ

Challenges to the Development of New Agents for Molecularly Defined Patient Subsets: Lessons From BRCA1/2-Associated Breast Cancer

2011 ◽  
Vol 29 (32) ◽  
pp. 4224-4226 ◽  
Author(s):  
Susan M. Domchek ◽  
Gillian Mitchell ◽  
Geoffrey J. Lindeman ◽  
Nadine M. Tung ◽  
Judith Balmaña ◽  
...  
Keyword(s):  
Breast Cancer ◽  
New Agents

scholarly journals Patients with uterine leiomyoma exhibit a high incidence but low mortality rate for breast cancer

Oncotarget ◽  
2017 ◽  
Vol 8 (20) ◽  
pp. 33014-33023 ◽  
Author(s):  
Te-Chun Shen ◽  
Te-Chun Hsia ◽  
Chieh-Lun Hsiao ◽  
Cheng-Li Lin ◽  
Chih-Yi Yang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mortality Rate ◽  
Uterine Leiomyoma ◽  
High Incidence

scholarly journals Taxane therapy in the adjuvant treatment of breast cancer in Italy: economic evaluation

2006 ◽  
Vol 7 (1) ◽  
pp. 63-69
Author(s):  
Simona Ravera ◽  
Lorenzo G. Mantovani
Keyword(s):  
Breast Cancer ◽  
Cost Minimization ◽  
Disease Free Survival ◽  
Developed Countries ◽  
Preventive Therapy ◽  
Point Of View ◽  
Adjuvant Setting ◽  
Screening Programs ◽  
Equivalent Efficacy ◽  
Dosing Regimens

Breast cancer (BC) is one of the leading cause of death in developed Countries and every year more than a million new cases are diagnosed worldwide. In Italy the prevalence of BC was estimated to be 1,070 per 100,000 at 31 December 1992. Nevertheless, despite the increase in incidence, mortality rate for BC are decreased in the last decades probably due to several factors such as implementation of screening programs, early diagnosis and new adjuvant therapies. Important types of adjuvant chemotherapy include anthracyclines and taxanes and these treatments continue to be evaluated to determine optimal combinations and dosing regimens. The efficacy of paclitaxel and docetaxel in adjuvant setting for the treatment of early BC has been assessed in different trials where the two taxanes showed a significant increase in both Disease Free Survival (DFS) and Overall Survival (OS) in comparison with nontaxane therapy. In particular results from one of the last studies comparing paclitaxel and docetaxel show equivalent efficacy for both drugs. At the light of the recent findings, the objective of this work is to perform a cost minimization analysis of paclitaxel vs docetaxel in the adjuvant setting for treatment of early BC in Italy. The analysis was conducted from the National Health Service’s point of view, assuming equivalent efficacy in terms of DFS and OS for both taxanes. Costs were evaluated on the basis of therapeutic schemes used in the analyzed trials. Results show that paclitaxel, administered every 3 weeks for 4 cycles after doxorubicin and cyclophosphamide, represents the less costly therapy. This is a conservative costs estimate based on data from literature that does not take into account possible additional costs associated to the treatment of febrile neutropenia (FN) as adverse event related to chemotherapy. Since, on the basis of scientific literature data, FN seems to be more related with docetaxel than with paclitaxel administration, it is likely that in clinical practice the Growth–Colony Stimulating Factor is often prescribed as a preventive therapy when Docetaxel is administred, giving rise to treatment costs.

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