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An Îto stochastic differential equations model for the dynamics of the MCF-7 breast cancer cell line treated by radiotherapy

Oroji A, Omar M, Yarahmadian S

J Theor Biol, 2016 10 21;407:128-137.
PMID: 27457094 DOI: 10.1016/j.jtbi.2016.07.035

In this paper, a new mathematical model is proposed for studying the population dynamics of breast cancer cells treated by radiotherapy by using a system of stochastic differential equations. The novelty of the model is essentially in capturing the concept of the cell cycle in the modeling to be able to evaluate the tumor lifespan. According to the cell cycle, each cell belongs to one of three subpopulations G, S, or M, representing gap, synthesis and mitosis subpopulations. Cells in the M subpopulation are highly radio-sensitive, whereas cells in the S subpopulation are highly radio-resistant. Therefore, in the process of radiotherapy, cell death rates of different subpopulations are not equal. In addition, since flow cytometry is unable to detect apoptotic cells accurately, the small changes in cell death rate in each subpopulation during treatment are considered. Subsequently, the proposed model is calibrated using experimental data from previous experiments involving the MCF-7 breast cancer cell line. Consequently, the proposed model is able to predict tumor lifespan based on the number of initial carcinoma cells. The results show the effectiveness of the radiation under the condition of stability, which describes the decreasing trend of the tumor cells population.

Matched MeSH terms: Breast Neoplasms/pathology*; Breast Neoplasms/radiotherapy*
Fulltext Computational approach to discriminate human and mouse sequences in patient-derived tumour xenografts

Callari M, Batra AS, Batra RN, Sammut SJ, Greenwood W, Clifford H, et al.

BMC Genomics, 2018 01 05;19(1):19.
PMID: 29304755 DOI: 10.1186/s12864-017-4414-y

BACKGROUND: Patient-Derived Tumour Xenografts (PDTXs) have emerged as the pre-clinical models that best represent clinical tumour diversity and intra-tumour heterogeneity. The molecular characterization of PDTXs using High-Throughput Sequencing (HTS) is essential; however, the presence of mouse stroma is challenging for HTS data analysis. Indeed, the high homology between the two genomes results in a proportion of mouse reads being mapped as human.
RESULTS: In this study we generated Whole Exome Sequencing (WES), Reduced Representation Bisulfite Sequencing (RRBS) and RNA sequencing (RNA-seq) data from samples with known mixtures of mouse and human DNA or RNA and from a cohort of human breast cancers and their derived PDTXs. We show that using an In silico Combined human-mouse Reference Genome (ICRG) for alignment discriminates between human and mouse reads with up to 99.9% accuracy and decreases the number of false positive somatic mutations caused by misalignment by >99.9%. We also derived a model to estimate the human DNA content in independent PDTX samples. For RNA-seq and RRBS data analysis, the use of the ICRG allows dissecting computationally the transcriptome and methylome of human tumour cells and mouse stroma. In a direct comparison with previously reported approaches, our method showed similar or higher accuracy while requiring significantly less computing time.
CONCLUSIONS: The computational pipeline we describe here is a valuable tool for the molecular analysis of PDTXs as well as any other mixture of DNA or RNA species.

Matched MeSH terms: Breast Neoplasms/genetics; Breast Neoplasms/metabolism
Fulltext Characterization of BRCA1 and BRCA2 variants in multi-ethnic Asian cohort from a Malaysian case-control study

Lai KN, Ho WK, Kang IN, Kang PC, Phuah SY, Mariapun S, et al.

BMC Cancer, 2017 02 22;17(1):149.
PMID: 28222693 DOI: 10.1186/s12885-017-3099-6

BACKGROUND: Genetic testing for BRCA1 and BRCA2 has led to the accurate identification of individuals at higher risk of cancer and the development of new therapies. Approximately 10-20% of the genetic testing for BRCA1 and BRCA2 leads to the identification of variants of uncertain significance (VUS), with higher proportions in Asians. We investigated the functional significance of 7 BRCA1 and 25 BRCA2 variants in a multi-ethnic Asian cohort using a case-control approach.
METHODS: The MassARRAY genotyping was conducted in 1,394 Chinese, 406 Malay and 310 Indian breast cancer cases and 1,071 Chinese, 167 Malay and 255 Indian healthy controls. The association of individual variant with breast cancer risk was analyzed using logistic regression model adjusted for ethnicity, age and family history.
RESULTS: Our study confirmed BRCA2 p.Ile3412Val is presented in >2% of unaffected women and is likely benign, and BRCA2 p.Ala1996Thr which is predicted to be likely pathogenic by in-silico models is presented in 2% of healthy Indian women suggesting that it may not be associated with breast cancer risk. Single-variant analysis suggests that BRCA1 p.Arg762Ser may be associated with breast cancer risk (OR = 7.4; 95% CI, 0.9-62.3; p = 0.06).
CONCLUSIONS: Our study shows that BRCA2 p.Ile3412Val and p.Ala1996Thr are likely benign and highlights the need for population-specific studies to determine the likely functional significance of population-specific variants. Our study also suggests that BRCA1 p.Arg762Ser may be associated with increased risk of breast cancer but other methods or larger studies are required to determine a more precise estimate of breast cancer risk.

Matched MeSH terms: Breast Neoplasms/ethnology; Breast Neoplasms/genetics*
Education Moderates the Relationship Between Spirituality with Quality of Life and Stress Among Malay Muslim Women with Breast Cancer

Pahlevan Sharif S, Ong FS

J Relig Health, 2019 Aug;58(4):1060-1071.
PMID: 29511922 DOI: 10.1007/s10943-018-0587-1

The purpose of this study was to investigate the relationship between spirituality with quality of life and stress of Malay Muslim breast cancer patients in Malaysia. In addition, the moderating role of education on this relationship was examined. Participants consisted of 145 conveniently selected Malay breast cancer patients. The results indicated that the more spiritual respondents reported a higher level of quality of life and lower level of stress. Moreover, education weakened the relationship between spirituality with quality of life and stress.

Matched MeSH terms: Breast Neoplasms/ethnology*; Breast Neoplasms/psychology*
Fulltext Psychosocial outcome and health behaviour intent of breast cancer patients with BRCA1/2 and PALB2 pathogenic variants unselected by a priori risk

Padmanabhan H, Hassan NT, Wong SW, Lee YQ, Lim J, Hasan SN, et al.

PLoS One, 2022;17(2):e0263675.
PMID: 35167615 DOI: 10.1371/journal.pone.0263675

There is an increasing number of cancer patients undertaking treatment-focused genetic testing despite not having a strong family history or high a priori risk of being carriers because of the decreasing cost of genetic testing and development of new therapies. There are limited studies on the psychosocial outcome of a positive result among breast cancer patients who are at low a priori risk, particularly in women of Asian descent. Breast cancer patients enrolled under the Malaysian Breast Cancer Genetic Study between October 2002 and February 2018 were tested for BRCA1, BRCA2 and PALB2 genes. All 104 carriers identified were invited by a research genetic counsellor for result disclosure. Of the 104 carriers, 64% (N = 66) had low a priori risk as determined by PENN II scores. Psychosocial, risk perception and health behaviour measures survey were conducted at baseline (pre-result disclosure), and at two to six weeks after result disclosure. At baseline, younger carriers with high a priori risk had higher Cancer Worry Scale scores than those with low a priori risk but all scores were within acceptable range. Around 75% and 55% of high a priori risk carriers as well as 80% and 67% of low a priori risk carriers had problems in the "living with cancer" and "children" psychosocial domains respectively. All carriers regardless of their a priori risk demonstrated an improved risk perception that also positively influenced their intent to undergo risk management procedures. This study has shown that with sufficient counselling and support, low a priori risk carriers are able to cope psychologically, have improved perceived risk and increased intent for positive health behaviour despite having less anticipation from a family history prior to knowing their germline carrier status.

Matched MeSH terms: Breast Neoplasms/genetics; Breast Neoplasms/psychology*
Fulltext Psychometric properties of the Malay version of the Breast Module (BR23)

Yusoff N, Low WY, Yip CH

Singapore Med J, 2012 Jan;53(1):36-9.
PMID: 22252181

The Breast Module (BR23) is increasingly being used worldwide in breast cancer research. This study evaluates the appropriateness of the translated version (i.e. BR23-Malay version) as a useful tool for the Malaysian population who could understand Malay, and examines the reliability and validity of the BR23-Malay version.

Matched MeSH terms: Breast Neoplasms/diagnosis*; Breast Neoplasms/surgery
Fulltext Mutation analysis of the BRCA1 gene in Malaysian breast cancer patients

Balraj P, Khoo AS, Volpi L, Tan JA, Nair S, Abdullah H

Singapore Med J, 2002 Apr;43(4):194-7.
PMID: 12188064

Thirty patients with early onset breast cancer or familial breast cancer from Malaysia were analysed for germline mutation in the early onset breast cancer I gene (BRCA1). Direct sequencing of the entire coding region of BRCA1 identified a frameshift mutation, c.5447-5448insC (insC5447) (codon 1776 of exon 21) in a patient aged 32 of the Malay ethnic origin, who had no family history of breast and/or ovarian cancer. Eight polymorphisms (2201C > T, 2430T > C, P871L, E1038G, K1183R, 4427T > C, S1613G and IVS8-57delT) were identified in the samples tested.

Matched MeSH terms: Breast Neoplasms/ethnology; Breast Neoplasms/genetics*
Fulltext Experience with hookwire localisation excision biopsy at a medical centre in Malaysia

Ng CH, Lee KT, Taib NA, Yip CH

Singapore Med J, 2010 Apr;51(4):306-10.
PMID: 20505908

With an increasing number of women undergoing breast screening, an effective method of removing non-palpable lumps detected by mammography or sonography is by hookwire localisation excision biopsy (HWLB). The aim of this paper was to audit the practice of HWLB at the University Malaya Medical Centre.

Matched MeSH terms: Breast Neoplasms/diagnosis*; Breast Neoplasms/surgery*
Fulltext Risk factors of breast cancer in women in Kelantan, Malaysia

Afifi M

Singapore Med J, 2006 Jun;47(6):551; author reply 552-3.
PMID: 16752028

Comment on: Norsaʼadah B, Rusli BN, Imran AK, Naing L, Winn T. Risk factors of breast cancer in women in Kelantan, Malaysia. Singapore Med J 2005;
46:698-705

Matched MeSH terms: Breast Neoplasms/etiology; Breast Neoplasms/epidemiology*
Fulltext Prognostic value of an index for serum globulin compensation in colon and breast cancers

Al-Joudi FS

Singapore Med J, 2005 Dec;46(12):710-3.
PMID: 16308645

INTRODUCTION: Decreased serum albumin (SA) levels have been used extensively as prognostic indicators in many chronic debilitating diseases. The decrease may be partly compensated by globular proteins. The failure of globulins to compensate may reflect advanced disease. We examined the prognostic value of the level of serum globulins in colorectal and breast cancers.
METHODS: Data of 80 patients with advanced colon and breast cancers were analysed. Of these, 46 patients died within six months of measurement of their serum proteins, and the rest were followed-up for more than six months after measurements of their serum proteins were taken. A mathematical formula, representing the globulin compensation index (GCI), was recently developed from the measured SA levels and globulins. Patients were then classified into three categories: negative GCI and negative compensation; GCI of 0 to less than 1.0 with partial compensation; and GCI equal or greater than 1.0 with full compensation.
RESULTS: Among the deceased patients, 45.7 percent had negative GCI, compared to 26.5 percent of patients in the survivors group. For partial compensation, 30.4 percent of patients were from the deceased group, and 32.4 percent were from the survivors group. For full compensation (elevated GCI), 23.9 percent of patients were from the deceased group, compared to 41.1 percent from the survivors group (p-value equals 0.031).
CONCLUSION: Patients with low GCI are more likely to have bad prognoses, whereas those with higher GCI have more favourable prognoses. Globulin compensation may be a reliable prognostic factor in advanced colorectal and breast cancers, and possibly in other chronic illnesses. The GCI may serve as a useful tool in the measurement of this compensation.

Matched MeSH terms: Breast Neoplasms/blood; Breast Neoplasms/diagnosis*
Fulltext Re-evaluating genetic variants identified in candidate gene studies of breast cancer risk using data from nearly 280,000 women of Asian and European ancestry

Yang Y, Shu X, Shu XO, Bolla MK, Kweon SS, Cai Q, et al.

EBioMedicine, 2019 Oct;48:203-211.
PMID: 31629678 DOI: 10.1016/j.ebiom.2019.09.006

BACKGROUND: We previously conducted a systematic field synopsis of 1059 breast cancer candidate gene studies and investigated 279 genetic variants, 51 of which showed associations. The major limitation of this work was the small sample size, even pooling data from all 1059 studies. Thereafter, genome-wide association studies (GWAS) have accumulated data for hundreds of thousands of subjects. It's necessary to re-evaluate these variants in large GWAS datasets.
METHODS: Of these 279 variants, data were obtained for 228 from GWAS conducted within the Asian Breast Cancer Consortium (24,206 cases and 24,775 controls) and the Breast Cancer Association Consortium (122,977 cases and 105,974 controls of European ancestry). Meta-analyses were conducted to combine the results from these two datasets.
FINDINGS: Of those 228 variants, an association was observed for 12 variants in 10 genes at a Bonferroni-corrected threshold of P breast cancer risk, we found 14 variants showing an association. Our findings warrant further functional investigation of these variants. FUND: National Institutes of Health.

Matched MeSH terms: Breast Neoplasms/genetics*; Breast Neoplasms/epidemiology*
Fulltext Breast Cancer Risk Factors and Survival by Tumor Subtype: Pooled Analyses from the Breast Cancer Association Consortium

Morra A, Jung AY, Behrens S, Keeman R, Ahearn TU, Anton-Culver H, et al.

Cancer Epidemiol Biomarkers Prev, 2021 Apr;30(4):623-642.
PMID: 33500318 DOI: 10.1158/1055-9965.EPI-20-0924

BACKGROUND: It is not known whether modifiable lifestyle factors that predict survival after invasive breast cancer differ by subtype.
METHODS: We analyzed data for 121,435 women diagnosed with breast cancer from 67 studies in the Breast Cancer Association Consortium with 16,890 deaths (8,554 breast cancer specific) over 10 years. Cox regression was used to estimate associations between risk factors and 10-year all-cause mortality and breast cancer-specific mortality overall, by estrogen receptor (ER) status, and by intrinsic-like subtype.
RESULTS: There was no evidence of heterogeneous associations between risk factors and mortality by subtype (P adj > 0.30). The strongest associations were between all-cause mortality and BMI ≥30 versus 18.5-25 kg/m2 [HR (95% confidence interval (CI), 1.19 (1.06-1.34)]; current versus never smoking [1.37 (1.27-1.47)], high versus low physical activity [0.43 (0.21-0.86)], age ≥30 years versus <20 years at first pregnancy [0.79 (0.72-0.86)]; >0-<5 years versus ≥10 years since last full-term birth [1.31 (1.11-1.55)]; ever versus never use of oral contraceptives [0.91 (0.87-0.96)]; ever versus never use of menopausal hormone therapy, including current estrogen-progestin therapy [0.61 (0.54-0.69)]. Similar associations with breast cancer mortality were weaker; for example, 1.11 (1.02-1.21) for current versus never smoking.
CONCLUSIONS: We confirm associations between modifiable lifestyle factors and 10-year all-cause mortality. There was no strong evidence that associations differed by ER status or intrinsic-like subtype.
IMPACT: Given the large dataset and lack of evidence that associations between modifiable risk factors and 10-year mortality differed by subtype, these associations could be cautiously used in prognostication models to inform patient-centered care.

Matched MeSH terms: Breast Neoplasms/mortality*; Breast Neoplasms/pathology*
Changes in Health- Related Quality of Life and Psychosocial Well-being of Breast Cancer Survivors: Findings from a Group- Based Intervention Program in Malaysia

Dominic NA, Thirunavuk Arasoo VJ, Botross NP, Riad A, Biding C, Ramadas A

Asian Pac J Cancer Prev, 2018 Jul 27;19(7):1809-1815.
PMID: 30049192

Background: There is a lack of evidence on the effectiveness of multifaceted group-based interventions to improve psychological well-being and health-related quality of life (HRQOL) of breast cancer (BCa) survivors in Malaysia. This study is aimed at assessing the effectiveness of such intervention program among the BCa survivors. Materials and Methods: This was a group-based intervention program with pre- and post-test design, carried out among BCa survivors (n=37) who were members of Breast Cancer Support Group Centre, Johor Bahru. A validated self-administered questionnaire was used to assess the impact of the program on psychosocial well-being and HRQOL of the participants. Results: The mean age of BCa survivors was 58.1 years (SD=9.7), with mean age at diagnosis of 49.9 years (SD=9.6). Majority of them were of Chinese ethnicity, married and had secondary level education, but were unemployed. More than 86% of them were diagnosed to have early BCa diagnosis and have since completed the treatment. There were significant decreases in median depression (p=0.001), anxiety (p<0.001) and stress (p<0.001) scores at post-intervention. More than 85% of the participants rated themselves to have a good or very good QOL at post-intervention, as opposed to 75.9% at pre-intervention. Significant improvements in several HR-QOL domain scores were seen, with psychological score improving the most (p<0.001), followed by social relationship (p=0.002) and physical health (p=0.004). Conclusions: Group-based multifaceted intervention can be a viable solution to improve psychosocial well-being of BCa survivors.

Matched MeSH terms: Breast Neoplasms/psychology*; Breast Neoplasms/rehabilitation*
Fulltext Risk of second primary malignancies in women with breast cancer: Results from the European prospective investigation into cancer and nutrition (EPIC)

Ricceri F, Fasanelli F, Giraudo MT, Sieri S, Tumino R, Mattiello A, et al.

Int J Cancer, 2015 Aug 15;137(4):940-8.
PMID: 25650288 DOI: 10.1002/ijc.29462

Women with a diagnosis of breast cancer are at increased risk of second primary cancers, and the identification of risk factors for the latter may have clinical implications. We have followed-up for 11 years 10,045 women with invasive breast cancer from a European cohort, and identified 492 second primary cancers, including 140 contralateral breast cancers. Expected and observed cases and Standardized Incidence Ratios (SIR) were estimated using Aalen-Johansen Markovian methods. Information on various risk factors was obtained from detailed questionnaires and anthropometric measurements. Cox proportional hazards regression models were used to estimate the role of risk factors. Women with breast cancer had a 30% excess risk for second malignancies (95% confidence interval-CI 18-42) after excluding contralateral breast cancers. Risk was particularly elevated for colorectal cancer (SIR, 1.71, 95% CI 1.43-2.00), lymphoma (SIR 1.80, 95% CI 1.31-2.40), melanoma (2.12; 1.63-2.70), endometrium (2.18; 1.75-2.70) and kidney cancers (2.40; 1.57-3.52). Risk of second malignancies was positively associated with age at first cancer, body mass index and smoking status, while it was inversely associated with education, post-menopausal status and a history of full-term pregnancy. We describe in a large cohort of women with breast cancer a 30% excess of second primaries. Among risk factors for breast cancer, a history of full-term pregnancy was inversely associated with the risk of second primary cancer.

Matched MeSH terms: Breast Neoplasms/epidemiology*; Breast Neoplasms/pathology*
Fulltext Vegetable and fruit consumption and the risk of hormone receptor-defined breast cancer in the EPIC cohort

Emaus MJ, Peeters PH, Bakker MF, Overvad K, Tjønneland A, Olsen A, et al.

Am J Clin Nutr, 2016 Jan;103(1):168-77.
PMID: 26607934 DOI: 10.3945/ajcn.114.101436

BACKGROUND: The recent literature indicates that a high vegetable intake and not a high fruit intake could be associated with decreased steroid hormone receptor-negative breast cancer risk.
OBJECTIVE: This study aimed to investigate the association between vegetable and fruit intake and steroid hormone receptor-defined breast cancer risk.
DESIGN: A total of 335,054 female participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort were included in this study (mean ± SD age: 50.8 ± 9.8 y). Vegetable and fruit intake was measured by country-specific questionnaires filled out at recruitment between 1992 and 2000 with the use of standardized procedures. Cox proportional hazards models were stratified by age at recruitment and study center and were adjusted for breast cancer risk factors.
RESULTS: After a median follow-up of 11.5 y (IQR: 10.1-12.3 y), 10,197 incident invasive breast cancers were diagnosed [3479 estrogen and progesterone receptor positive (ER+PR+); 1021 ER and PR negative (ER-PR-)]. Compared with the lowest quintile, the highest quintile of vegetable intake was associated with a lower risk of overall breast cancer (HRquintile 5-quintile 1: 0.87; 95% CI: 0.80, 0.94). Although the inverse association was most apparent for ER-PR- breast cancer (ER-PR-: HRquintile 5-quintile 1: 0.74; 95% CI: 0.57, 0.96; P-trend = 0.03; ER+PR+: HRquintile 5-quintile 1: 0.91; 95% CI: 0.79, 1.05; P-trend = 0.14), the test for heterogeneity by hormone receptor status was not significant (P-heterogeneity = 0.09). Fruit intake was not significantly associated with total and hormone receptor-defined breast cancer risk.
CONCLUSION: This study supports evidence that a high vegetable intake is associated with lower (mainly hormone receptor-negative) breast cancer risk.

Matched MeSH terms: Breast Neoplasms/metabolism; Breast Neoplasms/prevention & control*
Fulltext Macrophage-derived interleukin-1beta promotes human breast cancer cell migration and lymphatic adhesion in vitro

Storr SJ, Safuan S, Ahmad N, El-Refaee M, Jackson AM, Martin SG

Cancer Immunol Immunother, 2017 Oct;66(10):1287-1294.
PMID: 28551814 DOI: 10.1007/s00262-017-2020-0

Lymphovascular invasion (LVI), encompassing blood and lymphatic vessel invasion, is an important event in tumourigenesis. Macrophages within the tumour microenvironment are linked to the presence of LVI and angiogenesis. This study investigates the role of macrophage-derived, caspase-1-dependent interleukin-1beta (IL-1β) in an in vitro model of LVI. IL-1β significantly augmented the adhesion and transmigration of breast cancer cell lines MCF7 and MDA-MB-231 across endothelial cell barriers. MDA-MB-231 and MCF7 showed a higher percentage of adhesion to lymphatic endothelial cells than blood endothelial cells following endothelial cell IL-1β stimulation (P breast cancer cells and their adhesion to, and transmigration across, blood and lymphatic endothelial cells. Results suggest that IL-1β may play a role in the adhesion to lymphatic endothelial cells in particular.

Matched MeSH terms: Breast Neoplasms/genetics*; Breast Neoplasms/pathology
Fulltext The functional ALDH2 polymorphism is associated with breast cancer risk: A pooled analysis from the Breast Cancer Association Consortium

Ugai T, Milne RL, Ito H, Aronson KJ, Bolla MK, Chan T, et al.

Mol Genet Genomic Med, 2019 Jun;7(6):e707.
PMID: 31066241 DOI: 10.1002/mgg3.707

BACKGROUND: Epidemiological studies consistently indicate that alcohol consumption is an independent risk factor for female breast cancer (BC). Although the aldehyde dehydrogenase 2 (ALDH2) polymorphism (rs671: Glu>Lys) has a strong effect on acetaldehyde metabolism, the association of rs671 with BC risk and its interaction with alcohol intake have not been fully elucidated. We conducted a pooled analysis of 14 case-control studies, with individual data on Asian ancestry women participating in the Breast Cancer Association Consortium.
METHODS: We included 12,595 invasive BC cases and 12,884 controls for the analysis of rs671 and BC risk, and 2,849 invasive BC cases and 3,680 controls for the analysis of the gene-environment interaction between rs671 and alcohol intake for BC risk. The pooled odds ratios (OR) with 95% confidence intervals (CI) associated with rs671 and its interaction with alcohol intake for BC risk were estimated using logistic regression models.
RESULTS: The Lys/Lys genotype of rs671 was associated with increased BC risk (OR = 1.16, 95% CI 1.03-1.30, p = 0.014). According to tumor characteristics, the Lys/Lys genotype was associated with estrogen receptor (ER)-positive BC (OR = 1.19, 95% CI 1.05-1.36, p = 0.008), progesterone receptor (PR)-positive BC (OR = 1.19, 95% CI 1.03-1.36, p = 0.015), and human epidermal growth factor receptor 2 (HER2)-negative BC (OR = 1.25, 95% CI 1.05-1.48, p = 0.012). No evidence of a gene-environment interaction was observed between rs671 and alcohol intake (p = 0.537).
CONCLUSION: This study suggests that the Lys/Lys genotype confers susceptibility to BC risk among women of Asian ancestry, particularly for ER-positive, PR-positive, and HER2-negative tumor types.

Matched MeSH terms: Breast Neoplasms/genetics*; Breast Neoplasms/epidemiology
Fulltext Recent advances in nanotheranostics for triple negative breast cancer treatment

Thakur V, Kutty RV

J Exp Clin Cancer Res, 2019 Oct 28;38(1):430.
PMID: 31661003 DOI: 10.1186/s13046-019-1443-1

Triple-negative breast cancer (TNBC) is the most complex and aggressive type of breast cancer encountered world widely in women. Absence of hormonal receptors on breast cancer cells necessitates the chemotherapy as the only treatment regime. High propensity to metastasize and relapse in addition to poor prognosis and survival motivated the oncologist, nano-medical scientist to develop novel and efficient nanotherapies to solve such a big TNBC challenge. Recently, the focus for enhanced availability, targeted cellular uptake with minimal toxicity is achieved by nano-carriers. These smart nano-carriers carrying all the necessary arsenals (drugs, tracking probe, and ligand) designed in such a way that specifically targets the TNBC cells at site. Articulating the targeted delivery system with multifunctional molecules for high specificity, tracking, diagnosis, and treatment emerged as theranostic approach. In this review, in addition to classical treatment modalities, recent advances in nanotheranostics for early and effective diagnostic and treatment is discussed. This review highlighted the recently FDA approved immunotherapy and all the ongoing clinical trials for TNBC, in addition to nanoparticle assisted immunotherapy. Futuristic but realistic advancements in artificial intelligence (AI) and machine learning not only improve early diagnosis but also assist clinicians for their workup in TNBC. The novel concept of Nanoparticles induced endothelial leakiness (NanoEL) as a way of tumor invasion is also discussed in addition to classical EPR effect. This review intends to provide basic insight and understanding of the novel nano-therapeutic modalities in TNBC diagnosis and treatment and to sensitize the readers for continue designing the novel nanomedicine. This is the first time that designing nanoparticles with stoichiometric definable number of antibodies per nanoparticle now represents the next level of precision by design in nanomedicine.

Matched MeSH terms: Triple Negative Breast Neoplasms/pathology; Triple Negative Breast Neoplasms/therapy*
Fulltext Effect of restricted pacifier use in breastfeeding term infants for increasing duration of breastfeeding

Jaafar SH, Ho JJ, Jahanfar S, Angolkar M

Cochrane Database Syst Rev, 2016 Aug 30;2016(8):CD007202.
PMID: 27572944 DOI: 10.1002/14651858.CD007202.pub4

BACKGROUND: To successfully initiate and maintain breastfeeding for a longer duration, the World Health Organization's Ten Steps to Successful Breastfeeding recommends total avoidance of artificial teats or pacifiers for breastfeeding infants. Concerns have been raised that offering the pacifier instead of the breast to calm the infant may lead to less frequent episodes of breastfeeding and as a consequence may reduce breast-milk production and shorten duration of breastfeeding.
OBJECTIVES: To assess the effect of restricted versus unrestricted pacifier use in healthy full-term newborns whose mothers have initiated breastfeeding and intend to exclusively breastfeed, on the duration of breastfeeding, other breastfeeding outcomes and infant health.
SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 June 2016) and reference lists of retrieved studies.
SELECTION CRITERIA: Randomised and quasi-randomised controlled trials comparing restricted versus unrestricted pacifier use in healthy full-term newborns who have initiated breastfeeding.
DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. The quality of the evidence was assessed using the GRADE approach.
MAIN RESULTS: We found three trials (involving 1915 babies) for inclusion in the review, but have included only two trials (involving 1302 healthy full-term breastfeeding infants) in the analysis. Meta-analysis of the two combined studies showed that pacifier use in healthy breastfeeding infants had no significant effect on the proportion of infants exclusively breastfed at three months (risk ratio (RR) 1.01; 95% confidence interval (CI) 0.96 to 1.07, two studies, 1228 infants), and at four months of age (RR 1.01; 95% CI 0.94 to 1.09, one study, 970 infants, moderate-quality evidence), and also had no effect on the proportion of infants partially breastfed at three months (RR 1.00; 95% CI 0.98 to 1.02, two studies, 1228 infants), and at four months of age (RR 0.99; 95% CI 0.97 to 1.02, one study, 970 infants). None of the included trials reported data on the other primary outcomes, i.e. duration of partial or exclusive breastfeeding, or secondary outcomes: breastfeeding difficulties (mastitis, cracked nipples, breast engorgement); infant's health (dental malocclusion, otitis media, oral candidiasis; sudden infant death syndrome (SIDS)); maternal satisfaction and level of confidence in parenting. One study reported that avoidance of pacifiers had no effect on cry/fuss behavior at ages four, six, or nine weeks and also reported no effect on the risk of weaning before age three months, however the data were incomplete and so could not be included for analysis.
AUTHORS' CONCLUSIONS: Pacifier use in healthy term breastfeeding infants, started from birth or after lactation is established, did not significantly affect the prevalence or duration of exclusive and partial breastfeeding up to four months of age. Evidence to assess the short-term breastfeeding difficulties faced by mothers and long-term effect of pacifiers on infants' health is lacking.

Matched MeSH terms: Breast Feeding/psychology; Breast Feeding/statistics & numerical data*
Optimisation of the continuum of supportive and palliative care for patients with breast cancer in low-income and middle-income countries: executive summary of the Breast Health Global Initiative, 2014

Distelhorst SR, Cleary JF, Ganz PA, Bese N, Camacho-Rodriguez R, Cardoso F, et al.

Lancet Oncol, 2015 Mar;16(3):e137-47.
PMID: 25752564 DOI: 10.1016/S1470-2045(14)70457-7

Supportive care and palliative care are now recognised as critical components of global cancer control programmes. Many aspects of supportive and palliative care services are already available in some low-income and middle-income countries. Full integration of supportive and palliative care into breast cancer programmes requires a systematic, resource-stratified approach. The Breast Health Global Initiative convened three expert panels to develop resource allocation recommendations for supportive and palliative care programmes in low-income and middle-income countries. Each panel focused on a specific phase of breast cancer care: during treatment, after treatment with curative intent (survivorship), and after diagnosis with metastatic disease. The panel consensus statements were published in October, 2013. This Executive Summary combines the three panels' recommendations into a single comprehensive document covering breast cancer care from diagnosis through curative treatment into survivorship, and metastatic disease and end-of-life care. The recommendations cover physical symptom management, pain management, monitoring and documentation, psychosocial and spiritual aspects of care, health professional education, and patient, family, and caregiver education.

Matched MeSH terms: Breast Neoplasms/diagnosis; Breast Neoplasms/economics; Breast Neoplasms/psychology; Breast Neoplasms/therapy*

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