The impact of patient advocacy: the case of innovative breast cancer drug reimbursement

There has been substantial interest in the impact of ATP-binding cassette (ABC) transporter variability on breast cancer drug resistance. Here, we provide a systematic review of ABC variants in breast cancer therapy. Notably, most studies used small heterogeneous cohorts and their identified associations lack statistical stringency, replication and mechanistic support. We conclude that commonly studied ABC polymorphisms are not suitable to accurately predict therapy response or toxicity in breast cancer patients and cannot guide treatment decisions. However, recent research shows that ABC transporters harbor a plethora of rare variants with individually small effect sizes, and we argue that a shift in strategy from target variant interrogation to comprehensive profiling might hold promise to drastically improve the predictive power of outcome models.

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An Optimized Modeling Algorithm for Breast Cancer Drug Candidates Based on NSGAII

Frontiers in Business, Economics and Management ◽

10.54097/fbem.v2i3.193 ◽

2021 ◽

Vol 2 (3) ◽

pp. 50-57

Author(s):

Chenyao Fan ◽

Huawei Mei

Keyword(s):

Breast Cancer ◽

Biological Activity ◽

Malignant Tumors ◽

Molecular Descriptor ◽

Classification Model ◽

Cancer Drug ◽

Residual Network ◽

Drug Candidates ◽

Starting Point ◽

The Impact

Breast cancer is one of the most common malignant tumors in women. It seriously threatens the safety of women worldwide. It is an important and urgent task to research and develop anti-breast cancer drugs and improve the therapeutic effect of breast cancer. Taking the actual sample data as the main starting point, firstly, the prediction model of pIC50 is established by ResNet residual network and neural network (NN) to judge the biological activity. Then the classification model of ADMET property is established by ResNet residual network and LightGBM, and the model fusion is realized by Choquet fuzzy integral. Finally, the NSGAII multi-objective optimization algorithm is used to determine the range of values that each molecular descriptor obtains in the range of good biological activity, and ultimately to optimize the modeling of anti-breast cancer drug candidates. The experimental results show that the algorithm improves the prediction accuracy of biological activity, realizes the efficient and accurate classification of ADMET properties, and accurately describes the impact of molecular descriptors on biological activity.

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Retrospective cohort analysis of prescription patterns of cancer medications during periods of drug stockouts in Botswana

BMJ Open ◽

10.1136/bmjopen-2021-049574 ◽

2021 ◽

Vol 11 (7) ◽

pp. e049574

Author(s):

Sonya Davey ◽

Surbhi Grover ◽

Warren B Bilker ◽

Dipho I Setlhako ◽

Tlotlo B Ralefala ◽

...

Keyword(s):

Breast Cancer ◽

Retrospective Cohort ◽

Cohort Analysis ◽

Kaposi Sarcoma ◽

Sub Saharan Africa ◽

Secondary Outcome ◽

Cancer Drug ◽

Breast Cancer Patients ◽

Prescription Patterns ◽

The Impact

ObjectiveCancer drug stockouts occur at high frequencies globally, however, their effects on treatment are understudied in sub-Saharan Africa (SSA). We aimed to determine whether causes of suboptimal cancer treatment prescriptions differed between periods of stockout and full treatment supply.DesignA retrospective cohort study of systemic therapy prescriptions for patients diagnosed with the twelve most common solid tumour cancers treated in 2016.SettingPrincess Marina Hospital in Gaborone, Botswana.ParticipantsPatients in the retrospective cohort who experienced any suboptimal treatment events, defined as ≥7 days delay or switch from guideline-concordant initiated therapy.Primary and secondary outcome measuresFrequency of delays and patterns of prescription changes for specific regimens and cancer types.Results167/378 patients contributed to 320 suboptimal events (115 therapy switches, 167 delays and 38 events with both), over 1452 total chemotherapy cycles received. Events during stockout were 43% delays, 43% switches and 14% both during stockout periods and 67.2% delays, 24.4% switches and 8.4% both during non-stockout periods (p<0.001). Majority of switches involved de-escalation of initially prescribed guideline-recommended regimens in patients with breast cancer, Kaposi sarcoma and patients with colorectal cancer, which occurred more frequently during periods of drug stockouts. Among patients with breast cancer, substitution of docetaxel for paclitaxel event occurred exclusively during paclitaxel drug stockout. Delays of ≥7 days events were most frequent in breast cancer patients receiving paclitaxel during stockout, and combination doxorubicin and cyclophosphamide even during periods of non-stockout.ConclusionsThe aetiology of suboptimal events differed during stockout and non-stockout periods. Prescription patterns that involved de-escalation of initiated therapy and substitution of paclitaxel with docetaxel occurred frequently during periods of drug stockout. Further research needs to be conducted to understand the impact of stockout on survival and barriers to maintaining essential cancer medicines supplies in SSA, and the factors driving frequent delays in therapy delivery.

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Breast cancer drug gets helpmate

Nature ◽

10.1038/news040823-4 ◽

2004 ◽

Author(s):

Helen Pearson

Keyword(s):

Breast Cancer ◽

Cancer Drug

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The impact of HER2 phenotype of circulating tumor cells in metastatic breast cancer: a study in 107 patients

Geburtshilfe und Frauenheilkunde ◽

10.1055/s-0034-1388600 ◽

2014 ◽

Vol 74 (S 01) ◽

Author(s):

M Wallwiener ◽

AD Hartkopf ◽

S Riethdorf ◽

J Nees ◽

FA Taran ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Metastatic Breast ◽

The Impact

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Clinical application of polymorphic variants of the genes ESR1 and CYP2D6*4 in patients with breast and endometrial cancer

HEALTH OF WOMAN ◽

10.15574/hw.2017.118.132 ◽

2017 ◽

pp. 132-138

Author(s):

O.V. Paliychuk ◽

◽

L.Z. Polishchuk ◽

Z.I. Rossokha ◽

◽

...

Keyword(s):

Breast Cancer ◽

Endometrial Cancer ◽

Hormone Therapy ◽

Molecular Genetic ◽

Cancer Syndrome ◽

Genetic Characteristics ◽

Multiple Tumors ◽

Receptor Status ◽

Genetic Examination ◽

The Impact

The objective: determining gene polymorphism features ERS1, CYP2D6 in patients with breast cancer (RHZ) and endometrial cancer (EC) and the impact assessment studied genetic characteristics compared to receptor status (immunohistochemical determination of expression levels of ER, PR) tumors and the results of the treatment. Patients and methods. article presents the results of complex clinical, morphological, clinical-genealogical, and molecular-genetic examination of 28 females: 19 patients with breast cancer (BC), 9 patients with endometrial cancer (EC), including 5 patients with primary-multiple tumors (PMT) with and without tumor pathology aggregation in families. Results. The It was determined that in patients’ families malignant tumors of breast, uterine body and/or ovaries prevail that corresponds to Lynch type II syndrome (family cancer syndrome). Molecular-genetic examination of genomic DNA of peripheral blood and histological sections for the presence of SNPs of ESR and CYP2D6*4 genes comparing with the results of immunohistochemical study of tumors for receptors ER and PR status have not found associations between these characteristics; although among EC patients the occurrence of genotypes 397ТТ and 351АА was significantly higher comparing with BC patients (55.55% and 10.5% for genotype 397ТТ,and 15.8% for genotype 351АА, respectively). At the same time the patients with BC and primary-multiple tumors (PMT) of female reproductive system organs (FRSO) that carried mutations in BRCA1 in all the cases demonstrated positive ER and PR receptor status and adverse combinations of polymorphous variants of the genes ESR1 (397СС, 397ТС) and CYP2D6*4 (1846G, 1846GA), suggesting combined effect of these factors on the development of malignant neoplasias of FRSO in families with positive family cancer history. In BC patients, receiving standard hormone therapy with tamoxifen, those, who had genotype 1846GG of the gene CYP2D6*4, in 3 patients (15.8%) of 19 (100%) patients disease recurrence was diagnosed. Conclusion. The obtained results allow clinical use of the assessment of polymorphism frequency of the genes ESR1 and CYP2D6*4 for selection of individual hormone therapy regimens schemes for BC patients, to increase efficacy of dispensary observation after finishing of special therapy for such patients, and also personalization of complex and combined treatment regimens. Key words: breast cancer, endometrial cancer, family cancer syndrome, single nucleotide polymorphisms (SNPs) of the genes ESR1, CYP2D6*4.

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