Current Approaches and Challenges in Monitoring Treatment Responses in Breast Cancer

Graham, Lindsey J.; Shupe, Matthew P.; Schneble, Erika J; Flynt, Frederick L.; Clemenshaw, Michael N.; Kirkpatrick, A.; Gallagher, Chris; Nissan, Aviram; Henry, Leonard R.; Stojadinovic, Alexander; Peoples, George E.; Shumway, Nathan M.

doi:10.7150/jca.7047

Cited by 97 publications

(74 citation statements)

References 67 publications

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“…Conventional tumor markers, such as carcinoembryonic antigen (CEA), cancer antigen (CA)15-3 [6–8], and circulating tumor cell (CTC) count [9], are clinically available. However, their usefulness is mostly limited to patients with advanced and metastatic BC (MBC).…”

Section: Introductionmentioning

confidence: 99%

Circulating cell-free DNA-based epigenetic assay can detect early breast cancer

Uehiro

Sato

et al. 2016

Breast Cancer Res

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BackgroundCirculating cell-free DNA (cfDNA) has recently been recognized as a resource for biomarkers of cancer progression, treatment response, and drug resistance. However, few have demonstrated the usefulness of cfDNA for early detection of cancer. Although aberrant DNA methylation in cfDNA has been reported for more than a decade, its diagnostic accuracy remains unsatisfactory for cancer screening. Thus, the aim of the present study was to develop a highly sensitive cfDNA-based system for detection of primary breast cancer (BC) using epigenetic biomarkers and digital PCR technology.MethodsArray-based genome-wide DNA methylation analysis was performed using 56 microdissected breast tissue specimens, 34 cell lines, and 29 blood samples from healthy volunteers (HVs). Epigenetic markers for BC detection were selected, and a droplet digital methylation-specific PCR (ddMSP) panel with the selected markers was established. The detection model was constructed by support vector machine and evaluated using cfDNA samples.ResultsThe methylation array analysis identified 12 novel epigenetic markers (JAK3, RASGRF1, CPXM1, SHF, DNM3, CAV2, HOXA10, B3GNT5, ST3GAL6, DACH1, P2RX3, and chr8:23572595) for detecting BC. We also selected four internal control markers (CREM, GLYATL3, ELMOD3, and KLF9) that were identified as infrequently altered genes using a public database. A ddMSP panel using these 16 markers was developed and detection models were constructed with a training dataset containing cfDNA samples from 80 HVs and 87 cancer patients. The best detection model adopted four methylation markers (RASGRF1, CPXM1, HOXA10, and DACH1) and two parameters (cfDNA concentration and the mean of 12 methylation markers), and, and was validated in an independent dataset of 53 HVs and 58 BC patients. The area under the receiver operating characteristic curve for cancer-normal discrimination was 0.916 and 0.876 in the training and validation dataset, respectively. The sensitivity and the specificity of the model was 0.862 (stages 0-I 0.846, IIA 0.862, IIB-III 0.818, metastatic BC 0.935) and 0.827, respectively.ConclusionOur epigenetic-marker-based system distinguished BC patients from HVs with high accuracy. As detection of early BC using this system was comparable with that of mammography screening, this system would be beneficial as an optional method of screening for BC.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-016-0788-z) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Circulating cell-free DNA-based epigenetic assay can detect early breast cancer

Uehiro

Sato

et al. 2016

Breast Cancer Res

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“…As a result breast DCE-MRI has been recommended by American Cancer Society as an adjunct screening tool to mammography for women with life time breast cancer risk greater than 20%–25% since 2007 (3). In addition, breast MRI has played an important role in classifying breast tumors (i.e., ductal carcinoma in situ (DCIS) or invasive ductal carcinoma (IDC) with and without metastasis-positive lymph nodes (4)) and evaluate the tumor response to chemotherapy by comparing two sets of breast MR images acquired pre- and post-chemotherapy (5). …”

Section: Introductionmentioning

confidence: 99%

Applying a new quantitative global breast MRI feature analysis scheme to assess tumor response to chemotherapy

Aghaei

Tan

Hollingsworth

et al. 2016

Magnetic Resonance Imaging

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Purpose To develop a new quantitative global kinetic breast MRI features analysis scheme and assess its feasibility to assess tumor response to neoadjuvant chemotherapy. Methods A dataset involving breast MR images acquired from 151 cancer patients before neoadjuvant chemotherapy was used. Among them, 63 patients had complete response (CR) and 88 had partial response (PR) to chemotherapy based on the RECIST criterion. A computer-aided detection (CAD) scheme was applied to segment breast region depicted on the breast MR images and computed a total of 10 kinetic image features to represent parenchyma enhancement either from the entire two breasts or the bilateral asymmetry between the two breasts. To classify between CR and PR cases, we tested an attribution selected classifier that integrates with an artificial neural network and a Wrapper Subset Evaluator. The classifier was trained and tested using a leave-one-case-out (LOCO) based cross-validation method. The area under a receiver operating characteristic curve (AUC) was computed to assess classifier performance. Results From the pool of initial 10 features, 4 features were selected by more than 90% times in the LOCO cross-validation iterations. Among them, 3 represent the bilateral asymmetry of kinetic features between two breasts. Using the classifier yielded AUC = 0.83±0.04, which is significantly higher than using each individual feature to classify between CR and PR cases (p < 0.05). Conclusion This study demonstrated that quantitative analysis of global kinetic features computed from breast MR images acquired pre-chemotherapy has potential to generate a useful clinical marker that is associated with tumor response to neoadjuvant chemotherapy.

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“…), resulting in improved survival rates and a growing cohort of breast cancer survivors (Graham et al . ). Today, women with a history of breast cancer constitute the largest group of cancer survivors (Rowland et al .…”

Section: Introductionmentioning

confidence: 97%

‘Dropped from the system’: the experiences and challenges of long‐term breast cancer survivors

Matthews

Semper

2017

Journal of Advanced Nursing

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'Dropped from the system': the experiences and challenges of long term breast cancer survivors. AbstractAims: The aim of this study was to explore breast cancer patients' experiences during survivorship. Particular attention is given to the role of specialist breast care nurses in supporting women throughout this phase.Background: There is a relative lack of research involving long term breast cancer survivors.Yet, many survivors experience substantial psychosocial and iatrogenic harms created by diagnosis, symptoms of disease and treatment. A more comprehensive understanding may assist in supporting the needs of breast cancer survivors.Design: An exploratory qualitative approach was used to collect data on breast cancer survivors' experiences during 2013.Methods: Semi-structured interview data were collected from seven British women aged 38-80 years exploring the support received during survivorship. Data were analysed using Interpretive Phenomenological Analysis.Findings: Breast cancer survivors perceived a systemic absence in support from oncology teams and rapid deterioration of support from personal support networks. Despite this, survivors were able to find benefits from the cancer experience. This allowed for adjustment and enabled patients to assume a new identity as a breast cancer survivor. We recommend specialist breast care nurses would be suitably placed to provide extended support allowing for a salient transition from treatment to survivorship. How should the findings be used to influence policy, practise, research and education? Given the long-term unmet needs of breast cancer survivors and the continually increasing number of survivors, the findings of this study need to be more fully addressed both in terms of research and intervention. The findings of this study could be used as preliminary evidence, to highlight the need for continuation of support and phased termination of support, to replace the abrupt termination of support reported by breast cancer survivors at the end of treatment. Breast care nurses are a vital and somewhat limited resource. Consequently, resources should only be targeted at those who require additional support. The costeffectiveness of providing continuing support and the mode of administration (i.e. over the phone or videoconferencing) requires further research.

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Current Approaches and Challenges in Monitoring Treatment Responses in Breast Cancer

Cited by 97 publications

References 67 publications

Circulating cell-free DNA-based epigenetic assay can detect early breast cancer

Circulating cell-free DNA-based epigenetic assay can detect early breast cancer

Applying a new quantitative global breast MRI feature analysis scheme to assess tumor response to chemotherapy

‘Dropped from the system’: the experiences and challenges of long‐term breast cancer survivors

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