Abstract:
BACKGROUND:Breast cancer patients with early-stage disease are increasingly administered neoadjuvant chemotherapy (NAC) to downstage their tumors prior to surgery. In this setting, approximately 31% of patients fail to respond to therapy. This demonstrates the need for techniques capable of providing personalized feedback about treatment response at the earliest stages of therapy to identify patients likely to benefit from changing treatment. Diffuse optical spectroscopic imaging (DOSI) has emerged as a promising functional imaging technique for NAC monitoring. DOSI uses non-ionizing near-infrared light to provide non-invasive measures of absolute concentrations of tissue chromophores such as oxyhemoglobin. In 2011, we reported a new DOSI prognostic marker, oxyhemoglobin flare: a transient increase in oxyhemoglobin capable of discriminating NAC responders within the first day of treatment. In this follow-up study, DOSI was used to confirm the presence of the flare as well as to investigate whether DOSI markers of NAC response are regimen dependent. METHODS:This dual-center study examined 54 breast tumors receiving NAC measured with DOSI before therapy and the first week following chemotherapy administration. Patients were treated with either a standard of care maximum tolerated dose (MTD) regimen or an investigational metronomic (MET) regimen. Changes in tumor chromophores were tracked throughout the first week and compared to pathologic response and treatment regimen at specific days utilizing generalized estimating equations (GEE). RESULTS:Within patients receiving MTD therapy, the oxyhemoglobin flare was confirmed as a prognostic DOSI marker for response appearing as soon as day 1 with post hoc GEE analysis demonstrating a difference of 48.77% between responders and non-responders (p < 0.0001). Flare was not observed in patients receiving MET therapy. Within all responding patients, the specific treatment was a significant predictor of day 1 changes in oxyhemoglobin, showing a difference of 39.45% (p = 0.0010) between patients receiving MTD and MET regimens. CONCLUSIONS:DOSI optical biomarkers are differentially sensitive to MTD and MET regimens at early timepoints suggesting the specific treatment regimen should be considered in future DOSI studies. Additionally, DOSI may help to identify regimen-specific responses in a more personalized manner, potentially providing critical feedback necessary to implement adaptive changes to the treatment strategy.
journal_name
Breast Cancer Resjournal_title
Breast cancer research : BCRauthors
Tank A,Peterson HM,Pera V,Tabassum S,Leproux A,O'Sullivan T,Jones E,Cabral H,Ko N,Mehta RS,Tromberg BJ,Roblyer Ddoi
10.1186/s13058-020-01262-1subject
Has Abstractpub_date
2020-03-13 00:00:00pages
29issue
1eissn
1465-5411issn
1465-542Xpii
10.1186/s13058-020-01262-1journal_volume
22pub_type
杂志文章abstract:BACKGROUND:The underlying biological mechanisms through which epidemiologically defined breast cancer risk factors contribute to disease risk remain poorly understood. Identification of the molecular changes associated with cancer risk factors in normal tissues may aid in determining the earliest events of carcinogenes...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-017-0873-y
更新日期:2017-07-10 00:00:00
abstract:INTRODUCTION:Oestrogens can mediate some of their cell survival properties through a nongenomic mechanism that involves the mitogen-activated protein kinase (MAPK) pathway. The mechanism of this rapid signalling and its dependence on a membrane bound oestrogen receptor (ER), however, remains controversial. The role of ...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr1509
更新日期:2006-01-01 00:00:00
abstract:BACKGROUND:MicroRNAs (miRNAs) regulate gene expression and influence cancer. Primary transcripts of miRNAs (pri-miRNAs) are poorly annotated and little is known about the role of germline variation in miRNA genes and breast cancer (BC). We sought to identify germline miRNA variants associated with BC risk and tumor sub...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-018-0964-4
更新日期:2018-06-05 00:00:00
abstract:INTRODUCTION:The Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer (kConFab) is a multidisciplinary, collaborative framework for the investigation of familial breast cancer. Based in Australia, the primary aim of kConFab is to facilitate high-quality research by amassing a large and comp...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr1377
更新日期:2006-01-01 00:00:00
abstract:BACKGROUND:Metastasis is the major cause of death from breast cancer. Colonization and adaption of metastatic cells in distant organs is a rate-limiting step of the cancer spreading. The underlying mechanisms responsible for the colonization of breast cancer to lung metastatic niches are not fully understood. METHODS:...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-019-1114-3
更新日期:2019-02-12 00:00:00
abstract:INTRODUCTION:The amplification event occurring at chromosome locus 11q13, reported in several different cancers, includes a number of potential oncogenes. We have previously reported amplification of one such oncogene, namely CCND1, to be correlated with an adverse effect of tamoxifen in premenopausal breast cancer pat...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr2150
更新日期:2008-01-01 00:00:00
abstract::A new gene associated with a high risk of breast cancer, termed BRCAX, may exist on chromosome 13q. Tumours from multicase Nordic breast cancer families, in which mutations in BRCA1 and BRCA2 had been excluded, were analyzed using comparative genomic hybridization in order to identify a region of interest, which was a...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,评审
doi:10.1186/bcr290
更新日期:2001-01-01 00:00:00
abstract::Breast cancer arises from multiple genetic events that together contribute to the established, irreversible malignant phenotype. The development of inducible tissue-specific transgenics has allowed a careful dissection of the events required for induction and subsequent maintenance of tumorigenesis. Mammary gland targ...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr297
更新日期:2001-01-01 00:00:00
abstract:INTRODUCTION:Breast cancer researchers use cell lines to model myriad phenomena ranging from DNA repair to cancer stem cell phenotypes. Though appropriate, and even requisite, for many studies, the suitability of cell lines as tumour models has come into question owing to possibilities of tissue culture artefacts and c...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-015-0613-0
更新日期:2015-08-20 00:00:00
abstract::The concept of cancer stem cells responsible for tumour origin, maintenance, and resistance to treatment has gained prominence in the field of breast cancer research. The therapeutic targeting of these cells has the potential to eliminate residual disease and may become an important component of a multimodality treatm...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,评审
doi:10.1186/bcr2111
更新日期:2008-01-01 00:00:00
abstract:BACKGROUND:While dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) is recognized as the most sensitive examination for breast cancer detection, it has a substantial false positive rate and gadolinium (Gd) contrast agents are not universally well tolerated. As a result, alternatives to diagnosing breast can...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-017-0902-x
更新日期:2017-10-24 00:00:00
abstract:INTRODUCTION:Primary breast cancer involving four or more axillary lymph nodes carries a poor prognosis. We hypothesized that use of an immunohistochemical biomarker scoring system could allow for identification of variable risk subgroups. METHODS:Patients with four or more positive axillary nodes were identified from...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,随机对照试验
doi:10.1186/bcr1847
更新日期:2008-01-01 00:00:00
abstract::Hypoxia-inducible factor-1 (HIF), which is centrally involved in physiological oxygen homeostasis, is also activated in the majority of tumours. Activation of HIF can occur through genetic mechanisms or as a result of hypoxia within the tumour microenvironment. In some cases HIF activation appears to be intimately lin...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,评审
doi:10.1186/bcr313
更新日期:2001-01-01 00:00:00
abstract:BACKGROUND:Recent genome-wide profiling by sequencing and distinctive chromatin signatures has identified thousands of long non-coding RNA (lncRNA) species (>200 nt). LncRNAs have emerged as important regulators of gene expression, involving in both developmental and pathological processes. While altered expression of ...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-017-0853-2
更新日期:2017-05-30 00:00:00
abstract:INTRODUCTION:Protein tyrosine kinase 6 (PTK6) is a non-receptor tyrosine kinase that is highly expressed in Human Epidermal Growth Factor 2(+) (Her2(+)) breast cancers. Overexpression of PTK6 enhances anchorage-independent survival, proliferation, and migration of breast cancer cells. We hypothesized that PTK6 inhibiti...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-015-0594-z
更新日期:2015-06-19 00:00:00
abstract:INTRODUCTION:Molecular apocrine (MA) tumors are estrogen receptor (ER) negative breast cancers characterized by androgen receptor (AR) expression. We analyzed a group of 58 transcriptionally defined MA tumors and proposed a new tool to identify these tumors. METHODS:We performed quantitative reverse transcription PCR ...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr3421
更新日期:2013-05-11 00:00:00
abstract::The potential for a reduction in dietary fat or for an increase in dietary fiber to reduce breast cancer risk has been debated for some years. It is argued here that available research data, even though extensive, leave open hypotheses ranging from little or no potential to major public health potential for breast can...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,评审
doi:10.1186/bcr68
更新日期:2000-01-01 00:00:00
abstract:BACKGROUND:Mammographic density (MD) is a strong and heritable intermediate phenotype of breast cancer, but much of its genetic variation remains unexplained. METHODS:We conducted a genetic association study of volumetric MD in a Swedish mammography screening cohort (n = 9498) to identify novel MD loci. Associations w...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-018-0954-6
更新日期:2018-04-17 00:00:00
abstract:INTRODUCTION:Increased mammographic breast density is one of the strongest risk factors for breast cancer. While two-thirds of the variation in mammographic density appears to be genetically influenced, few variants have been identified. We examined the association of inherited variation in genes from pathways that med...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr3088
更新日期:2012-01-07 00:00:00
abstract:INTRODUCTION:Mammographic density is one of the strongest risk factors for breast cancer and is believed to represent epithelial and stromal proliferation. Because of the high heritability of breast density, and the role of the insulin-like growth factor (IGF) pathway in cellular proliferation and breast development, w...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr1655
更新日期:2007-01-01 00:00:00
abstract:BACKGROUND:Breast cancer is a highly heterogeneous disease characterized by multiple histologic and molecular subtypes. While a myriad of breast cancer cell lines have been developed over the past 60 years, estrogen receptor alpha (ER)+ disease and some mutations associated with this subtype remain underrepresented. He...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-020-01300-y
更新日期:2020-06-23 00:00:00
abstract:INTRODUCTION:Surgery is currently the definitive treatment for early-stage breast cancer. However, the rate of positive surgical margins remains unacceptably high. The human sodium iodide symporter (hNIS) is a naturally occurring protein in human thyroid tissue, which enables cells to concentrate radionuclides. The hNI...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr3404
更新日期:2013-03-18 00:00:00
abstract:BACKGROUND:Breast cancer stem cells (BCSCs) are typically seed cells of breast tumor that initiate and maintain tumor growth. MiR-7, as a cancer inhibitor, decreases the BCSC subset and inhibits tumor progression through mechanisms that remain unknown. METHODS:We examined miR-7 expression in breast cancer and develope...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-020-01264-z
更新日期:2020-03-06 00:00:00
abstract:INTRODUCTION:Reliable predictive and prognostic markers for routine diagnostic purposes are needed for breast cancer patients treated with neoadjuvant chemotherapy. We evaluated protein biomarkers in a cohort of 116 participants of the GeparDuo study on anthracycline/taxane-based neoadjuvant chemotherapy for operable b...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1186/bcr2363
更新日期:2009-01-01 00:00:00
abstract::PIK3CA mutations represent one of the most common genetic aberrations in breast cancer. They have been reported to be present in over one-third of cases, with enrichment in the luminal and in human epidermal growth factor receptor 2-positive subtypes. Substantial preclinical data on the oncogenic properties of these m...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,评审
doi:10.1186/bcr3605
更新日期:2014-01-23 00:00:00
abstract:INTRODUCTION:Activated leukocyte cell adhesion molecule (ALCAM) (CD166) is an immunoglobulin molecule that has been implicated in cell migration. The present study examined the expression of ALCAM in human breast cancer and assessed its prognostic value. METHODS:The immunohistochemical distribution and location of ALC...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr815
更新日期:2004-01-01 00:00:00
abstract::It is generally accepted that early detection of breast cancer has great impact on patient survival, emphasizing the importance of early diagnosis. In a widely recognized model of breast cancer development, tumor cells progress through chronological and well defined stages. However, the molecular basis of disease prog...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,评审
doi:10.1186/bcr1528
更新日期:2006-01-01 00:00:00
abstract::Homeobox (HOX) genes play key roles in embryogenesis and tissue differentiation. Recently, a number of groups have reported altered HOX gene expression in breast cancer. However, the mechanism of HOX gene regulation and the search for direct targets of its transcriptional regulatory function have been minimally fruitf...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr2600
更新日期:2010-01-01 00:00:00
abstract::Transforming growth factor-beta (TGF-beta) is a tumor suppressor, the function of which is compromised in many types of human cancer, including breast cancer. The tumor suppressive effects of TGF-beta are caused by potent inhibition of cell proliferation due to cell cycle arrest in the G1 phase. Such antiproliferative...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,评审
doi:10.1186/bcr42
更新日期:2000-01-01 00:00:00
abstract:INTRODUCTION:Metastasis is the main cause of breast cancer morbidity and mortality. Processes that allow for tumor cell migration and invasion are important therapeutic targets. Here we demonstrate that receptor-interacting protein kinase 2 (RIP2), a kinase known to be involved in inflammatory processes, also has novel...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr3629
更新日期:2014-03-19 00:00:00