Abstract:
BACKGROUND:We recently showed PAM50 gene expression data can be represented by five quantitative, orthogonal, multi-gene breast tumor traits. These novel tumor 'dimensions' were superior to categorical intrinsic subtypes for clustering in high-risk breast cancer pedigrees, indicating potential to represent underlying genetic susceptibilities and biological pathways. Here we explore the prognostic and predictive utility of these dimensions in a sub-study of GEICAM/9906, a Phase III randomized prospective clinical trial of paclitaxel in breast cancer. METHODS:Tumor dimensions, PC1-PC5, were calculated using pre-defined coefficients. Univariable and multivariable Cox proportional hazards (PH) models for disease-free survival (DFS) were used to identify associations between quantitative dimensions and prognosis or response to the addition of paclitaxel. Results were illustrated using Kaplan-Meier curves. RESULTS:Dimensions PC1 and PC5 were associated with DFS (Cox PH p = 6.7 [Formula: see text] 10-7 and p = 0.036), remaining significant after correction for standard clinical-pathological prognostic characteristics. Both dimensions were selected in the optimal multivariable model, together with nodal status and tumor size (Cox PH p = 1.4 [Formula: see text] 10-12). Interactions with treatment were identified for PC3 and PC4. Response to paclitaxel was restricted to tumors with low PC3 and PC4 (log-rank p = 0.0021). Women with tumors high for PC3 or PC4 showed no survival advantage. CONCLUSIONS:Our proof-of-concept application of quantitative dimensions illustrated novel findings and clinical utility beyond standard clinical-pathological characteristics and categorical intrinsic subtypes for prognosis and predicting chemotherapy response. Consideration of expression data as quantitative tumor dimensions offers new potential to identify clinically important patient subsets in clinical trials and advance precision medicine.
journal_name
Breast Cancer Res Treatjournal_title
Breast cancer research and treatmentauthors
Camp NJ,Madsen MJ,Herranz J,Rodríguez-Lescure Á,Ruiz A,Martín M,Bernard PSdoi
10.1007/s10549-018-05097-5subject
Has Abstractpub_date
2019-05-01 00:00:00pages
129-139issue
1eissn
0167-6806issn
1573-7217pii
10.1007/s10549-018-05097-5journal_volume
175pub_type
杂志文章abstract::The sub-nipple tissue (SNT) examination has been used by surgeons to preserve, or not, the nipple in nipple-sparing mastectomy. However, it is uncertain whether SNT evaluation can predict nipple involvement. The aim of this study was to evaluate the accuracy, sensitivity, specificity, PPV, and NPV of the intraoperativ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-015-3568-z
更新日期:2015-10-01 00:00:00
abstract::False-positive results may influence adherence to mammography screening. The effectiveness of breast cancer screening is closely related to adequate adherence among the target population. The objective of this study was to evaluate how false-positives and women's characteristics affect the likelihood of reattendance a...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-011-1581-4
更新日期:2011-11-01 00:00:00
abstract::The association between promoter methylation status and survival was investigated in a large cohort of women with breast cancer, participants in the Long Island Breast Cancer Study Project. Archived tumor tissues (n = 839) were collected from women diagnosed with a first primary invasive or in situ breast cancer in 19...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-011-1712-y
更新日期:2012-01-01 00:00:00
abstract::The effects of pituitary adenylate cyclase activating polypeptide (PACAP) analogs were investigated using breast cancer cells. 125I-PACAP-27 bound with high affinity (Kd = 5 nM) to T47D cells (Bmax = 29,000 per cell). Specific 125I-PACAP-27 binding was inhibited half maximally by PACAP-27, PACAP-38, PACAP(6-38) and PA...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1023/a:1006262611290
更新日期:1999-07-01 00:00:00
abstract::Methylthioadenosine (MTA) phosphorylase activity was measured in 47 biopsies from primary breast cancers (n = 34) and metastatic tumors (n = 13). Most specimens were also evaluated by DNA flow cytometry and determination of estrogen and progesterone receptor contents. Median MTA phosphorylase activity was 317 pmol/mg ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/BF01806694
更新日期:1987-01-01 00:00:00
abstract::Invasion factors uPA/PAI-1 are guideline-recommended (ASCO, AGO) biomarkers for decision support regarding adjuvant chemotherapy (CTX) in women with primary breast cancer. They define a high-risk group with strong benefit from adjuvant CTX and a low-risk group with uncertain benefit and excellent survival without CTX....
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,随机对照试验
doi:10.1007/s10549-013-2496-z
更新日期:2013-04-01 00:00:00
abstract::Estrogen has an important role in stimulating the growth of breast carcinomas. Inhibition of estrogen production is therefore a logical treatment strategy. A number of selective inhibitors have been developed against aromatase, a cytochrome P-450 enzyme which catalyzes the rate limiting step in the biosynthesis of est...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,评审
doi:10.1007/BF00682736
更新日期:1994-01-01 00:00:00
abstract::To determine the incidence of microsatellite instability (MSI) and its relationship with both clinicopathologic parameters and patient survival, 101 cases of breast cancer were investigated. In addition, transforming growth factor-beta (TGF-beta) receptor type II (RII) gene mutation was also examined to clarify the re...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1023/a:1006167210269
更新日期:1999-01-01 00:00:00
abstract:BACKGROUND:After experiencing a distant recurrence, breast cancer patients have a poor prognosis; fewer than 5% survive for ten or more years. However, the time to death is highly variable, ranging from a few months to many years. The purpose of this study is to identify, in a large hospital-based series of patients wi...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-018-5002-9
更新日期:2019-01-01 00:00:00
abstract::The transition from screen-film to digital mammography may have altered diagnostic evaluation of women following a positive screening examination. This study compared the use and timeliness of diagnostic imaging and biopsy for women screened with screen-film or digital mammography. Data were obtained from 35,321 posit...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,多中心研究
doi:10.1007/s10549-013-2466-5
更新日期:2013-04-01 00:00:00
abstract::The AZURE trial is an ongoing phase III, academic, multi-centre, randomised trial designed to evaluate the role of zoledronic acid (ZOL) in the adjuvant therapy of women with stage II/III breast cancer. Here, we report the safety and tolerability profile of ZOL in this setting. Eligible patients received (neo)adjuvant...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,随机对照试验
doi:10.1007/s10549-011-1429-y
更新日期:2011-06-01 00:00:00
abstract::Mammographic density is strongly associated with breast cancer risk. Inflammation is involved in breast carcinogenesis, perhaps through effects on mammographic density. We evaluated associations between inflammatory markers interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) and mammogr...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-010-1249-5
更新日期:2011-06-01 00:00:00
abstract:PURPOSE:The American Society of Clinical Oncology recommends concurrent palliative care (PC) for patients with metastatic cancer. Recent data show benefits of early PC (at least 90 days before death). However, little is known about PC among patients who die from metastatic breast cancer. METHODS:Patients with metastat...
journal_title:Breast cancer research and treatment
pub_type: 临床试验,杂志文章
doi:10.1007/s10549-017-4556-2
更新日期:2018-02-01 00:00:00
abstract:PURPOSE:Compared to breast cancer risk genes such as BRCA2, ATM, PALB2, and NBN, no defined phenotype is currently associated with biallelic pathogenic variants (PVs) in CHEK2. This study compared the prevalence of breast and other cancers in women with monoallelic and biallelic CHEK2 PVs. METHODS:CHEK2 PV carriers we...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-020-05543-3
更新日期:2020-04-01 00:00:00
abstract:PURPOSE:Extending adjuvant endocrine therapy (ET) beyond 5 years has been shown to improve outcomes in breast cancer; however, limited data are available about if and why women pursue extended ET. The primary objective was to estimate the proportion of women who were willing to receive extended ET if recommended by the...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-019-05145-8
更新日期:2019-05-01 00:00:00
abstract:PURPOSE:The stage-specific survival of young breast cancer patients has improved, likely due to diagnostic and treatment advances. We addressed whether survival improvements have reached all socioeconomic groups in a country with universal health care and national treatment guidelines. METHODS:Using Norwegian registry...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-020-05698-z
更新日期:2020-07-01 00:00:00
abstract::We evaluated the question of whether the chemosensitizers verapamil and quinine given orally to breast cancer patients failing combination chemotherapy alone would result in additional clinical responses. In vitro studies reported here showed verapamil sensitization of Adriamycin resistance in 18.8% of fresh human bre...
journal_title:Breast cancer research and treatment
pub_type: 临床试验,杂志文章
doi:10.1023/a:1005716214718
更新日期:1997-01-01 00:00:00
abstract::Indole-3-carbinol (I3C) is a promising phytochemical agent in chemoprevention of breast cancer. Our present study is the first description of I3C that significantly inhibits the cell adhesion, spreading and invasion associated with an up-regulation of PTEN (a tumor suppressor gene) and E-cadherin (a regulator of cell-...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1023/a:1006495824158
更新日期:2000-09-01 00:00:00
abstract::Metformin may exert anti-cancer effects through indirect (insulin-mediated) or direct (insulin-independent) mechanisms. We report results of a neoadjuvant "window of opportunity" study of metformin in women with operable breast cancer. Newly diagnosed, untreated, non-diabetic breast cancer patients received metformin ...
journal_title:Breast cancer research and treatment
pub_type: 临床试验,杂志文章
doi:10.1007/s10549-012-2223-1
更新日期:2012-10-01 00:00:00
abstract::Detection of disseminated tumour cells (DTCs) in bone marrow by immunocytochemistry (ICC) includes morphological evaluation of cytokeratin immunopositive cells. The aim of this study was to disclose the prognostic significance of different morphological categories of ICC-positive cells according to treatment status an...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-013-2439-8
更新日期:2013-04-01 00:00:00
abstract::The proportional hazards model is frequently used in analyzing the results of clinical trials, when it is often the case that the outcomes are right-censored. This model allows one to measure treatment effects and simultaneously identify and adjust for prognostic factors that might influence the outcome. In this paper...
journal_title:Breast cancer research and treatment
pub_type: 临床试验,杂志文章
doi:10.1007/BF01840837
更新日期:1992-01-01 00:00:00
abstract::Mammographic density is a strong risk factor for breast cancer, but limited data are available in African American (AA) women. We examined the association between mammographic density and breast cancer risk in AA and white women. Cases (n = 491) and controls (n = 528) were from the Carolina Breast Cancer Study (CBCS) ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-012-2185-3
更新日期:2012-09-01 00:00:00
abstract::The early spread of tumor cells in primary breast cancer patients may occur either through lymphatic or hematogenous dissemination. Lymph node (LN) status and presence of disseminated tumor cells (DTC) in bone marrow (BM) are independent predictors of poor outcome. It is unknown which factors determine one or the othe...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-011-1802-x
更新日期:2012-01-01 00:00:00
abstract::The aromatase inhibitors (AIs) are used to treat estrogen receptor-positive (ER+) breast tumors in post-menopausal women, and function by blocking the conversion of adrenal androgens to estrogens by the enzyme CYP19 aromatase. Breast cancer patients receiving AI therapy have circulating estrogen levels below the level...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-008-0080-8
更新日期:2009-05-01 00:00:00
abstract::Macroautophagy (autophagy), a process for lysosomal degradation of organelles and long-lived proteins, has been linked to various pathologies including cancer and to the cellular response to anticancer therapies. In the human estrogen receptor positive MCF7 breast adenocarcinoma cell line, treatment with the endocrine...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-007-9873-4
更新日期:2008-12-01 00:00:00
abstract:PURPOSE:The selective treatment of internal mammary lymph nodes (IMNs) in breast cancer is controversial. The purpose of this research was to determine the subpopulation patients with high risk of internal mammary lymph nodes metastasis who received extended radical mastectomy without any preoperative treatment from 19...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-007-9561-4
更新日期:2008-02-01 00:00:00
abstract::Sustained breast cancer growth and metastasis requires paracrine signals between the tumor cells and the normal surrounding host tissue. One crucial function of these signals is to recruit endothelial cells and thus new blood vessels for the nourishment of the expanding tumor mass. This proliferation and migration of ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,评审
doi:10.1007/BF00666148
更新日期:1994-01-01 00:00:00
abstract:PURPOSE:Time to surgery (TTS) is a potentially modifiable factor associated with survival after breast cancer diagnosis and can serve as a proxy for quality of oncologic care coordination. We sought to determine whether factors associated with delays in TTS vary between patients who receive neoadjuvant systemic therapy...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-020-06012-7
更新日期:2020-11-18 00:00:00
abstract::Although younger women with breast cancer have the most to gain from receipt of optimal care, few data are available regarding their receipt of locoregional breast cancer treatments. We identified 317,596 women aged 18-64 who were diagnosed with invasive breast cancer at hospitals reporting to the National Cancer Data...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-012-2156-8
更新日期:2012-10-01 00:00:00
abstract::Co-transfection studies indicate that HER2 (erbB-2) overexpression results in the phosphorylation and enhanced transcriptional activity of the androgen receptor (AR). This amplification of AR action is further enhanced by the expression of ARA70, a putative co-activator with a predilection for the AR. Because androgen...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1023/a:1017938608460
更新日期:2001-06-01 00:00:00