Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Post-treatment breast cancer prognosis

a breast cancer and prognosis technology, applied in the field of gene expression profiles, can solve the problems of breast cancer-free subjects treated for five years with tamoxifen, no means of direct letrozole treatment, and no means of providing letrozole treatment, and achieve the effect of superior stratification of the risk of recurren

Inactive Publication Date: 2013-10-24
THE GENERAL HOSPITAL CORP +1
View PDF2 Cites 12 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The patent discusses a way to determine the chances of its patients with cancer to come back or die from the disease. This is done by analyzing patterns of gene expression. This is an objective measure, separate from traditional methods that were based on subjective interpretation. Combining these patterns with other subjective criteria can lead to a more accurate assessment of a patient's outcome.

Problems solved by technology

Unfortunately, data from the field indicate that more than half of all breast cancer recurrences occur after five years of treatment with adjuvant tamoxifen.
But Goss et al. provided no means by which to predict which subjects, treated for five years with tamoxifen, would benefit from subsequent letrozole treatment.
Therefore, there was no means to direct letrozole treatment only to the subjects for whom a benefit is expected.
So letrozole treatment was applied to subjects for whom no benefit would have been expected, resulting in an overtreatment of the population of breast cancer-free subjects treated with for five years with tamoxifen.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Examples

Experimental program
Comparison scheme
Effect test

example i

General

Patients and Tumor Samples

[0096]Samples from the NCIC CTG MA.17 cohort (see Goss et al., J. Clin. Oncol., 26(12):1948-1955, 2008) were used. 100 cases with 200 controls were used. The 100 cases included 61 cases of distant cancer recurrence; 17 cases of local cancer recurrence; 5 cases of regional cancer recurrence; 16 cases of contralateral recurrences; and 1 unknown case. Of these, the contralateral and unknown cases were excluded.

[0097]Clinical follow-up data were available for the samples used, which were formalin-fixed paraffin-embedded (FFPE) tumor blocks from the time of diagnosis. Odds ratios were calculated with analysis of BCI, H:I, HoxB13 and MGI as continuous and categorical variables. Multivariate analysis also included age, tumor grade and treatment in the analysis. Treatment interaction: age and tumor grade were also included in the analysis. P-values were calculated for the interaction term.

[0098]Table 1 summarizes characteristics for the cases and controls (N...

example ii

Prognostic Performance

[0113]Table 2 shows the distribution of the cases and controls to the continuous BCI risk groups.

TABLE 2BCI group, (%)Cases (n = 83)Controls (n = 166)Low43.4%57.8%Intermediate22.9%18.1%High33.7%24.1%

[0114]Table 3 shows the univariate analysis in relation to cancer recurrence in MA.17 subjects.

TABLE 3Univariate analysis in relation to cancer recurrenceOdds Ratio (95% CI)P-valueTreatment (Placebo vs2.02 (1.17-3.47)0.01Letrozole)Tumor Grade0.28II vs. I1.73 (0.61-4.88)0.30III vs. I2.53 (0.81-7.90)0.11Analysis of BCIBCI2.38 (1.21-4.69)0.01BCI, High vs Low1.87 (1.00-3.50)0.05Analysis of components of BCIHoxB131.34 (1.05-1.70)0.02HoxB13, High vs Low2.17 (1.27-3.69)0.004H:I2.52 (1.08-5.85)0.03H:I, High vs Low1.68 (1.00-2.81)0.049MGI1.83 (0.93-3.58)0.08MGI, High vs Low1.49 (0.87-2.56)0.15

[0115]Table 4 shows multivariate analysis in relation to cancer recurrence

TABLE 4Multivariate analysis in relation to cancer recurrenceOdds Ratio (95% CI)P-valueAnalysis with BCIBCI2.37...

example iii

Biomarker and Treatment Interaction

[0117]Table 5 shows interactions between the gene expression analyzed and treatment.

TABLE 5Biomarker and Treatment InteractionP-valueHoxB130.047H:I0.97MGI0.06BCI0.42BCI High vs Intermediate + Low0.08

[0118]Table 6 shows the distribution of HoxB13 gene expression in relation to treatments used. HoxB13 expression at diagnosis predicts patient benefit from extended endocrine therapy with letrozole after 5 years of adjuvant tamoxifen therapy.

TABLE 6LetrozolePlaceboControlsCasesControlsCasesP-valueLow HoxB134814 (23%)4616 (26%)0.83High HoxB134317 (28%)2936 (55%)0.004

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

PropertyMeasurementUnit
timeaaaaaaaaaa
timeaaaaaaaaaa
timeaaaaaaaaaa
Login to View More

Abstract

The disclosure includes the identification and use of gene expression profiles, or patterns, with clinical relevance to extended treatment and cancer-free survival in a patient. In particular, the disclosure includes the identities of genes that are expressed in correlation with benefit in a switch in endocrine therapy used to treat a patient. The levels of gene expression are disclosed as a molecular index for predicting clinical outcome, and so prognosis, for the patient. The disclosure further includes methods for predicting cancer recurrence, and / or predicting occurrence of metastatic cancer, after initial treatment with an anti-estrogen agent. The disclosure further includes methods for determining or selecting the treatment of a subject based upon the likelihood of life expectancy, cancer recurrence, and / or cancer metastasis.

Description

RELATED APPLICATIONS[0001]This application is a continuation of PCT Application PCT / US2011 / 064290, filed Dec. 9, 2011 and published as WO 2012 / 079059 with designation of the U.S., and which claims benefit of priority to U.S. Provisional Patent Application 61 / 421,627, filed Dec. 9, 2010, both of which is hereby incorporated by reference in their entireties as if fully set forth herein.[0002]This application is related to International Application No. PCT / US2008 / 075528, filed on Sep. 6, 2008 (published as WO 2009 / 108215 A1) with designation of the U.S., and to U.S. patent application Ser. No. 12 / 718,973, filed Mar. 6, 2010. Both applications are hereby incorporated by reference as if fully set forth herein.FIELD OF THE DISCLOSURE[0003]The disclosure relates to the identification and use of gene expression profiles, or patterns, with clinical relevance to breast cancer. In particular, the disclosure is based in part on the identities of genes that are expressed in correlation with the ...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(United States)
IPC IPC(8): C12Q1/68
CPCC12Q1/6886A61P35/00C12Q2600/106C12Q2600/118C12Q2600/158
Inventor SGROI, DENNISERLANDER, MARK G.ZHANG, YISCHNABEL, CATHERINE A.
Owner THE GENERAL HOSPITAL CORP
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products