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
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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
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