US2015079591A1PendingUtilityA1
Predicting response to chemotherapy using gene expression markers
Est. expiryNov 5, 2024(expired)· nominal 20-yr term from priority
A61P 35/00C12Q 1/6886G16B 20/00C12Q 2600/158G16B 25/00C12Q 2600/106G16B 20/20G16B 25/10
59
PatentIndex Score
0
Cited by
0
References
0
Claims
Abstract
The present invention provides gene expression information useful for predicting whether a cancer patient is likely to have a beneficial response to treatment with chemotherapy, comprising measuring, in a biological sample comprising a breast tumor sample obtained from the patient, the expression levels of gene subsets to obtain a risk score associated with a likelihood of a beneficial response to chemotherapy, wherein the score comprises at least one of the following variables: (i) Recurrence Score, (ii) ESRI Group Score; (iii) Invasion Group Score; (iv) Proliferation Group Score; and (v) the expression level of the RNA transcript of at least one of MYBL2 and SCUBE2, or the corresponding expression product. The invention further comprises a molecular assay-based algorithm to calculate the likelihood that the patient will have a beneficial response to chemotherapy based on the risk score.
Claims
exact text as granted — not AI-modified1 .- 41 . (canceled)
42 . A method for predicting the likelihood of a beneficial response to treatment with chemotherapy of a human patient diagnosed with breast cancer and treated with tamoxifen, comprising
(a) measuring a level of an RNA transcript of each of the genes BIRC5, MKi67, MYBL2, CCNB1, STK6, MMP11, SCUBE2, ERBB2, GRB7, ESR1, PGR, BCL2, CTSL2, GSTM1, CD68, and BAG1, in a biological sample comprising a breast tumor sample obtained from said human patient, (b) normalizing the level of the RNA transcript of each of the genes to obtain a normalized gene expression level for each gene, (c) determining the values of the following variables:
(i) Recurrence Score;
(ii) ESR1 Group Score;
(iii) Invasion Group Score; and
(iv) Proliferation Group Threshold Score
and,
(d) predicting the likelihood of a beneficial response to treatment with chemotherapy of the patient based on the values of the variables of step (c), (e1) for every unit of an increase in the value of one or more of (i), (iii), or (iv), said human patient is identified to have a proportionately increased likelihood of a beneficial response to said treatment; and (e2) for every unit of an increase in the value of (ii), said subject is identified to have a proportionately decreased likelihood of a beneficial response to said treatment; and (e3) for every unit of an increase in the value of (i), said human patient is identified as having an increased likelihood of a beneficial response to said treatment, as measured by a reduced risk of breast cancer recurrence; wherein ESR1 Group Score, (ESR1+PGR+BCL2+SCUBE2)/4; Invasion Group Score=(CTSL2+MMP11)/2; Proliferation Group Threshold Score equals 6.5, if a Proliferation Group Score is less than 6.5; and the Proliferation Group Threshold Score equals a Proliferation Group Score, if the Proliferation Group Score is 6.5 or more; wherein the Proliferation Group Score=(BIRC5+MKI67+MYBL2+CCNB 1+STK6)/5; and
Recurrence
Score
RS
=
{
0
if
20
×
(
RS
U
-
6.7
)
<
0
20
×
(
RS
U
-
6.7
)
if
0
≤
20
×
(
RS
U
-
6.7
)
≤
100
100
if
20
×
(
RS
U
-
6.7
)
>
100
wherein
RSu
(
Recurrence
Score
unscaled
)
=
0.47
×
GRB
7
Group
Threshold
Score
-
0.34
×
ESR
1
Group
Score
+
1.04
×
Proliferation
Group
Threshold
Score
+
0.10
×
Invasion
Group
Score
+
0.05
×
CD
68
-
0.08
×
GSTM
1
-
0.07
×
BAG
1
wherein the GRB7 Group Threshold Score equals 8, if a GRB7 Group Score is less than 8; and the GRB7 Group Threshold Score equals a GRB7 Group Score, if the GRB7 Group Score is 8 or more; wherein the GRB7 Group Score=0.9×GRB7+0.1×ERBB2;
wherein the gene symbols in the equations represent the normalized expression levels of the RNA transcripts of the respective genes.
43 . The method of claim 42 , wherein the normalized expression levels of all genes included in variables (i)-(iv) are normalized relative to the mean of the expression levels of ACTB, GAPD, GUSB, RPLPO, and TFRC.
44 . The method of claim 42 , wherein said breast cancer is ESR1 positive.
45 . The method of claim 42 , wherein said treatment is an adjuvant chemotherapy.
46 . The method of claim 42 , wherein said chemotherapy comprises an inhibitor of nucleotide biosynthesis.
47 . The method of claim 46 , wherein the inhibitor of nucleotide biosynthesis is selected from methotrexate, mercaptopurine, fluorouracil, and hydroxyurea.
48 . The method of claim 42 , wherein said chemotherapy comprises an anthracycline-based chemotherapy.
49 . The method of claim 48 , wherein said anthracycline-based chemotherapy is doxorubicin or adriamycin.
50 . The method of claim 42 , wherein said chemotherapy comprises a taxane derivative.
51 . The method of claim 50 , wherein said taxane derivative is paclitaxel or docetaxel.
52 . The method of claim 42 , wherein said chemotherapy comprises a topoisomerase inhibitor.
53 . The method of claim 42 , wherein said chemotherapy comprises cyclophosphamide, methotrexate, and fluorouracil.
54 . The method of claim 42 , wherein said tumor sample is from fine needle, core, or other types of biopsy.
55 . The method of claim 42 , wherein said measuring is quantitative.
56 . The method of claim 42 , wherein measurement of said level of an RNA transcript of at least one gene includes quantitative RT-PCR.
57 . The method of claim 42 , further comprising the step of creating a report summarizing said likelihood of beneficial response.
58 . The method of claim 42 , wherein the biological sample is a fixed, paraffin-embedded biological sample.Join the waitlist — get patent alerts
Track US2015079591A1 — get alerts on status changes and closely related new filings.
We store only your email — no account needed. See our privacy policy.