Granted Patent
B2
US 12,571,798 · App. 13/094,729 · Granted Mar 10, 2026
Cancer biomarkers and methods of use thereof
Inventors:
Karla Kerlikowske (San Anselmo, CA); Thea D. Tlsty (San Francisco, CA); Mona L. Gauthier (Toronto, CA); Hal K. Berman (San Francisco, CA); Troy Bremer (Irvine, CA); Annette M. Molinaro (New Haven, CT)
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Abstract
Embodiments are provided for characterizing a biological sample. In some embodiments, one can estimate the risk that a subject with ductal carcinoma in situ will have a subsequent DCIS event and/or invasive cancers.
Claims (48)
1 . A method of treating breast cancer in a subject, comprising:
collecting a tissue sample from an initial DCIS lesion from a subject;
analyzing a cell signature of the tissue sample, comprising:
contacting the tissue sample with an antibody protein specific for Ki67, detecting staining of at least 10% of tumor cells in the tissue sample by the antibody protein specific for Ki67, and identifying the sample as positive for Ki67;
contacting the tissue sample with an antibody protein specific for PR, detecting staining of less than 10% of tumor cells in the tissue sample by the antibody protein specific for PR, and identifying the sample as negative for PR; and
contacting the tissue sample with an antibody protein specific for ERBB2, detecting moderate or strong membrane staining of at least 10% of tumor cells in the tissue sample by the antibody protein specific for ERBB2, and identifying the sample as positive for ERBB2;
determining that the cell signature of the tissue sample is at least: positive for Ki67, negative for PR, and positive for ERBB2;
placing the subject in a high risk of recurrence category for subsequent ipsilateral breast cancer based on at least the analysis of the cell signature; and
treating the subject for the initial DCIS lesion, wherein the treatment comprises: removing the DCIS lesion by performing a lumpectomy with an adjuvant therapy; or performing a mastectomy on the subject, to thereby reduce a risk of subsequent ipsilateral breast cancer in the subject.
2 . The method of claim 1 , wherein the subject is less than 50 years old.
3 . The method of claim 1 , wherein the subject is 40-49 years old.
4 . The method of claim 2 , wherein analyzing the cell signature of the tissue sample further comprises:
detecting whether said sample is positive for COX-2, comprising contacting the tissue sample with at least one of an antibody protein, nucleic acid probe, or nucleic acid primer specific for COX-2 and detecting binding or absence of binding of the antibody protein, nucleic acid probe, or nucleic acid primer specific for COX-2;
detecting whether said sample is positive for p16, comprising contacting the tissue sample with at least one of an antibody protein, nucleic acid probe, or nucleic acid primer specific for p16 and detecting binding or absence of binding of the antibody protein, nucleic acid probe, or nucleic acid primer specific for p16;
determining that the cell signature of the tissue sample is further: p16 positive and COX-2 negative.
5 . The method of claim 4 , wherein
the sample is positive for p16 when at least 25% of tumor cells in the tissue sample is stained by the antibody protein specific for p16, and
the sample is positive for COX-2 when the tissue sample has an Allred score of at least 5 when stained with the antibody protein specific for COX-2.
6 . The method of claim 2 , wherein the adjuvant therapy is radiation therapy.
7 . The method of claim 2 , wherein a tumor-free margin of the removed DCIS lesion is 2 mm or greater.
8 . The method of claim 2 , wherein placing the subject in the risk category for subsequent breast cancer is independent of the nuclear grade of the initial DCIS lesion.
9 . The method of claim 2 , wherein the initial DCIS lesion does not have high nuclear grade.
10 . The method of claim 2 , further comprising, before collecting the tissue sample:
detecting the DCIS lesion by one or more of palpation, mammography, and magnetic resonance imaging (MRI); and
identifying the subject as in need of treating the DCIS lesion.
11 . A method of treating breast cancer in a subject, comprising:
having a tissue sample collected from an initial DCIS lesion from a subject;
having an analysis of a cell signature carried out on the tissue sample, the analysis of the cell signature comprising:
contacting the tissue sample with an antibody protein specific for Ki67, detecting staining of at least 10% of tumor cells in the tissue sample by the antibody protein specific for Ki67, and identifying the sample as positive for Ki67;
contacting the tissue sample with an antibody protein specific for PR, detecting staining of less than 10% of tumor cells in the tissue sample by the antibody protein specific for PR, and identifying the sample as negative for PR; and
contacting the tissue sample with an antibody protein specific for ERBB2, detecting moderate or strong membrane staining of at least 10% of tumor cells in the tissue sample by the antibody protein specific for ERBB2, and identifying the sample as positive for ERBB2;
receiving a report comprising a treatment recommendation based on at least the analysis that the cell signature of said sample that is at least positive for Ki67, negative for PR, and positive for ERBB2, wherein the subject is placed in a high risk category for subsequent ipsilateral breast cancer based on at least the analysis of the cell signature;
wherein the recommended treatment is commensurate with the subject's risk category for subsequent ipsilateral breast cancer; and
receiving the recommended treatment for the initial DCIS lesion, wherein the recommended treatment comprises: a lumpectomy with an adjuvant therapy or a mastectomy, to thereby reduce a risk of subsequent ipsilateral breast cancer.
12 . The method of claim 11 , wherein the subject is less than 50 years old.
13 . The method of claim 11 , wherein the subject is 40-49 years old.
14 . The method of claim 12 , wherein said antibody protein specific for Ki67, said antibody protein specific for PR, and said antibody protein specific for ERBB2 are part of a reagent panel consisting of:
said antibody protein specific for Ki67;
said antibody protein specific for PR; and
antibody protein specific for ERBB2.
15 . The method of claim 12 , wherein the analysis of the cell signature further comprises:
detecting whether said sample is positive for COX-2, comprising contacting the tissue sample with at least one of an antibody protein, nucleic acid probe, or nucleic acid primer specific for COX-2 and detecting binding or absence of binding of the antibody protein, nucleic acid probe, or nucleic acid primer specific for COX-2; and
detecting whether said sample is positive for p16, comprising contacting the tissue sample with at least one of an antibody protein, nucleic acid probe, or nucleic acid primer specific for p16 and detecting binding or absence of binding of the antibody protein, nucleic acid probe, or nucleic acid primer specific for p16.
16 . The method of claim 15 , wherein
the sample is positive for p16 when at least 25% of tumor cells in the tissue sample is stained by the antibody protein specific for p16, and
the sample is positive for COX-2 when the tissue sample has an Allred score of at least 5 when stained with the antibody protein specific for COX-2.
17 . The method of claim 12 , wherein the adjuvant therapy is radiation therapy.
18 . The method of claim 12 , wherein a tumor-free margin of the removed DCIS lesion is 2 mm or greater.
Assignments (6)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Apr 1, 2025
From: BREMER, TROY M.
To: PRELUDE CORPORATION
Reel/Frame 070698/0090 →
CORRECTIVE ASSIGNMENT TO CORRECT THE ASSIGNEE'S NAME PREVIOUSLY RECORDED AT REEL: 026978 FRAME: 0841. ASSIGNOR(S) HEREBY CONFIRMS THE ASSIGNMENT.
Recorded Jun 18, 2019
From: BREMER, TROY M.
To: PRELUDE CORPORATION
Reel/Frame 049512/0232 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Sep 20, 2011
From: BREMER, TROY M.
To: PRELUDE, INC.
Reel/Frame 026978/0841 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Sep 20, 2011
From: KERLIKOWSKE, KARLA; TLSTY, THEA D.; BERMAN, HAL K.; GAUTHIER, MONA L.
To: REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE
Reel/Frame 026978/0844 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Sep 20, 2011
From: MOLINARO, ANNETTE M.
To: YALE UNIVERSITY
Reel/Frame 026978/0883 →
CONFIRMATORY LICENSE
Recorded Jun 21, 2011
From: UNIVERSITY OF CALIFORNIA SAN FRANCISCO
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 026468/0928 →
Continuity (2)
Provisional Application
61328565
· Apr 27, 2010
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