Malignancy-risk signature from histologically normal breast tissue
View Patent ↗The invention provides for malignancy-risk gene signatures that predict the risk of developing breast cancer, the recurrence of breast cancer, and/or the metastasis of breast cancer. These signatures have numerous clinical applications including assessing risk of breast cancer development following routine breast biopsy, assessing the need for adjuvant radiotherapy after lumpectomy, and determining the need for completion mastectomy following lumpectomy for the breast cancer patient and other treatment plans that are personalized for the patient.
1. A method for treating invasive ductal carcinoma, ductal carcinoma in situ, lobular carcinoma in situ or invasive lobular carcinoma in a human patient, the method comprising:
(a) staining a breast tissue sample from the patient;
(b) Identifying and isolating a stained breast tissue comprising only histologically normal cells;
(c) assaying the identified and isolated breast tissue comprising only histologically normal cells for mRNA levels of malignancy-risk genes comprising BIRC5, BUB1B, CCNB1, CCNB2, CDC20, CEP55 and PRC1 to obtain a first mRNA expression profile;
(d) comparing the first mRNA expression profile to a control mRNA expression profile obtainable by analyzing mRNA levels of the malignancy-risk genes in normal breast tissue;
(e) observing the first mRNA expression profile is at least 2-fold higher than the control mRNA expression profile obtained from normal breast tissue; and
(f) treating the patient for invasive ductal carcinoma, ductal carcinoma in situ, lobular carcinoma in situ or invasive lobular carcinoma.
2. The method of claim 1 wherein the patient is suspected of having breast cancer or has had breast cancer.
3. The method of claim 1 wherein the patient has had or currently has atypical hyperplasia.
4. The method of claim 1 wherein the patient has had or currently has fibroadenoma.
5. The method of claim 1 wherein the breast cancer is invasive ductal carcinoma (IDC) or ductal carcinoma in situ (DCIS).
6. The method of claim 1 wherein the patient has had a surgical procedure to remove breast cancer, breast tumor, or breast lesion.
7. The method of claim 6 wherein the surgical procedure is a lumpectomy or a mastectomy.
8. The method of claim 7 wherein the patient has initiated chemotherapy treatment either before, or after the surgical procedure.
9. The method of claim 1 wherein the breast tissue sample is obtained ipsilaterally with the cancer, tumor, or lesion.
10. A method for treating the spread of invasive ductal carcinoma, ductal carcinoma in situ, lobular carcinoma in situ or invasive lobular carcinoma in a human patient, the method comprising:
(a) staining a breast tissue sample from the patient;
(b) Identifying and isolating a stained breast tissue comprising only histologically normal cells;
(c) assaying the identified and isolated breast tissue sample comprising only histologically normal cells for mRNA levels of malignancy-risk genes comprising BIRC5, BUB1B, CCNB1, CCNB2, CDC20, CEP55 and PRC1 to obtain a first mRNA expression profile;
(d) comparing the first mRNA expression profile to a control mRNA expression profile obtainable by analyzing mRNA levels of the malignancy-risk genes in normal breast tissue;
(e) observing the first mRNA expression profile is at least 2-fold higher than the control mRNA expression profile obtained from normal breast tissue; and
(f) treating the patient for the spread of invasive ductal carcinoma, ductal carcinoma in situ, lobular carcinoma in situ or invasive lobular carcinoma.
11. The method of claim 10 wherein the breast cancer is invasive ductal carcinoma (IDC) or ductal carcinoma in situ (DCIS).
12. The method of claim 10 wherein the spread of cancer is metastasis.
13. The method of claim 10 wherein the patient had had a surgical procedure to remove breast cancer.
14. The method of claim 13 wherein the surgical procedure is a lumpectomy or a mastectomy.
15. The method of claim 14 wherein the patient has initiated chemotherapy or radiation treatment before or after the surgical procedure.
16. The method of either claim 1 or 10 wherein the malignancy-risk genes further comprise one or more genes selected from ANLN, BUB1, BUB3, CDC2, CDKN3, CENPA, CENPF, CKS2, DPP3, DTL, FOXM1, HN1, KPNA2, MELK, MLF1IP, NDC80, NME, NUSAP1, PAFAH1B3, PBK, PCNA, RACGAP1, RRM2, SMC4, SQLE, TK1, TOP2A and TYMS.
17. The method of either claim 1 or 10 wherein the malignancy-risk genes further comprise one or more genes selected from the group consisting of APOB EC3B, C60rf115, CASC5, CORO2A, FAM83D, HIST1H2BF, MOBK1B, WDSOF1, IQGAP3, AMOTL2, CCDC50, CHRDL1, GPRASP1, MAGI2, RBMS3, SYNPO2, Affymetrix probe set id 213158_at, Affymetrix probe set id 226250_at, Affymetrix probe set id 226252_at, Affymetrix probe set id 227082_at, Affymetrix probe set id 227121_at, Affymetrix probe set id 227646_at, Affymetrix probe set id 227719_at, Affymetrix probe set id 235556_at, Affymetrix probe set id 235570_at, and Affymetrix probe set id 243584_at.
18. The method of either claim 1 or 10 wherein the malignancy-risk genes further comprise one or more genes selected from the genes in ANLN, BUB1, CCNE2, CDC2, CDKN3, CENPA, CENPF, CKAP2, DLG7, EZH2, H2AFZ, KIAA0101, KIF23, MCM2, MELK, NEK2, NME1, NUSAP1, RACGAP1, RRM2, SQLE, TK1, TOP2A, TTK and ZWINT.
19. The method of either claim 1 or 10 wherein the malignancy-risk genes further comprise one or more genes selected from the genes in ARFGEF1, CDCA3, CDKN1C, CENPK, CFL2, DKFZp762E1312, DST, DTL, FANCI, GPC3, IQGAP3, MCM2, MT1M, NEK2, NUSAP1, PDZD2, RACGAP1, SQLE, UBE2T, UTRN, WDR32, ZBTB20 and FLJ11029.
20. The method of either claim 1 or 10 wherein the malignancy-risk genes further comprise one or more genes selected from the genes in ANLN, AURKA, BUB1, BUB3, CCNE2, CDC2, CDKN3, CENPA, CENPF, CTPS, DEPDC1, DKFZp762E1312, DLG7, DTL, EZH2, H2AFZ, HMGB3, HN1, KIAA0101, KIF20A, KIF23, KIF4A, KNTC2, KPNA2, LAGE3, LEPR, MAD2L1, MELK, NEK2, NUSAP1, PAK3, PCNA, RACGAP1, RRM2, TK1, TTK, TYMS, UBE2S, UBE2T, UHRF1 and ZWINT.
21. The method of either claim 1 or 10 wherein the malignancy-risk genes further comprise one or more genes selected from the genes in ANLN, ARF1, ARF4, BUB1, BUB3, CCNE2, CDC2, CDKN1C, CDKN3, CENPA, CENPF, CFL2, CKAP2, CKS2, CTPS, DONSON, DPP3, ECM2, FOXM1, GPC3, H2AFX, H2AFZ, HMMR, HN1, KIAA0101, KIF4A, LEPR, MAPK13, MCM2, MCM4, MRPL42, NCPB1, NME1, PAFAH1B3, PPIF, RACGAP1, CDPR, SPP1, SQLE, TIMELESS, TK1, TOP2A, TTK, TYMS, UTRN and ZWINT.
22. The method of either claim 1 or 10 wherein the malignancy-risk genes further comprise one or more genes selected from the genes in BUB1, C20orf1, CBX7, CDC2, CDKN1C, CDKN3, CENPA, CENPF, DXS9879E, E2-EPF, EZH2, KIAA0101, KIF11, KIF23, KPNA2, MAD2L1, NEK2, NME1, SMC4L1, SQLE, STK6, TOP2A, UBE2C and ZWINT.