TP53-positive clones are responsible for drug-tolerant persister and recurrence of HER2-positive breast cancer
Purpose The prognosis of HER2-positive breast cancer has improved with the development of anti-HER2 therapies. In order to further improve the prognosis of HER2-positive breast cancer, it is essential to elucidate the cells that survive during the therapy (drug-tolerant persister DTP). Methods Of th...
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| Autor*in: |
Watanabe, Hideki [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2022 |
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© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022. Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. |
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| Übergeordnetes Werk: |
Enthalten in: Breast cancer research and treatment - Dordrecht [u.a.] : Springer Science + Business Media B.V., 1981, 196(2022), 2 vom: 10. Sept., Seite 255-266 |
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| Übergeordnetes Werk: |
volume:196 ; year:2022 ; number:2 ; day:10 ; month:09 ; pages:255-266 |
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| DOI / URN: |
10.1007/s10549-022-06731-z |
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SPR048408212 |
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| 100 | 1 | |a Watanabe, Hideki |e verfasserin |4 aut | |
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| 520 | |a Purpose The prognosis of HER2-positive breast cancer has improved with the development of anti-HER2 therapies. In order to further improve the prognosis of HER2-positive breast cancer, it is essential to elucidate the cells that survive during the therapy (drug-tolerant persister DTP). Methods Of the 2022 breast cancer patients operated at our institution during 2004–2018, 240 (12%) had HER2-positive breast cancer. Neo-adjuvant chemotherapy including trastuzumab (Tr-NAC) was administered to 94 of them. Forty-six of them were complete remission (CR), and 48 were non-CR. After 6.9 ± 3.7 years of follow-up, all 46 CR cases showed no recurrence (Cohort A), and 48 non-CR cases were divided into 31 cases with no recurrence (Cohort B) and 17 cases with recurrence (Cohort C). In addition to clinical backgrounds, we compared genomic profiles for 27 patients (Cohort A; 15/48, B; 7/31, and C; 5/17) who consented to genomic analysis. Results Genomic abnormalities of TP53 and PIK3CA were frequently observed in biopsy samples pre Tr-NAC, but we found no differences between CR (Cohort A) and non-CR (Cohorts B + C). Then, we examined both of pre and post Tr-NAC samples of Cohort B (7) and C (5) to see the relationship between recurrence and genomic abnormalities. TP53 mutations were significantly more prevalent in Cohort C (5/5, 100%) than cohort B (3/7, 43%) in the surgical sample after treatment (p = 0.04). PyClone analysis of TP53 mutations showed that the cellular frequency of TP53 clones increased in 4 of 5 patients in Cohort C and none of B. On the other hand, we found no enhancement of PIK3CA mutant clones in Cohort C. Conclusions The DTP after Tr-NAC associated with subsequent relapse had TP53 mutations, suggesting that overcoming DTP with TP53 mutations is the most important clinical challenge. Trial registration Not applicable. | ||
| 650 | 4 | |a Drug-tolerant persister |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a HER2-positive breast cancer |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Genome profiling |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a TP53-positive clones |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Trastuzumab |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Nakagomi, Hiroshi |0 (orcid)0000-0002-0068-4487 |4 aut | |
| 700 | 1 | |a Hirotsu, Yosuke |4 aut | |
| 700 | 1 | |a Amemiya, Kenji |4 aut | |
| 700 | 1 | |a Mochizuki, Hitoshi |4 aut | |
| 700 | 1 | |a Inoue, Masayuki |4 aut | |
| 700 | 1 | |a Kimura, Ayako |4 aut | |
| 700 | 1 | |a Omata, Masao |4 aut | |
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10.1007/s10549-022-06731-z doi (DE-627)SPR048408212 (SPR)s10549-022-06731-z-e DE-627 ger DE-627 rakwb eng Watanabe, Hideki verfasserin aut TP53-positive clones are responsible for drug-tolerant persister and recurrence of HER2-positive breast cancer 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022. Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. Purpose The prognosis of HER2-positive breast cancer has improved with the development of anti-HER2 therapies. In order to further improve the prognosis of HER2-positive breast cancer, it is essential to elucidate the cells that survive during the therapy (drug-tolerant persister DTP). Methods Of the 2022 breast cancer patients operated at our institution during 2004–2018, 240 (12%) had HER2-positive breast cancer. Neo-adjuvant chemotherapy including trastuzumab (Tr-NAC) was administered to 94 of them. Forty-six of them were complete remission (CR), and 48 were non-CR. After 6.9 ± 3.7 years of follow-up, all 46 CR cases showed no recurrence (Cohort A), and 48 non-CR cases were divided into 31 cases with no recurrence (Cohort B) and 17 cases with recurrence (Cohort C). In addition to clinical backgrounds, we compared genomic profiles for 27 patients (Cohort A; 15/48, B; 7/31, and C; 5/17) who consented to genomic analysis. Results Genomic abnormalities of TP53 and PIK3CA were frequently observed in biopsy samples pre Tr-NAC, but we found no differences between CR (Cohort A) and non-CR (Cohorts B + C). Then, we examined both of pre and post Tr-NAC samples of Cohort B (7) and C (5) to see the relationship between recurrence and genomic abnormalities. TP53 mutations were significantly more prevalent in Cohort C (5/5, 100%) than cohort B (3/7, 43%) in the surgical sample after treatment (p = 0.04). PyClone analysis of TP53 mutations showed that the cellular frequency of TP53 clones increased in 4 of 5 patients in Cohort C and none of B. On the other hand, we found no enhancement of PIK3CA mutant clones in Cohort C. Conclusions The DTP after Tr-NAC associated with subsequent relapse had TP53 mutations, suggesting that overcoming DTP with TP53 mutations is the most important clinical challenge. Trial registration Not applicable. Drug-tolerant persister (dpeaa)DE-He213 HER2-positive breast cancer (dpeaa)DE-He213 Genome profiling (dpeaa)DE-He213 TP53-positive clones (dpeaa)DE-He213 Trastuzumab (dpeaa)DE-He213 Nakagomi, Hiroshi (orcid)0000-0002-0068-4487 aut Hirotsu, Yosuke aut Amemiya, Kenji aut Mochizuki, Hitoshi aut Inoue, Masayuki aut Kimura, Ayako aut Omata, Masao aut Enthalten in Breast cancer research and treatment Dordrecht [u.a.] : Springer Science + Business Media B.V., 1981 196(2022), 2 vom: 10. Sept., Seite 255-266 (DE-627)320433722 (DE-600)2004077-5 1573-7217 nnns volume:196 year:2022 number:2 day:10 month:09 pages:255-266 https://dx.doi.org/10.1007/s10549-022-06731-z lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 196 2022 2 10 09 255-266 |
| spelling |
10.1007/s10549-022-06731-z doi (DE-627)SPR048408212 (SPR)s10549-022-06731-z-e DE-627 ger DE-627 rakwb eng Watanabe, Hideki verfasserin aut TP53-positive clones are responsible for drug-tolerant persister and recurrence of HER2-positive breast cancer 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022. Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. Purpose The prognosis of HER2-positive breast cancer has improved with the development of anti-HER2 therapies. In order to further improve the prognosis of HER2-positive breast cancer, it is essential to elucidate the cells that survive during the therapy (drug-tolerant persister DTP). Methods Of the 2022 breast cancer patients operated at our institution during 2004–2018, 240 (12%) had HER2-positive breast cancer. Neo-adjuvant chemotherapy including trastuzumab (Tr-NAC) was administered to 94 of them. Forty-six of them were complete remission (CR), and 48 were non-CR. After 6.9 ± 3.7 years of follow-up, all 46 CR cases showed no recurrence (Cohort A), and 48 non-CR cases were divided into 31 cases with no recurrence (Cohort B) and 17 cases with recurrence (Cohort C). In addition to clinical backgrounds, we compared genomic profiles for 27 patients (Cohort A; 15/48, B; 7/31, and C; 5/17) who consented to genomic analysis. Results Genomic abnormalities of TP53 and PIK3CA were frequently observed in biopsy samples pre Tr-NAC, but we found no differences between CR (Cohort A) and non-CR (Cohorts B + C). Then, we examined both of pre and post Tr-NAC samples of Cohort B (7) and C (5) to see the relationship between recurrence and genomic abnormalities. TP53 mutations were significantly more prevalent in Cohort C (5/5, 100%) than cohort B (3/7, 43%) in the surgical sample after treatment (p = 0.04). PyClone analysis of TP53 mutations showed that the cellular frequency of TP53 clones increased in 4 of 5 patients in Cohort C and none of B. On the other hand, we found no enhancement of PIK3CA mutant clones in Cohort C. Conclusions The DTP after Tr-NAC associated with subsequent relapse had TP53 mutations, suggesting that overcoming DTP with TP53 mutations is the most important clinical challenge. Trial registration Not applicable. Drug-tolerant persister (dpeaa)DE-He213 HER2-positive breast cancer (dpeaa)DE-He213 Genome profiling (dpeaa)DE-He213 TP53-positive clones (dpeaa)DE-He213 Trastuzumab (dpeaa)DE-He213 Nakagomi, Hiroshi (orcid)0000-0002-0068-4487 aut Hirotsu, Yosuke aut Amemiya, Kenji aut Mochizuki, Hitoshi aut Inoue, Masayuki aut Kimura, Ayako aut Omata, Masao aut Enthalten in Breast cancer research and treatment Dordrecht [u.a.] : Springer Science + Business Media B.V., 1981 196(2022), 2 vom: 10. Sept., Seite 255-266 (DE-627)320433722 (DE-600)2004077-5 1573-7217 nnns volume:196 year:2022 number:2 day:10 month:09 pages:255-266 https://dx.doi.org/10.1007/s10549-022-06731-z lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 196 2022 2 10 09 255-266 |
| allfields_unstemmed |
10.1007/s10549-022-06731-z doi (DE-627)SPR048408212 (SPR)s10549-022-06731-z-e DE-627 ger DE-627 rakwb eng Watanabe, Hideki verfasserin aut TP53-positive clones are responsible for drug-tolerant persister and recurrence of HER2-positive breast cancer 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022. Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. Purpose The prognosis of HER2-positive breast cancer has improved with the development of anti-HER2 therapies. In order to further improve the prognosis of HER2-positive breast cancer, it is essential to elucidate the cells that survive during the therapy (drug-tolerant persister DTP). Methods Of the 2022 breast cancer patients operated at our institution during 2004–2018, 240 (12%) had HER2-positive breast cancer. Neo-adjuvant chemotherapy including trastuzumab (Tr-NAC) was administered to 94 of them. Forty-six of them were complete remission (CR), and 48 were non-CR. After 6.9 ± 3.7 years of follow-up, all 46 CR cases showed no recurrence (Cohort A), and 48 non-CR cases were divided into 31 cases with no recurrence (Cohort B) and 17 cases with recurrence (Cohort C). In addition to clinical backgrounds, we compared genomic profiles for 27 patients (Cohort A; 15/48, B; 7/31, and C; 5/17) who consented to genomic analysis. Results Genomic abnormalities of TP53 and PIK3CA were frequently observed in biopsy samples pre Tr-NAC, but we found no differences between CR (Cohort A) and non-CR (Cohorts B + C). Then, we examined both of pre and post Tr-NAC samples of Cohort B (7) and C (5) to see the relationship between recurrence and genomic abnormalities. TP53 mutations were significantly more prevalent in Cohort C (5/5, 100%) than cohort B (3/7, 43%) in the surgical sample after treatment (p = 0.04). PyClone analysis of TP53 mutations showed that the cellular frequency of TP53 clones increased in 4 of 5 patients in Cohort C and none of B. On the other hand, we found no enhancement of PIK3CA mutant clones in Cohort C. Conclusions The DTP after Tr-NAC associated with subsequent relapse had TP53 mutations, suggesting that overcoming DTP with TP53 mutations is the most important clinical challenge. Trial registration Not applicable. Drug-tolerant persister (dpeaa)DE-He213 HER2-positive breast cancer (dpeaa)DE-He213 Genome profiling (dpeaa)DE-He213 TP53-positive clones (dpeaa)DE-He213 Trastuzumab (dpeaa)DE-He213 Nakagomi, Hiroshi (orcid)0000-0002-0068-4487 aut Hirotsu, Yosuke aut Amemiya, Kenji aut Mochizuki, Hitoshi aut Inoue, Masayuki aut Kimura, Ayako aut Omata, Masao aut Enthalten in Breast cancer research and treatment Dordrecht [u.a.] : Springer Science + Business Media B.V., 1981 196(2022), 2 vom: 10. Sept., Seite 255-266 (DE-627)320433722 (DE-600)2004077-5 1573-7217 nnns volume:196 year:2022 number:2 day:10 month:09 pages:255-266 https://dx.doi.org/10.1007/s10549-022-06731-z lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 196 2022 2 10 09 255-266 |
| allfieldsGer |
10.1007/s10549-022-06731-z doi (DE-627)SPR048408212 (SPR)s10549-022-06731-z-e DE-627 ger DE-627 rakwb eng Watanabe, Hideki verfasserin aut TP53-positive clones are responsible for drug-tolerant persister and recurrence of HER2-positive breast cancer 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022. Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. Purpose The prognosis of HER2-positive breast cancer has improved with the development of anti-HER2 therapies. In order to further improve the prognosis of HER2-positive breast cancer, it is essential to elucidate the cells that survive during the therapy (drug-tolerant persister DTP). Methods Of the 2022 breast cancer patients operated at our institution during 2004–2018, 240 (12%) had HER2-positive breast cancer. Neo-adjuvant chemotherapy including trastuzumab (Tr-NAC) was administered to 94 of them. Forty-six of them were complete remission (CR), and 48 were non-CR. After 6.9 ± 3.7 years of follow-up, all 46 CR cases showed no recurrence (Cohort A), and 48 non-CR cases were divided into 31 cases with no recurrence (Cohort B) and 17 cases with recurrence (Cohort C). In addition to clinical backgrounds, we compared genomic profiles for 27 patients (Cohort A; 15/48, B; 7/31, and C; 5/17) who consented to genomic analysis. Results Genomic abnormalities of TP53 and PIK3CA were frequently observed in biopsy samples pre Tr-NAC, but we found no differences between CR (Cohort A) and non-CR (Cohorts B + C). Then, we examined both of pre and post Tr-NAC samples of Cohort B (7) and C (5) to see the relationship between recurrence and genomic abnormalities. TP53 mutations were significantly more prevalent in Cohort C (5/5, 100%) than cohort B (3/7, 43%) in the surgical sample after treatment (p = 0.04). PyClone analysis of TP53 mutations showed that the cellular frequency of TP53 clones increased in 4 of 5 patients in Cohort C and none of B. On the other hand, we found no enhancement of PIK3CA mutant clones in Cohort C. Conclusions The DTP after Tr-NAC associated with subsequent relapse had TP53 mutations, suggesting that overcoming DTP with TP53 mutations is the most important clinical challenge. Trial registration Not applicable. Drug-tolerant persister (dpeaa)DE-He213 HER2-positive breast cancer (dpeaa)DE-He213 Genome profiling (dpeaa)DE-He213 TP53-positive clones (dpeaa)DE-He213 Trastuzumab (dpeaa)DE-He213 Nakagomi, Hiroshi (orcid)0000-0002-0068-4487 aut Hirotsu, Yosuke aut Amemiya, Kenji aut Mochizuki, Hitoshi aut Inoue, Masayuki aut Kimura, Ayako aut Omata, Masao aut Enthalten in Breast cancer research and treatment Dordrecht [u.a.] : Springer Science + Business Media B.V., 1981 196(2022), 2 vom: 10. Sept., Seite 255-266 (DE-627)320433722 (DE-600)2004077-5 1573-7217 nnns volume:196 year:2022 number:2 day:10 month:09 pages:255-266 https://dx.doi.org/10.1007/s10549-022-06731-z lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 196 2022 2 10 09 255-266 |
| allfieldsSound |
10.1007/s10549-022-06731-z doi (DE-627)SPR048408212 (SPR)s10549-022-06731-z-e DE-627 ger DE-627 rakwb eng Watanabe, Hideki verfasserin aut TP53-positive clones are responsible for drug-tolerant persister and recurrence of HER2-positive breast cancer 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022. Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. Purpose The prognosis of HER2-positive breast cancer has improved with the development of anti-HER2 therapies. In order to further improve the prognosis of HER2-positive breast cancer, it is essential to elucidate the cells that survive during the therapy (drug-tolerant persister DTP). Methods Of the 2022 breast cancer patients operated at our institution during 2004–2018, 240 (12%) had HER2-positive breast cancer. Neo-adjuvant chemotherapy including trastuzumab (Tr-NAC) was administered to 94 of them. Forty-six of them were complete remission (CR), and 48 were non-CR. After 6.9 ± 3.7 years of follow-up, all 46 CR cases showed no recurrence (Cohort A), and 48 non-CR cases were divided into 31 cases with no recurrence (Cohort B) and 17 cases with recurrence (Cohort C). In addition to clinical backgrounds, we compared genomic profiles for 27 patients (Cohort A; 15/48, B; 7/31, and C; 5/17) who consented to genomic analysis. Results Genomic abnormalities of TP53 and PIK3CA were frequently observed in biopsy samples pre Tr-NAC, but we found no differences between CR (Cohort A) and non-CR (Cohorts B + C). Then, we examined both of pre and post Tr-NAC samples of Cohort B (7) and C (5) to see the relationship between recurrence and genomic abnormalities. TP53 mutations were significantly more prevalent in Cohort C (5/5, 100%) than cohort B (3/7, 43%) in the surgical sample after treatment (p = 0.04). PyClone analysis of TP53 mutations showed that the cellular frequency of TP53 clones increased in 4 of 5 patients in Cohort C and none of B. On the other hand, we found no enhancement of PIK3CA mutant clones in Cohort C. Conclusions The DTP after Tr-NAC associated with subsequent relapse had TP53 mutations, suggesting that overcoming DTP with TP53 mutations is the most important clinical challenge. Trial registration Not applicable. Drug-tolerant persister (dpeaa)DE-He213 HER2-positive breast cancer (dpeaa)DE-He213 Genome profiling (dpeaa)DE-He213 TP53-positive clones (dpeaa)DE-He213 Trastuzumab (dpeaa)DE-He213 Nakagomi, Hiroshi (orcid)0000-0002-0068-4487 aut Hirotsu, Yosuke aut Amemiya, Kenji aut Mochizuki, Hitoshi aut Inoue, Masayuki aut Kimura, Ayako aut Omata, Masao aut Enthalten in Breast cancer research and treatment Dordrecht [u.a.] : Springer Science + Business Media B.V., 1981 196(2022), 2 vom: 10. Sept., Seite 255-266 (DE-627)320433722 (DE-600)2004077-5 1573-7217 nnns volume:196 year:2022 number:2 day:10 month:09 pages:255-266 https://dx.doi.org/10.1007/s10549-022-06731-z lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 196 2022 2 10 09 255-266 |
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Enthalten in Breast cancer research and treatment 196(2022), 2 vom: 10. Sept., Seite 255-266 volume:196 year:2022 number:2 day:10 month:09 pages:255-266 |
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Enthalten in Breast cancer research and treatment 196(2022), 2 vom: 10. Sept., Seite 255-266 volume:196 year:2022 number:2 day:10 month:09 pages:255-266 |
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Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Purpose The prognosis of HER2-positive breast cancer has improved with the development of anti-HER2 therapies. In order to further improve the prognosis of HER2-positive breast cancer, it is essential to elucidate the cells that survive during the therapy (drug-tolerant persister DTP). Methods Of the 2022 breast cancer patients operated at our institution during 2004–2018, 240 (12%) had HER2-positive breast cancer. Neo-adjuvant chemotherapy including trastuzumab (Tr-NAC) was administered to 94 of them. Forty-six of them were complete remission (CR), and 48 were non-CR. After 6.9 ± 3.7 years of follow-up, all 46 CR cases showed no recurrence (Cohort A), and 48 non-CR cases were divided into 31 cases with no recurrence (Cohort B) and 17 cases with recurrence (Cohort C). In addition to clinical backgrounds, we compared genomic profiles for 27 patients (Cohort A; 15/48, B; 7/31, and C; 5/17) who consented to genomic analysis. Results Genomic abnormalities of TP53 and PIK3CA were frequently observed in biopsy samples pre Tr-NAC, but we found no differences between CR (Cohort A) and non-CR (Cohorts B + C). Then, we examined both of pre and post Tr-NAC samples of Cohort B (7) and C (5) to see the relationship between recurrence and genomic abnormalities. TP53 mutations were significantly more prevalent in Cohort C (5/5, 100%) than cohort B (3/7, 43%) in the surgical sample after treatment (p = 0.04). PyClone analysis of TP53 mutations showed that the cellular frequency of TP53 clones increased in 4 of 5 patients in Cohort C and none of B. On the other hand, we found no enhancement of PIK3CA mutant clones in Cohort C. Conclusions The DTP after Tr-NAC associated with subsequent relapse had TP53 mutations, suggesting that overcoming DTP with TP53 mutations is the most important clinical challenge. 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Watanabe, Hideki |
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Watanabe, Hideki misc Drug-tolerant persister misc HER2-positive breast cancer misc Genome profiling misc TP53-positive clones misc Trastuzumab TP53-positive clones are responsible for drug-tolerant persister and recurrence of HER2-positive breast cancer |
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TP53-positive clones are responsible for drug-tolerant persister and recurrence of HER2-positive breast cancer Drug-tolerant persister (dpeaa)DE-He213 HER2-positive breast cancer (dpeaa)DE-He213 Genome profiling (dpeaa)DE-He213 TP53-positive clones (dpeaa)DE-He213 Trastuzumab (dpeaa)DE-He213 |
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tp53-positive clones are responsible for drug-tolerant persister and recurrence of her2-positive breast cancer |
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TP53-positive clones are responsible for drug-tolerant persister and recurrence of HER2-positive breast cancer |
| abstract |
Purpose The prognosis of HER2-positive breast cancer has improved with the development of anti-HER2 therapies. In order to further improve the prognosis of HER2-positive breast cancer, it is essential to elucidate the cells that survive during the therapy (drug-tolerant persister DTP). Methods Of the 2022 breast cancer patients operated at our institution during 2004–2018, 240 (12%) had HER2-positive breast cancer. Neo-adjuvant chemotherapy including trastuzumab (Tr-NAC) was administered to 94 of them. Forty-six of them were complete remission (CR), and 48 were non-CR. After 6.9 ± 3.7 years of follow-up, all 46 CR cases showed no recurrence (Cohort A), and 48 non-CR cases were divided into 31 cases with no recurrence (Cohort B) and 17 cases with recurrence (Cohort C). In addition to clinical backgrounds, we compared genomic profiles for 27 patients (Cohort A; 15/48, B; 7/31, and C; 5/17) who consented to genomic analysis. Results Genomic abnormalities of TP53 and PIK3CA were frequently observed in biopsy samples pre Tr-NAC, but we found no differences between CR (Cohort A) and non-CR (Cohorts B + C). Then, we examined both of pre and post Tr-NAC samples of Cohort B (7) and C (5) to see the relationship between recurrence and genomic abnormalities. TP53 mutations were significantly more prevalent in Cohort C (5/5, 100%) than cohort B (3/7, 43%) in the surgical sample after treatment (p = 0.04). PyClone analysis of TP53 mutations showed that the cellular frequency of TP53 clones increased in 4 of 5 patients in Cohort C and none of B. On the other hand, we found no enhancement of PIK3CA mutant clones in Cohort C. Conclusions The DTP after Tr-NAC associated with subsequent relapse had TP53 mutations, suggesting that overcoming DTP with TP53 mutations is the most important clinical challenge. Trial registration Not applicable. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022. Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. |
| abstractGer |
Purpose The prognosis of HER2-positive breast cancer has improved with the development of anti-HER2 therapies. In order to further improve the prognosis of HER2-positive breast cancer, it is essential to elucidate the cells that survive during the therapy (drug-tolerant persister DTP). Methods Of the 2022 breast cancer patients operated at our institution during 2004–2018, 240 (12%) had HER2-positive breast cancer. Neo-adjuvant chemotherapy including trastuzumab (Tr-NAC) was administered to 94 of them. Forty-six of them were complete remission (CR), and 48 were non-CR. After 6.9 ± 3.7 years of follow-up, all 46 CR cases showed no recurrence (Cohort A), and 48 non-CR cases were divided into 31 cases with no recurrence (Cohort B) and 17 cases with recurrence (Cohort C). In addition to clinical backgrounds, we compared genomic profiles for 27 patients (Cohort A; 15/48, B; 7/31, and C; 5/17) who consented to genomic analysis. Results Genomic abnormalities of TP53 and PIK3CA were frequently observed in biopsy samples pre Tr-NAC, but we found no differences between CR (Cohort A) and non-CR (Cohorts B + C). Then, we examined both of pre and post Tr-NAC samples of Cohort B (7) and C (5) to see the relationship between recurrence and genomic abnormalities. TP53 mutations were significantly more prevalent in Cohort C (5/5, 100%) than cohort B (3/7, 43%) in the surgical sample after treatment (p = 0.04). PyClone analysis of TP53 mutations showed that the cellular frequency of TP53 clones increased in 4 of 5 patients in Cohort C and none of B. On the other hand, we found no enhancement of PIK3CA mutant clones in Cohort C. Conclusions The DTP after Tr-NAC associated with subsequent relapse had TP53 mutations, suggesting that overcoming DTP with TP53 mutations is the most important clinical challenge. Trial registration Not applicable. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022. Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. |
| abstract_unstemmed |
Purpose The prognosis of HER2-positive breast cancer has improved with the development of anti-HER2 therapies. In order to further improve the prognosis of HER2-positive breast cancer, it is essential to elucidate the cells that survive during the therapy (drug-tolerant persister DTP). Methods Of the 2022 breast cancer patients operated at our institution during 2004–2018, 240 (12%) had HER2-positive breast cancer. Neo-adjuvant chemotherapy including trastuzumab (Tr-NAC) was administered to 94 of them. Forty-six of them were complete remission (CR), and 48 were non-CR. After 6.9 ± 3.7 years of follow-up, all 46 CR cases showed no recurrence (Cohort A), and 48 non-CR cases were divided into 31 cases with no recurrence (Cohort B) and 17 cases with recurrence (Cohort C). In addition to clinical backgrounds, we compared genomic profiles for 27 patients (Cohort A; 15/48, B; 7/31, and C; 5/17) who consented to genomic analysis. Results Genomic abnormalities of TP53 and PIK3CA were frequently observed in biopsy samples pre Tr-NAC, but we found no differences between CR (Cohort A) and non-CR (Cohorts B + C). Then, we examined both of pre and post Tr-NAC samples of Cohort B (7) and C (5) to see the relationship between recurrence and genomic abnormalities. TP53 mutations were significantly more prevalent in Cohort C (5/5, 100%) than cohort B (3/7, 43%) in the surgical sample after treatment (p = 0.04). PyClone analysis of TP53 mutations showed that the cellular frequency of TP53 clones increased in 4 of 5 patients in Cohort C and none of B. On the other hand, we found no enhancement of PIK3CA mutant clones in Cohort C. Conclusions The DTP after Tr-NAC associated with subsequent relapse had TP53 mutations, suggesting that overcoming DTP with TP53 mutations is the most important clinical challenge. Trial registration Not applicable. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022. Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. |
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| score |
7.399351 |