The Prognostic Impact of Intratumoral Aryl Hydrocarbon Receptor in Primary Breast Cancer Depends on the Type of Endocrine Therapy: A Population-Based Cohort Study
The aryl hydrocarbon receptor (AhR) is a master regulator of multiple pathways involved in breast cancer, and influences the estrogen receptor alpha (ER) and aromatase/CYP19A1. The purpose of this study was to elucidate the interplay between intratumoral levels of AhR and aromatase, patient characte...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-05-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.642768/full |
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| author | Helga Tryggvadottir Emma Sandén Sofie Björner Alessandra Bressan Maria Ygland Rödström Somayeh Khazaei Dean P. Edwards Björn Nodin Karin Jirström Karolin Isaksson Karolin Isaksson Signe Borgquist Signe Borgquist Helena Jernström |
| author_facet | Helga Tryggvadottir Emma Sandén Sofie Björner Alessandra Bressan Maria Ygland Rödström Somayeh Khazaei Dean P. Edwards Björn Nodin Karin Jirström Karolin Isaksson Karolin Isaksson Signe Borgquist Signe Borgquist Helena Jernström |
| author_sort | Helga Tryggvadottir |
| collection | DOAJ |
| description | The aryl hydrocarbon receptor (AhR) is a master regulator of multiple pathways involved in breast cancer, and influences the estrogen receptor alpha (ER) and aromatase/CYP19A1. The purpose of this study was to elucidate the interplay between intratumoral levels of AhR and aromatase, patient characteristics (including AhR and CYP19A1 genotypes), clinicopathological features, and prognosis in breast cancer patients receiving adjuvant treatments. A prospective cohort of 1116 patients with primary breast cancer in Sweden, included 2002–2012, was followed until June 30th 2019 (median 8.7 years). Tumor‐specific AhR (n=920) and aromatase levels (n=816) were evaluated on tissue microarrays using immunohistochemistry. Associations between cytoplasmatic (AhRcyt) and nuclear (AhRnuc) AhR levels, intratumoral aromatase, clinicopathological features, and prognosis in different treatment groups were analyzed. Low AhRcyt levels (n=183) and positive intratumoral aromatase (n=69) were associated with estrogen receptor (ER)– status and more aggressive tumors. Genotypes were not associated with their respective protein levels. The functional AhRArg554Lys GG genotype was associated with recurrence-free survival in switch-therapy (sequential tamoxifen/aromatase inhibitors (AI) or AI/tamoxifen) treated patients (HRadj 0.42; 95% CI 0.22–0.83). High AhRcyt levels were associated with longer recurrence-free survival during the first 10 years of follow-up among tamoxifen-only treated patients (HRadj 0.40; 95% CI 0.23–0.71) compared to low AhRcyt levels, whereas an almost inverse association was seen in patients with switch-therapy (Pinteraction=0.023). Intratumoral aromatase had little prognostic impact. These findings warrant confirmation in an independent cohort, preferably in a randomized clinical trial comparing different endocrine regimens. They might also guide the selection of breast cancer patients for clinical trials with selective AhR modulators. |
| first_indexed | 2024-12-20T05:00:36Z |
| format | Article |
| id | doaj.art-1a080f780df64b5cb7c55bdd4e05c12e |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-20T05:00:36Z |
| publishDate | 2021-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-1a080f780df64b5cb7c55bdd4e05c12e2022-12-21T19:52:33ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-05-011110.3389/fonc.2021.642768642768The Prognostic Impact of Intratumoral Aryl Hydrocarbon Receptor in Primary Breast Cancer Depends on the Type of Endocrine Therapy: A Population-Based Cohort StudyHelga Tryggvadottir0Emma Sandén1Sofie Björner2Alessandra Bressan3Maria Ygland Rödström4Somayeh Khazaei5Dean P. Edwards6Björn Nodin7Karin Jirström8Karolin Isaksson9Karolin Isaksson10Signe Borgquist11Signe Borgquist12Helena Jernström13Division of Oncology, Department of Clinical Sciences, Lund, Lund University and Skåne University Hospital, Lund, SwedenDivision of Oncology, Department of Clinical Sciences, Lund, Lund University and Skåne University Hospital, Lund, SwedenDivision of Oncology, Department of Clinical Sciences, Lund, Lund University and Skåne University Hospital, Lund, SwedenDivision of Oncology, Department of Clinical Sciences, Lund, Lund University and Skåne University Hospital, Lund, SwedenDivision of Oncology, Department of Clinical Sciences, Lund, Lund University and Skåne University Hospital, Lund, SwedenDivision of Oncology, Department of Clinical Sciences, Lund, Lund University and Skåne University Hospital, Lund, SwedenDepartment of Molecular & Cellular Biology and Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, United StatesDivision of Oncology and Therapeutic Pathology, Department of Clinical Sciences, Lund, Lund University and Skåne University Hospital, Lund, SwedenDivision of Oncology and Therapeutic Pathology, Department of Clinical Sciences, Lund, Lund University and Skåne University Hospital, Lund, SwedenDivision of Surgery, Department of Clinical Sciences, Lund, Lund University, Lund, SwedenDepartment of Surgery, Kristianstad Hospital, Kristianstad, SwedenDivision of Oncology, Department of Clinical Sciences, Lund, Lund University and Skåne University Hospital, Lund, SwedenDepartment of Oncology, Aarhus University and Aarhus University Hospital, Aarhus, DenmarkDivision of Oncology, Department of Clinical Sciences, Lund, Lund University and Skåne University Hospital, Lund, SwedenThe aryl hydrocarbon receptor (AhR) is a master regulator of multiple pathways involved in breast cancer, and influences the estrogen receptor alpha (ER) and aromatase/CYP19A1. The purpose of this study was to elucidate the interplay between intratumoral levels of AhR and aromatase, patient characteristics (including AhR and CYP19A1 genotypes), clinicopathological features, and prognosis in breast cancer patients receiving adjuvant treatments. A prospective cohort of 1116 patients with primary breast cancer in Sweden, included 2002–2012, was followed until June 30th 2019 (median 8.7 years). Tumor‐specific AhR (n=920) and aromatase levels (n=816) were evaluated on tissue microarrays using immunohistochemistry. Associations between cytoplasmatic (AhRcyt) and nuclear (AhRnuc) AhR levels, intratumoral aromatase, clinicopathological features, and prognosis in different treatment groups were analyzed. Low AhRcyt levels (n=183) and positive intratumoral aromatase (n=69) were associated with estrogen receptor (ER)– status and more aggressive tumors. Genotypes were not associated with their respective protein levels. The functional AhRArg554Lys GG genotype was associated with recurrence-free survival in switch-therapy (sequential tamoxifen/aromatase inhibitors (AI) or AI/tamoxifen) treated patients (HRadj 0.42; 95% CI 0.22–0.83). High AhRcyt levels were associated with longer recurrence-free survival during the first 10 years of follow-up among tamoxifen-only treated patients (HRadj 0.40; 95% CI 0.23–0.71) compared to low AhRcyt levels, whereas an almost inverse association was seen in patients with switch-therapy (Pinteraction=0.023). Intratumoral aromatase had little prognostic impact. These findings warrant confirmation in an independent cohort, preferably in a randomized clinical trial comparing different endocrine regimens. They might also guide the selection of breast cancer patients for clinical trials with selective AhR modulators.https://www.frontiersin.org/articles/10.3389/fonc.2021.642768/fullbreast canceraryl hydrocarbon receptorintratumoral aromataseendocrine therapypolymorphismsprognosis |
| spellingShingle | Helga Tryggvadottir Emma Sandén Sofie Björner Alessandra Bressan Maria Ygland Rödström Somayeh Khazaei Dean P. Edwards Björn Nodin Karin Jirström Karolin Isaksson Karolin Isaksson Signe Borgquist Signe Borgquist Helena Jernström The Prognostic Impact of Intratumoral Aryl Hydrocarbon Receptor in Primary Breast Cancer Depends on the Type of Endocrine Therapy: A Population-Based Cohort Study Frontiers in Oncology breast cancer aryl hydrocarbon receptor intratumoral aromatase endocrine therapy polymorphisms prognosis |
| title | The Prognostic Impact of Intratumoral Aryl Hydrocarbon Receptor in Primary Breast Cancer Depends on the Type of Endocrine Therapy: A Population-Based Cohort Study |
| title_full | The Prognostic Impact of Intratumoral Aryl Hydrocarbon Receptor in Primary Breast Cancer Depends on the Type of Endocrine Therapy: A Population-Based Cohort Study |
| title_fullStr | The Prognostic Impact of Intratumoral Aryl Hydrocarbon Receptor in Primary Breast Cancer Depends on the Type of Endocrine Therapy: A Population-Based Cohort Study |
| title_full_unstemmed | The Prognostic Impact of Intratumoral Aryl Hydrocarbon Receptor in Primary Breast Cancer Depends on the Type of Endocrine Therapy: A Population-Based Cohort Study |
| title_short | The Prognostic Impact of Intratumoral Aryl Hydrocarbon Receptor in Primary Breast Cancer Depends on the Type of Endocrine Therapy: A Population-Based Cohort Study |
| title_sort | prognostic impact of intratumoral aryl hydrocarbon receptor in primary breast cancer depends on the type of endocrine therapy a population based cohort study |
| topic | breast cancer aryl hydrocarbon receptor intratumoral aromatase endocrine therapy polymorphisms prognosis |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2021.642768/full |
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