Abstract
Background: Single nucleotide polymorphisms (SNPs) in the estrogen receptor 1 (ESR1) and cytochrome P450 19A1 (CYP19A1) genes have been associated with breast cancer risk, endocrine therapy response and side effects, mainly in postmenopausal women with early breast cancer. This analysis aimed to assess the association of selected germline CYP19A1 and ESR1 SNPs with early-onset hot flashes, sweating and musculoskeletal symptoms in premenopausal patients enrolled in the Tamoxifen and Exemestane Trial (TEXT). Methods: Blood was collected from consenting premenopausal women with hormone-responsive early breast cancer, randomly assigned to 5-years of tamoxifen plus ovarian suppression (OFS) or exemestane plus OFS. DNA was extracted with QIAamp kits and genotyped for two CYP19A1 (rs4646 and rs10046) and three ESR1 (rs2077647, rs2234693 and rs9340799) SNPs by a real-time pyrosequencing technique. Adverse events (AEs) were recorded at baseline and 3-monthly during the first year. Associations of the genotype variants with grade ≥2 early-onset targeted AEs of hot flashes/sweating or musculoskeletal events were assessed using logistic regression models. Results: There were 2660 premenopausal patients with breast cancer in the intention-to-treat population of TEXT, and 1967 (74 %) are included in this translational study. The CYP19A1 rs10046 variant T/T, represented in 23 % of women, was associated with a reduced incidence of grade ≥2 hot flashes/sweating (univariate odds ratio (OR) = 0.78; 95 % CI 0.63-0.97; P = 0.03), more strongly in patients assigned exemestane + OFS (TT vs CT/CC: OR = 0.65, 95 % CI = 0.48-0.89) than assigned tamoxifen + OFS (OR = 0.94, 95 % CI = 0.69-1.27, interaction P = 0.03). No association with any of the CYP19A1/ESR1 genotypes and musculoskeletal AEs was found. Conclusion: The CYP19A1 rs10046 variant T/T favors lower incidence of hot flashes/sweating under exemestane + OFS treatment, suggesting endocrine-mediated effects. Based on findings from others, this SNP may potentially enhance treatment adherence and treatment efficacy. We plan to evaluate the clinical impact of this polymorphism during time, pending sufficient median follow up. Trial registration: ClinicalTrials.gov NCT00066703, registered August 6, 2003.
Original language | English |
---|---|
Article number | 110 |
Journal | Breast Cancer Research |
Volume | 18 |
Issue number | 1 |
DOIs | |
State | Published - 8 Nov 2016 |
Keywords
- Aromatase inhibitors
- Breast cancer
- CYP19A1
- ESR1
- Ovarian suppression
- Side effects
- Tamoxifen
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Impact of CYP19A1 and ESR1 variants on early-onset side effects during combined endocrine therapy in the TEXT trial. / the TEXT principal investigators.
In: Breast Cancer Research, Vol. 18, No. 1, 110, 08.11.2016.Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - Impact of CYP19A1 and ESR1 variants on early-onset side effects during combined endocrine therapy in the TEXT trial
AU - the TEXT principal investigators
AU - Johansson, Harriet
AU - Gray, Kathryn P.
AU - Pagani, Olivia
AU - Regan, Meredith M.
AU - Viale, Giuseppe
AU - Aristarco, Valentina
AU - Macis, Debora
AU - Puccio, Antonella
AU - Roux, Susanne
AU - Maibach, Rudolf
AU - Colleoni, Marco
AU - Rabaglio, Manuela
AU - Price, Karen N.
AU - Coates, Alan S.
AU - Gelber, Richard D.
AU - Goldhirsch, Aron
AU - Kammler, Roswitha
AU - Bonanni, Bernardo
AU - Walley, Barbara A.
AU - Stewart, J.
AU - Chirgwin, J.
AU - van der Westhuizen, A.
AU - Briscoe, K.
AU - Koczwara, B.
AU - Gauden, S.
AU - Moylan, E.
AU - Francis, P. A.
AU - Nottage, M.
AU - Boadle, D.
AU - Bayliss, E.
AU - Snyder, R.
AU - Sardelic, F.
AU - Abdi, E.
AU - Chipman, M.
AU - Gombos, A.
AU - Barbeaux, A.
AU - Jerusalem, G.
AU - Neven, P.
AU - Láng, I.
AU - Plugisi, F.
AU - Crivellari, D.
AU - Pavesi, L.
AU - Gianni, L.
AU - Pinotti, G.
AU - Tondini, C.
AU - Di Leo, A.
AU - Graiff, C.
AU - Gomez, H.
AU - Skof, E.
AU - Van Echo, D. C.
N1 - Funding Information: The translational project presented here is supported by Susan G. Komen for the Cure Promise Grant (KG080081 to GV, OP, MMR). The translational project in Australia and New Zealand was supported by an Australia and New Zealand Breast Cancer Trials Group (ANZBCTG) Discretionary Funding Research Grant (PF, AC). TEXT receives financial support for trial conduct from Pfizer, the International Breast Cancer Study Group and the US National Cancer Institute. Pfizer and Ipsen provided the drug supply, and the IBCSG received funding from Ipsen for additional data analyses. Support for the coordinating group, IBCSG: Frontier Science and Technology Research Foundation, Swiss Group for Clinical Cancer Research (SAKK), US National Cancer Institute (NCI) (CA75362), Cancer Research Switzerland/Oncosuisse, and the Foundation for Clinical Cancer Research of Eastern Switzerland (OSKK). Neither the pharmaceutical companies nor Susan G. Koment for the Cure have a role in the reporting or interpretation of the results, other than a minority representation on the Steering Committee. Grant support of cooperative groups: ANZBCTG (NHMRC 351161, 510788, 1105058); SWOG (US NIH CA32102); Alliance/CALGB (US NIH U10CA180821); ECOG-ACRIN (US NIH CA21115 and CA16116); NSABP/NRG (US NIH U10-CA-12027, U10-CA-69651, U10-CA-37377, U10-CA-69974); NCIC (US NIH CA077202 and CCSRI 015469 and 021039). Funding Information: The authors thank the patients who participated and the staff who conducted the study at the participating centers, and the CALGB Pathology Coordinating Office. Investigators and the International Breast Cancer Study Group participants include Steering Committee: P.A. Francis (Chair, SOFT Co- Chair), G.F. Fleming (SOFT Co-Chair), O. Pagani (TEXT Co-Chair), B. A. Walley (TEXT Co-Chair), M.M. Regan (Trial Statistician), L. Blacher, H. Bonnefoi, E. Ciruelos, A.S. Coates, M. Colleoni, N. Dif, R.D. Gelber, A. Goldhirsch, A. Hiltbrunner, R. Kammler, R. Maibach, O. Ortmann, K.N. Price, M. Rabaglio, B. Ruepp, H. Shaw, G. Viale, G. von Minckwitz, V. Katkade (Pfizer), E. Chetaille (Ipsen). IBCSG Scientific Executive Committee: M. Colleoni, F. Boyle, A. DiLeo, G. Jerusalem, K.N. Price, M.M. Regan, G. Viale. IBCSG Foundation Council: R. Stahl (President), S. Aebi, A.S. Coates, M. Colleoni, R.D. Gelber, A. Goldhirsch, P. Karlsson, I. Kössler. IBCSG Coordinating Center, Bern, Switzerland: A. Hiltbrunner (Director), R. Kammler, R. Maibach, M. Rabaglio, S. Roux, B. Ruepp, P. Sicher. IBCSG Statistical Center, Dana-Farber Cancer Institute, Boston, MA, USA: R.D. Gelber (Director), M.M. Regan (Group Statistician), M. Bonetti, Y. Feng, A. Giobbie-Hurder, K.P. Gray, H. Huang, W. Luo, K.N. Price, L. Zickl. IBCSG Data Management Center, Frontier Science & Technology Research Foundation, Amherst, NY, USA: L. Blacher (Director), K. Scott (DM Section Head), M. Blackwell, A. Cesario, A. Dickinson, K. Donahue, M. Greco, P. Gonzalez, T. Heckman-Scolese, R. Hecker, R. Hinkle, M. Kalera, K. Lupejkis, A. Mora de Karausch, V. Palermo, H. Shaw, R. Starkweather, J. Swick-Jemison. IBCSG Central Biomarker Laboratory, European Institute of Oncology, Division of Cancer Prevention and Genetics, Milan, Italy: B. Bonanni, H. Johansson, D. Macis. IBCSG Central Pathology Office, European Institute of Oncology, Division of Pathology, Milan, Italy: G. Viale, D. Lepanto, O. Pala. IBCSG Quality of Life Office, Bern, Switzerland: J. Bernhard, K. Ribi. U.S. National Cancer Institute: J. Abrams, J.A. Zujewski. U.S. NCI Clinical Trials Support Unit (CTSU)/ Westat: M. Hering, M. Greene, A. Nelson, M. Balois-Ouellette, S. Riordan, O. Santos. ALMAC: W. Mahon, E. Whitney, J. Bryant. CTSU Regulatory Office: R. Catalano, D. Marinucci, B. Niewood, R. Lambersky. Alliance (CALGB) Pathology Coordinating Office, Ohio State University, Columbus, OH, USA: W. Frankel, S. Jewell. Dana-Farber Cancer Institute, Boston, MA, USA (US FDA IND): E.P. Winer, J. Savoie. Pfizer Study Support: B. Campanelli, S. Duong, J.A. Graham, C. Grant, B. Klingele, J. Passmore. Ipsen Study Support: E. Chetaille, J. Amauri Soares, C. Descot, S. Hemont-Dacosta, F. Bismuth, P. Chevreau, H. Bibas. TEXT Participating Centers and Principal Investigators include Centers with accrual of more than one patient: Breast International Group (BIG); International Breast Cancer Study Group (IBCSG). Australia and New Zealand Breast Cancer Trials Group (ANZBCTG): Austin Health, Heidelberg, Victoria: J. Stewart; Box Hill Hospital, Box Hill, Victoria: J. Chirgwin; Calvary Mater Newcastle, Waratah, New South Wales: A. van der Westhuizen; Coffs Harbour Health Campus, Coffs Harbour, New South Wales: K. Briscoe; Flinders Medical Centre, Bedford Park, South Australia: B. Koczwara; Launceston General Hospital, Launceston, Tasmania: S. Gauden; Liverpool Hospital, Liverpool, New South Wales: E. Moylan; Maroondah Hospital, Ringwood East, Victoria: J. Chirgwin; Peter MacCallum Cancer Centre, East Melbourne, Victoria: P. A. Francis; Royal Brisbane and Women's Hospital, Herston, Queensland: M. Nottage; Royal Hobart Hospital, Hobart, Tasmania: D. Boadle; Royal Perth Hospital, Perth, Western Australia: E. Bayliss; St. Vincent's Hospital Melbourne, Fitzroy, Victoria: R. Snyder; Tamworth Rural Referral Hospital, Tamworth, New South Wales: F. Sardelic; Tweed Hospital, The, Tweed Heads, New South Wales: E. Abdi; Victorian Breast and Oncology Care, East Melbourne, Victoria: M. Chipman. Belgium: Institute Jules Bordet, Brussels: A. Gombos; Centre Hospitalier Peltzer-La Tourelle, Verviers: A. Barbeaux; Centre Hospitalier Universitarie Sart Tilman, Liège: G. Jerusalem; U.Z. Gasthuisberg, Leuven: P. Neven. Hungary: National Institute of Oncology, Budapest; I. Láng. Italy: Dipartimento di Oncologia, Azienda Ospedaliero-Universitaria di Udine, Udine: F. Plugisi; Centro di Riferimento Oncologico, Aviano: D. Crivellari; Fondazione Salvatore Maugeri, Pavia: L. Pavesi; Istituto Europeo di Oncologia, Milano: M. Colleoni; Ospedale degli Infermi, Rimini: L. Gianni; Ospedale di Circolo e Fondazione Macchi, Varese: G. Pinotti; Ospedali Riuniti di Bergamo, Bergamo: C. Tondini; Sandro Pitigliani Medical Oncology Unit, Hospital of Prato, Prato: A. Di Leo; Azienda Sanitaria di Bolzano, Bolzano: C. Graiff. Peru: Instituto de Enfermedades Neoplásicas, Lima: H. Gomez. Slovenia: Institute of Oncology, Ljubljana: E. Skof. South Africa: Sandton Oncology Centre, Johannesburg; D. Vorobiof. Sweden: Sahlgrenska University Hospital, Gothenburg; P. Karlsson. Switzerland: Swiss Association for Clinical Cancer Research (SAKK), Centre Hospitalier Universitaire Vaudois, Lausanne: K. Zamin; Inselspital, Bern: M. Rabaglio; Oncocare Engeried, Bern: K. Buser; Institute of Oncology of Southern Switzerland (Ospedale San Giovanni, Bellinzona; Ospedale Regionale di Lugano, (Civico & Italiano), Lugano; Ospedale Regionale Beata Vergine, Mendrisio; Ospedale Regionale La Carità, Locarno; Istituto Cantonale di Patologia, Locarno): O. Pagani; Kantonsspital St. Gallen, St. Gallen: T. Ruhstaller; Rätisches Kantonos-/Regionalspital, Chur: R. von Moos; Kantonsspital Basel, Basel: C. Rochlitz; Onkologiezentrum Thun-Berner Oberland, Thun: D. Rauch; Zürich Frauenklinik, Zürich: N. Gabriel. Germany: German Breast Group (GBG), Caritas-Krankenhaus St. Josef, Regensburg: S. Buchholz; Dr. Horst Schmidt Kliniken, Wiesbaden: F. Lorenz-Salehi. North American Breast Cancer Group: American College of Surgeons Oncology Group (ACOSOG, now part of Alliance for Clinical Trials in Oncology); Cancer and Leukemia Group B (CALGB, now part of Alliance for Clinical Trials in Oncology); Eastern Cooperative Oncology Group (ECOG, now part of ECOGACRIN Cancer Research Group); NCIC Clinical Trials Group (NCIC CTG); National Surgical Adjuvant Breast and Bowel Project (NSABP, now part of NRG Oncology); North Central Cancer Treatment Group (NCCTG, now part of Alliance for Clinical Trials in Oncology); Radiation Therapy Oncology Group (RTOG, now part of NRG Oncology); South West Oncology Group (SWOG); North American Participating Centers. Canada: Cross Cancer Institute, Edmonton, Alberta: K.S. Tonkin; Tom Baker Cancer Center, Calgary, Alberta: B.A. Walley (Chair), M. Webster (PI); London Regional Cancer Center, London, Ontario: K.R. Potvin; Juravinski Cancer Centre at Hamilton Health Sciences, Hamilton, Ontario: R.G. Tozer; Trillium Health Centre - W Toronto, Toronto, Ontario: J.A. Gapski; Hôpital Charles LeMoyne, Greenfield Park, Quebec: C. Prady; Allan Blair Cancer Center, Regina, Saskatchewan; M. Salim; Saskatoon Cancer Center, Saskatoon, Saskatchewan: A. Sami; The Vitalite Health Network - Dr. Leon Richard Oncology Centre, Moncton, New Brunswick: P. Whitlock. USA: Presbyterian Hospital, Whittier, CA: J.H. Freimann; University of California at San Diego, San Diego, CA: J.E. Mortimer; St. Joseph Medical Center, Burbank, CA: R.R. Mena; San Francisco General, San Francisco, CA: H.S. Rugo; University of California at San Francisco, San Francisco, CA: C.J. Ryan; University of California San Diego Cancer Center, San Diego, CA: B.A. Parker; University of Colorado, Aurora, CO: A.D. Elias; The Shaw Regional Cancer Center, Aurora, CO: A.D. Elias; University of Connecticut, Farmington, CT: S. Tannenbaum; Walter Reed Army Medical Center, Washington, DC: D.C. Van Echo; Northeast Georgia Medical Center, Gainesville, GA: R.J. LoCicero; Siouxland Hematology - Oncology Associates, Sioux City, IA: D.B. Wender; Saint Luke's Mountain States Tumor Institute, Boise, ID: T.A. Walters; Evanston Northwestern Healthcare, Evanston, IL: D.E. Merkel; Resurrection Medical Center, Chicago, IL: C. G. Rose; University of Chicago, Chicago, IL: H.L. Kindler; Saint Joseph's Medical Center, South Bend, IN: R.H. Ansari; Memorial Hospital of South Bend, South Bend, IN: R.H. Ansari; Northern Indiana Cancer Research Co, South Bend, IN: R.H. Ansari; Mount Carmel Regional Cancer Center, Pittsburg, KS; Stormont-Vail Regional Health Center, Topeka, KS: S.J. Vogel; Cancer Center of Kansas Wichita, Wichita, KS: S.R. Dakhil; Via Christi Regional Medical Center, Wichita, KS: S.R. Dakhil; Addison Gilbert, Gloucester, MA: A.P. McIntyre; Tufts Medical Center, Boston, MA: J.K. Erban; Massachusetts General Hospital, Boston, MA: H.J. Burstein; Dana-Farber Cancer Institute, Boston, MA: H.J. Burstein; Beth Israel Deaconess Medical Center, Boston, MA: H.J. Burstein; Faulkner Hospital, Boston, MA: H.J. Burstein; North Shore Cancer Center, Salem, MA: K.J. Krag; Emerson Hospital, Boston, MA: H.J. Burstein; Suburban Hospital, Bethesda, MD: C.B. Hendricks; University of Maryland Greenebaum Cancer Center, Baltimore, MD: K.H. Rak Tkaczuk; Mercy Medical Center, Baltimore, MD: D.A. Riseberg; Frederick Memorial Hospital, Frederick, MD: E.D. Eskander; William Beaumont Hospital, Royal Oak, MI: D. Zakalik; United Hospital, St. Paul, MN: P.J. Flynn; Abbott-Northwestern Hospital, St. Louis Park, MN: P.J. Flynn; Mercy Hospital, Coon Rapids, MN: P.J. Flynn; Mayo Clinic, Rochester, MN: J.N. Ingle; Saint John's Hospital - Healtheast, Minneapolis, MN: D.J. Schneider; Metro-Minnesota CCOP, Minneapolis, MN: P.J. Flynn; Washington School of Medicine, St Louis, MO: M.J. Naughton; Kansas City CCOP, Kansas City, MO: W.T. Stephenson; Moses H. Cone Memorial, Greensboro, NC: J.E. Feldmann; Mission Hospitals Inc, Asheville, NC: M.J. Messino; Hope, A Women's Cancer Center, Asheville, NC: D.J. Hetzel; Medcenter One Health Systems, Bismarck, ND: E.J. Wos; Dakota Clinic, Fargo, ND: K. Sen; University of Nebraska Medical Center, Omaha, NE: E.C. Reed; Portsmouth Regional Hospital, Portsmouth, NH: E.M. Bonnem; South Jersey Healthcare, Vineland, NJ: D.H. Blom; New York University Medical Center, New York, NY: A.D. Tiersten; Albert Einstein College/Medicine, Bronx, NY: C.M. Pellegrino; Roswell Park Cancer Institute, Buffalo, NY: E.G. Levine; Geisinger Medical Center, Danville, PA: G.D.A. Padula; Greenville CCOP, Greenville, SC: J.K. Giguere; Sioux Valley Clinic - Oncology, Sioux Falls, SD: M.A. Mazurczak; University of Vermont, Burlington, VT: S. Burdette-Radoux; Mountainview Medical, Berlin, VT: S. Burdette-Radoux; Swedish Hospital Medical Center, Seattle, WA: S.E. Rivkin; University of Washington Medical Center, Seattle, WA: S.E. Rivkin; Aspirus Wausau Hospital Center, Wausau, WI: U. Gautam; Oncology Alliance-Glendale, Glendale, WI: R.D. Hart; West Virginia University, Morgantown, WV: J. Abraham. The translational project presented here is supported by Susan G. Komen for the Cure Promise Grant (KG080081 to GV, OP, MMR). The translational project in Australia and New Zealand was supported by an Australia and New Zealand Breast Cancer Trials Group (ANZBCTG) Discretionary Funding Research Grant (PF, AC). TEXT receives financial support for trial conduct from Pfizer, the International Breast Cancer Study Group and the US National Cancer Institute. Pfizer and Ipsen provided the drug supply, and the IBCSG received funding from Ipsen for additional data analyses. Support for the coordinating group, IBCSG: Frontier Science and Technology Research Foundation, Swiss Group for Clinical Cancer Research (SAKK), US National Cancer Institute (NCI) (CA75362), Cancer Research Switzerland/Oncosuisse, and the Foundation for Clinical Cancer Research of Eastern Switzerland (OSKK). Neither the pharmaceutical companies nor Susan G. Koment for the Cure have a role in the reporting or interpretation of the results, other than a minority representation on the Steering Committee. Grant support of cooperative groups: ANZBCTG (NHMRC 351161, 510788, 1105058); SWOG (US NIH CA32102); Alliance/CALGB (US NIH U10CA180821); ECOG-ACRIN (US NIH CA21115 and CA16116); NSABP/NRG (US NIH U10-CA-12027, U10-CA-69651, U10-CA-37377, U10-CA-69974); NCIC (US NIH CA077202 and CCSRI 015469 and 021039). Publisher Copyright: © 2016 The Author(s).
PY - 2016/11/8
Y1 - 2016/11/8
N2 - Background: Single nucleotide polymorphisms (SNPs) in the estrogen receptor 1 (ESR1) and cytochrome P450 19A1 (CYP19A1) genes have been associated with breast cancer risk, endocrine therapy response and side effects, mainly in postmenopausal women with early breast cancer. This analysis aimed to assess the association of selected germline CYP19A1 and ESR1 SNPs with early-onset hot flashes, sweating and musculoskeletal symptoms in premenopausal patients enrolled in the Tamoxifen and Exemestane Trial (TEXT). Methods: Blood was collected from consenting premenopausal women with hormone-responsive early breast cancer, randomly assigned to 5-years of tamoxifen plus ovarian suppression (OFS) or exemestane plus OFS. DNA was extracted with QIAamp kits and genotyped for two CYP19A1 (rs4646 and rs10046) and three ESR1 (rs2077647, rs2234693 and rs9340799) SNPs by a real-time pyrosequencing technique. Adverse events (AEs) were recorded at baseline and 3-monthly during the first year. Associations of the genotype variants with grade ≥2 early-onset targeted AEs of hot flashes/sweating or musculoskeletal events were assessed using logistic regression models. Results: There were 2660 premenopausal patients with breast cancer in the intention-to-treat population of TEXT, and 1967 (74 %) are included in this translational study. The CYP19A1 rs10046 variant T/T, represented in 23 % of women, was associated with a reduced incidence of grade ≥2 hot flashes/sweating (univariate odds ratio (OR) = 0.78; 95 % CI 0.63-0.97; P = 0.03), more strongly in patients assigned exemestane + OFS (TT vs CT/CC: OR = 0.65, 95 % CI = 0.48-0.89) than assigned tamoxifen + OFS (OR = 0.94, 95 % CI = 0.69-1.27, interaction P = 0.03). No association with any of the CYP19A1/ESR1 genotypes and musculoskeletal AEs was found. Conclusion: The CYP19A1 rs10046 variant T/T favors lower incidence of hot flashes/sweating under exemestane + OFS treatment, suggesting endocrine-mediated effects. Based on findings from others, this SNP may potentially enhance treatment adherence and treatment efficacy. We plan to evaluate the clinical impact of this polymorphism during time, pending sufficient median follow up. Trial registration: ClinicalTrials.gov NCT00066703, registered August 6, 2003.
AB - Background: Single nucleotide polymorphisms (SNPs) in the estrogen receptor 1 (ESR1) and cytochrome P450 19A1 (CYP19A1) genes have been associated with breast cancer risk, endocrine therapy response and side effects, mainly in postmenopausal women with early breast cancer. This analysis aimed to assess the association of selected germline CYP19A1 and ESR1 SNPs with early-onset hot flashes, sweating and musculoskeletal symptoms in premenopausal patients enrolled in the Tamoxifen and Exemestane Trial (TEXT). Methods: Blood was collected from consenting premenopausal women with hormone-responsive early breast cancer, randomly assigned to 5-years of tamoxifen plus ovarian suppression (OFS) or exemestane plus OFS. DNA was extracted with QIAamp kits and genotyped for two CYP19A1 (rs4646 and rs10046) and three ESR1 (rs2077647, rs2234693 and rs9340799) SNPs by a real-time pyrosequencing technique. Adverse events (AEs) were recorded at baseline and 3-monthly during the first year. Associations of the genotype variants with grade ≥2 early-onset targeted AEs of hot flashes/sweating or musculoskeletal events were assessed using logistic regression models. Results: There were 2660 premenopausal patients with breast cancer in the intention-to-treat population of TEXT, and 1967 (74 %) are included in this translational study. The CYP19A1 rs10046 variant T/T, represented in 23 % of women, was associated with a reduced incidence of grade ≥2 hot flashes/sweating (univariate odds ratio (OR) = 0.78; 95 % CI 0.63-0.97; P = 0.03), more strongly in patients assigned exemestane + OFS (TT vs CT/CC: OR = 0.65, 95 % CI = 0.48-0.89) than assigned tamoxifen + OFS (OR = 0.94, 95 % CI = 0.69-1.27, interaction P = 0.03). No association with any of the CYP19A1/ESR1 genotypes and musculoskeletal AEs was found. Conclusion: The CYP19A1 rs10046 variant T/T favors lower incidence of hot flashes/sweating under exemestane + OFS treatment, suggesting endocrine-mediated effects. Based on findings from others, this SNP may potentially enhance treatment adherence and treatment efficacy. We plan to evaluate the clinical impact of this polymorphism during time, pending sufficient median follow up. Trial registration: ClinicalTrials.gov NCT00066703, registered August 6, 2003.
KW - Aromatase inhibitors
KW - Breast cancer
KW - CYP19A1
KW - ESR1
KW - Ovarian suppression
KW - Side effects
KW - Tamoxifen
UR - http://www.scopus.com/inward/record.url?scp=85005976027&partnerID=8YFLogxK
U2 - 10.1186/s13058-016-0771-8
DO - 10.1186/s13058-016-0771-8
M3 - Article
C2 - 27825388
AN - SCOPUS:85005976027
SN - 1465-5411
VL - 18
JO - Breast Cancer Research
JF - Breast Cancer Research
IS - 1
M1 - 110
ER -