Predictive markers in elderly patients with estrogen receptor-positive breast cancer treated with aromatase inhibitors: an array-based pharmacogenetic study.
So far, no reliable predictive clinicopathological markers of response to aromatase inhibitors (AIs) have been identified, and little is known regarding the role played by host genetics. To identify constitutive predictive markers, an array-based association study was performed in a cohort of 55 elderly hormone-dependent breast cancer (BC) patients treated with third-generation AIs. The array used in this study interrogates variants in 225 drug metabolism and disposition genes with documented functional significance. Six variants emerged as associated with response to AIs: three located in ABCG1, UGT2A1, SLCO3A1 with a good response, two in SLCO3A1 and one in ABCC4 with a poor response. Variants in the AI target CYP19A1 resulted associated with a favourable response only as haplotype; haplotypes with increased response association were also detected for ABCG1 and SLCO3A1. These results highlight the relevance of host genetics in the response to AIs and represent a first step toward precision medicine for elderly BC patients.
Immunology and Molecular Oncology Unit, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy.
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0000-0002-1142-0006
E
Rumiato
Medical Oncology 1 Unit, Department of Clinical and Experimental Oncology, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy.
A
A
Brunello
Medical Oncology 1 Unit, Department of Clinical and Experimental Oncology, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy.
S
S
Ahcene-Djaballah
Hemato-Oncology Unit, Medical Science Department ULSS 13, Mirano, Venezia, Italy.
L
L
Borgato
Division of Oncology, Rovigo General Hospital, ULSS 18, Rovigo, Italy.
M
M
Gusella
Division of Oncology, Rovigo General Hospital, ULSS 18, Rovigo, Italy.
D
D
Menon
Division of Oncology, Rovigo General Hospital, ULSS 18, Rovigo, Italy.
F
F
Pasini
Immunology and Molecular Oncology Unit, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy.|Department of Surgery, Oncology, and Gastroenterology, Oncology Section, University of Padova, Padova, Italy.
A
A
Amadori
Immunology and Molecular Oncology Unit, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy.
D
D
Saggioro
Medical Oncology 1 Unit, Department of Clinical and Experimental Oncology, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy.
V
V
Zagonel
D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1 / Q000235:genetics / Q000378:metabolism; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects / Q000627:therapeutic use*; D001141:Aromatase / Q000235:genetics* / Q000378:metabolism; D047072:Aromatase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism; D006239:Haplotypes; D006801:Humans; D007558:Italy; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D027361:Organic Anion Transporters / Q000235:genetics / Q000378:metabolism; D010597:Pharmacogenetics / Q000379:methods*; D000071185:Pharmacogenomic Testing / Q000379:methods*; D000071184:Pharmacogenomic Variants; D010641:Phenotype; D057285:Precision Medicine; D011237:Predictive Value of Tests; D011960:Receptors, Estrogen / Q000378:metabolism*; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018931:Antineoplastic Agents, Hormonal; D001141:Aromatase; D047072:Aromatase Inhibitors; D014408:Biomarkers, Tumor; D014453:Glucuronosyltransferase; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D027361:Organic Anion Transporters; D011960:Receptors, Estrogen; C073492:ABCC4 protein, human; C419353:ABCG1 protein, human; C479544:SLCO3A1 protein, human; C561410:CYP19A1 protein, human; C577641:UGT2A1 protein, human