PMID- 33799547
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210409
IS  - 2072-6694 (Print)
IS  - 2072-6694 (Electronic)
IS  - 2072-6694 (Linking)
VI  - 13
IP  - 6
DP  - 2021 Mar 11
TI  - Potential Utility of Pre-Emptive Germline Pharmacogenetics in Breast Cancer.
LID - 10.3390/cancers13061219 [doi]
LID - 1219
AB  - Patients with breast cancer often receive many drugs to manage the cancer, side 
      effects associated with cancer treatment, and co-morbidities (i.e., 
      polypharmacy). Drug-drug and drug-gene interactions contribute to the risk of 
      adverse events (AEs), which could lead to non-adherence and reduced efficacy. 
      Here we investigated several well-characterized inherited (germline) 
      pharmacogenetic (PGx) targets in 225 patients with breast cancer. All relevant 
      clinical, pharmaceutical, and PGx diplotype data were aggregated into a single 
      unifying informatics platform to enable an exploratory analysis of the cohort and 
      to evaluate pharmacy ordering patterns. Of the drugs recorded, there were 38 for 
      which high levels of evidence for clinical actionability with PGx was available 
      from the US FDA and/or the Clinical Pharmacogenetics Implementation Consortium 
      (CPIC). These data were associated with 10 pharmacogenes: DPYD, CYP2C9, CYP2C19, 
      CYP2D6, CYP3A5, CYP4F2, G6PD, MT-RNR1, SLCO1B1, and VKORC1. All patients were 
      taking at least one of the 38 drugs and had inherited at least one actionable PGx 
      variant that would have informed prescribing decisions if this information had 
      been available pre-emptively. The non-cancer drugs with PGx implications that 
      were common (prescribed to at least one-third of patients) included 
      anti-depressants, anti-infectives, non-steroidal anti-inflammatory drugs, 
      opioids, and proton pump inhibitors. Based on these results, we conclude that 
      pre-emptive PGx testing may benefit patients with breast cancer by informing drug 
      and dose selection to maximize efficacy and minimize AEs.
FAU - Bernard, Philip S
AU  - Bernard PS
AD  - ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, UT 84108, 
      USA.
AD  - Department of Pathology, University of Utah, Salt Lake City, UT 84112, USA.
AD  - Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA.
FAU - Wooderchak-Donahue, Whitney
AU  - Wooderchak-Donahue W
AD  - ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, UT 84108, 
      USA.
AD  - Department of Pathology, University of Utah, Salt Lake City, UT 84112, USA.
FAU - Wei, Mei
AU  - Wei M
AD  - Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA.
AD  - Division of Oncology, Department of Internal Medicine, University of Utah, Salt 
      Lake City, UT 84112, USA.
FAU - Bray, Steven M
AU  - Bray SM
AD  - LifeOmic Inc., Indianapolis, IN 46202, USA.
FAU - Wood, Kevin C
AU  - Wood KC
AD  - LifeOmic Inc., Indianapolis, IN 46202, USA.
FAU - Parikh, Baiju
AU  - Parikh B
AD  - LifeOmic Inc., Indianapolis, IN 46202, USA.
FAU - McMillin, Gwendolyn A
AU  - McMillin GA
AD  - ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, UT 84108, 
      USA.
AD  - Department of Pathology, University of Utah, Salt Lake City, UT 84112, USA.
LA  - eng
GR  - P30 CA042014/CA/NCI NIH HHS/United States
PT  - Journal Article
DEP - 20210311
PL  - Switzerland
TA  - Cancers (Basel)
JT  - Cancers
JID - 101526829
PMC - PMC7998388
OTO - NOTNLM
OT  - CYP2D6
OT  - breast cancer
OT  - genotyping
OT  - pharmacogenomics
OT  - supportive care
COIS- The authors declare no conflict of interest. The funders had no role in the 
      design of the study; in the collection, analyses, or interpretation of data; in 
      the writing of the manuscript, or in the decision to publish the results.
EDAT- 2021/04/04 06:00
MHDA- 2021/04/04 06:01
PMCR- 2021/03/11
CRDT- 2021/04/03 01:03
PHST- 2021/01/16 00:00 [received]
PHST- 2021/03/05 00:00 [revised]
PHST- 2021/03/06 00:00 [accepted]
PHST- 2021/04/03 01:03 [entrez]
PHST- 2021/04/04 06:00 [pubmed]
PHST- 2021/04/04 06:01 [medline]
PHST- 2021/03/11 00:00 [pmc-release]
AID - cancers13061219 [pii]
AID - cancers-13-01219 [pii]
AID - 10.3390/cancers13061219 [doi]
PST - epublish
SO  - Cancers (Basel). 2021 Mar 11;13(6):1219. doi: 10.3390/cancers13061219.