Abstract
Individual response to chemotherapy in patients with breast cancer is variable. Obesity and exercise are associated with better and worse outcomes, respectively, and it is known that both impact the systemic cytokine milieu. Cytochrome P450 (CYP) enzymes are responsible for the metabolism of many chemotherapy agents, and CYP enzyme activity has been shown to be modified by inflammatory cytokines in vitro and in vivo. Cytokine-associated changes in CYP metabolism may alter chemotherapy exposure, potentially affecting treatment response and patient survival. Therefore, better understanding of these biological relationships is required. This exploratory single arm open label trial investigated changes in in vivo CYP activity in twelve women treated for stage II or III breast cancer, and demonstrated for the first time the feasibility and safety of utilising the Inje phenotyping cocktail to measure CYP activity in cancer patients receiving chemotherapy. Relative CYP activity varied between participants, particularly for CYP2C9 and CYP2D6, and changes in serum concentrations of the inflammatory cytokine monocyte chemoattractant protein 1 inversely correlated to CYP3A4 activity during chemotherapy. Future use of phenotyping cocktails in a clinical oncology setting may help guide drug dosing and improve chemotherapy outcomes.Clinical Trial Registration: Trial was retrospectively registered to the Australia New Zealand Clinical Trial Registry (ANZCTR). ACTRN12620000832976, 21 Aug 2020, https://www.anzctr.org.au/ACTRN12620000832976.aspx.
Highlights
Hepatic cytochrome P450 (CYP) drug metabolising enzymes are involved in metabolism of chemotherapy drugs used to treat breast cancer (BC), such as tamoxifen, cyclophosphamide, dexamethasone, doxorubicin and paclitaxel[1,2]
This study recruited a total of twelve women with stage II or III breast cancer (BC) receiving standard of care doxorubicin-cyclophosphamide and paclitaxel (AC-Pac) neoadjuvant (n = 6) and adjuvant (n = 6) chemotherapy at Christchurch Hospital
This study confirmed the safety and feasibility of using the Inje cocktail to assess the in vivo activity of CYP2C9, CYP2C19, CYP2D6, and CYP3A4 in women receiving chemotherapy for breast cancer (BC)
Summary
Hepatic cytochrome P450 (CYP) drug metabolising enzymes are involved in metabolism of chemotherapy drugs used to treat breast cancer (BC), such as tamoxifen, cyclophosphamide, dexamethasone, doxorubicin and paclitaxel[1,2]. Individual studies and investigations of pooled data across studies describe inverse correlation between higher body mass index (BMI = kg/m2) at diagnosis and pathological complete response rates in BC patients treated with neoadjuvant chemotherapies[31,35,36,37,38]. These findings suggest obesity and inflammation may share a common pathway to poorer response via alterations in chemotherapy metabolism
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
