Case Histories

Medications and Genomics

A post-menopausal woman (age 63) was diagnosed with Estrogen Receptor positive (ER+) breast cancer. An OncotypeDX analysis was performed; this test identified the DNA of the tumor, calculated a recurrence score, determined whether chemotherapy and/or radiation was (were) necessary or whether tamoxifen (a selective estrogen receptor modulator or SERM) was the drug of choice to prevent recurrence.

Her results indicated a low recurrence score and therefore, Tamoxifen was prescribed. Tamoxifen must undergo a biotransformation to endoxifen, which is the active SERM, via cytochrome P450 enzyme 2D6 (CYP 2D6). Rather than assume that the woman had an active CYP 2D6 gene, a functional genomic test was conducted by IIM and the results showed that her CYP 2D6 gene was impaired and, therefore, Tamoxifen would not have been an effective treatment.

The results were conveyed to her oncologist and another drug (Femara) was prescribed; while Femara is not a SERM but an aromatase enzyme inhibitor, the oncologist concluded that given the SNP (single nucleotide polymorphism) on CYP2D6, this drug would reduce the synthesis of estradiol and therefore decrease her risk of breast cancer recurrence.

Femara is detoxified by CYP 3A4 and because her genomic results showed that this gene did not possess a SNP, there was little risk of an adverse drug reaction to Femara.

In summary, functional genomic testing not only identified the most effective breast cancer treatment from two choices, it also revealed that the selected choice had a low likelihood of side effects.

References:

CYP2D6 polymorphisms and the impact on tamoxifen therapy
Beverage JN, TM Sissung, AM Sion, R Danesi and WD Figg
Journal of Pharmacological Science 96: 2224-2231 (2007)

Cytochrome P450 2D6 activity predicts discontinuation of tamoxifen therapy in breast cancer patients.
Rae, J, MJ Sikora, NL Henry, L Li, S Kim et al.
The Pharmacogenomics Journal 9:258-264 (2009)

Pharmacogenetics in the Treatment of Breast Cancer.
Stearns V. et al.
Pharmacogenomics Journal 4:143-153. (2004)