Barcelona, Spain: Recently published research has shown that some breast cancer patients taking tamoxifen may not be getting the full benefit of their treatment because they have also been taking selective serotonin reuptake inhibitors (SSRIs), prescribed drugs that inhibit the effect of an important enzyme. Now researchers have developed a strategy for overcoming this problem, the seventh European Breast Cancer Conference (EBCC7) in Barcelona will hear today (Wednesday). Mr. Sean Hopkins, a clinical pharmacy specialist in breast cancer at the Ottawa Hospital Regional Cancer Centre, Ottawa, Canada, will present his research which shows that changing drug therapy at an early stage can help patients get the full benefit of tamoxifen and aid the effectiveness of their treatment.
Tamoxifen is used both to prevent development of oestrogen-receptor-positive cancer and as a therapy to stop it coming back. Taking medications such as fluoxetine (Prozac) and paroxetine for depression (and in some patients hot flashes), and bupropion (Zyban) for smoking cessation, can inhibit the action of CYP2D6, an enzyme that is related to drug metabolism and response to treatment, and which is crucial to the metabolism of tamoxifen for breast cancer.
Mr. Hopkins and his team set out to investigate how many patients taking hormonal therapy for breast cancer were also being prescribed CYP2D6 inhibitors. Research has shown that up to 25% of breast cancer patients have depressive disorders, and many of them are prescribed SSRIs. Additionally, many patients with cancer try to give up smoking and may use non-nicotine replacement therapies, such as buproprion.
“The study published recently by the Toronto group1 looked at how outcomes were related to treatments that the patients were taking concurrently,” says Mr. Hopkins. “Our study differs in that we have been able to take action as soon as we have discovered that a patient is taking interacting medication(s) by contacting the prescribing doctor in order to get them to switch to a different medication with no deleterious effect on tamoxifen metabolism.”
In many cases, Mr. Hopkins was able to identify those patients using interacting SSRIs before starting tamoxifen treatment, either to give them time to be weaned off onto another class of drug or to start them on a different cancer therapy such as an aromatase inhibitor (AI). CYP2D6 inhibitors do not have the same effect on AIs, but one in five patients discontinue taking AIs because of side effects2; if they change to tamoxifen while continuing to take enzyme inhibitors, there may be a longer overlap of therapies, says Mr. Hopkins.
“For these patients, having the knowledge to be able to plan effectively in advance is important, as it can take many weeks to wean patients off CYP2D6 inhibitors, and this may affect their breast cancer therapy. The findings mean that good communication between all healthcare providers is more important than ever in order to eliminate the risk of reducing the efficacy of prescribed therapy,” he will say.
Using drug data from his hospital’s Breast Cancer Disease Site Group clinical database, the researchers logged any patient on tamoxifen or AI therapy as well as those on CYP2D6 inhibitors. A total of 531 patients were found to be eligible for the study; 463 received one of the prescribed hormonal therapies, while 68 were on a CYP2D6 inhibitor but not receiving hormonal treatment. Seven patients receiving tamoxifen and 16 taking an AI were also on a strong CYP2D6 inhibitor – five percent of all the patients studied. One patient on tamoxifen and six on an AI were also receiving a moderate enzyme inhibitor, and 24 on tamoxifen and 40 on an AI were taking weak CYP2D6 inhibitors.
Tamoxifen must be metabolised in the liver before it can become active. “We have known for a while that patients with a deficiency in CYP2D6 activity did not derive the full benefit from tamoxifen because they cannot metabolise it to endoxifen, its active metabolite,” says Mr. Hopkins. “CYP2D6 medications can mimic this pharmacogenomic phenotype by inhibiting the metabolism of tamoxifen and hence reducing its therapeutic effect.”
The team now intends to follow up the work by expanding quality assurance on therapies to every breast cancer patient currently under treatment at the centre – over 6000 a year – and by exploring CYP2D6 testing for some of those patients. Such tests before treatment begins can help doctors identify those patients with a CYP2D6 deficiency and allow the possibility of offering AI rather than tamoxifen therapy from the outset.
“The work we have done demonstrates why good communication and seamless data transfer is so important in health care,” says Mr. Hopkins. “Patients can receive care from many different health care professionals – oncologists, other specialists, family doctors etc – and they can receive medications from multiple pharmacies. If there is insufficient information transfer between the individuals who care for a patient, the risks of drug interactions increase, and this can affect the quality and efficacy of care being given.
“I believe that we need to have policies in place to require health care providers and their agencies, including private insurance companies, to provide better access to information for health care professionals involved in patient care. If these organisations try to protect their information in an unreasonable manner it can seriously impact care and outcomes for patients.”
1 C. M. Kelly et al, BMJ 2010;340:c693
2 S.F. Dent et al, Breast Cancer Res Treat 106 (Suppl. 1) (2007), p. S111