Nav: Home

Gene mutation and use of certain antidepressants may decrease effects of breast cancer drug

June 05, 2004

Researchers from the Johns Hopkins Kimmel Cancer Center, Indiana University and the University of Michigan have found that some women have a gene mutation that may decrease the effectiveness of tamoxifen, a commonly used breast cancer drug. The findings, to be reported at the 40th annual meeting of the American Society of Clinical Oncology on June 5, may tell physicians which women might have reduced benefit from tamoxifen therapy. Results also suggest that some frequently prescribed antidepressants may reduce tamoxifen's effects because the antidepressants affect a similar metabolic pathway.

Although a test for the mutation in the CYP2D6 gene is not widely available, the investigators recommend that women currently on long-term tamoxifen therapy and using such antidepressants as paroxetine and sertraline consult their health care provider for guidance. These drugs, known as selective serotonin reuptake inhibitors (SSRIs) include such well-known brands as Paxil and Zoloft. The investigators estimate the prevalence of the CYP2D6 mutation to be approximately 40 percent, and in this study of 80 women, 35 percent had the mutation.

"There's no evidence from this study that a woman who is taking tamoxifen should automatically stop using a particular antidepressant if it is helping her," says Vered Stearns, M.D., assistant professor of oncology at the Johns Hopkins Kimmel Cancer Center. But the researchers advise that women on tamoxifen who are considering antidepressant therapy, may opt to use an antidepressant, such as venlafaxine, which may not alter tamoxifen's metabolism and has less of an effect on tamoxifen.

"Our findings are leading us in the direction of recommending therapies based on an individual's genetic profile," says Stearns. "If a woman has a particular gene mutation, we may be able to predict how she'll react to a therapy."

Tamoxifen is widely prescribed to reduce the risk of breast cancer recurrence or spread and increasingly is given in efforts to prevent breast cancer in women at high risk for the disease.

The CYP2D6 gene controls production of an enzyme that breaks down and processes tamoxifen. Mutations in the gene reduce the enzyme's ability to properly break down tamoxifen.

The women in the study had taken tamoxifen daily for four months. Analysis of blood levels of a newly characterized byproduct, called endoxifen, were approximately 75 percent lower in women with a CYP2D6 mutation in both copies of the gene. The lower levels of endoxifen suggest that mutation alters the metabolism of tamoxifen and may affect potency of the drug.

"At this point, we do not know precisely what lower levels of endoxifen signify, or if other byproducts of tamoxifen metabolism are equally or more important to measure for monitoring tamoxifen's effectiveness," cautions Stearns.

The investigators also found lower endoxifen levels in women taking antidepressant drugs regardless of whether or not they had a CYP2D6 gene mutation. Certain antidepressant drugs, such as paroxetine and sertraline, are known to block the CYP2D6 enzyme. Antidepressants are being prescribed in up to 20 percent of breast cancer patients for depression, anxiety, other psychiatric disorders or hot flashes, a common side effect of tamoxifen.

In upcoming studies, the investigators will compare antidepressant therapies in women taking tamoxifen and how gene variations in the estrogen receptors of breast cancer patients may impact the effectiveness of tamoxifen.
-end-
This research was funded by the National Institutes of Health (NIH/NIGMS).

Additional participants in this research were Yan Jin, Bryan Ward, Todd Skaar, Anna Maria Storniolo, Anne Nguyen, Zeruesenay Desta and David A. Flockhard from Indiana University School of Medicine; and Linda Ullmer, Jill Hayden and Daniel F. Hayes from the University of Michigan.

Abstract #508, Proceeding of the American Society of Clinical Oncology, 2004.

Links:
ASCO: http://www.asco.org
Johns Hopkins Kimmel Cancer Center: http://www.hopkinskimmelcancercenter.org

Johns Hopkins Medicine

Related Antidepressants Articles:

Antibodies: the body's own antidepressants
Antibodies can be a blessing or a curse to the brain -- it all depends on their concentration.
Are some antidepressants less risky for pregnant women?
About one in ten women in Québec will suffer from depression during pregnancy.
The effect of taking antidepressants during pregnancy
Exposure to antidepressants during pregnancy and the first weeks of life can alter sensory processing well into adulthood, according to research in mice recently published in eNeuro.
Significantly fewer pregnant women take antidepressants
A pregnancy is not always a happy event and as many as 10-15% of pregnant women in Denmark have depressive symptoms.
Antidepressants reduce deaths by more than a third in patients with diabetes
Antidepressants reduce deaths by more than a third in patients with diabetes and depression, according to a study published in the Endocrine Society's Journal of Clinical Endocrinology & Metabolism.
Antidepressants can reduce the empathic empathy
Depression is a disorder that often comes along with strong impairments of social functioning.
Possible link between autism and antidepressants use during pregnancy
An international team led by Duke-NUS Medical School has found a potential link between autistic-like behaviour in adult mice and exposure to a common antidepressant in the womb.
When neurons are out of shape, antidepressants may not work
Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed medication for major depressive disorder (MDD), yet scientists still do not understand why the treatment does not work in nearly thirty percent of patients with MDD.
Next-generation metabolomics may facilitate the discovery of new antidepressants
Antidepressants have become one of the most commonly prescribed drugs.
Male birds sing less to females on antidepressants
Female starlings who have ingested dilute concentrations of antidepressants while feeding on worms, maggots and flies at sewage treatment plants appear to be less attractive to the opposite sex.
More Antidepressants News and Antidepressants Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Making Amends
What makes a true apology? What does it mean to make amends for past mistakes? This hour, TED speakers explore how repairing the wrongs of the past is the first step toward healing for the future. Guests include historian and preservationist Brent Leggs, law professor Martha Minow, librarian Dawn Wacek, and playwright V (formerly Eve Ensler).
Now Playing: Science for the People

#565 The Great Wide Indoors
We're all spending a bit more time indoors this summer than we probably figured. But did you ever stop to think about why the places we live and work as designed the way they are? And how they could be designed better? We're talking with Emily Anthes about her new book "The Great Indoors: The Surprising Science of how Buildings Shape our Behavior, Health and Happiness".
Now Playing: Radiolab

The Third. A TED Talk.
Jad gives a TED talk about his life as a journalist and how Radiolab has evolved over the years. Here's how TED described it:How do you end a story? Host of Radiolab Jad Abumrad tells how his search for an answer led him home to the mountains of Tennessee, where he met an unexpected teacher: Dolly Parton.Jad Nicholas Abumrad is a Lebanese-American radio host, composer and producer. He is the founder of the syndicated public radio program Radiolab, which is broadcast on over 600 radio stations nationwide and is downloaded more than 120 million times a year as a podcast. He also created More Perfect, a podcast that tells the stories behind the Supreme Court's most famous decisions. And most recently, Dolly Parton's America, a nine-episode podcast exploring the life and times of the iconic country music star. Abumrad has received three Peabody Awards and was named a MacArthur Fellow in 2011.