Antipsychotic drugs may increase risk of breast cancer

by Jim Dryden, Washington University School of Medicine in St. Louis

Credit: Pixabay/CC0 Public Domain

Tracking medications provided to over a half million U.S. women, researchers at Washington University School of Medicine in St. Louis have found that many commonly prescribed older antipsychotic medications, and some newer ones, are associated with a significant increase in risk of breast cancer. Antipsychotics are prescribed for a broad range of conditions, including depression, bipolar disorder, schizophrenia, dementia and autism spectrum disorders.

26 dec 2021--While earlier studies have uncovered links between antipsychotic drug use and breast cancer risk, this is the first study to compare newer antipsychotics to older drugs, and to look at how the drugs affect levels of a hormone called prolactin. Increased levels of prolactin have been associated with breast cancer.

Prolactin is an important hormone involved in puberty, pregnancy and breastfeeding. However, many antipsychotics elevate prolactin levels and can produce side effects such as menstrual cycle irregularities, abnormal breast milk production and abnormal breast tissue growth.

The findings will be published in the February issue of the Journal of Clinical Psychopharmacology but are available online.

"Many women with psychiatric illnesses such as schizophrenia and bipolar disorder will take antipsychotics for decades, and they are essential to keeping symptoms in check," said the paper's first author, Tahir Rahman, MD, associate professor of psychiatry. "But both older antipsychotic medicines and some newer drugs raise levels of prolactin and increase the risk of breast cancer, which is concerning. Our study confirms findings from a smaller European study that advised women and their doctors to first try drugs that don't affect prolactin levels. We agree with that advice and believe psychiatrists should start to monitor prolactin levels in their patients taking antipsychotics."

The researchers classified antipsychotic drugs into three categories, based on their established effects on prolactin. Category 1 included drugs associated with high prolactin levels, such as haloperidol, paliperidone and risperidone. Category 2 drugs, which had mid-range effects on prolactin, included the drugs iloperidone, lurasidone and olanzapine. Category 3 included drugs with less of an effect on prolactin levels, such as aripiprazole, asenapine, brexpiprazole, cariprazine, clozapine, quetiapine and ziprasidone.

The researchers compared the effects of all three categories of antipsychotic drugs to anticonvulsant drugs and lithium, which also often are prescribed to treat psychiatric disorders. When compared with those drugs, the relative risk of breast cancer was 62% higher for women who took Category 1 drugs and 54% higher for those taking Category 2 drugs, whereas Category 3 antipsychotics were not associated with any increase in breast cancer risk.

"Certain drugs are known to elevate prolactin, and the women taking those drugs were more likely to have breast cancer," Rahman said. "But we didn't detect any increased risk in women taking antipsychotics that don't raise prolactin levels."

In mouse models, prolactin can contribute to a weakening of cellular systems that keep precancerous lesions from becoming breast cancer. In people, prolactin levels tend to be lower in women who have had more children at a younger age than in women who have fewer children or wait until they are older to do so.

In this study using data collected from 2012 through 2016, the research team performed a retrospective, observational study of breast cancer risk in women ages 18 through 64 who took antipsychotics. The data came from the IBM MarketScan and Multi-State Medicaid databases, which contain anonymized medical information on more than 170 million people.

Rahman and his colleagues used billing codes from the databases to learn which patients were treated for breast cancer during a 12-month period. Next, they matched that information to patients taking antipsychotic drugs. Of the 540,737 women in the database taking antipsychotics, only 914 were identified as having breast cancer. But a significant number of those women were taking drugs known to increase prolactin.

"Antipsychotic medications can be lifesaving for patients who have psychotic episodes where they experience symptoms such as hallucinations and delusions," Rahman said. "In recent years, the drugs have been approved to treat other conditions, too, including depression and bipolar disorder. As those high-prolactin agents are used more widely, the number at risk could increase. We've been advising against using these high-prolactin agents in women who already have breast cancer, but we'd like to investigate whether keeping prolactin levels lower even might prevent some of these cancers."

In another recent study, his team analyzed blood samples from women who took the antipsychotic drug aripiprazole (Abilify) as an add-on treatment for depression. They found that their prolactin levels did not increase and that a few women who began the study with high prolactin levels experienced decreases in prolactin levels after 12 weeks of treatment.

Those findings—combined with preclinical evidence of the anticancer effects of some antipsychotics—have inspired Rahman and his colleagues to propose repurposing some antipsychotic drugs in the fight against breast cancer.

"We don't want to alarm patients taking antipsychotic drugs for life-threatening mental health problems, but we also think it is time for doctors to track prolactin levels and vigilantly monitor their patients who are being treated with antipsychotics," Rahman said.

---

More information: Tahir Rahman et al, Risk of Breast Cancer With Prolactin Elevating Antipsychotic Drugs, Journal of Clinical Psychopharmacology (2021). DOI: 10.1097/JCP.0000000000001513

Provided by Washington University School of Medicine in St. Louis 

Five things women should know about breast cancer

UC San Francisco's Dr. Laura Esserman leads the Athena Breast Health Network. Credit: Susan Merrell/UC San Francisco

Dr. Laura Esserman is filled with hope this Breast Cancer Awareness Month. The UC San Francisco surgeon is gearing up for a five-year study that will tap into technology to improve breast cancer screening and patient outcomes.

03 oct 2015--Esserman leads the Athena Breast Health Network, a collaboration of the five University of California medical centers and partners that will soon launch the WISDOM study. The study—Women Informed to Screen Depending on Measures of Risk—with $14.1 million from the Patient-Centered Outcomes Research Institute, will investigate whether a personalized approach to breast cancer screening is as safe and effective as annual mammograms.
Breast cancer is the most common kind of cancer among American women, except for skin cancer, and the second leading cause of cancer death in women, exceeded only by lung cancer.
But emerging knowledge offers reason for optimism. Here are five things women should know about breast cancer, according to Esserman.

1. Breast cancer isn't one disease.
"Breast cancer is, in fact, many diseases," Esserman said. "Some can be indolent (unlikely to cause patients harm) and some can be very aggressive. We don't want to treat them the same. Two people might walk into my office, both age 50, have the same size tumor, but it might be appropriate to have different treatments. A patient may have a condition that doesn't make radiation possible. You have to make sure patients understand all of their options and are comfortable with their decisions because there's more than one choice."

2. Not all breast cancer is life threatening.
More than 1 in 5 new cases of breast cancer diagnosed in U.S. women are ductal carcinoma in situ (DCIS or "stage zero" cancer), according to the American Cancer Society. While this often is treated aggressively, evidence suggests that may be unnecessary for some patients, Esserman said.
"Low-grade DCIS, I think, should not be called cancer at all," she said. "These conditions can be watched and not treated as aggressively. One size does not fit all. We've got lots of data. It's time to take what we've learned and change practice. We can continue to refine screening so low-grade DCIS doesn't have to be a target for screening. It's not just about finding every abnormality in the breast; it's about finding people at high risk, finding consequential cancers and changing outcomes with interventions early on."

3. Not everyone needs the same approach to screening.
The annual mammogram recommendation is based on 30-year-old evidence, Esserman said.
"It's high time to have a modern trial where we try to figure out who is at risk for different types of breast cancer. That's what the WISDOM study is all about: Set up a framework where we can learn much more quickly. We are going to test what many people still consider to be the gold standard: one mammogram a year for women 40 and over.
"We're working with a next-generation sequencing company, Color Genomics. We're trying to define from the genetics side what influences risk and then we're going to test it to see if it improves screening. We'll integrate the data on a Salesforce platform. We're going to generate a risk for women and that will trigger when to start screening, when to stop screening and how often to screen.
"Over time we'll learn who is at risk for breast cancer and who is at risk for different interventions. If this works, this could be a good paradigm to approach any disease."

4. Consider participating in a clinical trial.
Improvements in clinical care depend on scientific research. Currently only 3 to 5 percent of women participate in clinical trials. The goal is to get consideration of clinical trials to be the norm rather than the exception.
Esserman encourages women to join the WISDOM study.
"We're trying to recruit 100,000 women for the WISDOM study," Esserman said. "We're asking women to share their stories and their wisdom. The only way to know better is to study the alternatives. In screening, the only way to know better is to be part of the WISDOM study.
"We're asking providers to be open. We hope at the end of this trial, we'll have a better model for risk assessment.
"We're asking payers and insurers to step up to the plate and implement coverage for risk-based screening, just as they currently do for annual screening. UC Health is supporting this program for all the people who get benefits from UC Care. Blue Shield has stepped up, too. We're in conversation with a number of companies and insurers to participate as well."

5. Precision medicine shows promise.
"The essence of precision medicine is being able to tailor treatment to biology, patient preference and clinical performance," Esserman said.
"The WISDOM study is precision screening. We want to be smarter. We want to do it just right. It's 'Moneyball' for medicine. The story of the Oakland A's is how people discovered that statistics tell a story that can actually affect strategies and improve outcomes. Think about the data on every player that you have at your fingertips – data that can help to make better decisions. We need that same kind of data at our fingertips in medicine, so that we can keep improving the field. That's what our partnership with Salesforce is all about: How do we take advantage of technology to make medicine better?
"This is not a study that any one institution could accomplish on its own. UC is really interested in population health, and we have the power to collect and address these big issues that matter to the public. I think that we're going to find this is a much more efficient way to screen. It will help us figure out how best to prevent breast cancer," Esserman said.


Provided by University of California, San Francisco

Bisphosphonates for osteoporosis not associated with reduced breast cancer risk

An analysis of data from two randomized clinical trials finds that three to four years of treatment with bisphosphonates to improve bone density is not linked to reduced risk of invasive postmenopausal breast cancer.

12 aug 2014--The authors are Trisha F. Hue, Ph.D., M.P.H., of the University of California, San Francisco, and colleagues.

Some studies have suggested that bisphosphonates, which are commonly used to treat osteoporosis, may have antitumor and antimetastatic properties. Some observational studies have suggested bisphosphonates may protect women from breast cancer.

The authors analyzed the relationship of postmenopausal breast cancer and bisphosphonate use by examining data from two randomized, double-blind, placebo-controlled trials. The Fracture Intervention Trial (FIT) randomly assigned 6,459 women (ages 55 to 81 years) to alendronate or placebo with an average follow-up of 3.8 years. The Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly-Pivotal Fracture Trial (HORIZON-PFT) randomly assigned 7,765 women (ages 65 to 89 years) to annual intravenous zoledronic acid or placebo with an average follow-up of 2.8 years. The authors compared rates of breast cancer in the bisphosphonate treatment groups to the placebo groups.

There was no significant difference in breast cancer rates between the bisphosphonate and placebo groups. In FIT, the breast cancer rate was 1.5 percent in the placebo group and 1.8 percent in the alendronate group. In HORIZON-PFT the rate was 0.8 percent in the placebo group and 0.9 percent in the zoledronic acid group. There also was no significant difference when data from the two trials were combined.

"These data provide evidence that three to four years of treatment with bisphosphonate, alendronate or zoledronic acid, therapy does not reduce the risk of incident breast cancer in postmenopausal women. The discrepancy between our results and the reports of associations in observational studies may be an example of indication bias and illustrates the limitation and hazard of drawing conclusions about treatment effects from observational studies (even those that are very well done) and emphasizes the value of confirming such associations in randomized trials. The effect of bisphosphonate treatment on breast cancer risk in nonosteoporotic populations should be investigated in other randomized trials."

In a related editor's note, Joseph S. Ross, M.D., M.H.S., a JAMA Internal Medicine associate editor, writes: "Whereas these findings highlight why it is so important for new therapies to be evaluated using RCTs (randomized clinical trials), they also reinforce the importance of assessing the methodological rigor of observational studies before interpreting real-world effects."

"Just as we closely scrutinize RCT design, so must we understand the quality and statistical power of the data used for observational studies, how participants were identified, the duration of follow-up, the end points examined, and the analytical strategy used. Observational studies are particularly valuable for clinical situations unlikely to be tested using RCTs, and many provide valid and reliable real-world evidence," Ross continues.

"Thus, whereas we all can remember examples of when RCTs and observational studies differed, less memorable are the even more numerous examples in which results were consistent. In the end, we should be open to all types of evidence and rely on rigorous clinical science to guide practice," Ross concludes.

More information: JAMA Intern Med. Published online August 11, 2014. DOI: 10.1001/jamainternmed.2014.3634

Provided by The JAMA Network Journals

Radiation benefits women with early breast cancer

NEW YORK, 07 feb 2009– A review of published studies confirms that the addition of radiation therapy to breast-conserving surgery in the treatment of a noninvasive early form of breast cancer called ductal carcinoma in situ (DCIS) substantially decreases the risk of recurrence of either DCIS or invasive breast cancer in the affected breast.

In addition, there appear to be no long-term side effects from the radiation, such as damage to the heart or lungs.

The review, conducted by Dr. Annabel Goodwin at The University of Sydney in Camperdown, Australia and colleagues, is published in the latest online issue of The Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates medical research.

The investigators identified four well-designed, randomized controlled trials involving 3,925 women that compared the addition of radiation therapy to breast-conserving lumpectomy.

All the subgroups analyzed benefited from addition of radiation, Goodwin and colleagues found.

Specifically, the data suggest that the addition of radiation therapy after breast conserving surgery reduces the risk of recurrence of either DCIS or invasive breast cancer in the treated breast by 51 percent.

In a comment from the Health Behavior News Service, Dr. Monica Morrow of Memorial Sloan-Kettering Cancer Center in New York said that the review confirms what is currently recommend by most doctors for their patients with DCIS who undergo breast-conserving treatment.

"The best way to minimize the chance of recurrence is with radiation," Morrow said.

Most physicians will recommend breast-conserving surgery for DCIS. However, "studies show that the bigger the patient's role in decision-making, the greater the likelihood the patient will end up with mastectomy," she said.

"This is because most patients don't distinguish between DCIS and invasive breast cancer, because a lot of the stuff they find on the Internet is written about invasive cancer."

Morrow pointed out that there is little difference in survival rates between mastectomy and breast-conserving surgery for women with DCIS.

"What I tend to emphasize to my patients with DCIS is that no matter which treatment they choose, their risk over the next 15 years of dying of something else is greater than their risk of dying of breast cancer."

SOURCE: Cochrane Database of Systematic Reviews 2009.