Risk of breast cancer in risperidone users:

a nationwide cohort study

32nd ICPE Conference, August 2016, Dublin, Ireland

Johan Reutfors, MD, PhD, Associate Professor of Psychiatry

Centre for Pharmacoepidemiology,

Karolinska Institutet, Stockholm, Sweden
 Authors

Johan Reutfors, MD, PhD (1)*

Louise Wingård, MD (1)*
Lena Brandt, MSc (1)
Yiting Wang, PhD (2)
Hong Qiu, MD, PhD (2)
Helle Kieler, MD, PhD (1)
Shahram Bahmanyar, MD, PhD (1)

(1) Centre for Pharmacoepidemiology, Karolinska Institutet, Stockholm, Sweden

(2) Department of Epidemiology, Janssen Research and Development, Titusville, NJ, United States
* Shared first authorship

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Conflict of interest / Disclosure

The study was conducted according to pre-specified study

protocol and statistical analysis plan, with funding provided
by Janssen Research and Development. YW and HQ are
employees of Janssen Research and Development. The
other authors declare no personal conflict of interest.

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Background
 Antipsychotics work by blocking dopamine receptors and
dopamine inhibits prolactin release
 Therefore, several antipsychotics are known to increase serum
prolactin
 Risperidone has a strong anti-dopaminergic
profile which increases the risk of
hyperprolactinemia
 Hyperprolactinemia has been associated
with an increased incidence of mammary
gland tumors in animal studies
 Breast cancer is the most common invasive
cancer in women, affecting about 12% of
women worldwide

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Aim

 To investigate the risk of breast cancer in a nationwide cohort of

women using risperidone or other antipsychotics

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Methods
 All women aged 18 years or older who initiated treatment with
risperidone or any other antipsychotic between 2006 and 2012

 Swedish nationwide registers

 The Prescribed Drug Register: all prescription drugs dispensed by
Swedish pharmacies since July 1, 2005
 Swedish Cancer Register
 Swedish Patient Register: psychiatric diagnoses and somatic
comorbidities
 The Swedish Multi-Generation Register: child birth and parity

 Patients with two recorded consecutive dispensations of the

same antipsychotic drug (i.e., index drug) within 3 months, no
index drug in the 6 months prior, no previous cancer diagnosis,
and no recorded dispensations of paliperidone were included

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Methods, continued
 A Cox regression model was used to estimate the hazard ratio
(HR) and 95% confidence interval (CI) for the association
between exposure to risperidone and other antipsychotics and
breast cancer
 Total cohort follow-up in the primary analysis: from index drug
exposure to breast cancer, or death, or emigration, or end of
data
 Active treatment follow-up as a sensitivity analysis: from index
drug exposure to breast cancer, or death, or emigration, or end
of data, or discontinuation of the index drug (1 year gap in
prescription)
 Sub-analysis among the treatment-naive, no antipsychotic drug
exposure within 6 months prior to first (i.e., index) antipsychotic
exposure

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Characteristics of cohorts

Risperidone Other atypical Typical

N=22908 N=24524 N=8544
Age at first dispensation (years)
Mean (SD) 71 (21) 46 (18) 67 (19)

Person-year total cohort follow-up

Total 54408 65616 23561
Mean (SD) 2.4 (1.7) 2.7 (1.7) 2.8 (1.8)

Number of breast cancer events 130 134 84

Person-year active treatment follow-up time

Total 29583 32878 14254
Mean (SD) 1.3 (1.4) 1.3 (1.5) 1.7 (1.6)

Number of breast cancer events

in active treatment 81 77 55

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 Association between use of antipsychotics
and breast cancer
Events/ Adjusted HR
PYRa Events 100 000 PYRa Crude HR (95%CI) (95%CI)b
Overall
Other atypical antipsychotics 65,616 134 204 Reference Reference
Risperidone 54,406 130 239 1.17 (0.92-1.49) 0.94 (0.72-1.22)
Typical antipsychotics 23,561 84 357 1.75 (1.33-2.29) 1.25 (0.94-1.66)
Stage 0-1
Other atypical antipsychotics 65,616 33 50 Reference Reference
Risperidone 54,406 22 40 0.80 (0.47-1.37) 0.99 (0.56-1.74)
Typical antipsychotics 23,561 21 89 1.76 (1.02-3.04) 1.53 (0.88-2.69)
Stage 2
Other atypical antipsychotics 65,616 33 50 Reference Reference
Risperidone 54,406 47 86 1.69 (1.09-2.64) 0.96 (0.58-1.60)
Typical antipsychotics 23,561 22 93 1.87 (1.09-3.20) 1.14 (0.64-2.01)
Stage 3-4
Other atypical antipsychotics 65,616 45 69 Reference Reference
Risperidone 54,406 45 83 1.21 (0.80-1.83) 0.92 (0.58-1.00)
Typical antipsychotics 23,561 24 102 1.49 (0.91-2.44) 1.02 (0.61-1.71)
a
Pers on-yea r
b
Adjus ted for a ge
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 Association between use of antipsychotics
and breast cancer by time on active
treatment and restricted to treatment naïve
patients

Events/ Crude HR Adjusted HR

PYRa Events a
100 000 PYR (95%CI) (95%CI)b
Time on active treatment
Other atypical antipsychotics 32 878 77 234 Reference Reference
Risperidone 29 583 81 274 1.18 (0.86-1.61) 0.96 (0.68-1.36)
Typical antipsychotics 14 254 55 386 1.63 (1.15-2.30) 1.23 (0.86-1.75)

Only treatment-naïve patients

Other atypical antipsychotics 51 426 100 189 Reference Reference
Risperidone 45 132 103 228 1.17 (0.89-1.54) 0.90 (0.66-1.23)
Typical antipsychotics 22 635 83 329 1.89 (1.41-2.53) 1.33 (0.98-1.80)
a
Pers on-yea r
b
Adjus ted for a ge

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Strengths
 The largest study to evaluate the risk of breast
cancer related to risperidone use
 Population-based cohort design, large sample size
 All data were prospectively recorded, minimal loss to
follow-up

Limitations
 Follow up maximum of six years, mean follow-up time
2.5 years
 Prescriptions recorded in pharmacy claims may not
coincide with actual drug intake

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Conclusion

 Risperidone use does not confer a short-term increased risk of

breast cancer compared with other antipsychotic agents

 Analyses stratified by stage of tumor, using active treatment

follow-up time or restricting the data to treatment naïve patients
did not reveal any noteworthy change in the results

 An increase in overall breast cancer crude incidence seen in

patients treated with typical antipsychotics could be explained
by the higher age of patients in this group

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Thank you!

johan.reutfors@ki.se

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