Skip to main content

Table 4 Sensitivity and subgroup analysis for the association between antipsychotic use and breast cancer mortality

From: Post-diagnostic antipsychotic use and cancer mortality: a population based cohort study

  N Person years Cancer deaths All antipsychotics Prolactin elevating antipsychotics Prolactin –sparing antipsychotics
Adjusted HRa Adjusted HRa Adjusted HRa
All breast cancer patients
Main analysis 23,695 126,296 3061 2.25 (1.90–2.67) 2.27 (1.90–2.72) 1.27 (0.87–1.87)
Outcome definition
  All-cause mortality 23,695 126,296 6268 2.07 (1.84–2.31) 2.02 (1.78–2.28) 1.68 (1.36–2.08)
  Breast cancer on death certificate 23,695 126,296 3726 2.19 (1.88–2.54) 2.13 (1.81–2.50) 1.54 (1.14–2.10)
Exposure definition
  Year after diagnosisb 23,695 126,296 3061 1.70 (1.38–2.09) 1.63 (1.30–2.04) 1.43 (0.94–2.18)
  6 month lag 24,973 138,467 3442 2.76 (2.40–3.18) 2.91 (2.51–3.37) 1.41 (1.01–1.95)
  2 year lag 21,097 103,895 2278 1.47 (1.15–1.88) 1.39 (1.06–1.81) 1.30 (0.81–2.10)
  4 year lag 15,508 67,078 1190 1.17 (0.78, 1.73) 1.12 (0.74, 1.71) 0.92 (0.39, 2.15)
  Prolactin elevating versus sparing antipsychoticsc1   3190 165 1.22 (0.80–1.86) 1.00
  Prolactin elevating versus sparing antipsychoticsc2   3190 165 1.64 (1.10–2.46) 1.00
Stratified analysis
  Tamoxifen or AI used 14,657 80,780 1707 2.19 (1.76–2.71) 2.09 (1.65–2.65) 1.67 (1.09–2.57)
  No hormonal therapy used 9038 45,516 1354 2.28 (1.73–2.99) 2.46 (1.86–3.25) 0.67 (0.30–1.52)
  Prior antipsychotic usee 389 1828 65 0.97 (0.51–1.84) 0.77 (0.45–1.33) 1.27 (0.66–2.42)
  No prior antipsychotic usee 23,306 124,468 2996 2.83 (2.34–3.42) 3.08 (2.53–3.76) 1.10 (0.63–1.91)
Additional adjustment
  Stage adjusted using CCf 9778 51,043 1080 2.30 (1.70–3.10) 2.46 (1.80–3.36) 0.98 (0.47–2.06)
  Stage adjusted using MIg 23,686 126,258 3059 2.27 (1.89–2.71) 2.31 (1.91–2.80) 1.22 (0.82–1.81)
  Stage (CC in cancer registries highest availabilityh) 2612 13,311 338 2.40 (1.29, 4.47) 2.83 (1.53, 5.26) 0.91 (0.23, 3.52)
  Smoking and BMI adjusted using CCf 18,135 95,342 2167 2.42 (1.97–2.96) 2.53 (2.05–3.14) 1.21 (0.73–2.01)
  Smoking and BMI adjusted using MIg 23,686 126,258 3059 2.24 (1.89–2.65) 2.25 (1.88–2.70) 1.27 (0.86–1.87)
Patients with severe mental illness prior to diagnosis
Main analysis 334 1556 48 1.11 (0.58–2.14) 0.86 (0.44–1.68) 1.19 (0.58–2.44)
All-cause mortality 334 1556 121 1.13 (0.75–1.71) 1.13 (0.76–1.68) 1.12 (0.70–1.77)
6 month lag 364 1730 60 1.17 (0.66–2.08) 1.07 (0.60–1.92) 1.22 (0.64–2.30)
2 year lag 288 1245 35 1.60 (0.72, 3.58) 1.17 (0.53, 2.58) 1.74 (0.73, 4.17)
4 year lag 187 771 14 2.04 (0.50, 8.34) 1.00 (0.27, 3.66) 2.65 (0.67, 10.47)
Tamoxifen or AI used 230 1109 31 1.02 (0.41–2.56) 0.86 (0.36–2.06) 1.27 (0.47–3.40)
Stage adjusted using MIg 334 1556 48 1.16 (0.58–2.32) 1.02 (0.49–2.10) 1.01 (0.46–2.20)
  1. aModel contains age, year of diagnosis, treatment within 6 months (separate variables for radiootherapy, chemotherapty, surgery, tamoxifen and aromatase inhibitor use), comorbidities (prior to diagnosis including serious mental illness (except when analysis restricted to patients with severe mental illness prior to diagnosis), chronic pulmonary disease, diabetes, renal disease, cerebrovascular disease, peripheral vascular disease, myocardial infarction, peptic ulcer disease and liver disease), hormonal medication use (oral contraceptive and hormone replacement therapy, prior to diagnosis), other medication use (statin and aspirin as time varying covariates) and deprivation (in fifths)
  2. b Anti-psychotic use based upon use in the year after breast cancer diagnosis adjusting for variables in a
  3. c1 Prolactin elevating antipsychotics versus prolactin non-elevating antipsychotics (only prolactin elevating or both prolactin elevating and non-elevating, versus only prolactin non-elevating)
  4. c2 Prolactin elevating antipsychotics versus prolactin non-elevating antipsychotics (only prolactin elevating, versus both prolactin elevating and non-elevating or only prolactin non-elevating)
  5. d Stratified based upon hormonal therapy use (AI or tamoxifen) in the 6 months after diagnosis
  6. e Stratified based upon use of any antipsychotic medication in the year prior to diagnosis
  7. f Complete case analysis, adjusted analysis additionally adjusted for exposure (stage or smoking and BMI)
  8. g Using multiple imputation to impute missing exposure (stage or smoking and BMI)
  9. h Complete case analysis additionally adjusting for stage restricted to two cancer registries in which stage was 85% complete