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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
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BMC Cancer

ISSN: 1471-2407

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