Abstract
Background:
Night shift work has been classified by the International Agency for Research on Cancer (IARC) as a probable carcinogen in humans. Several studies have assessed night shift work in relation to breast cancer risk, with inconsistent results.
Methods:
In the prospective Sister Study cohort, current and past occupational history was collected for 48,451 participants. We used Cox proportional hazards models to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between baseline work schedule characteristics and incident breast cancer.
Results:
During follow-up (mean=9.1 years), 3,191 incident cases were diagnosed. We observed little to no increase in risk associated with work schedule characteristics (ever working rotating shifts: HR=1.04, 95% CI: 0.91–1.20; ever working rotating night shifts: HR=1.08, 95% CI: 0.92–1.27; ever working at night: HR=1.01, 95% CI: 0.94–1.10; ever working irregular hours: HR=0.98, 95% CI: 0.91–1.06). While short-term night work (>0 to 5 years vs. never, HR=1.12, 95% CI: 1.00–1.26) or rotating shift work at night (>0 to 5 years vs. never, HR=1.30, 95% CI: 1.05–1.61) were associated with increased breast cancer risk, working nights for more than 5 years was not associated with risk.
Conclusions:
Overall, we observed little evidence that rotating shift work or work at night was associated with a higher risk of breast cancer, except possibly among those who participated in such work for short durations of time.
Impact:
This study indicates that if night shift work is associated with breast cancer, the increase in risk is small.
Introduction
In 2019, the International Agency for Research on Cancer classified night shift work as a probable human carcinogen1. Most evidence supporting higher breast cancer risk among night shift workers comes from case-control studies; cohort studies have observed largely null associations2.
Materials and Methods
The Sister Study is a prospective cohort of 50,884 women (2003–2009), aged 35–74 who had a sister with breast cancer but were breast cancer-free themselves3. Baseline occupational questionnaires asked about current job and past jobs held for ≥2 years. For each job, women were asked if they worked regular hours (starting/stopping at the same time every day) and if they worked at night (≥1 hour between 12:00–2:00 AM). If they reported not working regular hours, they were asked if they worked rotating shifts (number of shifts, usual start/stop times for each shift) or irregular hours. Rotating shift work (N=3,183) included women who reported ≥1 job with rotating shifts; rotating night shift work (N=2,275) was a subset of those women who also reported night work for the same job. Working irregular hours (N=15,895) could include women who reported night work for ≥1 job. Any work at night (N=13,992) included all women, regardless of schedule type, who met our definition of night work for ≥1 job. Self-reported incident breast cancer, confirmed with medical records3, was classified as invasive breast cancer or ductal carcinoma in situ. Women were followed through September 15, 2017 (data release 7.2). The final sample included 48,451 women who completed the occupational questionnaire and were not missing covariate data.
Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), with age as the timescale. For each analysis, women who reported never having that work schedule were the referent. Confounders were selected a priori and included race/ethnicity, education, marital status, and parity. We explored whether the association differed by time-varying menopausal status, timing of starting work relative to first childbirth, or time since stopping shift work.
Results
Over follow-up (average=9.1 years), 3,191 incident breast cancers were diagnosed. Study population characteristics are available elsewhere3. Although ever and never rotating night shift workers were similar, ever workers were more likely to have at least some college (92% vs. 84%), be nulliparous (21% vs. 18%), or have ever smoked (47% vs. 43%).
We observed little association between breast cancer and ever working shifts, night shifts, at night, or irregular hours (Table 1). However, compared to women who never worked rotating night shifts or at night, women who reported working night shifts (HRadj=1.30, 95% CI: 1.05–1.61) and who reported any work at night (HRadj=1.12, 95% CI: 1.00–1.26) for ≤5 years (“short-term”) had a greater risk of breast cancer. Associations were not seen for longer durations.
Table 1.
Associations between work schedule variables1 and breast cancer risk in the Sister Study
| Total (N=48,451) | Cases (N=3,191) | Person-years (N=442,550) | Age-adjusted HR (95% CI) | Multivariable-adjusted HR (95% CI)2 | ||
|---|---|---|---|---|---|---|
| Rotating shift work3 | Never | 43,771 | 2,883 | 400,318 | 1 (ref.) | 1 (ref.) |
| Ever | 3,183 | 214 | 29,042 | 1.04 (0.91, 1.20) | 1.04 (0.91, 1.20) | |
| >0–5 years | 1,548 | 114 | 14,172 | 1.15 (0.95, 1.39) | 1.15 (0.95, 1.38) | |
| >5–10 years | 768 | 48 | 7,020 | 0.97 (0.73, 1.30) | 0.98 (0.73, 1.30) | |
| >10 years | 867 | 52 | 7,850 | 0.91 (0.69, 1.19) | 0.91 (0.69, 1.20) | |
| Rotating night shift work3 | Never | 44,688 | 2,937 | 408,668 | 1 (ref.) | 1 (ref.) |
| Ever | 2,275 | 160 | 20,784 | 1.08 (0.92, 1.27) | 1.08 (0.92, 1.27) | |
| >0–5 years | 1,049 | 88 | 9,540 | 1.31 (1.06, 1.62) | 1.30 (1.05, 1.61) | |
| >5–10 years | 571 | 30 | 5,271 | 0.81 (0.57, 1.16) | 0.81 (0.57, 1.16) | |
| >10 years | 655 | 42 | 5,973 | 0.96 (0.71, 1.30) | 0.96 (0.71, 1.31) | |
| Work at night3 | Never | 29,147 | 1,949 | 266,951 | 1 (ref.) | 1 (ref.) |
| Ever | 13,992 | 914 | 126,757 | 1.01 (0.94, 1.10) | 1.01 (0.94, 1.10) | |
| >0–5 years | 4,744 | 334 | 42,938 | 1.12 (1.00, 1.26) | 1.12 (1.00, 1.26) | |
| >5–10 years | 3,522 | 230 | 32,068 | 1.04 (0.90, 1.19) | 1.04 (0.90, 1.19) | |
| >10 years | 5,726 | 350 | 51,751 | 0.92 (0.82, 1.03) | 0.92 (0.82, 1.03) | |
| Worked irregular hours3 | Never | 31,312 | 2,066 | 285,414 | 1 (ref.) | 1 (ref.) |
| Ever | 15,895 | 1,047 | 146,278 | 0.99 (0.92, 1.07) | 0.98 (0.91, 1.06) | |
| >0–5 years | 6,142 | 379 | 56,811 | 0.96 (0.86, 1.07) | 0.95 (0.85, 1.06) | |
| >5–10 years | 3,816 | 232 | 35,116 | 0.93 (0.81, 1.06) | 0.92 (0.80, 1.05) | |
| >10 years | 5,937 | 436 | 54,351 | 1.07 (0.96, 1.18) | 1.05 (0.95, 1.17) |
Rotating shift work and working irregular hours were a specific question on the questionnaire; rotating night shift work is the subset of rotating shift workers who reported working nights as one of their shifts; working at night was defined as working ≥1 hour between 12:00 and 2:00 AM, which includes all of the rotating night shift workers
Multivariable model adjusted for age, race/ethnicity (non-Hispanic white, non-Hispanic black, Hispanic, other), education (high school diploma or equivalent, some college or technical school, Bachelor’s or higher degree), marital status (never married, married or living as married, widowed/divorced/separated), and parity (nulliparous, 1 birth, 2 births, 3+ births)
Some women were missing information on work schedule: rotating shift work, N=94 cases, N=1,497 total women; rotating night shift work, N=94 cases, N=1,488 total women; work at night, N=328 cases, N=5,312 total women; worked irregular hours, N=78 cases, N=1,244 total women
The association between short-term work at night and breast cancer appeared stronger for premenopausal (HRadj=1.29, 95% CI: 1.02–1.63) than for postmenopausal women (HRadj=1.06, 95% CI: 0.93–1.22) (Table 2). Similar associations were seen for shift and night shift work. These associations did not differ by age started working (before first childbirth) or time since stopping.
Table 2.
Work schedules and breast cancer risk, stratified by menopausal status at time of diagnosis (N=48,451)1
| Premenopausal (N = 5,136) | Postmenopausal (N = 43,179) | ||||
|---|---|---|---|---|---|
| Cases | Multivariable-adjusted HR (95% CI)2 | Cases | Multivariable-adjusted HR (95% CI)2 | ||
| Rotating shift work | Never | 494 | 1 (ref.) | 2,378 | 1 (ref.) |
| Ever | 36 | 0.99 (0.70, 1.38) | 175 | 1.04 (0.89, 1.21) | |
| >0–5 years | 24 | 1.25 (0.83, 1.88) | 87 | 1.09 (0.88, 1.35) | |
| >5 years | 12 | 0.70 (0.39, 1.23) | 88 | 0.99 (0.80, 1.23) | |
| Rotating night shift work | Never | 507 | 1 (ref.) | 2,419 | 1 (ref.) |
| Ever | 23 | 0.92 (0.61, 1.40) | 134 | 1.09 (0.92, 1.30) | |
| >0–5 years | 19 | 1.53 (0.97, 2.42) | 66 | 1.20 (0.94, 1.53) | |
| >5 years | <5 | NE3 | 68 | 1.01 (0.79, 1.28) | |
| Work at night | Never | 320 | 1 (ref.) | 1,622 | 1 (ref.) |
| Ever | 173 | 1.02 (0.85, 1.23) | 734 | 1.00 (0.92, 1.10) | |
| >0–5 years | 87 | 1.29 (1.02, 1.63) | 243 | 1.06 (0.93, 1.22) | |
| >5 years | 86 | 0.84 (0.66, 1.07) | 491 | 0.98 (0.89, 1.09) | |
| Worked irregular hours | Never | 356 | 1 (ref.) | 1,699 | 1 (ref.) |
| Ever | 176 | 0.95 (0.80, 1.15) | 868 | 0.99 (0.91, 1.08) | |
| >0–5 years | 91 | 1.04 (0.83, 1.31) | 285 | 0.92 (0.81, 1.04) | |
| >5 years | 85 | 0.88 (0.69, 1.11) | 583 | 1.03 (0.94, 1.13) | |
N=136 women missing menopausal status
Multivariable model adjusted for age, race/ethnicity (non-Hispanic white, non-Hispanic black, Hispanic, other), education (high school diploma or equivalent, some college or technical school, Bachelor’s or higher degree), marital status (never married, married or living as married, widowed/divorced/separated), and parity (nulliparous, 1 birth, 2 births, 3+ births)
NE= Not estimated due to cell size <5
Discussion
Night shift work, classified as a probable carcinogen, is hypothesized to act via light at night (LAN)-related circadian disruption, by decreasing levels of melatonin2,4. Melatonin suppresses estrogen production, functions as an antioxidant, and has apoptotic and anti-proliferative effects in breast cancer cells4. Other potential mechanisms include oxidative stress and chronic inflammation resulting from disrupted circadian rhythm2.
Some, but not all, case-control studies have suggested that increasing duration and frequency of night shift work may be associated with an increased breast cancer risk2. Although the Nurses’ Health Study II observed an increased risk for long-term (20+ years) rotating night shift work5, results from other cohort studies have been mostly null2, consistent with our findings. The discrepancy between study types is possibly due to more comprehensive lifetime exposure data in the case-control studies, although retrospective data collection is a limitation. Despite our comprehensive lifetime exposure assessment, we observed that only short-term night shift work and work at night were associated with breast cancer risk. Although we had a wide age distribution and most women (65%) were still working at baseline, we cannot dismiss the possibility of left-truncation or healthy-worker bias in our study. While these could be chance findings, one possibility is that some women who worked shifts or at night short-term may have switched to a daytime schedule sooner because of difficulties adjusting to a rotating or night schedule. There is some evidence that individuals who are “night owls” tend to tolerate shift work better than those who are “early birds”6 and that early-bird women who work at night short-term have higher odds of breast cancer7. We did not assess chronotype in our study.
Conclusion
We observed little evidence that either night or shift work was associated with breast cancer risk, except in those who participated in night work for short durations.
Acknowledgements.
This research was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (D.P. Sandler: Z01-ES044005, A.J. White: Z01-ES103332-01) and a National Institute of Environmental Health Sciences training grant to the University of North Carolina (M.R. Sweeney: 5T32ES007018-43).
Footnotes
Conflicts of Interest: None declared.
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