Question

BACKGROUND & METHODS

The relationship between stress and breast cancer has been examined in many epidemiological studies, the results of which have yielded mixed results. One reason for these differences is the use of different measures of stress. For example, death of a spouse or close relative is a major acute stressor, whereas stress experienced in daily life is more moderate and chronic in nature. As these different types of stress likely have different physiological and psychological impacts, the observed relationship with breast cancer risk may differ.

While the relationship between the acute stress of major life events and the risk of breast cancer has been assessed in several studies, less attention has been paid to perceived daily stress. A number of studies have shown that prolonged, low-level stress of daily life results in a persistent activation of stress hormones, which may impair estrogen synthesis, and may thereby be related to a lower risk of breast cancer. Finally, daily stress may also indirectly affect the risk of breast cancer through variations in health related behavior.

A study was launched in Copenhagen, Denmark to assess the relationship between self reported intensity and frequency of stress and first time incidence of primary breast cancer. The study recruited a population-based sample of n=7,018 Danish women. All women were asked about their perceived level of stress at baseline (2000-2001). Women were excluded if they had been diagnosed with breast cancer before the start of the study (n=120) or if they provided no information on stress or other variables (n=209). The remaining 6,689 women were followed until 2015, with n=26 (< 0.1%) lost to follow-up.

Women in the study were asked about their level of stress in terms of intensity and frequency. In the questionnaire, stress was defined as the sensation of tension, nervousness, impatience, anxiety, or sleeplessness. The women were asked to report their stress intensity as none (0), light (1), moderate (2) or high (3) and the frequency as never/hardly ever (0), monthly (1), weekly (2) or daily (3). The responses of the two questions were then added together to obtain a composite score ranging from 0 to 6. This stress score was also categorized as low (0-1), medium (2-4) and high stress (5-6). Participants were followed from the date of the baseline examination until the end of the study period in December 2015, during which time there were n=251 first diagnoses of primary breast cancer.

Using the data presented in Table 2 calculate:
a. the unadjusted risk ratio for the high versus low stress groups
b. risk difference for the high versus low stress groups
c. What information do the risk ratio and risk difference provide with respect to causal inference AND public health relevance?

Table 2: Incidence and risk ratio of primary breast cancer associated with stress score in n=6,689 Danish women (2000 – 2015) No. of Incidence Model 1: Model 2: breast per 100,000 Age-adjusted risk Fully adjusted risk women per ratio (95% CI) ratioa (95% CI) year Stress score 0-6 (per unit 0.93 (0.87-1.01) 0.92 (0.85-0.99) increase) p-value p=0.06 p=0.04 cancers Categorized stress score Low stress (n=2823) 120 285 1 1 Medium stress (n=3201) 112 229 0.84 (0.65-1.09) 0.80 (0.62-1.04) High stress (n=665) 19 194 0.63 (0.39-1.02) 0.60 (0.37-0.97) p-value for trend test p=0.04 p=0.02 Adjusted for age, current oral contraceptive use, other hormone therapy, menopausal status, number of children, body mass index, alcohol consumption, physical activity in leisure time and education.

Using the continuous (0-6) stress score reported in Table 2, describe the effect of stress on the risk of breast cancer when adjusting for age only (make sure to explain the risk ratio, 95% confidence interval and p-value).

Answer 1

a) The unadjusted risk ratio for high versus low stress groups = (Incidence of breast cancer in high stress group) /(Incidence of breast cancer in low stress group)

= ( Proportion of women developing breast cancer in high stress group) / ( Proportion of women developing breast cancer in low stress group)

= (120/2823)/(19/655)

= 0.042/0.028

= 1.5

b) Risk difference for high versus low stress group = (Incidence of breast cancer in high stress group) - (Incidence of breast cancer in low stress group)

= 0.042 - 0.028

= 0.014

c) Since, risk ratio > 1 , it indicates that the high stress is a risk factor for breast cancer.

Risk difference has positive sign indicating that incidence of breast cancer in high stress group is higher than the low stress group indicating that the high stress is the risk factor for the breast cancer.