Psychologic stress, reduced NK cell activity, and cytokine dysregulation in women experiencing diagnostic breast biopsy

Abstract

The purpose of this study was to evaluate a woman's psychological and immunological response to breast biopsy before and after the procedure. Women were enrolled into the study when notified of the need for breast biopsy. Psychological and immunological assessments were made at enrollment, on the day of breast biopsy, as well as 1 month and 4 months after notification of biopsy results. Psychological assessments demonstrated that perceived stress, anxiety, and mood disturbance were heightened before biopsy and remained elevated after biopsy regardless of the diagnosis. Immunologically, the women exhibited reduced natural killer cell activity and INF gamma production before biopsy with reductions significant 1 month after the procedure. In contrast, IL-4, IL-6, and IL-10 production were increased before and after the procedure with most significant increases prior to the procedure and continuing 1 month after the procedure. These results demonstrate that undergoing biopsy of the breast for cancer diagnosis is an emotional experience, characterized by increased perceived stress, anxiety, and mood disturbance. This emotional distress is accompanied by reduced NK cell activity and cytokine dysregulation. The psychological and immunological impact of breast biopsy is not transient, but persists well beyond the actual experience of the biopsy procedure. Noteworthy is the observation that women with benign or malignant biopsy results experienced similar psycho-immune consequences. Hence, these observations are of relevance not only to women diagnosed with malignancy, who face the challenges of cancer treatment and adaptation to illness, but also to women with benign biopsy findings.

Figures

Figure 1

Psychological measure of perceived stress, anxiety, and mood disturbance are separately depicted for women who ultimately had Benign or Malignant findings and for a non-biopsied, comparison group of Control women. Perceived stress was measured using Cohen’s Perceived Stressor Scale (PSS). Anxiety was measured using Spielberger’s State Anxiety Inventory (STATE ANXIETY). Mood state was measured using the Profile of Mood States (POMS) and the total mood disturbance (POMS-TMD) is depicted. Bars represent the mean values +/− S.E. and are indicated for pre biopsy time points (T1 and T2) and post biopsy time points (T3 and T4). T1 was the time of notification of a need for breast biopsy, T2 was day of breast biopsy immediately before the procedure, T3 was the first post-biopsy time point (approximately 1- month after notification of results), and T4 was the second post-biopsy time point (approximately 2–3 months after T3). Statistical comparisons (ANOVA followed by Tukey’s HSD post hoc test) were between experimental mean and Control as well as between Benign and Malignant at each time period. Bars represent the mean values +/− S.E.

Figure 2

The subscales of the POMS are depicted for women with Benign and Malignant findings and for a non-biopsied, comparison group of Control women. Results are presented as in Figure 1. Bars represent the mean values +/− S.E.

Figure 3

NKCA, expressed as lytic units at 20%, and IFN γ production by PBMC of women with Benign and Malignant findings and for a non-biopsied, comparison group of Control women are illustrated. NKCA for PBMC was measured using K562 tumor cells as the target. PBMC were activated with PMA/PHA and culture supernatants were collected at 48 hr. Cytokine concentration was determined by ELISA. Results are presented as in Figure 1. Bars represent the mean values +/− S.E.

Figure 4

IL-6, IL-4, and IL-10 production by PBMC of women with Benign and Malignant findings and for a non-biopsied, comparison group of Control women are illustrated. PBMC were activated with PMA/PHA and culture supernatants were collected at 48 hr. Cytokine concentration was determined by ELISA. Results are presented as in Figure 1. Bars represent the mean values +/− S.E.

Figure 4

IL-6, IL-4, and IL-10 production by PBMC of women with Benign and Malignant findings and for a non-biopsied, comparison group of Control women are illustrated. PBMC were activated with PMA/PHA and culture supernatants were collected at 48 hr. Cytokine concentration was determined by ELISA. Results are presented as in Figure 1. Bars represent the mean values +/− S.E.

Figure 5

Phenotypic analysis of PBMC for women who were biopsied. Bars represent the mean values +/− S.E.