Postoperative hormonal therapy prevents recovery of neurological damage after surgery in patients with breast cancer

Scientific Reports, Oct 2016

Cancer survivors are exposed to several risk factors for cognitive dysfunction, such as general anesthesia, surgical trauma, and adjuvant therapies. In our recent study we showed that thalamic volume reduction and attentional dysfunction occurred shortly after surgery. Here, we examined the 6-month prognosis of the 20 patients with breast cancer who underwent surgery. Seven patients did not receive any adjuvant therapy after the surgery and 13 patients received a hormonal therapy after the surgery. We assessed their attentional functions, and thalamic volumes shortly after and 6 months after surgery. We found a significant group x time interaction in the attentional functions (p = 0.033) and the right thalamus (p <  0.05, small volume correction), suggesting the thalamic volume reduction and attentional dysfunction recovered in patients without adjuvant therapy. Our findings provide a better understanding of the potential role of hormonal therapy in relation to the cognitive dysfunction of cancer survivors.

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Postoperative hormonal therapy prevents recovery of neurological damage after surgery in patients with breast cancer

Abstract Cancer survivors are exposed to several risk factors for cognitive dysfunction, such as general anesthesia, surgical trauma, and adjuvant therapies. In our recent study we showed that thalamic volume reduction and attentional dysfunction occurred shortly after surgery. Here, we examined the 6-month prognosis of the 20 patients with breast cancer who underwent surgery. Seven patients did not receive any adjuvant therapy after the surgery and 13 patients received a hormonal therapy after the surgery. We assessed their attentional functions, and thalamic volumes shortly after and 6 months after surgery. We found a significant group x time interaction in the attentional functions (p = 0.033) and the right thalamus (p <  0.05, small volume correction), suggesting the thalamic volume reduction and attentional dysfunction recovered in patients without adjuvant therapy. Our findings provide a better understanding of the potential role of hormonal therapy in relation to the cognitive dysfunction of cancer survivors. Introduction Cancer survivors are exposed to several risk factors for cognitive dysfunction, such as general anesthesia, surgical trauma, the occurrence of complications, and adjuvant therapies1,2,3,4,5. The cognitive dysfunction after surgery is known as postoperative cognitive dysfunction (POCD)1,2,3. General anesthesia and inflammation due to surgical trauma or complications are considered the principal causes of POCD6,7,8. Similarly, the cognitive dysfunction caused by chemotherapy is a side effect of cancer therapy. Many anticancer drugs have neurotoxic effects, which cause cognitive dysfunction and brain atrophy9 termed “Chemo-brain”4,10. The maintenance of cognitive function is important to preserve the quality of life (QOL) for breast cancer survivors11,12, because of the long-term survivorship. Previous studies have reported that cognitive dysfunction in patients with breast cancer may originate in neuron injuries caused by chemotherapy13, represented by abnormalities of specific brain structures14,15 and brain functions16,17. Similarly, cognitive functions were reported impaired by hormonal therapy5,18 and improved after the cessation of treatment19. However, a neuropathology of the cognitive dysfunction due to hormonal therapy remains unclear. In our recent study, we investigated the cognitive dysfunction and brain structural changes shortly after surgery in patients with breast cancer and found thalamic volume reduction and attentional dysfunction were early responses to general anesthesia20. The results suggest the early postoperative response to anesthesia may represent an intermediate phenotype of POCD. Based on the previous findings of high incidence of POCD shortly after surgery, and rapid attenuation of symptoms as time progressed2, we assumed patients who underwent surgery with general anesthesia were similarly affected by the anesthesia and that a majority of these patients would fully recover after surgery if not exposed to other risk factors. Therefore, further investigations to distinguish the effects of hormonal therapy on brain structural changes and cognitive dysfunction are necessary. To address this issue, we investigated these patients 6 months after surgery to clarify the prognosis of thalamic volume reduction and attentional dysfunction. To examine the effect of hormonal therapy, we controlled the risk factors for cognitive dysfunction after the surgery other than hormonal therapy. We hypothesized thalamic volume reduction and attentional dysfunction would recover in patients without hormonal therapy and not in those with hormonal therapy. Materials and Methods Participants Thirty-two patients from our previous study who underwent breast cancer surgery20 were screened for eligibility in the current follow-up study. To control the effects of chemotherapy on cognitive function and brain, four patients who received chemotherapy after the surgery were excluded. Furthermore, to control the effects of serum estrogen levels on the brain, three patients who received hormonal therapy with a selective estrogen receptor modulator (SERM) such as tamoxifen were excluded, because SERMs do not decrease serum estrogen levels, whereas an aromatase inhibitor (AI) does. Five patients declined to participate in this study because they were either uninterested, or too busy. Finally, 20 postmenopausal women with early-stage breast cancer were enrolled in the current follow-up study. Seven patients did not receive any adjuvant therapy after the surgery (age = 51–62 yrs.; Wo group), while 13 patients received hormonal therapy with an AI after the surgery (age = 54–77 yrs.; Ho group). Demographic characteristics of patients are shown in Table 1. Written informed consent was obtained from each subject. The Ethics Committee of the Tohoku University Graduate School of Medicine approved this study. The methods of this study were also carried out in accordance with the approved gui (...truncated)


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Atsushi Sekiguchi, Chiho Sato, Izumi Matsudaira, Yuka Kotozaki, Rui Nouchi, Hikaru Takeuchi, Masaaki Kawai, Hiroshi Tada, Takanori Ishida, Yasuyuki Taki, Noriaki Ohuchi, Ryuta Kawashima. Postoperative hormonal therapy prevents recovery of neurological damage after surgery in patients with breast cancer, Scientific Reports, 2016, Issue: 6, DOI: 10.1038/srep34671