Shigeru Imoto

Smaller regional volumes of brain gray and white matter demonstrated in breast cancer survivors exposed to adjuvant chemotherapy.

Previous studies have shown cognitive impairment in breast cancer survivors who were exposed to adjuvant chemotherapy. Neural damage by chemotherapy might have played some part in these findings. The current study explored the regional brain volume difference between breast cancer survivors exposed to adjuvant chemotherapy (C+) and those unexposed (C−).

Factors correlated with fatigue in disease-free breast cancer patients: application of the Cancer Fatigue Scale

Abstract Fatigue is one of the most frequent symptoms in cancer patients. However, the precise causes of this fatigue are still unknown, and this situation makes it difficult to combat the problem. The present study was conducted to investigate factors correlated with fatigue in disease-free breast cancer patients. A group of 134 randomly selected ambulatory breast cancer patients who had undergone successful surgical treatment participated. They completed the Cancer Fatigue Scale, the Hospital Anxiety and Depression Scale, the Mental Adjustment to Cancer Scale, and an ad hoc questionnaire detailing physical symptoms, social support, and demographic variables at home and returned them by mail the following day. Multiple regression analysis revealed that fatigue was significantly correlated with dyspnea, insufficient sleep, and depression, and that these three variables accounted for a total of 46% of variance in fatigue. Factors concerned with the cancer and treatment, such as disease stage, lymph node metastasis, number of days since operation, past intravenous chemotherapy, radiotherapy, current use of fluoropyrimidine compounds, and current use of tamoxifen citrate were not correlated with fatigue. The results suggest that fatigue in this population is determined by current physical and psychological distress rather than by the cancer itself and prior cancer treatments, and that the management of dyspnea, insomnia, and depression might be important in reducing fatigue in this population.

Prognostic Significance of Fibrotic Focus in Invasive Ductal Carcinoma of the Breast: A Prospective Observational Study

We have already reported invasive ductal carcinomas (IDCs) with fibrotic focus (FF) to be associated with significantly poorer survival than IDCs without FF. The purpose of this study was to prospectively investigate the effect of the presence of FF on the outcomes of 439 patients with IDCs to confirm the prognostic significance of FF, by the multivariate analysis, employing the Cox proportional hazard regression model, as compared with well-known clinicopathological parameters. We also precisely evaluated the prognostic significance of FF from the viewpoint of FF characteristics. The present study demonstrated that the presence of FF is a very useful parameter predicting tumor recurrence (TR), as well as initial distant organ metastasis (IDOM), in lymph node–negative IDCs (P = .024 and P = .026) and in IDCs positive for either or both estrogen receptor (ER) or progesterone receptor (PR) (P = .007 and P = .015), respectively. In addition, FF of >8 mm in diameter was found to be an independent prognostic parameter for TR and IDOM in lymph node–negative patients and patients with IDC positive for either or both ER or PR (P = .005 and P = .018). We conclude that the presence of FF is a very important histologic prognostic parameter for patients with IDCs of the breast.

Proliferative Activity of Intratumoral Fibroblasts Is Closely Correlated with Lymph Node and Distant Organ Metastases of Invasive Ductal Carcinoma of the Breast

Mitotic figures of fibroblasts are seen within invasive ductal carcinoma (IDC) of the breast. This suggests that the proliferative activity of fibroblasts may play an important role in IDC tumor progression. The purpose of this study was to examine whether the proliferative activity of fibroblasts can predict lymph node metastasis (LNM) or distant-organ metastasis (DOM) of IDCs. Two hundred four consecutive patients with IDC of the breast surgically treated at the National Cancer Center Hospital East constituted the basis of this study. Proliferative activity of fibroblasts was immunohistochemically evaluated by the mouse MIB-1 monoclonal antibody against Ki-67 antigen. The MIB-1 labeling index was the percentage of fibroblasts with positively stained nuclei, and fields for cell counting were selected in inner and outer areas within IDCs. In both areas, 300 fibroblasts were counted in each high-power field. The significance of proliferative activity of fibroblasts on LNM or DOM was compared with well-known prognostic parameters. Multivariate analyses demonstrated that a MIB-1 labeling index of more than 10% of fibroblasts in the inner area of IDCs significantly increased the relative risk of LNM and hazard rate of DOM (P < 0.001 and P = 0.007, respectively). The present study indicated that the metastatic ability of IDCs is closely dependent on proliferative activity of fibroblasts in the inner area.

Highly Proliferative Fibroblasts Forming Fibrotic Focus Govern Metastasis of Invasive Ductal Carcinoma of the Breast

We have already reported that invasive ductal carcinomas (IDCs) with fibrotic focus (FF) have more aggressive characteristics than those without FF. FF is composed of a mixture of fibroblasts and various amounts of collagen fibers, suggesting that highly proliferative fibroblasts forming FF increase the malignant potential of IDCs with FF. The purpose of this study was to examine whether there is a difference of proliferative activity of fibroblasts forming and not forming FF, which plays an important role in the tumor progression of IDCs. Two hundred three consecutive cases of IDC of the breast surgically treated at the National Cancer Center Hospital East formed the basis for this study. The proliferative activity of the fibroblasts forming the FF was immunohistochemically evaluated by using mouse MIB-1 monoclonal antibody against Ki-67 antigen. The MIB-1 labeling index (LI) is the percentage of fibroblasts forming FF that have positively stained nuclei, and 300 fibroblasts were counted in each FF. The significance of the proliferative activity of fibroblasts forming FF with regard to lymph node metastasis (LNM) or distant-organ metastasis (DOM) was compared with well-known prognostic parameters. Multivariate analysis demonstrated that high MIB-1 LI of fibroblasts forming FF significantly increased the relative risk of LNM and the hazard rate of DOM (P < .001 and P = .009). The present study indicated that the metastatic ability of IDCs with FF is highly dependent on the proliferative activity of the fibroblasts forming FF.

No adverse effects of adjuvant chemotherapy on hippocampal volume in Japanese breast cancer survivors.

SummaryWe investigated the adverse effects of adjuvant chemotherapy on the hippocampus in Japanese breast cancer survivors with (n=44) and without (n=31) adjuvant chemotherapy. There were no significant differences in hippocampal volume (magnetic resonance imaging) or additionally in memory function (Wechsler Memory Scale-Revised) between the two groups.

International Multicenter Tool to Predict the Risk of Nonsentinel Node Metastases in Breast Cancer

BACKGROUND Axillary treatment of breast cancer patients is undergoing a paradigm shift, as completion axillary lymph node dissections (ALNDs) are being questioned in the treatment of patients with tumor-positive sentinel nodes. This study aims to develop a novel multi-institutional predictive tool to calculate patient-specific risk of residual axillary disease after tumor-positive sentinel node biopsy. METHODS Breast cancer patients with a tumor-positive sentinel node and a completion ALND from five European centers formed the original patient series (N = 1000). Statistically significant variables predicting nonsentinel node involvement were identified in logistic regression analysis. A multivariable predictive model was developed and validated by area under the receiver operating characteristics curve (AUC), first internally in 500 additional patients and then externally in 1068 patients from other centers. All statistical tests were two-sided. RESULTS Nine tumor- and sentinel node-specific variables were identified as statistically significant factors predicting nonsentinel node involvement in logistic regression analysis. A resulting predictive model applied to the internal validation series resulted in an AUC of 0.714 (95% confidence interval [CI] = 0.665 to 0.763). For the external validation series, the AUC was 0.719 (95% CI = 0.689 to 0.750). The model was well calibrated in the external validation series. CONCLUSIONS We present a novel, international, multicenter, predictive tool to assess the risk of additional axillary metastases after tumor-positive sentinel node biopsy in breast cancer. The predictive model performed well in internal and external validation but needs to be further studied in each center before application to clinical use.

Cancer-Related Intrusive Thoughts as an Indicator of Poor Psychological Adjustment at 3 or More Years After Breast Surgery: A Preliminary Study

Intrusive thoughts are one of the re-experiencing symptoms in posttraumatic stress disorder, and have been suggested as a predictor for the continuous presence of psychological distress in cancer survivors. The aim of this preliminary study was to examine the possibility of using cancer-related intrusive thoughts (CITs) as an indicator of psychological distress and adjustment after breast surgery. A consecutive series of ambulatory breast cancer survivors at 3 or more years after surgery were given the Structured Clinical Interview for DSM-IV (SCID) and self-report questionnaires, including Profile Of Mood States (POMS), Impact of Event Scale (IES) and Mental Adjustment to Cancer (MAC) scale, to measure psychological distress and/or adjustment. The SCID identified a history of CITs in 34 (46%) of the 74 participants. No significant differences were found in the POMS and IES psychological distress scores between subjects with and without a history of CITs. Subjects with a history of CITs showed significantly higher levels of anxious preoccupation, one of the MAC subscale scores. The association continued to be significant after controlling for potential confounders such as social support, depression, avoidance, arousal, and neuroticism. The results indicated that CITs might be useful for indicating poor psychological adjustment, but not distress, in patients at 3 or more years after breast surgery.

Occurrence of fatigue and associated factors in disease-free breast cancer patients without depression

Goals of workStudies on fatigue in disease-free breast cancer patients have consistently found a significant association between fatigue and depression; and some characteristics of this fatigue may be confused with and/or concealed by those of depression. To clarify the characteristics of fatigue in disease-free breast cancer patients, we examined the frequency of fatigue and associated factors in disease-free breast cancer patients without major depression.Patients and methodsSeventy-nine ambulatory breast cancer patients without major depression who had been disease-free for more than 3 years since their surgery completed the Cancer Fatigue Scale (CFS), a multidimensional scale assessing cancer-related fatigue. Participants also completed the Short-form Eysenck Personality Questionnaire–Revised (EPQR) for assessing their personalities. Sociodemographic, physical, and treatment-related factors were also obtained by interview.Main resultsWe found that 36.7% of the patients exhibited fatigue and that fatigue was significantly associated with neuroticism.ConclusionsThese results suggest that a considerable number of disease-free breast cancer patients without major depression experience fatigue and that careful attention to those exhibiting high neuroticism may be of benefit in ameliorating their fatigue.

Feasibility study on radiofrequency ablation followed by partial mastectomy for stage I breast cancer patients

To evaluate the safety and reliability of thermal ablation therapy instead of breast-conserving surgery (BCS), we performed radiofrequency ablation (RFA) for clinical stage I breast cancer patients. Subjects were T1N0 breast cancer patients with no extensive intraductal components. Under general anesthesia, sentinel node biopsy was performed, followed by RFA and BCS. Resected specimens were examined at 5-mm intervals by hematoxylin-eosin (H&E) staining and nicotinamide adenine dinucleotide (NADH) diaphorase staining. Thirty of the 34 eligible patients were enrolled. RFA-related adverse events were observed in nine patients: two with skin burn and seven with muscle burn. Twenty-six patients (87%) showed pathological degenerative changes in tumor specimens with H&E staining. In 24 of the 26 cases (92%) examined by NADH diaphorase staining, tumor cell viability was diagnosed as negative. RFA proved to be reliable and feasible in clinical stage I breast cancer, with no extensive intraductal components. Randomized clinical trials are needed to compare RFA with BCS.