Effects of taxane-induced peripheral neuropathy on hand dexterity impairment: evaluation of quantitative and subjective assessments.

PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) commonly involves hand dexterity impairment. However, the factors affecting hand dexterity impairment are unknown and there is currently no established treatment. The purpose of the current study was to clarify factors influencing hand dexterity impairment in taxane-induced peripheral neuropathy using subjective and objective assessments. METHODS: We assessed patient characteristics, treatment-related factors, subjective symptoms of CIPN (Patient Neurotoxicity Questionnaire [PNQ]), psychological symptoms, and upper limb dysfunction (Quick Disabilities of the Arm, Shoulder and Hand [Quick DASH]). Quantitative assessments were pinch strength, sensory threshold, hand dexterity impairment, and grip force control. Multiple regression analysis was performed using hand dexterity impairment as the dependent variable and age and PNQ, Quick DASH, and control of grip force as independent variables. RESULTS: Forty-three breast cancer patients were included in the analysis. Hand dexterity impairment in taxane-induced peripheral neuropathy patients was significantly correlated with age, grip force control, and PNQ sensory scores (p < 0.008). Multiple regression analysis demonstrated that PNQ sensory scores and grip force control were significantly associated with hand dexterity impairment (p < 0.01). CONCLUSION: Subjective symptoms (numbness and pain) and grip force control contributed to impaired hand dexterity in taxane-induced peripheral neuropathy.

Predictors of persistent post-surgical pain intensity and interference at 1 year after breast cancer surgery: assessing central sensitization, central sensitivity symptoms, and psychological factors.

BACKGROUND: Persistent post-surgical pain (PPSP) is associated with upper limb dysfunction and decreased quality of life and causes long-term suffering for breast cancer survivors after surgery. However, the predictors of PPSP remain unclear. The purpose of this study was to examine predictors of PPSP intensity and interference at 1 year postoperatively, focusing on treatment-related factors, pre- and postoperative central sensitization (CS), CS-related symptoms (e.g., muscle stiffness, fatigue, sleep disturbances), and psychological factors. METHODS: Eighty-eight women with planned unilateral breast cancer surgery were included in this longitudinal study. CS, CS-related symptoms, and psychological factors were assessed preoperatively, 1 month postoperatively, and 1 year postoperatively. Analysis of covariance was used to compare the groups with and without PPSP, accounting for treatment-related factors. Multiple regression analysis was performed to identify predictors of PPSP intensity and interference at 1 year postoperatively. RESULTS: Even after adjusting for covariates, preoperative and 1-month postoperative Central Sensitization Inventory scores in the PPSP group were significantly higher than scores in the group without PPSP. Multiple regression analysis showed that axillary lymph node dissection (ALND) and 1-month postoperative CS-related symptoms were independent predictors of PPSP intensity and interference at 1 year postoperatively (p < 0.01). CONCLUSION: We found that ALND and 1-month postoperative CS-related symptoms were predictors of PPSP intensity and interference at 1 year postoperatively.

Effect of perioperative pain neuroscience education in patients with post-mastectomy persistent pain: a retrospective, propensity score-matched study.

PURPOSE: Central sensitization (CS)-related symptoms and pain catastrophizing contribute to persistent post-mastectomy pain (PPMP). Pain neuroscience education (PNE) is effective in reducing CS-related symptoms and pain catastrophizing in patients with chronic pain. However, to date, no intervention study of PNE has been conducted to patients with PPMP. This study was aimed to examine whether PNE is more effective than biomedical education (BME) for PPMP. METHODS: In this retrospective case-control study, 118 patients were included. We intervened different patients at different times as follows: (1) a BME group (n = 58) of patients who received BME combined with physiotherapy and (2) a PNE group (n = 60) of patients who received PNE combined with physiotherapy. One year after surgery, we assessed pain intensity and interference (brief pain inventory [BPI]), CS-related symptoms (central sensitization inventory [CSI]), and pain catastrophizing (pain catastrophizing scale [PCS]). Propensity score matching was used to reduce or minimize selection bias and confounding biases and to make the number of cases in both groups match 1:1. RESULTS: Propensity score matching generated the BME group (n = 51) and the PNE group (n = 51). The BPI score, CSI score, and PCS score were statistically significantly lower in the PNE group than in the BME group (all, p < 0.05). The effect sizes for the BPI intensity (r = 0.31) were moderate. CONCLUSIONS: PNE resulted in a better outcome of pain management with less functional disability and CS-related symptoms compared to BME after breast surgery.

Comparison of central sensitization-related symptoms and health-related quality of life between breast cancer survivors with and without chronic pain and healthy controls.

BACKGROUND: In breast cancer survivors, multiple risk factors for health-related quality of life (HRQoL) and chronic pain, including cancer treatment-related factors, psychosocial factors, and central sensitization (CS), have been suggested; however, there has been no comparative study between breast cancer survivors with and without pain. This study aimed to compare the demographic characteristics, psychological factors, and CS-related symptoms between breast cancer survivors with pain, those without pain, and healthy controls, and to investigate the relationships of these factors with HRQoL. METHODS: We conducted a cross-sectional survey of 218 women, including patients who underwent breast cancer surgery and adjuvant therapy and healthy women. RESULTS: Patients were divided into the pain group (n = 42), without-pain group (n = 51), and healthy group (n = 47); thus, among breast cancer survivors, 45% reported chronic pain. The proportion of participants who received breast cancer treatments, such as axillary lymph node dissection and chemotherapy, was higher in the pain group than in the without-pain group (p < 0.05). The Central Sensitization Inventory (CSI) and psychosocial factors in the pain group were higher than those in the without-pain group and healthy group (p < 0.01). The CSI and PCS showed larger effect sizes than treatment-related factors. Moreover, HRQoL was significantly correlated with CSI, PCS, Patient Health Questionnaire-2, and Generalized Anxiety Disorder-2 scale (all, p < 0.01). On multiple linear regression analysis, CSI accounted for 43% of the variance in HRQoL. CONCLUSIONS: CS and pain catastrophizing may be more associated with the development and/or maintenance of persistent pain than treatment-related factors.

Relationship between intrinsic subtypes and tumor responses to neoadjuvant chemotherapy in patients with locally advanced breast cancer.

BACKGROUND: For locally advanced breast cancer, neoadjuvant chemotherapy (NAC) is the standard of care for downstaging the tumor prior to surgery, and improved prognoses that are associated with pathological complete responses (pCR) have been noted, particularly in patients with human epidermal growth factor receptor 2 (HER2)-positive and triple negative (TN) tumors. OBJECTIVE: The aim of this study was to assess the differences in pathological responses among intrinsic subtypes of local lesions and status of axillary lymph nodes (Ax LN). METHODS: A consecutive series of 134 patients with locally advanced breast cancer who were treated with NAC was analyzed. Tumors were classified into the following 5 subtypes according to immunohistochemical staining results: Luminal A type, Luminal B type (HER2-negative and HER2-positive), HER2 type, and TN type. RESULTS: In Luminal A, Luminal B (HER2-negative), Luminal B (HER2-positive), HER2, and TN tumors, the pCR rates were 10% (4 of 40), 19% (8 of 42), 42% (8 of 19), 59% (10 of 17), and 38% (6 of 16), respectively. HER2-positive tumors showed good therapeutic effects, while Luminal A tumors showed less therapeutic effects. CONCLUSIONS: Strategies that are determined according to intrinsic subtypes are becoming very important in the treatment of locally advanced breast cancer.

Esthetic result of rhomboid flap repair after breast-conserving surgery for lower quadrant breast cancer lesion with skin invasion: report of two cases.

Breast-conserving surgery (BCS) has been increasingly performed as a standard operative strategy for patients with breast cancer. The primary purpose of BCS is to acquire both local control and good cosmetic results. An insignificant difference in cancer treatment results has been shown between BCS and total mastectomy. However, achieving sufficiently cosmetic results can be difficult, particularly in patients with tumors that are large or localized to the lower quadrant. To avoid breast deformities and asymmetries after BCS, immediate reconstruction using autologous tissue has been accepted as the standard option. Rhomboid skin and adipose flap repair is a simple, less invasive procedure than the myocutaneous flap, which has primarily been performed in patients with upper quadrant lesions. We herein report the cases of two patients with lower quadrant breast cancer with skin invasion, who underwent BCS with immediate breast repair using a rhomboid flap. This procedure is therefore worth considering as one of the first options for immediate repair after BCS.

Preoperative diagnosis of ductal carcinoma in situ arising within a mammary fibroadenoma: a case report.

Fibroadenoma is the most common form of benign breast tumor and the most common breast tumor in women under 30 years of age. However, carcinoma arising within a fibroadenoma is unusual, with over 100 cases reported in the literature. Histological diagnosis is typically unexpected. A 46-year-old female with no family history of breast malignancies was admitted for an elastic hard lump in the upper-outer quadrant of her right breast. At a clinic that she visited previously, her condition was diagnosed by core needle biopsy with four specimens showing fibroadenoma with borderline atypical ductal hyperplasia at pathology. Excisional biopsy was recommended for pathological diagnosis. The patient requested a definitive diagnosis and alternative treatment to tumorectomy. More biopsy specimens were needed for pathological diagnosis; therefore, ultrasonography-guided vacuum-assisted core needle biopsies were obtained, confirming ductal carcinoma in situ with questionable microinvasion of intracanalicular- and pericanalicular-type fibroadenoma. Right breast-conserving surgery and sentinel lymph node biopsy were immediately performed for radical therapy. We present this case to increase awareness of this entity and stress the need for histological evaluation of some breast masses.

Sentinel lymph node biopsy in breast cancer patients undergoing skin/nipple-sparing mastectomy and immediate autologous reconstruction.

Immediate breast reconstruction following mastectomy is an effective treatment for breast cancer patients. Among several implant options, a latissimus dorsi myocutaneous (LDM) flap is used mainly due to the ease and minimal invasiveness of the procedure. The role of sentinel lymph node (SLN) biopsy with total mastectomy is evolving. Since SLN biopsy is not included in health insurance coverage in the treatment of patients in Japan, it is not generally performed as a separate procedure due to its cost. The present study reviewed the results of seven patients who underwent initial-staged SLN biopsy followed by planned mastectomy and LDM flap reconstruction. Two patients with positive SLNs showed macrometastases and underwent modified radical mastectomy with immediate reconstruction. In contrast, cases showing negative results for sentinel lymph nodes underwent total mastectomy. There were no false-negative cases among the SLN biopsy-negative cases. When an SLN is found to be positive on final pathology, the patient with reconstruction by LDM flap generally requires a potentially difficult reoperation on the remaining axillary nodes. When initial SLN biopsy is generally performed as a separate procedure in Japan, it will be an effective method for screening the axilla for patients who wish to undergo LDM flap reconstruction.

Usefulness of intraoperative touch smear cytology in breast-conserving surgery.

In breast-conserving surgery, positive margins are closely related to intramammary recurrence, but methods of assessing resection stumps during breast-conserving surgery have not been standardized. The present study investigated the usefulness of intraoperative touch smear cytology in our department. From 2005 to 2008, a total of 420 patients underwent breast cancer surgery. Subjects comprised 160 patients who underwent breast-conserving surgery and touch smear cytology. Results of the touch smear cytology were compared to those of the histological tissue analysis. Touch smear cytology displayed 70% sensitivity (14/20), 97.1% specificity (136/140) and a diagnostic accuracy of 93.8% (150/160). Six false-negative cases and 4 false-positive cases were identified. Of the 6 false-negatives, cancer cells were noted in the ductal component in 5 cases, and the degree of cancer cell atypia in the stump was low. Residual cancer cells were noted in the stump in 18 cases, and additional resection was performed in 16 cases. Cancer cells were identified histologically in the additionally resected tissue in 8 of these 16 cases (50%). The direction of positive cytology was towards the nipple in 16 cases, lateral tissue in 5 cases and contralateral nipple in 2 cases. A greater cancer cell volume, as assessed by touch smear cytology, tended to be associated with higher frequency of positive margins, as assessed by histological tissue analysis. Touch smear cytology is easy to perform, offering a very useful technique yielding comparable results to histological tissue analysis.

High-resolution MR lymphography using ultrasmall superparamagnetic iron oxide (USPIO) in the evaluation of axillary lymph nodes in patients with early stage breast cancer: preliminary results.

BACKGROUND: The purpose of this study was to examine the utility of high-resolution magnetic resonance (MR) lymphography using ultrasmall superparamagnetic iron oxide (USPIO) in the evaluation of axillary lymph nodes in patients with early stage breast cancer. METHODS: Ten women with breast cancer without swollen axillary lymph nodes were enrolled in this study. High-resolution MR lymphography was performed 24 h after administration of USPIO. On the MR examination, a 3-inch surface coil was placed on the sentinel lymph node (SLN) parts as defined by a radioisotope (RI) scintigraphy method, and T2*-weighted (T2*W) and T1-weighted (T1W) images were obtained. Detected nodes were differentiated as normal or diseased nodes by the enhancement patterns. The day after MR examination, SLN biopsy (SNB) was performed. The imaging results were compared to the histopathologic findings. RESULTS: On MR images, the mean number of detectable nodes was 7.9 per patient. Eight patients who histopathologically had no metastatic lymph nodes were diagnosed as nonmetastatic and two patients who had 3- and 6-mm metastatic areas in the node, respectively, were diagnosed as metastatic preoperatively. No side effects were noted. CONCLUSIONS: High-resolution MR lymphography using USPIO enabled us to obtain good axillary lymph node evaluation results. These results suggest that this method of imaging may contribute to better preoperative lymph node staging.

Tau expression and efficacy of paclitaxel treatment in metastatic breast cancer.

PURPOSE: Paclitaxel is widely used for the treatment of patients with metastatic breast cancer (MBC). Although several mechanisms of paclitaxel resistance have been demonstrated, useful markers of paclitaxel resistance have not been available in clinical practice. METHODS: In this study, the clinical significance of tau expression in MBC cases was established by identifying candidates with paclitaxel administration. Tissue specimens obtained from 35 patients were examined. Status of tau expression was determined by immunohistochemistry. RESULTS: Fifteen cases were classified as tau-negative and 20 cases were classified as tau-positive, respectively. Sixty percent of tau-negative expression showed favorable response. Conversely, 85% of tau-positive expression showed progressive or stable disease after paclitaxel administration. Time to disease progression in tau-negative and tau-positive groups was 9.4 +/- 6.6 and 6.0 +/- 3.7 months, respectively. CONCLUSIONS: Patients with tau-positive expression may derive less benefit than tau-negative from paclitaxel therapy in MBC.

[Clinical effect and positioning of capecitabine for metastatic breast carcinoma].

We evaluated the effect of capecitabine for metastatic breast carcinoma. Of 18 metastatic breast carcinoma patients experienced in our institution from November 2002 to July 2007, all patients had resisted the anthracycline or taxanes therapy before. Of these patients, 7 had liver, 6 had bone, and 5 had lung metastases. The capecitabine response in these 18 patients was evaluated as follows: PR in 4, long SD in 6, SD in 3, and PD in 5. In particular, 3 patients with liver metastases showed remarkable tumor regression. Compared to the 3rd-and 4th-line, 2nd-line capecitabine proved more effective. Hand-foot syndrome was found in 4 patients. Only one patient discontinued the therapy due to nausea. These results showed that capecitabine may be a useful treatment regimen for chemotherapy-resistant metastatic breast carcinoma patients.

Detection of human epidermal growth factor receptor 2 protein and gene in fine needle aspiration cytology specimens and tissue sections from invasive breast cancer: can cytology specimens take the place of tissue sections?

Overexpression of HER2 protein and HER2 gene amplification in breast cancer are prognostic factors for the response to specific medical treatments such as trastuzumab, endocrine therapy, and chemotherapy. Whereas HER2 expression and gene amplification are generally examined in tissue sections, we investigated whether specimens from fine needle aspiration cytology (FNAC) are adequate for these analyses. HER2 protein overexpression and HER2 gene amplification were assessed in both FNAC specimens and tissue sections from 58 cases of invasive breast cancer. Immunohistochemistry assay for HER2 protein expression was performed according to the HercepTest protocol, and HER2 gene amplification was examined with the Spot-light CISH (chromogenic in situ hybridization) Detection kit. There was a significant positive correlation between assessments of HER2 protein status in the cytology specimens and tissue sections. The sensitivity, specificity, and accuracy of HER2 gene amplification detection in cytology specimens in relation to those in tissue sections were 84.0% (21/25 cases), 87.9% (29/33 cases), and 86.2% (50/58 cases), respectively. FNAC specimens are suitable for detection of HER2 overexpression and HER2 gene amplification in invasive breast cancer.

[Examination of therapy using trastuzumab in patients with metastatic breast carcinoma].

We evaluated the effect of combination therapy of trastuzumab and paclitaxel for metastatic breast carcinoma. Among the 23 metastatic breast carcinoma patients treated in our institution from September 2001 to December 2002, 10 (43%) patients were immunohistochemically positive for the HER2 protein. Four of these patients had bone, 3 had lung, 2 had liver and 1 had supraclavicular lymph node metastases. The combination chemotherapy for these 10 patients was evaluated as follows: CR in 1 patient, PR in 4, NC in 2, and PD in 3. Two patients with liver metastases showed remarkable tumor regression. Combination therapy did not have to be stopped in any of the patients due to side effects. These results show that combination therapy of trastuzumab and paclitaxel may be a useful treatment regimen for chemotherapy-resistant metastatic breast carcinoma patients.