A prospective comparison study utilizing patient-reported outcomes of taxane-related peripheral neuropathy between nab-paclitaxel and standard paclitaxel in patients with breast cancer.

BACKGROUND: Characteristics of taxane-induced peripheral neuropathy (PN) could be different between paclitaxel and nab-paclitaxel. The purpose of this prospective observational multicenter cohort study was to compare tri-weekly nab-paclitaxel to weekly standard paclitaxel regarding the severity, onset and recovery of sensory and motor PN in patients with breast cancer. METHODS: Patients with histologically confirmed breast cancer who were scheduled to receive standard weekly paclitaxel (80 mg/m2) or tri-weekly nab-paclitaxel (260 mg/m2) at institutions in our multicenter group were eligible for this study. Sensory and motor PN were evaluated every 3 weeks until PN improved for up to one year using patient-reported outcome. RESULTS: Between February 2011 and April 2013, 115 patients were enrolled, including 57 and 58 in the paclitaxel and nab-paclitaxel groups, respectively. The incidence of moderate or severe sensory PN was not significantly different between the two groups (p = 0.40). The incidence of moderate or higher motor PN was more frequent in the nab-paclitaxel group than in the paclitaxel group (p = 0.048). The median period for demonstrating PN were shorter in the nab-paclitaxel group than in the paclitaxel group (sensory, p = 0.003; motor, p = 0.001). The recovery of motor PN was slower in the nab-paclitaxel group than in the paclitaxel group (p = 0.035), while the recovery period of sensory PN was not statistically different. CONCLUSION: Nab-paclitaxel induced sensory PN sooner than paclitaxel, and no difference was observed in the severity and recovery duration between the two agents. Motor PN was more severe, started sooner, and improved over a longer period in the nab-paclitaxel-treated patients than in the paclitaxel-treated patients.

Clinicopathological Characteristics and Prognosis of Triple-Negative Apocrine Carcinoma: A Case-Control Study.

Background: With a prevalence of only 1% among all breast cancers in Japan, apocrine carcinoma (AC) is a rare type of breast cancer, and its clinicopathological characteristics remain unclear. The aim of this study was to evaluate the characteristics and prognosis of AC, in relation to the presence or absence of androgen receptor (AR). Methods: We conducted a retrospective multi-center case-control study (Yokohama Clinical Oncology Group (YCOG): YCOG1701 study) in Japan. A total of 53 patients were registered who were diagnosed with AC between 2000 and 2017 in YCOG-affiliated hospitals. Results: The median age of the patients was 67 (43 - 94) years, and the median observation time was 6.1 years. Among the 53 cases, 24 had triple-negative pure AC (TN-PAC; AR-positive), whereas 29 had other types of AC (other-AC; estrogen receptor-positive and/or human epidermal growth factor receptor 2-positive or AR-negative). Tumor size was smaller (1.4 vs. 2.1 cm, P = 0.024) and metastasis occurred in fewer nodes (12.5% vs. 37.9%, P = 0.036) in the TN-PAC group than in the other-AC group. The number of patients who were administered perioperative adjuvant chemotherapy did not significantly differ between the two groups (TN-PAC/other-AC = 50.0%/55.2%, P = 0.525); however, there was no recurrence in the TN-PAC group, compared to five cases with relapse in the other-AC group. Conclusions: AR-positive AC patients showed a favorable prognosis without adjuvant chemotherapy, even with the TN subtype. A clinical trial exploring the possibility of treatment de-escalation is anticipated.

Pectoralis Major Myocutaneous Flap Revisited as a Workhorse for Reconstruction for Defects in the Upper Arm: A Case Report.

Many previous reviews of the literature have described the grafts and techniques for management of defects in the upper arm. However, the alternatives are limited in cases where some conventional flaps are not available and the nearby donor vessels have been previously sacrificed for free flaps. A 77-year-old man presented with a tumor in the right upper arm just above the axilla. The patient had already undergone surgeries for three recurrences of low-grade myxofibrosarcoma, the primary site of which was around the right scapula. The pectoralis major musculocutaneous flap was used for the defect caused by tumor resection, since there was no other available option. An acceptable result was obtained without any major complications. Thus, the pectoralis major myocutaneous flap may be a candidate for reconstruction of defects in the proximal part of the upper arm.

Discrimination of hand-foot skin reaction caused by tyrosine kinase inhibitors based on direct keratinocyte toxicity and vascular endothelial growth factor receptor-2 inhibition.

Tyrosine kinase inhibitors (TKIs) are molecular-targeted anticancer drugs. Their benefits are limited by dermal toxicities, including hand-foot skin reaction (HFSR), which is commonly found in skin areas subjected to friction. The present study aimed to explain the incidence of HFSR in patients treated with TKIs by focusing on keratinocyte toxicity and inhibition of vascular endothelial growth factor receptor (VEGFR), which plays an essential role in angiogenesis. Mice with gene knockout for the immunosuppressive cytokine interleukin-10 exhibited HFSR-like phenotypes, such as cytotoxicity in keratinocytes and increased number and size of blood vessels after repeated doses of regorafenib, sorafenib, and pazopanib, all of which cause high incidence of HFSR, in combination with tape-stripping mimicking skin damage at the friction site. Comprehensive examination of the direct cytotoxic effects of 21 TKIs on primary cultured human keratinocytes revealed that 18 of them reduced the cell viability dose-dependently. Importantly, the ratio of the trough concentration in patients (Ctrough) to the LC50 values of cell viability reduction was higher than unity for four HFSR-inducing TKIs, suggesting that these TKIs cause keratinocyte toxicity at clinically relevant concentrations. In addition, eight HFSR-inducing TKIs caused inhibition of VEGFR-2 kinase activity, which was validated by their ratios of Ctrough to the obtained IC50,VEGFR-2 of more than unity. All 12 TKIs with no reported incidence of HFSR exhibited less than unity values for both Ctrough/LC50,keratinocytes and Ctrough/IC50,VEGFR-2. These results suggested that a combination of keratinocyte toxicity and VEGFR-2 inhibition may explain the incidence of HFSR upon TKI usage in humans.

Predicting Nonsentinel Lymph Node Metastasis in Breast Cancer: A Multicenter Retrospective Study.

BACKGROUND: Sentinel lymph node (SLN) biopsy has been the standard modality for breast cancer patients with clinically node negative disease. In patients who undergo axillary lymph node dissection (ALND) due to SLN metastasis, the harvested nodes (non-SLNs) often contain no metastasis. Here, we evaluated the predictive factors associated with non-SLN metastasis in breast cancer patients. MATERIALS AND METHODS: This was a retrospective study of patients with operable cT1-3, cN0 invasive breast cancer who underwent SLN biopsy followed by ALND due to SLN metastasis. The clinicopathologic factors and predictive factors of non-SLN metastasis were analyzed. The optimal cutoff for the Ki67 index and the number of positive and negative SLNs that were predictive of non-SLN metastasis were evaluated using receiver operating characteristic curves. RESULTS: The median number of SLN and non-SLN was 3 and 11, respectively. Of the 150 patients, 52 (35.0%) had metastases in non-SLNs. The optimal cutoffs for the Ki67 index and the number of positive and negative SLNs were of 12%, 2, and 1, respectively. In the univariate analysis, the Ki67 index and the number of positive SLNs≥2 and negative SLNs≤1 were higher in the non-SLN + group than that in the non-SLN - group. The number of negative SLNs was as a predictive factor for non-SLNs metastasis in the multivariate analysis. CONCLUSIONS: The number of negative SLNs predicts the risk of non-SLN metastasis in breast cancer. When deciding on whether to omit ALND, the number of positive and negative SLNs should be considered.

First-line Gemcitabine Versus Treatment of Physician's Choice for Metastatic Breast Cancer: A Prospective Cohort Study.

BACKGROUND/AIM: This study aimed to investigate the efficacy of first-line gemcitabine monotherapy for metastatic breast cancer (MBC) and its effect on health-related quality of life (HRQoL) compared with treatment of physician's choice (TPC). PATIENTS AND METHODS: We enrolled 96 patients into the first-line gemcitabine group (n=47) or other treatment of physician's choice (TPC) group (n=49) from May 2010 to April 2013. HRQoL was evaluated every 4 weeks. RESULTS: There was no significant difference in the median time to treatment failure (5.3 vs. 4.6 months, hazard ratio=0.87, p=0.546) and the incidence rates of grade 3/4 haematological toxicity (10.6% vs. 8.1%, p=0.677) and grade 3/4 non-haematological toxicity (4.2% vs. 8.1%, p=0.429) between the gemcitabine and TPC groups. Changes in HRQoL from baseline to 12 weeks were not significantly different. CONCLUSION: Gemcitabine achieves similar efficacy and HRQoL benefit to other chemotherapy and can be used as first-line treatment for MBC.

Development of an invasive ductal carcinoma in a contralateral composite nipple graft after an autologous breast reconstruction: a case report.

BACKGROUND: Nipple-areola complex (NAC) reconstruction is a technique used in breast reconstructive surgery, which is performed during the final stage of breast reconstruction after total mastectomy of primary breast cancer. Composite nipple grafts utilizing the contralateral NAC are common; however, to our knowledge, there are no reports of new primary invasive ductal carcinoma development within the graft. Here, we describe one such case for the first time. CASE PRESENTATION: A 54-year-old woman was referred to us by the Department of Plastic and Reconstructive Surgery in our medical center for further evaluation of right nipple erosion. She had undergone total mastectomy of the right breast following a breast cancer diagnosis 15 years ago, at which time tumor biological profiling revealed the following: estrogen receptor (ER), positive; progesterone receptor (PgR), negative; and human epidermal growth factor receptor 2 (HER2), undetermined. She received adjuvant chemotherapy and endocrine therapy. She defaulted endocrine therapy for a few years, and 7 years after surgery, she underwent autologous breast reconstruction with a deep inferior epigastric perforator (DIEP) flap. In the following year, NAC reconstruction was performed using a composite graft technique. Seven years after the NAC reconstruction, erosion appeared on the nipple grafted from its contralateral counterpart; scrape cytology revealed malignancy. The skin on the right side of her chest around the NAC and subcutaneous fat tissue consisted of transferred tissue from the abdomen, as the DIEP flap and grafted nipple were located on the graft skin. The right nipple carcinoma arose from the tissue taken from the left nipple. Magnetic resonance imaging (MRI) or computed tomography showed no malignant findings in the left breast. As the malignant lesion seemed limited to the area around the grafted right nipple on MRI, surgical resection with sufficient lateral and deep margins was performed around the right nipple. Pathological findings revealed invasive ductal carcinoma with comedo ductal components infiltrating the graft skin and underlying adipose tissue. Immunohistochemistry revealed positive for ER, PgR, and HER2. CONCLUSIONS: To our knowledge, this is the first case involving the development of invasive ductal carcinoma in a nipple graft constructed on the skin of a DIEP flap, with the origin from the contralateral breast's nipple.

Higher Systemic Exposure to Unbound Active Metabolites of Regorafenib Is Associated With Short Progression-Free Survival in Colorectal Cancer Patients.

Regorafenib treatment improves survival of patients with metastatic colorectal cancer, but it is also characterized by detrimental side effects that may require modified dosing or interval schedules. Regorafenib is metabolized by cytochrome P450 3A4 in the liver to its active metabolites, M-2 and M-5. We examined area under the unbound plasma concentration-time curve (AUCu) to these compounds to establish pharmacokinetic bases for individualized dosing strategies. The plasma protein binding of M-2 and M-5 was approximately 10-fold lower than that of regorafenib, whereas AUCu values for active metabolites on both days 1 and 15 were significantly higher than that of regorafenib. Patients with higher AUCu values of M-2 or M-5 on day 1 showed significantly shorter progression-free survival than others, likely due, at least in part, to treatment discontinuation as a result of adverse events, especially occurred during first cycle.

Matrix-producing Carcinoma as an Aggressive Triple-negative Breast Cancer: Clinicopathological Features and Response to Neoadjuvant Chemotherapy.

BACKGROUND: Breast matrix-producing carcinomas (MPCs) are rare, and usually triple-negative (TNBC; i.e. oestrogen receptor-, progesterone receptor-, and human epidermal growth factor receptor 2-negative). This study evaluated the clinical features, immunohistochemical profiles, and pathological response to neoadjuvant chemotherapy (NAC) of patients with MPCs. PATIENTS AND METHODS: Five MPCs were identified among 247 patients with TNBC receiving anthracycline- and taxane-based NAC. Pathological response was assessed using surgical specimens. RESULTS: All tumours were histological grade 3 according to pre-treatment core biopsies. Mean Ki-67 and p53 positivity were 65% and 90%, respectively. All tumours were TNBC, and epidermal growth factor receptor-, cytokeratin 5/6-, and vimentin-positive. Grade 3 (pathological complete response) was achieved in 0% (0/5) and 32% (77/242) of those with MPCs and with TNBCs of no specific histological type, respectively, and grade 1a (poor response) in 80% (4/5) and 13% (31/242), respectively. CONCLUSION: MPCs are basal-type TNBCs expressing epithelial-mesenchymal transition markers, with a poor response to standard NAC. Further studies are needed to improve the treatment of this rare but aggressive tumour.

A genome-wide association study identifies three novel genetic markers for response to tamoxifen: A prospective multicenter study.

PURPOSE: Although association studies of genetic variations with the clinical outcomes of breast cancer patients treated with tamoxifen have been reported, genetic factors which could determine individual response to tamoxifen are not fully clarified. We performed a genome-wide association study (GWAS) to identify novel genetic markers for response to tamoxifen. EXPERIMENTAL DESIGN: We prospectively collected 347 blood samples from patients with hormone receptor-positive and human epidermal growth factor receptor 2-negative, invasive breast cancer receiving preoperative tamoxifen monotherapy for 14 to 28 days. We used Ki-67 response in breast cancer tissues after preoperative short-term tamoxifen therapy as a surrogate marker for response to tamoxifen. We performed GWAS and genotype imputation using 275 patients, and an independent set of 72 patients was used for replication study. RESULTS: The combined result of GWAS and the replication study, and subsequent imputation analysis indicated possible association of three loci with Ki-67 response after tamoxifen therapy (rs17198973 on chromosome 4q34.3, rs4577773 on 6q12, and rs7087428 on 10p13, Pcombined = 5.69 x 10-6, 1.64 x 10-5, and 9.77 x 10-6, respectively). When patients were classified into three groups by the scoring system based on the genotypes of the three SNPs, patients with higher scores showed significantly higher after/before ratio of Ki-67 compared to those with lower scores (P = 1.8 x 10-12), suggesting the cumulative effect of the three SNPs. CONCLUSION: We identified three novel loci, which could be associated with clinical response to tamoxifen. These findings provide new insights into personalized hormonal therapy for the patients with breast cancer.

[Gallbladder Malignant Lymphoma Diagnosed after Surgery for Acute Cholecystitis - A Case Report].

An 84-year-old man visited our hospital with epigastralgia.Levels of hepatic and biliary enzymes and CRP were elevated, as detected by a blood test.On a CT scan, a swollen gallbladder with stones was detected.The patient was admitted to the hospital with a diagnosis of Grade I acute cholecystitis.Conservative treatment was continued with antibiotic administration and the patient was discharged from the hospital with improvement on day 6 after admission.Three months later, the patient underwent laparoscopic cholecystectomy.In the gallbladder, a 45×45 mm tumor was found.Upon pathological examination, diffuse proliferation of lymphocyte-like heterotypic cells and subserosal invasion were observed.Immunohistochemistry results were negative for MUM1 and positive for CD10 and Bcl6 markers.A malignant diffuse large B-cell lymphoma was diagnosed.We experienced a case of malignant lymphoma of the gallbladder diagnosed after surgery for acute cholecystitis, which we herein report with literature consideration.

Significant Effect of Polymorphisms in CYP2D6 on Response to Tamoxifen Therapy for Breast Cancer: A Prospective Multicenter Study.

Purpose: CYP2D6 is the key enzyme responsible for the generation of the potent active metabolite of tamoxifen, "endoxifen." There are still controversial reports questioning the association between CYP2D6 genotype and tamoxifen efficacy. Hence, we performed a prospective multicenter study to evaluate the clinical effect of CYP2D6 genotype on tamoxifen therapy.Experimental Design: We enrolled 279 patients with hormone receptor-positive and human epidermal growth factor receptor 2-negative, invasive breast cancer receiving preoperative tamoxifen monotherapy for 14 to 28 days. Ki-67 response in breast cancer tissues after tamoxifen therapy was used as a surrogate marker for response to tamoxifen. We prospectively investigated the effects of allelic variants of CYP2D6 on Ki-67 response, pathological response, and hot flushes.Results: Ki-67 labeling index in breast cancer tissues significantly decreased after preoperative tamoxifen monotherapy (P = 0.0000000000000013). Moreover, proportion and Allred scores of estrogen receptor-positive cells in breast cancer tissues were significantly associated with Ki-67 response (P = 0.0076 and 0.0023, respectively). Although CYP2D6 variants were not associated with pathologic response nor hot flushes, they showed significant association with Ki-67 response after preoperative tamoxifen therapy (P = 0.018; between two groups, one with at least one wild-type allele and the other without a wild-type allele).Conclusions: This is the first prospective study evaluating the relationship between CYP2D6 variants and Ki-67 response after tamoxifen therapy. Our results suggest that genetic variation in CYP2D6 is a key predictor for the response to tamoxifen in patients with breast cancer. Clin Cancer Res; 23(8); 2019-26. ©2016 AACR.

[The Case of HER2 Positive Advanced Gastric Cancer with Para-Aorta Lymph Node Recurrence Responding to Capecitabine plus CDDP plus Trastuzumab Chemotherapy].

We report the case of a 69-year-old man diagnosed with gastric cancer.The patient underwent distal gastrectomy(D2) and Billroth I reconstruction in March, 2010. Postoperative histopathological examination indicated M, Ant, Type 5, 100×50 mm, pap>por2>sig, T4aN3M0, pStage III C.We performed S-1 therapy as adjuvant chemotherapy.Abdominal CT showed para-aortic lymph node recurrence in February, 2015. Since HER2 protein was overexpressed in primary tumor immunostaining, he was treated with capecitabine plus CDDP plus trastuzumab therapy.After the chemotherapy, CEA levels decreased to the normal range and the enlarged lymph node was remarkably decreased in size in May, 2015.T he patient is alive 24 months after the chemotherapy with no evidence of recurrence.

Effectiveness of subarachnoid drug infusion for pediatric tumor-related pain.

Although the effectiveness of subarachnoid continuous drug infusion has been established in cancer pain management, its clinical use in children is rare. A 14-year-old girl with neurofibromatosis type I complained of right leg pain stemming from a growing tumor on her right buttock. Continuous and breakthrough right leg pain were unbearable, even at high doses of systemic opioids that caused severe constipation and deep sedation. Subsequent continuous infusion of bupivacaine and morphine through a subarachnoid catheter effectively relieved the girl's pain. The corresponding decrease in systemic opioid also improved her activities of daily living. The patient eventually died of cachexia due to the rapidly growing buttock lesion that was pathologically confirmed post-mortem as a malignant peripheral nerve sheath tumor. Subarachnoid continuous drug infusion may be very useful in controlling severe pain with few side-effects, even in the field of pediatric palliative care.

Effect of ALDH1 on prognosis and chemoresistance by breast cancer subtype.

Aldehyde dehydrogenase 1 (ALDH1) has been identified as a breast cancer stem cell marker, but its value as a predictor of prognosis and chemoresistance is controversial. This study investigated the effect of ALDH1 on prognosis and chemoresponse by breast cancer subtype. We immunohistochemically analyzed 653 invasive breast cancer specimens and evaluated correlations among clinicopathological factors, survival status, response to neoadjuvant chemotherapy, and ALDH1 expression. Of 653 specimens, 139 (21.3 %) expressed ALDH1 in tumor cells. ALDH1 expression was correlated significantly with larger tumor size, node metastasis, higher nuclear grade, and with HER2(+) and progesterone/estrogen receptor (HR)(-) subtypes. ALDH1 expression was significantly observed in HER2 type and triple-negative breast cancer (TNBC). Patients with ALDH1(+) cancers had significantly shorter disease-free survival (P < 0001) and overall survival (P = 0.044). ALDH1 expression significantly affected prognosis of luminal types, but not TNBC and HER2-enriched types. For the 234 patients treated with neoadjuvant chemotherapy, pathological complete response (pCR) rate was significantly lower in ALDH1(+) cases (13.5 vs. 30.3 %, P = 0.003). pCR and ALDH1 expression were significantly correlated in TNBC patients (P = 0.003). ALDH1(+) breast cancers tended to be aggressive, with poor prognoses. Although ALDH1(+) TNBC showed higher chemoresistance, ALDH1 had significant impact on prognosis in the luminal type but not in TNBC.

Fabrication and Characterization of Electronic and Optical Properties of Polyaniline Nanopatterns.

The authors conducted polyaniline (HA) polymerization on a micro-scale patterned Si water and nano-scale patterned Al surface. Polymerization was performed using a microliter solution droplet made of aniline, HCI and oxidation agent ammonium peroxodisulfate (APS). The droplet was dropped on a flat Si wafer, a micro-patterned Si wafer and a nanostructured Al surface. The SEM image showed that PA was densely polymerized on the circle edge of the dropped 1 mm sized droplet on the flat Si wafer because of large surface tension due to the flat surface. On the other hand, a droplet was broken on a circular trench pattern of 100 µm in diameter fabricated on a Si wafer. The width and depth of the trench were 1 µm and 1 µm, respectively. Tree-like polymer was intensively polymerized along the circular trench. Droplet was also dropped on a lattice trench pattern whose pitch was 10 µm. The width and the depth of the trench were 1 µm and 1 µm, respectively. The SEM image showed that dots of PA were fabricated along the trenches. Far smaller dots of PA were also observed on the flat area of the lattice. Thus, micro-scale structure affects the shape and size of PA in polymerization. Nanoscopic polymerization of PA was conducted locally in a nanoscale highly-oriented line pattern with nanoscale trenches formed on an Al surface. One of the characteristic fabricated patterns was a highly conductive PA line pattern whose pitch was 100 nm. In this case, point-contact IV characteristic measurement, step-like curve was observed. PL spectra of the PA line-pattern exhibited significantly enhanced emission peaks at 380, 450 anc 550 nm due to PA which were overlapped by the rippled PL pattern due to the Al nanostructure.

Neoadjuvant docetaxel/cyclophosphamide in triple-negative breast cancer: predictive value of class III-ß tubulin and non-basal subtype.

AIM: We aimed to clarify which breast cancer subtypes respond best to docetaxel/cyclophosphamide chemotherapy (TC) as neoadjuvant chemotherapy (NAC). PATIENTS AND METHODS: We analyzed pathological responses, clinicopathological characteristics and biological markers (estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER-2), Ki-67, p53, topoisomerase IIα, class III ß tubulin, cytokeratin 5/6, epidermal growth factor receptor (EGFR)) in specimens from 79 patients who received NAC-TC. RESULTS: Out of 79 patients, 33 (41.8%) achieved quasipathological complete responses (QpCR). Univariate analysis associated negative ER (p<0.001), negative PR (p=0.007), triple-negative subtype (TNBC; p=0.001), high Ki-67 (p=0.022) and low class III ß tubulin (p=0.032) with QpCR. Multivariate analyses associated only negative ER (p=0.050) and low class III ß tubulin (p=0.028) and only non-basal subtype in TNBC with QpCR. CONCLUSION: NAC-TC may be especially effective in ER-breast cancer with low class III ß tubulin or non-basal TNBC.

The Pathological Response to Anthracycline is Associated with Topoisomerase IIα Gene Amplification in the HER2 Breast Cancer Subset.

BACKGROUND: HER2-positive breast cancer sensitivity to anthracyclines is enhanced when topoisomerase IIα (TOP2A) is co-amplified under both adjuvant and metastatic settings. However, the relationship between anthracycline sensitivity and TOP2A amplification in HER2-positive breast cancers in neoadjuvant settings is not known. METHODS: The TOP2A gene status was examined by FISH in biopsies from 18 patients who received anthracycline and cyclophosphamide before surgery. RESULTS: The TOP2A gene was amplified in 6/17 patients and was significantly associated with pathological response to the chemotherapy regimen. CONCLUSIONS: TOP2A amplification could predict anthracycline-sensitivity. Thus, the HER2/TOP2A co-amplified subtype may be effectively treated by anthracycline-containing regimens alone.

Collapsin response mediator protein 2 is involved in regulating breast cancer progression.

BACKGROUND: Altered expression of collapsin response mediator proteins (CRMPs) has been reported in several malignant tumors, including downregulation of CRMP1 in lung cancer and upregulation of CRMP2 in colorectal cancer. This study aimed to investigate the relationship between CRMP expression and clinicopathological characteristics in patients with breast cancer. METHODS: Twenty-two breast cancer and four normal breast tissues were used to assess CRMP mRNA expression. The average expression level of each CRMP (CRMP1-5) mRNA was analyzed in a subset of breast cancer specimens and compared with that in normal breast tissue by real-time quantitative reverse-transcription polymerase chain reaction. Furthermore, 173 breast cancer specimens and matching normal breast controls were used for immunohistochemistry based on the tissue microarray technique. Levels of CRMP2 and phosphorylated CRMP2 protein were assessed, and possible correlations between the clinicopathological characteristics were evaluated. RESULTS: The expression of CRMP2 mRNA was significantly decreased in breast cancer tissues, while that of the other CRMPs was similar between normal and breast cancer tissues. Immunohistochemistry revealed that CRMP2 protein expression was also decreased in breast cancer tissues (P < 0.001). Phosphorylated CRMP2 was observed in the nuclei of breast cancer cells but not in normal mammary cells (P < 0.001). Furthermore, nuclear phosphorylated CRMP2 expression was increased in proportion to the histological grade and triple-negative subtype. CONCLUSIONS: Reduced CRMP2 expression and elevated expression of nuclear phosphorylated CRMP2 may be associated with breast cancer progression.