Optimizing smartphone psychotherapy for depressive symptoms in patients with cancer: Multiphase optimization strategy using a decentralized multicenter randomized clinical trial (J-SUPPORT 2001 Study).

AIM: Patients with cancer experience various forms of psychological distress, including depressive symptoms, which can impact quality of life, elevate morbidity risk, and increase medical costs. Psychotherapy and pharmacotherapy are effective for reducing depressive symptoms among patients with cancer, but most patients prefer psychotherapy. This study aimed to develop an efficient and effective smartphone psychotherapy component to address depressive symptom. METHODS: This was a decentralized, parallel-group, multicenter, open, individually randomized, fully factorial trial. Patients aged ≥20 years with cancer were randomized by the presence/absence of three cognitive-behavioral therapy (CBT) skills (behavioral activation [BA], assertiveness training [AT], and problem-solving [PS]) on a smartphone app. All participants received psychoeducation (PE). The primary outcome was change in the patient health questionnaire-9 (PHQ-9) total score between baseline and week 8. Secondary outcomes included anxiety. RESULTS: In total, 359 participants were randomized. Primary outcome data at week 8 were obtained for 355 participants (99%). The week 8 PHQ-9 total score was significantly reduced from baseline for all participants by -1.41 points (95% confidence interval [CI] -1.89, -0.92), but between-group differences in change scores were not significant (BA: -0.04, 95% CI -0.75, 0.67; AT: -0.16, 95% CI -0.87, 0.55; PS: -0.19, 95% CI -0.90, 0.52). CONCLUSION: As the presence of any of the three intervention components did not contribute to a significant additive reduction of depressive symptoms, we cannot make evidence-based recommendations regarding the use of specific smartphone psychotherapy.

Characterizing user demographics in posts related to breast, lung and colon cancer on Japanese twitter (X).

Various cancer-related information is spreading on social media. Our study aimed to examine the account types associated with cancer-related tweets (currently known as posts) on Twitter (currently known as X) in Japan, specifically focusing on breast, lung, and colon cancer. Using the Twitter application programming interface, we collected tweets containing keywords of the three cancers type in August-September 2022. The accounts were categorized into seven types: Survivor, Patient's family, Healthcare provider, Public organization, Private organization, News, and Other according to account name and texts. We analyzed the sources of the top 50 most liked and retweeted tweets. Out of 7753 identified tweets, breast cancer represented the majority (62.8%), followed by lung cancer (20.8%) and colon cancer (16.3%). Tweets came from 4976 accounts. Account types varied depending on the cancer type, with breast cancer topics more frequently from Survivor (16.0%) and lung cancer from Patient's family (16.3%). Healthcare provider and Public organization had minimal representation across three cancer types. The trends in the top 50 tweets mirrored the distribution of accounts for each cancer type. Breast cancer-related tweets had the highest frequency. There were few from public organizations. These findings emphasize the need to consider the characteristics of cancer-related information sources when sharing and gathering information on social media.

Ruptured breast implant removal because of patient anxiety in the absence of breast implant-associated anaplastic large cell lymphoma.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) has been regarded as a long-term problem after silicone breast implantations. We report a case in which BIA-ALCL and breast cancer were not detected preoperatively, with subsequent removal of a ruptured breast implant. A 52-year-old woman had silicone breast implants on both sides for breast augmentation 15 years ago. Right axillary lymphadenopathy and intracapsular ruptures were noted by magnetic resonance imaging. Right axillary lymph node biopsy was performed at our department of breast surgery. Flow cytometry for BIA-ALCL was also performed using the exudate around the implant. The results were negative for breast cancer and BIA-ALCL. However, taking into consideration exacerbation of breast implant rupture and the patient's anxiety about BIA-ALCL, ruptured bilateral implants were removed by total capsulectomy. The postoperative course was uneventful 1 year after the operation, and her anxiety was dispelled despite her breast deformity. Appropriate explantation and periodic examination may be required to prevent excessive anxiety.

Fact-Checking Cancer Information on Social Media in Japan: Retrospective Study Using Twitter.

BACKGROUND: The widespread use of social media has made it easier for patients to access cancer information. However, a large amount of misinformation and harmful information that could negatively impact patients' decision-making is also disseminated on social media platforms. OBJECTIVE: We aimed to determine the actual amount of misinformation and harmful information as well as trends in the dissemination of cancer-related information on Twitter, a representative social media platform. Our findings can support decision-making among Japanese patients with cancer. METHODS: Using the Twitter app programming interface, we extracted tweets containing the term "cancer" in Japanese that were posted between August and September of 2022. The eligibility criteria were the cancer-related tweets with the following information: (1) reference to the occurrence or prognosis of cancer, (2) recommendation or nonrecommendation of actions, (3) reference to the course of cancer treatment or adverse events, (4) results of cancer research, and (5) other cancer-related knowledge and information. Finally, we selected the top 100 tweets with the highest number of "likes." For each tweet, 2 independent reviewers evaluated whether the information was factual or misinformation, and whether it was harmful or safe with the reasons for the decisions on the misinformation and harmful tweets. Additionally, we examined the frequency of information dissemination using the number of retweets for the top 100 tweets and investigated trends in the dissemination of information. RESULTS: The extracted tweets totaled 69,875. Of the top 100 cancer-related tweets with the most "likes" that met the eligibility criteria, 44 (44%) contained misinformation, 31 (31%) contained harmful information, and 30 (30%) contained both misinformation and harmful information. Misinformation was described as Unproven (29/94, 40.4%), Disproven (19/94, 20.2%), Inappropriate application (4/94, 4.3%), Strength of evidence mischaracterized (14/94, 14.9%), Misleading (18/94, 18%), and Other misinformation (1/94, 1.1%). Harmful action was described as Harmful action (9/59, 15.2%), Harmful inaction (43/59, 72.9%), Harmful interactions (3/59, 5.1%), Economic harm (3/59, 5.1%), and Other harmful information (1/59, 1.7%). Harmful information was liked more often than safe information (median 95, IQR 43-1919 vs 75.0 IQR 43-10,747; P=.04). The median number of retweets for the leading 100 tweets was 13.5 (IQR 0-2197). Misinformation was retweeted significantly more often than factual information (median 29.0, IQR 0-502 vs 7.5, IQR 0-2197; P=.01); harmful information was also retweeted significantly more often than safe information (median 35.0, IQR 0-502 vs 8.0, IQR 0-2197; P=.002). CONCLUSIONS: It is evident that there is a prevalence of misinformation and harmful information related to cancer on Twitter in Japan and it is crucial to increase health literacy and awareness regarding this issue. Furthermore, we believe that it is important for government agencies and health care professionals to continue providing accurate medical information to support patients and their families in making informed decisions.

Low TINAGL1 expression is a marker for poor prognosis in breast cancer.

PURPOSE: Tubulointerstitial nephritis antigen-like 1 (TINAGL1) was reported to suppress tumor metastasis and growth in triple-negative (TN) breast cancer. We aimed to determine the associations of TINAGL1 expression with clinicopathological factors and prognosis in breast cancer patients with long-term follow-up. METHODS: A total of 599 consecutive primary invasive breast cancer patients with available tissue specimens from surgery in our hospital were included in the study. TINAGL1 mRNA expression was examined in all 599 tissue specimens using a TaqMan real-time PCR system. TINAGL1 protein expression was further examined in 299 patients with available tissue specimens for immunohistochemical staining. Survival analyses were performed using the Kaplan-Meier method and Cox proportional hazards models. RESULTS: The median follow-up period was 12.0 years. In the total patients, low TINAGL1 mRNA expression was associated with significantly shorter disease-free survival (DFS) and overall survival than high expression (P = 0.003 and P = 0.01, respectively). Furthermore, hormone receptor-positive/human epidermal growth factor receptor 2-negative breast cancer patients with low TINAGL1 mRNA expression had a worse prognosis. Multivariate analysis identified low TINAGL1 mRNA expression, combined with lymph node positivity, as an independent poor prognostic factor for DFS in invasive breast cancer patients (HR 1.41; 95% CI 1.02-1.96; P = 0.036). TINAGL1 mRNA expression also varied with menopausal status, with low TINAGL1 mRNA expression being positively associated with poor prognosis in premenopausal patients, but not in postmenopausal patients. CONCLUSION: Our findings demonstrate that TINAGL1 may be a promising candidate biomarker and therapeutic target in breast cancer patients.

Co-expression effect of LLGL2 and SLC7A5 to predict prognosis in ERα-positive breast cancer.

Lethal giant larvae homolog 2 (LLGL2) and solute carrier family 7 member 5 (SLC7A5) have been reported to be involved in resistance to endocrine therapy. This study aimed to assess the effects of LLGL2/SLC7A5 co-expression in predicting prognosis and response to tamoxifen therapy in ERα-positive breast cancer patients according to LLGL2/SLC7A5 mRNA and protein expression in long-term follow-up invasive breast cancer tissues. We identified that low LLGL2/SLC7A5 mRNA co-expression (LLGL2low/SLC7A5low) was associated with disease-free survival (DFS) compared with other combination groups in all breast cancer patients. In ERα-positive breast cancer patients, LLGL2low/SLC7A5low showed longer DFS and overall survival (OS) compared with LLGL2high/SLC7A5high and a positive trend of longer survival compared with the other combination groups. We also observed that LLGL2low/SLC7A5low showed longer survival compared with LLGL2high/SLC7A5high in ERα-positive breast cancer patients receiving adjuvant tamoxifen therapy. Multivariate analysis demonstrated that LLGL2low/SLC7A5low was an independent favorable prognostic factor of both DFS and OS, not only in all breast cancer patients, but also in ERα-positive breast cancer patients. High co-expression of LLGL2 and SLC7A5 protein showed a positive trend of shorter survival. Our study showed that co-expression of LLGL2 and SLC7A5 mRNA is a promising candidate biomarker in early breast cancer patients.

Granulocyte colony-stimulating factor-associated aortitis in a woman with breast cancer: a case report.

BACKGROUND: Granulocyte colony-stimulating factor (G-CSF) is increasingly used to prevent chemotherapy-associated febrile neutropenia. Generally, aortitis is not considered a side effect of G-CSF and is thought to be extremely rare. Aortitis is an inflammation of the aorta and occurs mainly in connective tissue diseases (Takayasu arteritis, giant cell arteritis, etc.) and infectious diseases (bacterial endocarditis, syphilis, etc.). We report herein a rare case of G-CSF associated with aortitis in a woman with breast cancer. CASE PRESENTATION: Here, we present a case involving a 63-year-old woman with luminal type stage IIa breast cancer. The patient's treatment was initiated with docetaxel and cyclophosphamide, with pegfilgrastim (PEG-G) as support. After PEG-G administration on day 3, the patient developed an intermittent fever of up to 39.4 °C on day 10 and visited our outpatient clinic on day 13 with persistent high fever. Laboratory tests revealed a high neutrophil count (14,000/µL) and a high C-reactive protein (CRP) level (42.8 mg/dL) without any other abnormalities. Contrast-enhanced computed tomography scanning revealed soft tissue thickening with weak enhancement around the wall of the thoraco-abdominal aorta, aortic arch and left subclavian artery. The patient did not respond to antimicrobial agents. On the basis of these observations, the patient was diagnosed with PEG-G-induced aortitis, and her condition rapidly improved without corticosteroids. CONCLUSIONS: Clinicians should be aware of aortitis as a potential complication in patients undergoing G-CSF chemotherapy. In cases with persistent high fever after PEG-G administration, and in the absence of infection, aortitis should be suspected.

Efficacy and impact of SARS-CoV-2 vaccination on cancer treatment for breast cancer patients: a multi-center prospective observational study.

PURPOSE: Vaccination is an essential strategy to prevent infection in the SARS-CoV-2 pandemic. However, there are concerns about vaccine efficacy and the impact of vaccination on cancer treatment. Additionally, the emergence of novel variants may affect vaccination efficacy. This multi-center, prospective, observational study investigated the efficacy and impact of vaccination against SARS-CoV-2 variants on treatment among breast cancer patients in Japan. METHODS: Patients with breast cancer scheduled to be vaccinated with the SARS-CoV-2 vaccine from May to November 2021 were prospectively enrolled (UMIN000045527). They were stratified into five groups according to their cancer treatment: no treatment, hormone therapy, anti-human epidermal growth factor receptor (HER)2 therapy, chemotherapy, and cyclin-dependent kinase 4/6 (CDK4/6) inhibitor. Serum samples for assessing serological responses were collected before the first vaccination and after the second vaccination. RESULTS: Eighty-five breast cancer patients were included. The overall seroconversion rate after second vaccination was 95.3% and the lowest seroconversion rate was 81.8% in the patients under chemotherapy. The overall positivity rate of neutralizing antibodies against the wild-type, α, Δ, κ, and omicron variants were 90.2%, 81.7%, 96.3%, 84.1%, and 8.5%, respectively. Among the patients under chemotherapy or CDK4/6 inhibitors, various degrees of decreased neutralizing antibody titers against SARS-CoV-2 variants were observed. Withdrawal or reduction of systemic therapy because of vaccination was observed in only one patient. CONCLUSION: Our data support SARS-CoV-2 vaccination for breast cancer patients. However, a reduction in neutralizing antibody titers was suggested during chemotherapy and CDK4/6 inhibitors, raising concerns about the impact on long-term infection prevention.

Low HECTD1 mRNA expression is associated with poor prognosis and may be correlated with increased mitochondrial respiratory function in breast cancer.

HECT domain E3 ubiquitin ligase 1 (HECTD1) has been reported to be a negative regulator of epithelial-mesenchymal transition and to decrease breast cancer invasion and metastasis. However, the clinical significance and detailed role of HECTD1 in breast cancer remain elusive. We investigated the role of HECTD1 in two large breast cancer cohorts at our institution and The Cancer Genome Atlas using mRNA expression and bioinformatics analysis. We also examined the prognostic significance of HECTD1 mRNA expression by multivariate analysis and HECTD1 protein expression by immunohistochemistry using our cohort. HECTD1 mRNA expression was significantly lower in breast cancer tissues compared with those in adjacent normal tissues (P<0.001). HECTD1 mRNA expression levels also differed among breast cancer subtypes. Decreased HECTD1 mRNA expression was significantly associated with aggressive tumor characteristics, including large tumor size and high histological grade. HECTD1 mRNA expression was inversely associated with mitochondrial cellular respiratory function (oxidative phosphorylation (P<0.001, FDR q-value <0.001) the respiratory chain complex (P<0.001, FDR q-value <0.001) and reactive oxygen species (P<0.001, FDR q-value <0.001), but not with epithelial-mesenchymal transition, in breast cancer tissues. Low expression of HECTD1 mRNA was associated with shorter disease-free survival (log-rank: P=0.013) and overall survival (log-rank: P=0.038) in breast cancer patients. Multivariate analysis also identified low HECTD1 mRNA expression level as an independent risk factor for disease-free (hazard ratio: 1.54, 95% confidence interval: 1.11-2.13, P=0.009) and overall (hazard ratio: 1.50, 95% confidence interval: 1.01-2.24, P=0.046) survival among breast cancer patients. There was no association of HECTD1 protein expression with HECTD1 mRNA expression and prognosis. In conclusion, we identified low expression of HECTD1 mRNA as an independent poor prognostic factor in breast cancer and showed that HECTD1 mRNA expression was inversely correlated with genes involved in mitochondrial cellular respiratory function in breast cancer.

Discovering novel mechanisms of taxane resistance in human breast cancer by whole-exome sequencing.

Taxanes are important drugs used in the treatment of breast cancer; however, some cancer types are taxane-resistant. The aim of the present study was to investigate the underlying mechanisms of taxane resistance using whole-exome sequencing (WES). Six patients with breast cancer whose tumors responded well to anthracycline treatment but grew rapidly during neoadjuvant taxane-based chemotherapy, were included in the present study. WES of samples from these patients was carried out to identify somatic mutations of candidate genes thought to affect taxane resistance, and the candidate proteins were structurally modeled. The mRNA and protein expression levels of these candidate genes in other breast cancers treated with taxanes were also examined. Nine variants common to all six patients were identified and two of these [R552P in V-type proton ATPase catalytic subunit A (ATP6V1A) and T114P in apolipoprotein B MRNA editing enzyme catalytic subunit 3F (APOBEC3F)] were selected. The results also showed that, protein-structure visualization suggested that these mutations may cause structural changes. The Kaplan-Meier analyses revealed that higher APT6V1A and APOBEC3F expression levels were significantly associated with poorer disease-free survival (DFS) and overall survival. Moreover, multivariate analysis identified high ATP6V1A mRNA expression as an independent risk factor for poor DFS. Two specific mutations that might affect taxane resistance were identified. Thus, these results suggest that breast cancer patients receiving taxanes who have high ATP6V1A or APOBEC3F expression levels may have shorter survival.

Predictive factors for patients who need treatment for chronic post-surgical pain (CPSP) after breast cancer surgery.

BACKGROUND: Although chronic postsurgical pain (CPSP) after breast cancer surgery is a common and prevalent postsurgical adverse event, the need for CPSP treatment has not been investigated. This study examined the proportion of patients who needed treatment for CPSP and associated predictors. METHODS: We conducted a cross-sectional study with female patients who underwent breast cancer surgery at our institution. Participants were aged ≤ 65 years at the time of this study and were at least 1 year post surgery. The questionnaire examined the presence of and need for treatment for CPSP and included the Japanese version of the Concerns about Recurrence Scale (CARS-J). Multivariate analyses were used to identify independent predictors of needing treatment for CPSP. RESULTS: In total, 305 patients completed the questionnaire. The mean time since surgery was 67.1 months; 156 (51%) patients developed CPSP after breast cancer surgery and 61 (39%) needed treatment for CPSP. Among patients that developed CPSP, the fear of breast cancer recurrence as assessed by the CARS-J (odds ratio [OR] 2.59, 95% confidence interval [CI] 1.14-6.28, P = 0.028) and ≥ 2 postsurgical pain regions (OR 2.52, 95% CI 1.16-5.57, P = 0.020) were independent predictors of needing treatment for CPSP. CONCLUSIONS: This study is the first to identify the proportion and predictors of patients who need treatment for CPSP. Fear of breast cancer recurrence and ≥ 2 postsurgical pain regions may predict the need for CPSP treatment among patients following breast cancer surgery.

Low RAI2 expression is a marker of poor prognosis in breast cancer.

PURPOSE: Retinoic acid-induced 2 (RAI2) has been shown to be a putative suppressor of the early hematogenous dissemination of tumor cells to the bone marrow in breast cancer. Here, we investigated the associations of RAI2 mRNA and protein expression with clinicopathological factors and prognosis in breast cancer patients with long-term follow-up. METHODS: Invasive breast cancer tissues (n = 604) were analyzed for RAI2 mRNA expression. We examined the associations of clinicopathological factors with the expression levels of RAI2 mRNA in these samples. We also analyzed RAI2 protein expression by immunohistochemistry in invasive breast cancer tissues (n = 422). RESULTS: We identified significant positive associations between low expression of RAI2 mRNA and shorter disease-free survival (DFS), breast-cancer-specific survival (BCSS), and overall survival (OS) in breast cancer patients. We also identified significant positive associations between negative for RAI2 protein expression and shorter DFS, BCSS, and OS in breast cancer patients. Low RAI2 mRNA and negative for RAI2 protein expression were positively associated with larger tumor size, higher tumor grade, and ERα-negativity. Multivariate analyses indicated that not only RAI2 mRNA but also RAI2 protein expression were independent risk factors for both DFS and BCSS in breast cancer patients. The median follow-up periods were 10.3 and 9.3 years for the RAI2 mRNA and protein expression analyses, respectively. CONCLUSIONS: Our findings suggest that RAI2 has a role in the metastasis of breast cancer, and that RAI2 expression could be a promising candidate biomarker of prognosis in breast cancer patients.

Brief collaborative care intervention to reduce perceived unmet needs in highly distressed breast cancer patients: randomized controlled trial.

OBJECTIVES: Our newly developed brief collaborative care intervention program has been suggested to be effective in reducing breast cancer patients' unmet needs and psychological distress; however, there has been no controlled trial to investigate its effectiveness. The purpose of this study was to examine the effectiveness of the program in relation to patients' perceived needs and other relevant outcomes for patients including quality of life, psychological distress and fear of recurrence (Clinical trial register; UMIN-CTR, Clinical registration number; R5172). METHODS: Fifty-nine highly distressed breast cancer patients receiving adjuvant chemotherapy and/or hormonal therapy were randomly assigned either to a treatment as usual group or to a collaborative care intervention, consisting of four sessions that mainly included assessment of the patients' perceived needs, learning skills of problem-solving treatment for coping with unmet needs and psycho-education provided by trained nurses supervised by a psycho-oncologist. RESULTS: Although >80% of the eligible patients agreed to participate, and >90% of participants completed the intervention, there were no significant differences with regard to patients' needs, quality of life, psychological distress and fear of recurrence, both at 1 and 3 months after intervention. CONCLUSION: Newly developed brief collaborative care intervention program was found to be feasible and acceptable. The trial, however, failed to show the effectiveness of the program on patients' relevant subjective outcomes. Further intervention program having both brevity and sufficient intensity should be developed in future studies.

Corrigendum to "Relapsed multiple myeloma manifesting as extramedullary plasmacytoma of the breast: Imaging findings" [Radiology Case Reports 14 (2019) 584-587].

[This corrects the article DOI: 10.1016/j.radcr.2019.02.018.].

Sentinel lymph node biopsy may be unnecessary for ductal carcinoma in situ of the breast that is small and diagnosed by preoperative biopsy.

BACKGROUND: Current guidelines do not recommend that sentinel lymph node biopsy is routinely performed for ductal carcinoma in situ; thus, indications for sentinel lymph node biopsy in patients with ductal carcinoma in situ remain controversial. In this study, we investigated whether sentinel lymph node biopsy can be safely omitted when ductal carcinoma in situ has been diagnosed by preoperative biopsy. METHODS: We retrospectively analysed sentinel lymph node metastasis rates and upstaging to invasive cancer in surgical specimens, performed receiver operating characteristic analysis for ductal carcinoma in situ lesion size and assessed correlations with preoperative clinicopathological factors of 277 patients with ductal carcinoma in situ diagnosed by preoperative biopsy at our institution. RESULTS: Among 277 patients with sentinel lymph node biopsy, six (2.2%) had sentinel lymph node metastasis. All six were upstaged to invasive cancer by pathological examination of surgical specimens. In total, 69 patients (24.9%) were upstaged to invasive cancer. The mean size of ductal carcinoma in situ lesions on preoperative imaging was significantly larger for the 69 upstaged patients (50.0 mm) than for the non-upstaged patients (34.4 mm; P < 0.0001). Of the 277 patients with sentinel lymph node biopsy, 117 (42.2%) had preoperative ductal carcinoma in situ lesions <31.8 mm, which was identified as the optimal cut-off size by receiver operating characteristic analysis. Of these 117 patients, 96 (82.1%, 95% confidence interval: 73.9-88.5%) could be safely omitted from sentinel lymph node biopsy because all of them remained as ductal carcinoma in situ and had negative sentinel lymph nodes at surgery. CONCLUSIONS: Size of ductal carcinoma in situ lesions on preoperative diagnostic imaging is a predictor of diagnosis of invasive cancer on pathological examination of surgical specimens. Sentinel lymph node biopsy may be unnecessary in ductal carcinoma in situ diagnosed by preoperative biopsy in patients with small lesions.

The standard form of CD44 as a marker for invasion of encapsulated papillary carcinoma of the breast.

Encapsulated papillary carcinoma (EPC), a rare variant of papillary carcinoma of the breast, is regarded as a transition form between carcinoma in situ and invasive carcinoma. Here, we tried to identify differences in immunohistochemical phenotype between 10 EPCs with invasive properties (EPC with invasion) and 17 non-invasive EPCs (EPC). We immunohistochemically assessed the expression of hormone receptors, matrix metalloproteinase (MMP) 2 and MMP9, vascular endothelial growth factor (VEGF), CD31, and D2-40, markers of tumor-associated macrophages (CD163, CD206), Ki-67 and stem cell markers (CD44 and CD24). The frequency of MMP9-positive cases and the number of tumor-associated macrophages infiltrating into the fibrous capsule were significantly higher in EPC with invasion than in EPC. The expression of the standard form of CD44 (CD44s) was significantly stronger in EPC with invasion than in EPC (P = 0.0036) and was correlated with MMP2 expression and M2-like macrophage infiltration. A multivariate logistic model analysis showed that CD44s expression in tumor cell and infiltration of CD163 positive macrophage in EPC capsule showed an independent odds ratio for invasion of EPC. Thus, CD44s may be a potential marker predicting invasive potential of EPC and could play an important role in progression to the invasive phase of EPC.

Prognostic impact of TP53INP1 gene expression in estrogen receptor α-positive breast cancer patients.

BACKGROUND: Tumor protein 53-induced nuclear protein 1 (TP53INP1) is a key stress protein with tumor suppressor function. Several studies have demonstrated TP53INP1 downregulation in many cancers. In this study, we investigated the correlations of TP53INP1 mRNA expression in breast cancer tissues with prognosis and the correlations of microRNAs that regulate TP53INP1 expression in breast cancer patients with long follow-up. METHODS: A total of 453 invasive breast cancer tissues were analyzed for TP53INP1 mRNA expression. We examined correlations of clinicopathological factors and expression levels of TP53INP1 mRNA in these samples. The expressions of miR-155, miR-569 and markers associated with tumor-initiating capacity were also analyzed. The median follow-up period was 9.0 years. RESULTS: We found positive correlations between low expression of TP53INP1 mRNA and shorter disease-free survival and overall survival in breast cancer patients (P = 0.0002 and P < 0.0001, respectively), as well as in estrogen receptor α (ERα)-positive patients receiving adjuvant endocrine therapy (P = 0.01 and P = 0.0008, respectively). No correlations were found in ERα-negative patients. Low TP53INP1 mRNA levels positively correlated with higher grade and ERα-negativity. Multivariate analysis indicated that TP53INP1 mRNA level was an independent risk factor for overall survival both in overall breast cancer patients (hazard ratio, 2.13; 95% confidence interval, 1.17-3.92) and ERα-positive patients (hazard ratio, 2.34; 95% confidence interval, 1.18-4.64). CONCLUSIONS: We show that low expression of TP53INP1 is an independent factor of poor prognosis in breast cancer patients, especially ERα-positive patients. TP53INP1 might be a promising candidate biomarker and therapeutic target in ERα-positive breast cancer patients.

Relapsed multiple myeloma manifesting as extramedullary plasmacytoma of the breast: Imaging findings.

Extramedullary plasmacytoma of the breast (EPB), a manifestation of multiple myeloma (MM), is very rare. It is important to recognize the imaging findings of EPB because it may be the first manifestation of relapsed MM. An 85-year-old woman presented with a lump in her right breast 4 years after the complete remission of MM. She underwent mammography and ultrasonography, which showed an oval circumscribed mass and an irregular circumscribed heterogeneous solid mass, respectively. Following ultrasound-guided vacuum-assisted breast biopsy, this lesion was confirmed to be EPB. Whole-body computed tomography showed multiple new osteolytic lesions and other multiple extramedullary lesions in addition to EPB in the right breast. The final diagnosis was relapsed MM with multiple extramedullary plasmacytoma.

Associations in tumor infiltrating lymphocytes between clinicopathological factors and clinical outcomes in estrogen receptor-positive/human epidermal growth factor receptor type 2 negative breast cancer.

The value of assessing tumor infiltrating lymphocytes (TILs) in estrogen receptor (ER) positive/human epidermal growth factor receptor type 2 (HER2) negative breast cancer has yet to be determined. In the present study, a total of 184 cases with early distant recurrence detected within 5 years following the primary operation, 134 with late distant recurrence diagnosed following 5 years or longer and 321 controls without recurrence for >10 years following starting the initial treatment for ER-positive/HER2 negative breast cancer, registered in 9 institutions, were analyzed. The distributions of TILs and their clinical relevance were investigated. TIL distributions did not differ significantly among the early, late and no recurrence groups, employing a 30% cut-off point as a dichotomous variable. In those who had received adjuvant chemotherapy as well as endocrine therapy, a trend toward higher TIL proportions was detected when the early recurrence group was compared with the no recurrence group employing the 30% cut-off point (P=0.064). The TIL distributions were significantly associated with nodal metastasis (P=0.004), ER status (P=0.045), progesterone receptor (PgR) status (P=0.002), tumor grade (P=0.021), and the Ki67 labeling index (LI) (P=0.002) in the no recurrence group and with the Ki67 LI in the recurrence groups (P=0.002 in early recurrence group, P=0.023 in late recurrence group). High TIL distributions also predicted shorter survival time following the detection of recurrence (P=0.026). However, these prognostic interactions were not significant in multivariate analysis (P=0.200). The present retrospective study demonstrated no significant interaction between TIL proportions and the timing of recurrence. However, higher TIL proportions were observed in breast cancer patients with aggressive biological phenotypes, which tended to be more responsive to chemotherapy. The clinical relevance of stromal TILs for identifying patients who would likely benefit from additional therapies merits further investigation in a larger patient population.