Breast cancer cell motility is promoted by 14-3-3γ The correct name of the corresponding author should be ‘‘Takahiro Mimae’’, and not ‘‘Emiko Hiraoka’’ as given in the original publication of the article.

Correction to: Neutropenia management with palbociclib in Japanese patients with advanced breast cancer The correct name of the last author should be “Masakazu Toi”, and not ‘‘Masakuzu Toi” as given in the original publication of the article.

Sentinel node mapping and ductal carcinoma in situ Abstract Background Pure ductal carcinoma in situ (DCIS) is typically unassociated with a risk of regional lymph node involvement. Retrospective series maintain that larger tumors or high-grade histopathology may harbor a risk of lymph node involvement. Purpose Our community hospital retrospectively reviewed a series wherein women with DCIS were subjected to sentinel lymph node biopsy based on large tumor size and/or high-grade histopathology. Materials and methods 232 consecutive women with a diagnosis of pure DCIS were evaluated independently by two breast surgeons, one who typically offers sentinel node mapping to patients with tumors larger than 10 mm and the other who offers sentinel node mapping to women with grade 3 tumors. 60 women (26%) underwent sentinel node mapping along with appropriate surgery directed to the breast. Women were offered risk-adjusted adjuvant radiotherapy and anti-endocrine therapy. Results At a median follow-up of 18 months (range 6–132 months), 9 women (15%) were identified with regional axillary nodal disease. A statistical analysis was conducted between women who did or did not undergo sentinel node mapping because there was overlap in large tumor size and high grade between the two groups. A univariate logistic regression statistic showed a trend toward a significant relationship between grade 3 tumors and a risk of occult nodal involvement. This was not confirmed by multivariate analysis. Conclusions In our moderate-sized surgical experience evaluating women with pure DCIS who underwent a sentinel node mapping due to large tumor size or high grade histology, we were unable to confirm that either is predictive of occult node involvement.

Impact of germinal center-associated nuclear protein polymorphisms on breast cancer risk and prognosis in a Japanese population Abstract Background Germinal center-associated nuclear protein (GANP) is a phosphoprotein involved in mRNA export and regulation of DNA recombination. Although GANP expression in human breast cancer tissue is associated with breast cancer prognosis, the association between the genetic background of GANP and susceptibility and prognosis of breast cancer is unclear. Methods We selected 694 breast cancer cases and 1376 age- and menopausal status-matched non-cancer controls from the Hospitable-based Epidemiologic Research Program, conducted at Aichi Cancer Center between 2001 and 2005. We evaluated the impact of two polymorphisms at the GANP locus (rs2839178 and rs11702450) on the susceptibility and prognosis of breast cancer. Reference alleles were defined as the A allele for rs2839178 and G allele for rs11702450. Results The GG genotype of rs2839178 was statistically significantly associated with breast cancer risk (odds ratio [OR] 0.48, 95% confidence interval [CI] 0.30–0.76, P = 0.002). In prognostic analysis, compared to those with AA genotype of rs2839178, patients with AG or GG genotypes had longer disease-free survival (DFS) (hazard ratio [HR] 0.71, 95% CI 0.49–1.04 and HR 0.42, 95% CI 013–1.42, respectively, P for trend = 0.04). eQTL analysis indicated that association with rs2839178 can be explained by the effect of rs2839173 on expression of GANP/MCM3AP. Conclusions The G allele of rs2839178 at the GANP locus was significantly associated with reduced breast cancer risk and longer DFS in breast cancer patients, showing a consistent direction in the association between susceptibility and clinical outcome. GANP is, therefore, important for the occurrence and progression of sporadic breast cancer.

Discrepancies of current recommendations in breast cancer follow-up: a systematic review Abstract Introduction Management and optimal follow-up of early breast cancer survivors remain up to this day a challenge due to the lack of well-established guidelines. Multiple medical societies, organizations and working groups have provided recommendations for follow-up but there is no uniform, globally approved algorithm to guide clinical practice. Methods A systematic review was performed to identify and evaluate discrepancies between available guidelines for the follow-up of breast cancer survivors. Results Differences in the follow-up schedule, laboratory and imaging investigations were noted. In the clinical practice setting, the situation is complicated further by clinicians who often request unnecessary tests not currently incorporated in any of the existing guidelines. Conclusions Follow-up of patients with early breast cancer needs to become standardized and prospective clinical trials focusing on optimal follow-up are more than mandatory.

Lateral thoracoaxillar dermal-fat flap for breast conserving surgery: the changes of the indication and long-term results Abstract Background Oncoplastic breast conserving surgery had been challenged to achieve both of local control and the cosmetic appearance of preserved breast. We developed the lateral thoracoaxillar dermal-fat flap (LTDF) as an oncoplastic procedure to fill the defect of breast-conserving surgery in 1999. Methods A total of 2338 breast cancer patients underwent surgery from January, 2000 to December, 2017. Mastectomy was performed in 706 patients (30%), and breast conservative surgery (BCS) was performed in 1634 patients (70%). The LTDF was adopted in 487/1634 (30%) of BCS cases to fill the large defect left by partial resection. we divided all patients into 3 groups: breast total mastectomy (BT group), the breast partial resection (BP) with LTDF (LTDF group), and Bp without LTDF (BP group) and compared the clinical characteristics, and recurrence rate. Results The Indications for LTDF increased up to 40% in 2010, while they decreased to 20%–30% in the most recent period, in accordance with the frequency of breast reconstruction increased. Patients who underwent BP + LTDF (LTDF group) included significantly higher proportions of stage II diseases and cases treated by neoadjuvant chemotherapy than those in BP or BT groups.. We found no marked difference of local recurrence and distant metastases between the LTDF and Bp groups. However, the rate of distant metastasis was significantly higher in BT group than in the Bp or LTDF group. Concerning the complications of LTDF, we experienced a few complications of Grade 3–4 requiring surgical management, namely one case of dislocation of the LTDF, three cases of bleeding, and five cases each of skin necrosis and fat necrosis. Conclusions We reported satisfying long-term outcomes of 487 cases treated by LTDF. LTDF is a suitable oncoplastic technique for BCS.

Neutropenia management with palbociclib in Japanese patients with advanced breast cancer Abstract Background The cyclin-dependent kinase 4/6 (CDK4/6) inhibitor palbociclib, in combination with endocrine therapy (ET), significantly prolonged progression-free survival in women with hormone receptor–positive, human epidermal growth factor receptor 2–negative advanced breast cancer (HR+/HER2− ABC) in PALOMA-2 and PALOMA-3. Neutropenia and palbociclib dose reductions/interruptions occurred more frequently in the Japanese versus overall populations. We evaluated neutropenia patterns, palbociclib dose management, and clinical responses after dose reduction in Japanese patients in PALOMA-2 and PALOMA-3 and a single-arm Japanese phase 2 study. Methods PALOMA-2 and the Japanese phase 2 study enrolled postmenopausal women with estrogen receptor–positive, HER2− ABC who had not received prior systemic therapy for advanced disease; PALOMA-3 enrolled women with HR+/HER2− ABC, regardless of menopausal status, whose disease had progressed after prior ET. Palbociclib (125 mg/day) was administered 3 weeks on/1 week off. Dose reduction/interruption, cycle delay, tumor response, and laboratory-assessed neutropenia were analyzed in Japanese patients who received palbociclib. Results A total of 101 Japanese patients received palbociclib + ET. Among Japanese patients in the 3 studies, the frequency of all-grade/grade 3/grade 4 neutropenia was 94%/53%/34%, 100%/69%/21%, and 100%/67%/26%, respectively. Twenty (63%), 28 (67%), and 15 (56%) patients required palbociclib dose reduction. Dose interruption or reduction did not affect palbociclib treatment duration, and durable tumor response was observed despite dose reduction. Conclusion Neutropenia was manageable with dose modifications, without affecting palbociclib treatment duration or efficacy. Trial registration Pfizer (NCT01740427, NCT01684215, NCT01942135).

PIM1 is responsible for IL-6-induced breast cancer cell EMT and stemness via c-myc activation Abstract Background Interleukin-6 (IL-6) has been demonstrated to be a critical factor for breast cancer malignancy. However, the molecular mechanisms by which IL-6 induce breast cancer cells epithelial–mesenchymal-transition (EMT) and stemness remain elusive. Methods Breast cancer cell lines T47D and MCF7 were exposed to IL-6, the expression of PIM1 was examined by quantitative real-time PCR (qRT-PCR) and western blot. Luciferase reporter assay was used to determine the transcriptional modulation of PIM1 by IL-6 and STAT3 inhibitor. Transwell assay was used to detect the invading ability of breast cancer cells induced by IL-6 or PIM1. The expressions of EMT and stemness markers were determined by qRT-PCR. Results IL-6 promoted PIM1 expression in a dose- and time-dependent manner, and this induction could be abrogated by inhibiting STAT3 activation, subsequently suppressing the transcriptional level of PIM1. Moreover, we noticed that knocking down of PIM1 in cells which was exposed to IL-6 significantly impaired the invasion ability and the expression of EMT and stemness markers. On the contrary, overexpression of PIM1 promoted cell invasion and upregulated the expression of EMT and stemness markers. In addition, we demonstrated that c-myc, the cofactor of PIM1, involved in the pro-oncogenic roles of PIM1. Knocking down of c-myc attenuated the PIM1-induced cell EMT and stemness. Conclusion This study proposed the upregulation of PIM1 by IL-6 contributed to breast cancer cell aggressiveness and targeting PIM1 or c-myc could be novel approaches for breast cancer treatment.

Relationships among personality, coping, and concurrent health-related quality of life in women with breast cancer Abstract Background Theory has suggested that personality plays an important role related to health behavior and results in health outcomes, but inconsistent with the findings exist. Moreover, limited research has focused on style of coping with personality traits and health-related quality of life (HRQOL) for patients with breast cancer. We tested how ways of coping and personality traits are associated with HRQOL in patients with breast cancer, after controlling for age, education, disease severity, and sleep disorders. Methods In a cross-sectional study of 207 patients with breast cancer, they completed a set of questionnaires at two general hospitals. The measures used were demographic and individual characteristics, personality traits, ways of coping, and health surveys. We used correlations and hierarchical regressions to determine all relationships among factors, sleep disorders, personality, coping, and HRQOL. Results Most participants were reported as having stage II (77, 37.2%) breast cancer. About 60% patients with breast cancer have poor sleep and sleep disorders having a negative association with HRQOL. Participants using more active coping, with lower neuroticism, and higher agreeableness traits are more likely to have a better physical quality of life (PQOL). In the PQOL regression model, clinical conditions (duration since cancer diagnosis; sleep disorders) and two personality traits (neuroticism and agreeableness) significantly explained 23% of variance. Moreover, fewer sleep disorders and two personality traits (neuroticism and conscientiousness) significantly explained 31% of variance in the mental quality-of-life (MQOL) regression model. Conclusions A high prevalence of sleep disorders for patients with breast cancer has occurred and sleep disorders were negatively associated with PQOL and MQOL. In addition, neuroticism was positively related to sleep disorders and could be relevant to psycho-educational interventions.

C677T and A1298C methylenetetrahydrofolate reductase polymorphisms and breast cancer susceptibility among Latinos: a meta-analysis Abstract Background Previous meta-analyses have shown an ethnic dependency of the C677T and the A1298C methylenetetrahydrofolate reductase (MTHFR) polymorphisms, with no focus on the Latino population. For Latinos, many studies have examined these polymorphisms and breast cancer susceptibility, yielding no concise result. Therefore, we undertook this meta-analysis to determine the effect these polymorphisms have on breast cancer risk for Latinos. Methods PubMed, EBSCO, LILACS, Scopus, and Latin American-specific databases were searched for studies exploring the association between the MTHFR polymorphisms and breast cancer susceptibility in Latinos until January 2019. Genotype distributions were extracted and, depending on the level heterogeneity determined by the ψ2-based Q test and the I2 test, fixed-effects or random-effects models were used to calculate pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) for the heterozygous, homozygous, dominant, recessive, and allelic genetic models. No publication bias was detected by the Begg–Mazumdar’s test and Egger’s test. Results Of the 280 retrieved publications, 9 studies were included: 9 for the C677T polymorphism and 5 for the A1298C polymorphism. For the C677T polymorphism, there was an elevated risk for the homozygous (OR 1.42, 95% CI 1.05–1.92), the dominant (OR 1.16, 95% CI 1.02–1.31), the recessive (OR 1.33, 95% CI 1.01–1.75), and the allelic model (OR 1.17, 95% CI 1.03–1.33, p < 0.01). No association between the A1298C polymorphism and the risk to develop breast cancer was determined. Conclusion The results indicated that, for Latinos, the C677T polymorphism is associated with a significant risk for developing breast cancer, whereas the A1289C polymorphism does not.