BackgroundMetastatic breast cancer (MBC) is a highly heterogeneous disease and bone is one of the most common metastatic sites. This retrospective study was conducted to investigate the clinical features, prognostic factors and benefits of surgery of breast cancer patients with initial bone metastases.MethodsFrom 2010 to 2015, 6,860 breast cancer patients diagnosed with initial bone metastasis were analyzed from Surveillance, Epidemiology, and End Results (SEER) database. Univariate and Multivariable analysis were used to identify prognostic factors. A nomogram was performed based on the factors selected from cox regression result. Survival curves were plotted according to different subtypes, metastatic burdens and risk groups differentiated by nomogram.ResultsHormone receptor (HR) positive/human epidermal growth factor receptor 2 (HER2) positive patients showed the best outcome compared to other subtypes. Patients of younger age (<60 years old), white race, lower grade, lower T stage (<=T2), not combining visceral metastasis tended to have better outcome. About 37% (2,249) patients received surgery of primary tumor. Patients of all subtypes could benefit from surgery. Patients of bone-only metastases (BOM), bone and liver metastases, bone and lung metastases also showed superior survival time if surgery was performed. However, patients of bone and brain metastasis could not benefit from surgery (p = 0.05). The C-index of nomogram was 0.66. Cutoff values of nomogram point were identified as 87 and 157 points, which divided all patients into low-, intermediate- and high-risk groups. Patients of all groups showed better overall survival when receiving surgery.ConclusionOur study has provided population-based prognostic analysis in patients with initial bone metastatic breast cancer and constructed a predicting nomogram with good accuracy. The finding of potential benefit of surgery to overall survival will cast some lights on the treatment tactics of this group of patients.

PurposeDespite the rapid growing of cancer survivors, prior cancer history is a commonly adopted exclusion criterion. Whether prior cancer will impact the survival of patients with advanced breast cancer (ABC) remains uncertain.Materials and MethodsPatients with ABC diagnosed between 2004 and 2010 were identified using Surveillance, Epidemiology, and End Results (SEER) database. Timing, stage, and type were used to characterize prior cancer. Multivariable analyses using propensity score–adjusted Cox regression and competing risk regression were conducted to evaluate the prognostic effect of prior cancer on overall survival (OS) and breast cancer-specific survival (BCSS).ResultsA total of 14,176 ABC patients were identified, of whom 10.5% carried a prior cancer history. The most common type of prior cancer was female genital cancer (32.4%); more than half (51.7%) were diagnosed at localized stage; most were diagnosed more than 5 years (42.9%) or less than 1 year (28.3%) prior to the index cancer. In multivariate analyses, patients with prior cancer presented a slightly worse OS (hazard ratio, 1.18; 95% confidence interval [CI], 1.07 to 1.30; p=0.001) but a better BCSS (subdistribution hazard ratio, 0.64; 95% CI, 0.56 to 0.74; p < 0.001). In subset analyses, no survival detriment was observed in patients with prior malignancy from head and neck or endocrine system, at in situ or localized stage, or diagnosed more than 4 years.ConclusionPrior cancer provides an inferior OS but a superior BCSS for patients with ABC. It does not affect the survival adversely in some subgroups and these patients should not be excluded from clinical trials.

Triple-negative breast cancer (TNBC) represents the most lethal subtype of breast cancer due to its aggressive clinical features and the lack of effective therapeutic targets. To identify novel approaches for targeting TNBC, we examined the role of protein phosphatases in TNBC progression and chemoresistance. Protein phosphatase 1 regulatory subunit 14B (PPP1R14B), a poorly defined member of the protein phosphatase 1 regulatory subunits, was aberrantly upregulated in TNBC tissues and predicted poor prognosis. PPP1R14B was degraded mainly through the ubiquitin-proteasome pathway. RPS27A recruited deubiquitinase USP9X to deubiquitinate and stabilize PPP1R14B, resulting in overexpression of PPP1R14B in TNBC tissues. Gain- and loss-of-function assays demonstrated that PPP1R14B promoted TNBC cell proliferation, colony formation, migration, invasion, and resistance to paclitaxel in vitro. PPP1R14B also induced xenograft tumor growth, lung metastasis and paclitaxel resistance in vivo. Mechanistic investigations revealed that PPP1R14B maintained phosphorylation and stability of oncoprotein stathmin 1 (STMN1), a microtubule-destabilizing phosphoprotein critically involved in cancer progression and paclitaxel resistance, which was dependent on PP1 catalytic subunits α and γ. Importantly, the tumor suppressive effects of PPP1R14B deficiency could be partially rescued by ectopic expression of wild-type but not phosphorylation-deficient STMN1. Moreover, PPP1R14B increased STMN1-mediated α-tubulin acetylation, microtubule stability, and cell-cycle progression, leading to resistance of TNBC cells to paclitaxel. Collectively, these findings uncover a functional and mechanistic role of PPP1R14B in TNBC progression and paclitaxel resistance, indicating PPP1R14B is a potential therapeutic target for TNBC.

Background: Patients with de novo metastatic breast cancer (MBC) constitute a heterogeneous group with different clinicopathologic characteristics and survival outcomes. Despite controversy regarding its prognostic value, primary tumor surgery may improve survival for selected patients. Patients and Methods: Patients with de novo MBC were identified using the SEER database and were then divided randomly into training and validation sets. A Fine-Gray competing risks model was developed to identify the variables associated with increased cancer-specific mortality in the training set. The M1 subdivision system was established based on the independent prognostic factors. Cumulative incidence curves were estimated and compared using Gray’s test. Results: Involvement of brain or liver and number of metastatic sites were identified as independent prognostic factors in multivariate analysis. The M1 category was subdivided into 3 subcategories: M1a, single site involvement except brain and liver; M1b, liver involvement only, or multiple site involvement except brain and liver; and M1c, brain involvement regardless of number of metastatic sites, or liver and other sites involvement except brain (M1b vs M1a: subdistribution hazard ratio [SHR], 1.48; 95% CI, 1.29–1.68; M1c vs M1a: SHR, 2.45; 95% CI, 2.18–2.75). Patients with the M1a subtype benefited most from primary tumor surgery in the adjusted competing risks model (M1a: SHR, 0.57; 95% CI, 0.48–0.67, M1b: SHR, 0.62; 95% CI, 0.47–0.83, and M1c: SHR, 0.59; 95% CI, 0.44–0.80), whereas benefits conferred by treatment with chemotherapy alone increased with the upstaging of metastatic disease (M1a: SHR, 0.72; 95% CI, 0.62–0.83, M1b: SHR, 0.54; 95% CI, 0.44–0.68, and M1c: SHR, 0.53; 95% CI, 0.45–0.61). Conclusions: Subdivision of M1 stage facilitates prognosis prediction and treatment planning for patients with de novo MBC. Treatment offered should be decided in a coordinated multidisciplinary setting. Primary tumor surgery may play an important role in the management of selected patients.

PurposeThis retrospective study aimed to evaluate the distribution pattern and prognostic value of 21-gene recurrence score (RS) in Chinese patients with mucinous breast cancer (MC) and compared with infiltrating ductal carcinoma (IDC).Materials and MethodsPatients diagnosed with MC or IDC from January 2010 to January 2017 were retrospectively recruited. Reverse transcriptase–polymerase chain reaction assay of 21 genes was conducted to calculate the RS. Univariate and multivariate analyses were performed to assess the association between RS and clinicopathological factors. Survival outcomes including disease-free survival (DFS) and overall survival (OS) were estimated by Kaplan-Meier method and compared by log-rank test.ResultsThe MC cohort included 128 patients and the IDC cohort included 707 patients. The proportions of patients with a low (RS < 18), intermediate (18-30), or high risk (RS > 30) were 32.0%, 48.4%, and 19.5% in MC cohort, and 26.9%, 46.8% and 26.3% in IDC cohort. The distribution of RS varied significantly according to different Ki-67 index and molecular subtype in both cohorts. Moreover, the receipt of chemotherapy was associated with RS in both cohorts. Among patients with MC, tumor stage was related to the DFS (p=0.040). No significant differences in DFS and OS were found among MC patients in different RS risk groups (OS, p=0.695; DFS, p=0.926).ConclusionRS was significantly related to Ki-67 index and molecular subtypes in MC patients, which is similar in IDC patients. However, RS was not able to predict DFS and OS in patients with MC.

The objective of this study was to evaluate the American Joint Committee on Cancer (AJCC) pathological prognostic stage among patients with invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) and to propose a modified score system if necessary. Methods: Women diagnosed with IDC and ILC during 2010-2015 in the Surveillance, Epidemiology, and End Results (SEER) database were retrospectively identified. Disease-specific survival (DSS) and overall survival (OS) were estimated by Kaplan-Meier method. Predictive performances of different staging systems were evaluated based on Harrell concordance index (C-index) and Akaike Information Criterion (AIC). Multivariate Cox models were conducted to build preferable score systems. Results: A total of 184,541 female patients were included in the final analyses, with a median follow-up of 30.0 months. In IDC cohort, the pathological prognostic stage (C-index, 0.8281; AIC, 110274.5) was superior to the anatomic stage (C-index, 0.8125; AIC, 112537.0; P < 0.001 for C-index) in risk stratification with respect to DSS. In ILC cohort, the prognostic stage (C-index, 0.8281; AIC, 7124.423) didn't outperform the anatomic stage (C-index, 0.8324; AIC, 7144.818; P = 0.748 for C-index) with respect to DSS. Similar results were observed with respect to OS. The score system defined by anatomic stage plus grade plus estrogen receptor and progesterone receptor (AS+GEP) allows for better staging (C-index, 0.8085; AIC, 7178.448) for ILC patients. Conclusion: Compared with anatomic stage, the pathological prognostic stage provided more accurate stratification for patients with IDC, but not for patients with ILC. The AS+GEP score system may fit ILC tumors better.

Breast cancer patients with HR + /HER2 + tumors have a different clinical behavior pattern compared with HR-/HER2 + patients, but PR has been rarely discussed in HER2 + patients. We found out that higher ER and PR level was a favorable predictor of survival outcome in HER2 + patients. Our study calls for more attention to PR expression in HER2 + breast cancer. Background: In human epidermal growth factor receptor 2 (HER2)-positive breast cancer, emerging evidence imply that clinical behaviors differ according to hormone receptor (HR) status. However, there is no conclusion about the relevance between estrogen receptor (ER) or progesterone receptor (PR) expression and clinical outcome of HER2 + breast cancer. Our study aimed to determine the influence of different ER/PR levels on survival outcome of HER2 + early breast cancer. Patients and Methods: Nine hundred and nineteen early HER2 + breast cancer patients treated between 2009 and 2016 were retrospectively reviewed and HR + /HER2 + patients were further divided based on ER level

Abstrak. Tujuan penelitian ini adalah untuk mengindentifikasi dan menganalisis serta memberikan gambaran tentang karakteristik sifat kualitatif ayam bangkok di Kota Kendari. Penelitian ini dilaksanakan pada bulan November 2021 sampai dengan Desember 2021 betempat di Kota Kendari Sulawesi Tenggara. Bahan yang digunakan dalam penelitian ini adalah 300 ekor ayam bangkok, terdiri dari 150 ekor ayam bangkok jantan dan 150 ekor ayam bangkok betina. Umur ayam bangkok yang digunakan dalam penelitian ini adalah dengan kisaran umur 6 bulan sampai 2 tahun. Variabel yang diamati pada penelitian ini adalah sifat kualitatif yang meliputi warna bulu, bentuk jengger, dan warna shank. Hasil penelitian menunjukkan bahwa frekuensi gen pengontrol tertinggi karakterisik eksternal pada ayam bangkok di Kota Kendari adalah warna bulu berwarna (ii) (100%), pola bulu liar (e+_) (37,00%), kerlip bulu emas (ss) (66,66%) corak bulu polos (bb) (73,66%), warna shank putih (idid) (50%) dan bentuk jengger pea (P_) (94,33%).Kata Kunci : Ayam Bangkok, Sifat Kualitatif, Kota Kendari