Schlafen-11 expression is associated with immune signatures and basal-like phenotype in breast cancer In the original publication of the article, the funding information was incorrectly published. The corrected funding statement is given in this correction article.

RE.: Impact of long-term lipid-lowering therapy on clinical outcomes in breast cancer

Double heterozygous mutation in the BRCA1 and ATM genes involved in development of primary metachronous tumours: a case report Abstract Purpose Between 5 and 10% of cases of breast cancer (BC) are attributable to a genetic susceptibility. The BRCA1 and BRCA2 genes described in the late 1990s are associated with an increased risk of breast and ovarian cancer, and the clinical management of carriers of pathogenic variants in these genes is defined in several clinical guidelines (Paluch-Shimon et al. in Ann Oncol 27(suppl 5):v103–v110, 2016; Llort et al. in Clin Transl Oncol 17(12):956–961, 2015). However, the pathogenic variants in BRCA1 and BRCA2 represent only a third of the causes of hereditary BC (Easton et al. in N Engl J Med 372:2243–2257, 2015). The incorporation of NGS (Next Generation Sequencing) techniques in the genetic diagnosis of this pathology, in addition to minimising the cost and time of analysis, allows the simultaneous study of other genes of high and moderate penetrance (Easton et al. in N Engl J Med 372:2243–2257, 2015; Op. Cit.; Tung et al. in Cancer 121(1):25–33, 2015). To date, there are not many cases or series of patients that describe the co-occurrence of two pathogenic variants in these genes of BC. Cases of double heterozygosis have been described with the presence of pathogenic variants in BRCA1, BRCA2, PALB2, CHEK2, BLM or NBN (Nomizu et al. in Breast Cancer 22(5):557–61, 2015; Heidemann et al. in Breast Cancer Res Treat 134(3):1229–1239, 2012; Zuradelli et al. in Breast Cancer Res Treat 124(1):251–258, 2010; Sokolenko et al. in Breast Cancer Res Treat 145(2):553–562, 2014). Methods We report the case of a patient diagnosed with multiple tumours who presented two pathogenic variants in heterozygosis. Results Two pathogenic variants, c.5123C > A (p.Ala1708Glu) in the BRCA1 gene and c.2413C > T (p.Arg805X) in the ATM gene were detected in heterozygosis. Said variants were confirmed by Sanger-type sequencing using specific primers. Conclusions The implementation of gene panels using NGS in the study of hereditary cancer involves the detection of heterozygous double mutations in genes of high and moderate penetrance for cancer, although with a low frequency.

Low-grade screen-detected ductal carcinoma in situ progresses more slowly than high-grade lesions: evidence from an international multi-centre study Abstract Purpose Nuclear grade is an important indicator of the biological behaviour of ductal carcinoma in situ (DCIS). De-escalation of treatment has been suggested for low-grade DCIS. Our aim is to estimate the relative rate of progression of DCIS by nuclear grade by analysing the distribution of nuclear grade by detection at initial or subsequent screening. Methods We asked International Cancer Screening Network sites to complete, based on their screening and clinical databases, an aggregated data file on DCIS detection, diagnosis and treatment. Results Eleven screening programs reported 5068 screen-detected pure DCIS in nearly 7 million screening tests in women 50–69 years of age. For all programs combined, low-grade DCIS were 20.1% (range 11.4–31.8%) of graded DCIS, intermediate grade 31.0% and high grade 48.9%. Detection rates decreased more steeply from initial to subsequent screening in low compared to high-grade DCIS: the ratios of subsequent to initial detection rates were 0.39 for low grade, 0.51 for intermediate grade, and 0.75 for high grade (p < 0.001). Conclusions These results suggest that the duration of the preclinical detectable phase is longer for low than for high-grade DCIS. The findings from this large multi-centre, international study emphasize that the management of low-grade DCIS should be carefully scrutinized in order to minimize overtreatment of screen-detected slow-growing or indolent lesions. The high variation by site in the proportion of low grade suggests that further pathology standardization and training would be beneficial.

Muscle composition and outcomes in patients with breast cancer: meta-analysis and systematic review Abstract Purpose Breast cancer is the most common cancer and leading cause of cancer death in women. Body composition parameters, especially those related to muscle, have become a growing focus of cancer research. In this review, we summarize the literature on breast cancer and muscle parameters as well as combine their outcomes for overall survival (OS), time to tumor progression (TTP), and chemotherapy toxicity in a meta-analysis. Methods A systematic search of the literature for randomized controlled trials and observational studies was conducted on MEDLINE, Cochrane CENTRAL, and EMBASE through May 1, 2019. Two reviewers independently searched and selected. Meta-analysis was conducted using a random-effects model. The risk of bias was evaluated using the Newcastle–Ottawa quality assessment for cohorts and GRADE summary of findings tool from Cochrane. Results A total of 754 articles were screened from which 6 articles and one abstract were selected. Using skeletal muscle index (SMI), patients classified as sarcopenic had a 68% greater mortality risk compared to non-sarcopenic patients (HR 1.68 95% CI 1.09–2.59, 5 studies) (p = .02) (i2 = 70%). Low muscle density was not predictive of OS (HR 1.44 95% CI 0.77–2.68, 2 studies) (p = .25) (i2 = 87%). Patients with sarcopenia (56%) had more grade 3–5 toxicity compared to non-sarcopenic (25%) (RR 2.17 95% CI 1.4–3.34, 3 studies) (p = .0005) (i2 = 0%). TTP was nearly 71 days longer in advanced/metastatic patients classified as non-sarcopenic compared to patients with sarcopenia (MD − 70.75 95% CI − 122.32 to − 19.18) (p = .007) (i2 = 0%). Conclusion Our synthesis of the literature shows that patients with sarcopenia have more severe chemotherapy toxicity as well as shorter OS and TTP, and that low muscle density is prognostic of OS for women with metastatic breast cancer. Our findings suggest that in clinical practice, body composition assessment is valuable as a prognostic parameter in breast cancer.

The prognostic significance of preoperative tumor marker (CEA, CA15-3) elevation in breast cancer patients: data from the Korean Breast Cancer Society Registry Abstract Purpose Tumor markers such as carcinoembryonic antigen (CEA) and cancer antigen 15-3 (CA15-3) are widely used for monitoring breast cancer. However, the prognostic efficacy of preoperative elevations of CEA and CA15-3 levels in breast cancer patients remains controversial. Methods We retrospectively analyzed the clinicopathological parameters of 149,238 patients in the Korean Breast Cancer Society Registry Database who underwent surgery between January 2000 and December 2015. Results The patients with elevated CA15-3/CEA levels had worse overall survival (OS) than the patients with normal CA15-3/CEA levels. For the luminal A subtype, the CA15-3- and CEA-elevated group had a hazard ratio (HR) of 2.14 (95% CI 1.01–4.55). The CA15-3-elevated group had an HR of 2.38 (95% CI 1.58–3.58) and the CEA-elevated group had an HR of 1.79 (95% CI 1.20–2.68) compared to the normal group. For the luminal B subtype, the CA15-3- and CEA-elevated group had an HR of 3.99 (95% CI 2.23–7.16), whereas the CA15-3-elevated group had an HR of 2.38 (95% CI 1.58–3.58) and the CEA-elevated group had an HR of 1.79 (95% CI 1.20–2.68). For the HER2 subtype, elevated CEA level was the only independent prognostic factor. However, for the triple-negative breast cancer (TNBC) subtype, elevated preoperative CEA and CA15-3 levels were not significant prognostic factors for OS. Conclusion Preoperative CEA and CA15-3 levels showed varying prognostic ability according to breast cancer subtype. Preoperative CA15-3 and CEA elevation are significant prognostic factors for luminal breast cancer, but they were not significant factors for TNBC.

Social determinants of breast cancer risk, stage, and survival Abstract Purpose Social determinants of health that have been examined in relation to breast cancer incidence, stage at diagnosis, and survival include socioeconomic status (income, education), neighborhood disadvantage, unemployment, racial discrimination, social support, and social network. Other social determinants of health include medical distrust, immigration, status, inadequate housing, food insecurity, and geographic factors such as neighborhood access to health services. Socioeconomic factors influence risk of breast cancer. For all racial/ethnic groups, breast cancer incidence rates tend to be positively associated with socioeconomic status. On the other hand, low socioeconomic status is associated with increased risk of aggressive premenopausal breast cancers as well as late stage of diagnosis and poorer survival. There are well-documented disparities in breast cancer survival by socioeconomic status, race, education, census-tract-level poverty, and access to health insurance and preventive care. Poverty is associated with other factors related to late stage at breast cancer diagnosis and poorer survival such as inadequate health insurance, lack of a primary care physician and poor access to health care. Results The results of this review indicate that social determinants such as poverty, lack of education, neighborhood disadvantage, residential segregation by race, racial discrimination, lack of social support, and social isolation play an important role in breast cancer stage at diagnosis and survival. Conclusion To address these social determinants and eliminate cancer disparities, effective interventions are needed that account for the social and environmental contexts in which cancer patients live and are treated.

Infiltration by myeloperoxidase-positive neutrophils is an independent prognostic factor in breast cancer Abstract Purpose Myeloperoxidase (MPO) is an enzyme secreted by neutrophil granulocytes as a result of phagocytosis during inflammation. In colorectal cancer, tumour infiltration by MPO expressing cells has been shown to be independently associated with a favourable prognosis. In this study, we explored the role of MPO-positive cell infiltration and its prognostic significance in invasive breast cancer. Methods We performed immunohistochemical staining for MPO on multiple tissue microarrays comprising a total of 928 human breast cancer samples with detailed clinical-pathological annotation and outcome data. Results MPO-positive cell infiltration (≥ 5 cells/tissue punch) was found in 150 (16%) of the 928 evaluable breast cancer cases. In univariate survival analyses, infiltration by MPO-positive cells was associated with a significantly better overall survival (p < 0.001). In subset univariate analyses, the infiltration by MPO-positive cells was associated with significantly better overall survival in the Luminal B/HER2-negative subtype (p = 0.005), the HER2 enriched subtype (p = 0.011), and the Triple Negative subtype (p < 0.001). In multivariate analysis, MPO expression proved to be an independent prognostic factor for improved overall survival (p < 0.001). Conclusions This is the first study to show that infiltration of MPO-positive cells is an independent prognostic biomarker for improved overall survival in human breast cancer.

Radiofrequency identification tag localization is comparable to wire localization for non-palpable breast lesions Abstract Purpose Radiofrequency identification (RFID) tag localization (TL) is a technique of localizing non-palpable breast lesions that can be performed prior to surgery. We sought to evaluate whether TL is comparable to wire localization (WL) in regard to specimen size, operative time, and re-excision rate. Methods A retrospective cohort analysis was performed on TL and WL excisional biopsies and lumpectomies performed by 5 surgeons at 2 institutions. Cases were stratified by surgery type and surgical indication. Associations between localization technique and specimen volume, operative time, and re-excision rate were assessed by univariate and multivariate analyses. Results A total of 503 procedures were included, 147 TL (29.2%) and 356 WL (70.8%). Nineteen (12.9%) RFID tags were placed before surgery, ranging 1–22 days. All intended targets were removed. TL and WL excisional biopsy and lumpectomy specimen volumes were similar (p = 0.560 and 0.494). TL and WL excisional biopsy and lumpectomy + SLNB operative times were similar (p = 0.152 and 0.158), but TL lumpectomies without SLNB took longer than WL (57 min vs 49 min; p = 0.027). Re-excision rates were similar by surgical procedure (p = 0.615), surgical indication (DCIS p = 0.145; invasive carcinoma p = 0.759), and confirmed by multivariable analysis (OR 0.754, 95% CI 0.392–1.450; p = 0.397). Conclusions TL has similar surgical outcomes to WL with added benefit that TL can occur prior to the day of surgery. TL is an acceptable alternative to WL and should be considered for non-palpable breast lesions.

The relationship between ring-type dedicated breast PET and immune microenvironment in early breast cancer Abstract Purpose 18F-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET) is related to the biological parameters and prognosis of breast cancer. However, whether whole-body PET (WBPET) and dedicated breast PET (DbPET) can reflect the tumor microenvironment is unclear. This study investigated the relationship between stromal tumor-infiltrating lymphocytes (TILs) and maximum standardized uptake value (SUVmax) in WBPET and DbPET. Methods A total of 125 invasive breast cancers underwent WBPET and ring-type DbPET and resected specimens were pathologically assessed. The impact of SUVmax on the tumor biological parameters and TILs was retrospectively evaluated. SUVmax was classified as high and low relative to the median values (WBPET-SUVmax: 2.2 and DbPET-SUVmax: 6.0). Results SUVmax correlated with tumor size, nuclear grade, Ki-67 labeling index, and TILs in both WBPET and DbPET (all p < 0.001). In multiple linear regression analysis, tumor size, Ki-67 labeling index, and TILs predicted SUVmax in WBPET and DbPET. The cutoff values of tumor size, Ki-67 labeling index, and TILs predicting high SUVmax were 20 mm, 20%, and 20%, respectively. In multivariate analysis, the predictive factors for high SUVmax were tumor size and Ki-67 labeling index for WBPET and tumor size and TILs for DbPET. High SUVmax in DbPET was related to high numbers of TILs after propensity score matching analysis; however, WBPET was not (p = 0.007 and p = 0.624, respectively). Conclusions Both SUVmax values in WBPET and DbPET predicted TIL concentration of the primary breast cancer. In DbPET, SUVmax represented the immune microenvironment after adjusting for tumor biological factors.