Breast Cancer Research and Treatment

Oral or intravenous vinorelbine plus capecitabine in heavily pretreated HER2 negative metastatic breast cancer; similar effect or quality of life?

Correction to: Anti-tumor and anti-metastasis efficacy of E6201, a MEK1 inhibitor, in preclinical models of triple-negative breast cancer Unfortunately in the original publication of the article, the author's funding support has been mentioned incorrectly. The correct funding statement should read as "This work was supported by the Morgan Welch Inflammatory Breast Cancer Research Program, the State of Texas Rare and Aggressive Breast Cancer Research Program, MD Anderson's Cancer Center Support Grant (P30CA016672, used the Characterized Cell Line Core Facility and Flow Cytometry and Cellular Imaging Facility), and Spirita Oncology, LLC." The first affiliations was incorrect in the original article. The correct information is given below.

Classifying sarcopenia: using median value or cut-off values?

Correction to: Second International Consensus Conference on lesions of uncertain malignant potential in the breast (B3 lesions) The article Second International Consensus Conference on lesions of uncertain malignant potential in the breast (B3 lesions), written by Christoph J Rageth, Elizabeth AM O'Flynn, Katja Pinker, Rahel A Kubik-Huch, Alexander Mundinger, Thomas Decker, Christoph Tausch, Florian Dammann, Pascal A. Baltzer, Eva Maria Fallenberg, Maria P Foschini, Sophie Dellas, Michael Knauer, Caroline Malhaire, Martin Sonnenschein, Andreas Boos, Elisabeth Morris, Zsuzsanna Varga, was originally published electronically on the publisher's internet portal (currently SpringerLink) on November 30, 2018 without open access.

Impact of invasive lobular carcinoma on long-term outcomes in Mexican breast cancer patients Abstract Purpose The aim of this study was to compare the difference in disease-free survival (DFS) and overall survival (OS) between invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) in our Hispanic population with breast cancer (BC). Methods We retrospectively analyzed a database of 4533 non-metastatic BC patients treated for BC at the National Cancer Institute in Mexico (INCan) between 2006 and 2016. We compared clinical characteristics, treatment and survival between women with invasive ductal and invasive lobular BC. We evaluated differences between survival curves with the log-rank test and used Cox's proportional hazards model for the multivariate analysis. Results Median follow-up time was 42.13 months (IQ25 25.2–IQ75 72.06). The median age was 50.9 years (IQ25 43.5–IQ75 59.8). DFS at 5 years was 80.8% for IDC versus 76.2% for ILC. 5 years OS was 88.7% for IDC versus 84.3% for ILC. Multivariate analysis showed that factors that negatively affected the 5-year DFS include: clinical stage III [hazard ratio (HR) 4.2, 95% CI 3.36–5.35; p < 0.001], triple negative phenotype (HR 1.4, 95% CI 1.08–1.81; p = 0.009), Ki67 ≥ 18 (HR 1.6, 95% CI 1.28–2.11; p < 0.001), and lobular histological type (HR 1.6, 95% CI 1.09–2.49; p = 0.017). Factors associated with a negative impact on OS were: clinical stage III (HR 4.5, 95% CI 3.15–6.54; p < 0.001), triple negative phenotype (HR 2.4, 95% CI 1.69–3.48; p < 0.001), and Ki67 ≥ 18% (HR 1.9, 95% CI 1.27–2.92; p = 0.02). Conclusion Our results highlight the different biology of ILC and show that long-term prognosis in terms of DFS is not as favorable as previously reported.

miR-106b-5p and miR-17-5p could predict recurrence and progression in breast ductal carcinoma in situ based on the transforming growth factor-beta pathway Abstract Purpose Ductal carcinoma in situ (DCIS) is well-known precursor of invasive ductal carcinoma (IDC). Parts of patients show recurrence as DCIS or IDC after local treatment, but there are no established markers predicting relapse. We analyzed changes in miRNA and oncogene expression during DCIS progression/evolution to identify potential markers predicting recurrence. Methods Forty archival tissues diagnosed as primary or recurrent DCIS and DCIS adjacent to IDC were analyzed. MiRNA hierarchical clustering showed up-regulation of miR-17-5p and miR-106b-5p in recurrent DCIS and DCIS adjacent to IDC. Target genes were predicted based on pre-formed miRNA databases and PanCancer Pathway panel. MiRNAs were transfected into MCF-10A and MCF-7 cells; western blot analysis was performed with MCF-7 cell line to evaluate the effects on TGF-β downstream pathway. Results miRNA hierarchical clustering showed 17 dysregulated miRNAs, including miR-17-5p and miR-106b-5p. Based on miRNA database and nCounter Pancancer pathway analysis, TGFβRII was selected as target of miR-106b-5p and miR-17-5p. MiR-106b-5p- and miR-17-5p-transfected MCF-7 cells showed decreased expression of TGFβRII, especially in cells transfected with both miRNAs. Conclusion miR-106b-5p and miR-17-5p might have a role in breast cancer recurrence and progression by suppressing TGF-β activity, leading to early breast cancer carcinogenesis.

The influence of neoadjuvant chemotherapy on complications of immediate DIEP flap breast reconstructions Abstract Purpose The impact of neoadjuvant chemotherapy on the surgical outcomes of immediate breast reconstruction remains controversial. The aim of this study was to analyze the incidence of complications of immediate deep inferior epigastric artery perforator (DIEP) flap breast reconstructions in patients who received neoadjuvant chemotherapy compared to patients without neoadjuvant chemotherapy prior to surgery. Methods A multicenter, retrospective cohort study was conducted of all patients who underwent immediate DIEP flap breast reconstruction between January 2010 and June 2017. Patients were divided in two groups as breast reconstructions with or without neoadjuvant chemotherapy, respectively. The primary outcome was the incidence of postoperative flap re-explorations, recipient-site complications and donor-site complications. Results In total 432 immediate DIEP flap breast reconstructions in 326 patients were included. Forty-eight patients (n = 67 flaps) received neoadjuvant chemotherapy prior to immediate breast reconstruction and 278 patients (n = 365 flaps) did not. No statistically significant differences for any major (4.5% vs. 10.4%; p = 0.175) or minor (16.4% vs. 24.7%; p = 0.191) recipient-site complication were observed. Donor-site complications were recorded in 9 (18.8%) and 62 (22.2%) patients, respectively (p = 0.587). There was no difference in need for flap re-exploration between groups (3.0% vs. 8.5%; p = 0.139). Correction for potential confounding variables did not result in significant differences. Conclusions This study demonstrated similar complication rates for patients with and without neoadjuvant chemotherapy prior to immediate breast reconstruction, indicating that it is safe to perform an immediate DIEP flap breast reconstruction after neoadjuvant chemotherapy.

Prognostic role of body mass index is different according to menopausal status and tumor subtype in breast cancer patients Abstract Purpose Although controversial, obesity and underweight may have a negative impact on breast cancer outcome. However, the relationship between body mass index (BMI) and breast cancer outcomes according to tumor subtype and menopausal status remains unclear. Methods This study investigated the association between BMI and breast cancer outcome in stage I–III breast cancer patients. The relationships were further evaluated according to tumor subtype and menopausal status. Results A total of 5919 patients, 3475 (58.7%) hormone receptor (HR)(+) human epidermal growth factor receptor 2 (HER2)(–), 608 (10.3%) HR(+)HER2(+), 621 (10.5%) HR(–)HER2(+), and 1079 (18.2%) HR(–)HER2(–) were included. Underweight and obesity had a negative impact on relapse-free survival but did not affect overall survival. Importantly, the prognostic role of BMI was different according to tumor subtype and menopausal status. In HR(+)HER2(–) patients, underweight was associated with poor relapse-free survival and overall survival in pre-menopausal women. In contrast, obesity had negative impact on relapse-free survival and overall survival in HR(+)HER2(–) post-menopausal patients. Underweight may have a negative prognostic role in HR(+)HER2(+) patients. However, BMI did not impact the outcome of HR(–)HER2(+) and HR(–)HER2(–) patients. Conclusions The impact of BMI on breast cancer outcome was dependent on tumor subtype and menopausal status. In HR(+)HER2(–) patients, underweight and obesity had a negative prognostic role in pre-menopausal and post-menopausal women, respectively. These findings in Asian population should be further evaluated and compared in Western population.

Examining the cost-effectiveness of baseline left ventricular function assessment among breast cancer patients undergoing anthracycline-based therapy Abstract Background There is a lack of consensus to guide which breast cancer patients require left ventricular function assessment (LVEF) prior to anthracycline therapy; the cost-effectiveness of screening this patient population has not been previously evaluated. Methods We performed a retrospective analysis of the Yale Nuclear Cardiology Database, including 702 patients with baseline equilibrium radionuclide angiography (ERNA) scan prior to anthracycline and/or trastuzumab therapy. We sought to examine associations between abnormal baseline LVEF and potential cardiac risk factors. Additionally, we designed a Markov model to determine the incremental cost-effectiveness ratio (ICER) of ERNA screening for women aged 55 with stage I–III breast cancer from a payer perspective over a lifetime horizon. Results An abnormal LVEF was observed in 2% (n = 14) of patients. There were no significant associations on multivariate analysis performed on self-reported risk factors. Our analysis showed LVEF screening is cost-effective with ICER of $45,473 per QALY gained. For a willingness-to-pay threshold of $100,000/ QALY, LVEF screening had an 81.9% probability of being cost-effective. Under the same threshold, screening was cost-effective for non-anthracycline cardiotoxicity risk of RR ≤ 0.58, as compared to anthracycline regimens. Conclusions Age, preexisting cardiac risk factors and coronary artery disease did not predict a baseline abnormal LVEF. While the prevalence of an abnormal baseline LVEF is low in patients with breast cancer, our results suggest that cardiac screening prior to anthracycline is cost-effective.

Temporal trends and regional variation in the utilization of low-value breast cancer care: has the Choosing Wisely campaign made a difference? Abstract Purpose Since 2012, about 80 specialty societies have released Choosing Wisely (CW) recommendations aimed at reducing the use of low-value, unproven, or ineffective medical services. The extent to which these recommendations have influenced the behavior of physicians and patients remains largely unknown. Methods Using MarketScan Commercial Claims and Medicare Supplemental and Coordination of Benefits databases, we identified annual cohorts of women with incident, early-stage breast cancer and estimated the prevalence of four initial treatment and six surveillance metrics deemed as low-value breast cancer care by CW. Multivariable logistic regressions were subsequently used to estimate temporal trends and regional variation in the use of these metrics, with a special focus on the year of CW's publication. Results There were 122,341 women identified as undergoing treatment for incident breast cancer between 2010 and 2014. Two of the four low-value initial treatment metrics and four of the six low-value surveillance metrics declined significantly over time. The temporal trend of declining use, however, preceded the release of CW's guidelines. Declines ranged from 11.0% for follow-up mammography to 40.6% for receipt of surgical biopsy without an attempted needle biopsy. There were marked regional differences in use of low-value breast cancer care for all metrics, much of which persisted after publication of CW. Conclusions With two notable exceptions, use of low-value breast cancer care has declined steadily since 2010. The declines, however, were not accelerated by the publication of CW recommendations.

Alexandros Sfakianakis
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alsfakia@gmail.com