scholarly journals Risk of Synchronous Distant Recurrence at Time of Locoregional Recurrence in Patients With Stage II and III Breast Cancer (AFT-01)

2018 ◽  
Vol 36 (10) ◽  
pp. 975-980 ◽  
Author(s):  
Heather B. Neuman ◽  
Jessica R. Schumacher ◽  
Amanda B. Francescatti ◽  
Taiwo Adesoye ◽  
Stephen B. Edge ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Chest Wall ◽  
Locoregional Recurrence ◽  
Distant Metastases ◽  
Distant Recurrence ◽  
Stage Ii ◽  
Factors Associated ◽  
Increased Risk ◽  
Synchronous Metastases

Purpose National Comprehensive Cancer Network guidelines recommend systemic staging imaging at the time of locoregional breast cancer recurrence. Limited data support this recommendation. We determined the rate of synchronous distant recurrence at the time of locoregional recurrence in high-risk patients and identified clinical factors associated with an increased risk of synchronous metastases. Methods A stage-stratified random sample of 11,046 patients with stage II to III breast cancer in 2006 to 2007 was selected from the National Cancer Database for participation in a Commission on Cancer special study. From medical record abstraction of imaging and recurrence data, we identified patients who experienced locoregional recurrence within 5 years of diagnosis. Synchronous distant metastases (within 30 days of locoregional recurrence) were determined. We used multivariable logistic regression to identify factors associated with synchronous metastases. Results Four percent experienced locoregional recurrence (n = 445). Synchronous distant metastases were identified in 27% (n = 120). Initial presenting stage ( P = .03), locoregional recurrence type ( P = .01), and insurance status ( P = .03) were associated with synchronous distant metastases. The proportion of synchronous metastases was highest for women with lymph node (35%), postmastectomy chest wall (30%), and in-breast (15%) recurrence; 54% received systemic staging imaging within 30 days of a locoregional recurrence. Conclusion These findings support current recommendations for systemic imaging in the setting of locoregional recurrence, particularly for patients with lymph node or chest wall recurrences. Because most patients with isolated locoregional recurrence will be recommended locoregional treatment, early identification of distant metastases through routine systemic imaging may spare them treatments unlikely to extend their survival.

High-early recurrence rate in a cohort of young women with breast cancer in Mexico.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e12560-e12560
Author(s):  
Cynthia Villarreal-Garza ◽  
Andrea Becerril Gaitan ◽  
Bryan Vaca-Cartagena ◽  
Fernanda Mesa-Chavez ◽  
Ana Sofia Ferrigno ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Recurrence Rate ◽  
Young Women ◽  
Distant Metastases ◽  
Disease Recurrence ◽  
Early Recurrence ◽  
Multivariate Model ◽  
Stage Ii ◽  
Factors Associated ◽  
Node Involvement

e12560 Background: Young women with breast cancer (YWBC) have worse survival outcomes compared to their older counterparts. Even though a higher recurrence rate has been previously documented in this population, there is still limited information regarding the timing, prevalence and type of disease recurrence. This study aims to describe the patterns of early recurrence in Mexican YWBC. Methods: Women aged ≤40 years at diagnosis, accrued in the Joven & Fuerte prospective cohort, with stage I-III BC and having at least a 2-year follow-up were analyzed. Recurrence-free survival (RFS) and overall survival (OS) at 2 years were evaluated using the Kaplan-Meier estimate. Log-rank and Fisher’s exact tests were employed for group comparisons; the Cox regression method was used to identify factors associated with RFS and OS. Results: A total of 210 patients with a median age at diagnosis of 36 years (range: 21-40) were analyzed. Most patients were diagnosed with stage II (50%) and III (39%). Distribution according to molecular subtype was: 50% HR+/HER2-, 26% TNBC, 17% HR+/HER2+, and 7% HR-/HER2+. In total, 31 (15%) patients experienced early disease recurrence. The two BC subtypes with the highest recurrence rate were TNBC (12/54; 22%) and HR+/HER2+ (6/35; 17%), followed by HR+/HER2- (12/106; 11%) and HR-/HER2+ (1/15; 7%). Stage at diagnosis was associated with a higher risk of recurrence (stage III: 21/82 (68%); stage II: 10/94 (32%); p= 0.003). Of the total recurrences, 23% were locorregional and the remaining 77% were distant metastases. The most common sites of distant metastases were lung (46%), bone (38%) and central nervous system (33%). Notably, 50% of distant recurrences affected multiple organs. Overall, RFS at 2 years was 85.2% (95%CI 79.7-89.4). In the univariate analysis, age ( < 35 v ≥35), type of surgery (conservative v mastectomy) and BMI ( < 25 v ≥25 kg/m²) were not significantly associated with RFS. In a multivariate model, node involvement (HR = 2.76; p= 0.044), not receiving chemotherapy (HR = 3.86; p= 0.024) and TNBC (HR = 2.47; p= 0.035) were independently associated with worse RFS. The OS found in this cohort was 92.9% (95%CI 88.4-95.6). In a multivariate model, TNBC (HR = 3.71; p= 0.029) and stage III at diagnosis (HR = 5.55; p= 0.008) were associated with worse OS. Conclusions: This cohort of YWBC experienced a low RFS at 2 years. As previously reported, patients with node involvement and TNBC faced a greater risk of early recurrence. Noteworthy, a high prevalence of distant metastases was observed, with half of them involving > 1 site. Future studies are warranted to elucidate the factors associated with early recurrence in YWBC. In addition, the incorporation of new treatment strategies is urgently needed to improve disease outcomes in this group.

Multi-center randomized study of pembrolizumab/carboplatin versus carboplatin alone in patients with chest wall disease from breast cancer: TBCRC 044.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS1111-TPS1111
Author(s):  
Neelima Vidula ◽  
Rita Nanda ◽  
Kathy D. Miller ◽  
Leisha A. Emens ◽  
Paula R Pohlmann ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Disease Control ◽  
Chest Wall ◽  
Performance Status ◽  
Distant Metastases ◽  
Response To Treatment ◽  
Advanced Lung Cancer ◽  
Blood Collection ◽  
Chest Wall Recurrence ◽  
Increased Risk

TPS1111 Background: Chest wall recurrence is a subtype of breast cancer that is challenging to treat, and associated with a short duration of response to treatment and an increased risk of development of distant metastases. Given the inflammatory nature of this disease and the association of chest wall disease with lymphovascular invasion, which is correlated with higher programmed cell death 1 (PD-1) expression, we hypothesized that immunotherapy may be beneficial as treatment. Combinations of immunotherapy and chemotherapy have a synergistic effect and demonstrated efficacy in the treatment of metastatic triple negative breast cancer (TNBC). This study is evaluating the efficacy of pembrolizumab, an anti-PD-1 antibody, in combination with carboplatin, in patients with chest wall infiltration from breast cancer. This drug combination has shown efficacy in advanced lung cancer. Methods: This is a multicenter, 2:1 randomized phase II study of pembrolizumab/carboplatin (Arm A, 56 patients) vs. carboplatin (Arm B, 28 patients) in 84 patients with chest wall disease from breast cancer, with or without distant metastases. Patients may have TNBC, hormone receptor positive/HER2 negative (following receipt of 2 prior hormone therapies), or HER2 positive breast cancer (with option to continue trastuzumab on study). Pembrolizumab is administered as 200 mg IV every 3 weeks, and carboplatin as AUC 5 IV every 3 weeks. Patients on Arm A may continue pembrolizumab +/- carboplatin (Arm Ax) after completion of 6 cycles of treatment, while patients in Arm B can cross-over to pembrolizumab (+/- carboplatin) on progression (Arm Bx). Patients must have adequate organ function, performance status ≤ 2, and may have received any number of lines of prior chemotherapy. Patients undergo serial chest wall photography and imaging (CT chest, abdomen, and pelvis, and bone scan) at baseline and every 6 weeks, as well as blood collection for correlative studies and chest wall biopsies at baseline and after 2 cycles of treatment. The primary endpoint is disease control rate (RECIST 1.1) at 18 weeks of treatment, and the study is powered to determine a 20% difference in disease control rates between arms (HR 0.52, a = 0.10, ß = 0.20). An interim analysis will occur for Arm B after 18 patients are enrolled, with a stopping rule for futility. Secondary endpoints include progression-free survival, toxicity (NCI CTCAE), and response based on irRECIST and tumor programmed death ligand 1 (PD-L1) expression. Exploratory objectives include evaluating changes in soluble PD-L1, tumor and peripheral blood immune composition, circulating tumor cells and cell-free DNA, and MYC oncogene expression. This study (NCT03095352) is open at 7 sites in the Translational Breast Cancer Research Consortium (TBCRC). 52 patients are enrolled. Grant funding is provided by Merck and UCSF. Clinical trial information: NCT03095352 .

scholarly journals Improved risk estimation of locoregional recurrence, secondary contralateral tumors and distant metastases in early breast cancer: the INFLUENCE 2.0 model

2021 ◽  
Author(s):  
Vinzenz Völkel ◽  
Tom A. Hueting ◽  
Teresa Draeger ◽  
Marissa C. van Maaren ◽  
Linda de Munck ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Locoregional Recurrence ◽  
Clinical Decision Making ◽  
Metastatic Breast ◽  
Distant Metastases ◽  
Time Dependent ◽  
Individual Risk ◽  
Primary Tumors ◽  
Statistical Approaches

Abstract Purpose To extend the functionality of the existing INFLUENCE nomogram for locoregional recurrence (LRR) of breast cancer toward the prediction of secondary primary tumors (SP) and distant metastases (DM) using updated follow-up data and the best suitable statistical approaches. Methods Data on women diagnosed with non-metastatic invasive breast cancer were derived from the Netherlands Cancer Registry (n = 13,494). To provide flexible time-dependent individual risk predictions for LRR, SP, and DM, three statistical approaches were assessed; a Cox proportional hazard approach (COX), a parametric spline approach (PAR), and a random survival forest (RSF). These approaches were evaluated on their discrimination using the Area Under the Curve (AUC) statistic and on calibration using the Integrated Calibration Index (ICI). To correct for optimism, the performance measures were assessed by drawing 200 bootstrap samples. Results Age, tumor grade, pT, pN, multifocality, type of surgery, hormonal receptor status, HER2-status, and adjuvant therapy were included as predictors. While all three approaches showed adequate calibration, the RSF approach offers the best optimism-corrected 5-year AUC for LRR (0.75, 95%CI: 0.74–0.76) and SP (0.67, 95%CI: 0.65–0.68). For the prediction of DM, all three approaches showed equivalent discrimination (5-year AUC: 0.77–0.78), while COX seems to have an advantage concerning calibration (ICI < 0.01). Finally, an online calculator of INFLUENCE 2.0 was created. Conclusions INFLUENCE 2.0 is a flexible model to predict time-dependent individual risks of LRR, SP and DM at a 5-year scale; it can support clinical decision-making regarding personalized follow-up strategies for curatively treated non-metastatic breast cancer patients.

scholarly journals An Exploration of Heart Failure Risk in Breast Cancer Patients Receiving Anthracyclines with or without Trastuzumab in Thailand: A Retrospective Study

2021 ◽  
Vol 11 (3) ◽  
pp. 484-493
Author(s):  
Jukapun Yoodee ◽  
Aumkhae Sookprasert ◽  
Phitjira Sanguanboonyaphong ◽  
Suthan Chanthawong ◽  
Manit Seateaw ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Cancer Patients ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Breast Cancer Patients ◽  
Ventricular Ejection Fraction ◽  
Factors Associated ◽  
Palliative Intent ◽  
Increased Risk

Anthracycline-based regimens with or without anti-human epidermal growth factor receptor (HER) 2 agents such as trastuzumab are effective in breast cancer treatment. Nevertheless, heart failure (HF) has become a significant side effect of these regimens. This study aimed to investigate the incidence and factors associated with HF in breast cancer patients treated with anthracyclines with or without trastuzumab. A retrospective cohort study was performed in patients with breast cancer who were treated with anthracyclines with or without trastuzumab between 1 January 2014 and 31 December 2018. The primary outcome was the incidence of HF. The secondary outcome was the risk factors associated with HF by using the univariable and multivariable cox-proportional hazard model. A total of 475 breast cancer patients were enrolled with a median follow-up time of 2.88 years (interquartile range (IQR), 1.59–3.93). The incidence of HF was 3.2%, corresponding to an incidence rate of 11.1 per 1000 person-years. The increased risk of HF was seen in patients receiving a combination of anthracycline and trastuzumab therapy, patients treated with radiotherapy or palliative-intent chemotherapy, and baseline left ventricular ejection fraction <65%, respectively. There were no statistically significant differences in other risk factors for HF, such as age, cardiovascular comorbidities, and cumulative doxorubicin dose. In conclusion, the incidence of HF was consistently high in patients receiving combination anthracyclines trastuzumab regimens. A reduced baseline left ventricular ejection fraction, radiotherapy, and palliative-intent chemotherapy were associated with an increased risk of HF. Intensive cardiac monitoring in breast cancer patients with an increased risk of HF should be advised to prevent undesired cardiac outcomes.

scholarly journals Regulatory T lymphocyte infiltration in metastatic breast cancer—an independent prognostic factor that changes with tumor progression

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Jenny Stenström ◽  
Ingrid Hedenfalk ◽  
Catharina Hagerling
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Lymph Node ◽  
Prognostic Factor ◽  
T Lymphocytes ◽  
T Lymphocyte ◽  
Metastatic Breast ◽  
Distant Metastases ◽  
Independent Prognostic Factor ◽  
Primary Tumors

Abstract Background Patients diagnosed with metastatic breast cancer have poor outcome with a median survival of approximately 2 years. While novel therapeutic options are urgently needed, the great majority of breast cancer research has focused on the primary tumor and less is known about metastatic breast cancer and the prognostic impact of the metastatic tumor microenvironment. Here we investigate the immune landscape in unique clinical material. We explore how the immune landscape changes with metastatic progression and elucidate the prognostic role of immune cells infiltrating primary tumors and corresponding lymph node and more importantly distant metastases. Methods Immunohistochemical staining was performed on human breast cancer tissue microarrays from primary tumors (n = 231), lymph node metastases (n = 129), and distant metastases (n = 43). Infiltration levels of T lymphocytes (CD3+), regulatory T lymphocytes (Tregs, FOXP3+), macrophages (CD68+), and neutrophils (NE+) were assessed in primary tumors. T lymphocytes and Tregs were further investigated in lymph node and distant metastases. Results T lymphocyte and Treg infiltration were the most clinically important immune cell populations in primary tumors. Infiltration of T lymphocytes and Tregs in primary tumors correlated with proliferation (P = 0.007, P = 0.000) and estrogen receptor negativity (P = 0.046, P = 0.026). While both T lymphocyte and Treg infiltration had a negative correlation to luminal A subtype (P = 0.031, P = 0.000), only Treg infiltration correlated to luminal B (P = 0.034) and triple-negative subtype (P = 0.019). In primary tumors, infiltration of T lymphocytes was an independent prognostic factor for recurrence-free survival (HR = 1.77, CI = 1.01–3.13, P = 0.048), while Treg infiltration was an independent prognostic factor for breast cancer-specific survival (HR = 1.72, CI = 1.14–2.59, P = 0.01). Moreover, breast cancer patients with Treg infiltration in their distant metastases had poor post-recurrence survival (P = 0.039). Treg infiltration levels changed with metastatic tumor progression in 50% of the patients, but there was no significant trend toward neither lower nor higher infiltration. Conclusion Treg infiltration could have clinical applicability as a prognostic biomarker, deciphering metastatic breast cancer patients with worse prognosis, and accordingly, could be a suitable immunotherapeutic target for patients with metastatic breast cancer. Importantly, half of the patients had changes in Treg infiltration during the course of metastatic progression emphasizing the need to characterize the metastatic immune landscape.

scholarly journals Snord67 promotes lymph node metastasis and regulates U6-mediated alternative splicing in breast cancer

2020 ◽  
Author(s):  
Yvonne L. Chao ◽  
Yinzhou Zhu ◽  
Hannah J. Wiedner ◽  
Yi-Hsuan Tsai ◽  
Lily Wilkinson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Alternative Splicing ◽  
Subsequent Development ◽  
Distant Metastases ◽  
Housekeeping Genes ◽  
Small Nuclear Rna ◽  
Alternatively Spliced ◽  
Rapid Autopsy ◽  
Splicing Patterns

AbstractSmall nucleolar RNAs (snoRNAs) have long been considered “housekeeping genes”, important for ribosomal biogenesis and protein synthesis. However, there is increasing evidence that this largely ignored class of non-coding RNAs (ncRNAs) also have wide-ranging, non-canonical functions in diseases, including cancer. SnoRNAs have been shown to have both oncogenic and tumor suppressor roles, yet whether snoRNAs regulate metastasis is unknown. Here we show that expression of certain snoRNAs are enriched in lymph node (LN) metastases in a micro-surgical, immune-competent mouse model of breast cancer. We identify the snoRNA Snord67 as a key regulator of LN metastasis. Knockout of Snord67 resulted in significantly decreased LN tumor growth and subsequent development of distant metastases. This was associated with loss of targeted 2’-O-methylation on the small nuclear RNA U6, a component of the spliceosome. RNA sequencing revealed distinct alternative splicing patterns in Snord67 knockout cells. Using rapid autopsy breast cancer cases, we found that matched human primary tumor and LN metastases revealed similar alternatively spliced genes, including several that are known to contribute to cancer. These results demonstrate that Snord67 is critical for growth of LN metastases and subsequent spread to distant metastases, and suggest that snoRNA-guided modifications of the spliceosome represent a previously unappreciated, yet targetable pathway in cancer.

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