Risk stratification in earl- stage luminal breast cancer patients treated with and without RT.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 568-568 ◽  
Author(s):  
Charlotta Wadsten ◽  
Pat W. Whitworth ◽  
Rakesh Patel ◽  
Jess Savala ◽  
Fredrik Warnberg ◽  
...  

568 Background: The goal was to develop and validate a biologic signature for 10-year ipsilateral invasive breast event (IBE) risk in luminal Stage 1 breast cancer (BC) patients treated surgically and either with or without radiation therapy (RT). Methods: This cohort was from Uppsala University and Västerås Hospitals diagnosed with Stage 1 BC and treated surgically between 1987 and 2004. Treatment was neither randomized nor strictly rules based, including adjuvant RT, Hormone Therapy (HT), and Chemotherapy (CT). Biomarkers (HER2, PR, Ki67, COX2, p16/INK4A, FOXA1 and SIAH2) were assessed on tissue microarrays in PreludeDx’s CLIA lab by board-certified pathologists. Risk groups were calculated using biomarkers and clinical factors age and size. A multivariate Cox proportional hazards analysis was used to determine hazard ratio for biologic signature. 10-year IBE risk was assessed using Kaplan-Meier survival analysis. Results: There were 423 luminal cases with biomarker data having 54 IBEs, and a median follow-up of 11.8 years. There were 372 patients treated with BCS and 51 with Mastectomy, and 325 received RT, 169 received HT, and 47 received CT. In a multivariate analysis, the biologic signature (HR = 1.6, p = 0.019) and RT (HR = 0.51, p = 0.027) were associated with IBE risk adjusting for other treatments (HT and CT) and Luminal A status (p = 0.37). For patients over 50 yrs of age with luminal A disease and treated without CT (n = 205), an elevated biologic signature identified a subset of patients with a 15% (+/- 14%) 10-year IBE risk without RT (n = 38) compared to a 4% (+/-6%) IBE risk with RT (n = 72), while patients with a low biologic signature had a 10-year IBE risk of 4% (+/- 4%) without RT (n = 26) and 3% (+/-5%) IBE risk with RT (n = 69). Conclusions: With further prospective validation, the biologic signature identified herein may provide a tool enabling improved management for women diagnosed with early luminal BC.

2021 ◽  
Vol 11 ◽  
Author(s):  
Ting-Hao Chen ◽  
Jun-Ru Wei ◽  
Jason Lei ◽  
Jian-Ying Chiu ◽  
Kuan-Hui Shih

BackgroundSeveral prognostic factors affect the recurrence of breast cancer in patients who undergo mastectomy. Assays of the expression profiles of multiple genes increase the probability of overexpression of certain genes and thus can potentially characterize the risk of metastasis.MethodsWe propose a 20-gene classifier for predicting patients with high/low risk of recurrence within 5 years. Gene expression levels from a quantitative PCR assay were used to screen 473 luminal breast cancer patients treated at Taiwan Hospital (positive for estrogen and progesterone receptors, negative for human epidermal growth factor receptor 2). Gene expression scores, along with clinical information (age, tumor stage, and nodal stage), were evaluated for risk prediction. The classifier could correctly predict patients with and without relapse (logistic regression, P<0.05).ResultsA Cox proportional hazards regression analysis showed that the 20-gene panel was prognostic with hazard ratios of 5.63 (95% confidence interval 2.77-11.5, univariate) and 5.56 (2.62-11.8, multivariate) for the “genetic” model, and of 8.02 (3.52-18.3, univariate) and 19.8 (5.96-65.87, multivariate) for the “clinicogenetic” model during a 5-year follow-up.ConclusionsThe proposed 20-gene classifier can successfully separate the patients into two risk groups, and the two risk group had significantly different relapse rate and prognosis. This 20-gene classifier can provide better estimation of prognosis, which can help physicians to make better personalized treatment plans.


2015 ◽  
Vol 25 (4) ◽  
pp. 751-757 ◽  
Author(s):  
Hitoshi Hareyama ◽  
Kenichi Hada ◽  
Kumiko Goto ◽  
Sawako Watanabe ◽  
Minako Hakoyama ◽  
...  

ObjectiveLower extremity lymphedema (LEL) is a major long-term complication of radical surgery. We aimed to estimate the incidence and grading of LEL in women who underwent lymphadenectomy and to evaluate risk factors associated with LEL.Materials and MethodsWe retrospectively reviewed 358 patients with cervical, endometrial, and ovarian cancer who underwent transabdominal complete systematic pelvic and para-aortic lymphadenectomy between 1997 and 2011. Lower extremity lymphedema was graded according to criteria of the International Society of Lymphology. Incidence of LEL and its correlation with various clinical characteristics were investigated using Kaplan-Meier survival and Cox proportional hazards methods.ResultsOverall incidence of LEL was 21.8% (stage 1, 60%; stage 2, 32%; and stage 3, 8%). Cumulative incidence increased with observation period: 12.9% at 1 year, 20.3% at 5 years, and 25.4% at 10 years. Age, cancer type, stage (International Federation of Gynecology and Obstetrics), body mass index, hysterectomy type, lymphocyst formation, lymph node metastasis, and chemotherapy were not associated with LEL. Multivariate analysis confirmed that removal of circumflex iliac lymph nodes (hazard ratio [HR], 4.28; 95% confidence interval [CI], 2.09–8.77; P < 0.0001), cellulitis (HR, 3.48; 95% CI, 2.03–5.98; P < 0.0001), and number of removed lymph nodes (HR, 0.99; 95% CI, 0.98–0.99; P = 0.038) were independent risk factors for LEL.ConclusionsPostoperative LEL incidence increased over time. The results of the present study showed a significant correlation with removal of circumflex iliac lymph nodes and cellulitis with the incidence of LEL. Multicenter or prospective studies are required to clarify treatment efficacies.


2020 ◽  
Vol 14 (16) ◽  
pp. 1537-1552
Author(s):  
Flavia R Mangone ◽  
Maira AV Valoyes ◽  
Renan G do Nascimento ◽  
Mércia PF Conceição ◽  
Daniel R Bastos ◽  
...  

Aim: The PHLDA (pleckstrin homology like domain, family A) gene family encodes proteins capable of inhibiting AKT (serine/threonine kinase) signaling through phosphoinositol binding competition. Results & methodology: Using in silico analysis, we found that Luminal A and B patients' short relapse-free survival was associated with low PHLDA1 or PHLDA3 and high PHLDA2 expression. In a cohort of 393 patients with luminal breast cancer evaluated by immunohistochemistry on tissue microarrays, we found a direct association of PHLDA3 expression with hormonal therapy response (p = 0.013). Conclusion: Our findings provide new information on the role played by the PHLDA family members as prognostic markers in breast cancer, and more importantly, we provide evidence that they might also predict a response to endocrine therapy.


2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Ying Liu ◽  
Xiaoli Chen ◽  
Xi Chen ◽  
Xiaobing Yang ◽  
Qingjie Song ◽  
...  

Objective. The synaptic adhesion-like molecule (SALM) family is largely restricted to neural tissues and is involved in the regulation of neurite outgrowth and synapse formation. However, the expression of SALM3 in gastric cancer (GC) and its clinical significance remain unclear. The aim of the present study was to investigate the prognostic value of SALM3 in patients with GC.Patients and Methods. Expression of SALM3 was validated by tissue microarrays from 730 GC patients and statistically assessed for correlations with the clinical parameters and the prognosis of the patients. The transcriptional and survival data of SALM3 in GC patients were also mined through the Oncomine and Kaplan-Meier Plotter databases.Results. SALM3 is overexpressed in the tumor cells and fibroblasts of clinical GC tissues, and a high level of SALM3 was significantly associated with tumor invasive characteristics. Cox proportional hazards univariate and multivariate regression analyses revealed SALM3 expression in tumor cells or stroma as an independent prognostic factor in the overall survival rate of GC patients. Furthermore, the survival of GC patients with high SALM3 expression in both tumor cells and fibroblasts was significantly poorer than that of the other groups. Oncomine and Kaplan-Meier Plotter analyses further confirmed high levels of SALM3 expression in GC, and high levels of SALM3 expression were associated with shorter survival in patients.Conclusion. SALM3 may be a prognostic factor for GC and may potentially be a high-priority therapeutic target.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 560-560 ◽  
Author(s):  
D. A. Patt ◽  
Z. Duan ◽  
G. Hortobagyi ◽  
S. H. Giordano

560 Background: Adjuvant chemotherapy for breast cancer is associated with the development of secondary AML, but this risk in an older population has not been previously quantified. Methods: We queried data from the Surveillance, Epidemiology, and End Results-Medicare (SEER-Medicare) database for women who were diagnosed with nonmetastatic breast cancer from 1992–1999. We compared the risk of AML in patients with and without adjuvant chemotherapy (C), and by differing C regimens. The primary endpoint was a claim with an inpatient or outpatient diagnosis of AML (ICD-09 codes 205–208). Risk of AML was estimated using the method of Kaplan-Meier. Cox proportional hazards models were used to determine factors independently associated with AML. Results: 36,904 patients were included in this observational study, 4,572 who had received adjuvant C and 32,332 who had not. The median patient age was 75.3 (66.0–103.3). The median follow up was 63 months (13–132). Patients who received C were significantly younger, had more advanced stage disease, and had lower comorbidity scores (p<0.001). The unadjusted risk of developing AML at 10 years after any adjuvant C for breast cancer was 1.6% versus 1.1% for women who had not received C. The adjusted HR for AML with adjuvant C was 1.72 (1.16–2.54) compared to women who did not receive C. HR for radiation was 1.21 (0.86–1.70). HR was higher with increasing age but p>0.05. An analysis was performed among women who received C. When compared to other C regimens, anthracycline-based therapy (A) conveyed a significantly higher hazard for AML HR 2.17 (1.08–4.38), while patients who received A plus taxanes (T) did not have a significant increase in risk HR1.29 (0.44–3.82) nor did patients who received T with some other C HR 1.50 (0.34–6.67). Another significant independent predictor of AML included GCSF use HR 2.21 (1.14–4.25). In addition, increasing A dose was associated with higher risk of AML (p<0.05). Conclusions: There is a small but real increase in AML after adjuvant chemotherapy for breast cancer in older women. The risk appears to be highest from A-based regimens, most of which also contained cyclophosphamide, and may be dose-dependent. T do not appear to increase risk. The role of GCSF should be further explored. No significant financial relationships to disclose.


2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 262-262
Author(s):  
S. Takayama ◽  
J. Matsui ◽  
N. Ando

262 Background: Consensus recommendations for breast cancer are come into wide use, and we believe clinical guidelines leads our patients to improved outcome. Recently, gene profiling can be available, and immunohistochemical surrogates for molecular subtyping can provide much of prognostic and predictive factors. We investigated the relationship between compliance with consensus recommendations and clinical outcome of each subtype on the hypothesis that conformity with consensus recommendations is associated with increased survival among all intrinsic subtypes. Methods: We investigated breast cancer patients operated in our hospital from 2002 to 2004. DCIS, Stage 4 and male breast cancer were excluded. Patients were divided into luminal A (ER+ and/or PgR+, HER2-, low nuclear grade (NG)), luminal B (ER+ and/or PgR+, HER2-, high NG), luminal-HER2 (ER+ and/or PgR+, HER2+), HER2 (ER-, PgR-, HER2+) and triple negative (TN), (ER-, PgR-, HER2-). All patients were divided into compliance group or non-compliance group according to their conformity with consensus recommendations. Kaplan-Meier analysis was used in statistical studies. Results: 121 breast cancer patients were eligible and investigated in this study. Median follow-up period was 6.7 years. Fifteen relapse cases (12.4%) were identified. Among luminal A patients, compliance group was significantly associated with better recurrence free survival compared with non-compliance group with Kaplan-Meier analysis (p<0.001). In contrast, there was no difference between compliance group and non-compliance group among the other subtypes. Median time to recurrence (4.2 year) in non-compliance group among luminal A was apparently longer than that (1.7 year) in compliance group among the other subtypes. Conclusions: Compliance group was significantly associated with better clinical outcome compared with non-compliance group among luminal A. This study suggests that cautious follow-up is required against non-compliance patients among luminal A, because time to recurrence of them was longer than that of both compliance and non-compliance subgroups among the other subtypes.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 11522-11522
Author(s):  
Mark Wroblewski ◽  
Janna-Lisa Velthaus ◽  
Raimund Bauer ◽  
Volkmar Müller ◽  
Christian Schem ◽  
...  

11522 Background: Resistance towards anti-angiogenic therapy (AAT) still represents a substantial clinical challenge. As mast cell (MC) density is known to correlate with tumor angiogenesis, we analyzed if inhibition of MC holds potential to increase efficacy of AAT in mice and cancer patients. Methods: C57BL/6J (WT), NSG or MC-deficient KitW-sh(Wsh) mice were subcutaneously injected with Panc02, EL4 or BxPC3 cells with or without bone marrow-derived MC. Tumors were treated with 20 mg/kg of anti-VEGFR2 antibodies (DC101) or 25 mg/kg cromoglicic acid. Tissue microarrays from n = 299 breast cancer patients from the GeparQuinto Phase 3 clinical trial were stained for MC and MC numbers were correlated with clinical data. Results: We observed that absence of MC reduced tumor growth and increased the efficacy of AAT in different tumor models. Intriguingly, AAT only initially reduced microvessel proliferation but this was abrogated over time as a result of MC-mediated resistance. We show that MC secrete increased amounts of granzyme b upon therapy, which mobilizes alternative pro-angiogenic factors from the tumor matrix. These factors act beside the targeted VEGFA-VEGFR2-axis and reinduce angiogenesis despite the presence of AAT. Importantly, MC-mediated resistance could be overcome using the FDA-approved MC inhibitor cromoglicic acid. In line with our preclinical data, high intratumoral MC density correlated with disease progression in HR+ breast cancer patients when Bevacizumab was added to standard neodjuvant chemotherapy (HR 8.45, p = 0.006). Accordingly, Kaplan-Meier curves indicated that disease free survival of patients with high tumoral MC density was numerically shorter in the whole cohort and significantly shorter in the HR+ cohort upon addition of AAT to chemotherapy (p = 0.168 and p = 0.004, respectively). Conclusions: Here we unravel a novel resistance mechanism, by which MC hamper efficacy of AAT in mice and cancer patients. In preclinical models this effect could be overcome by combining AAT with an FDA-approved MC inhibitor indicating high clinical relevance. Thus, combination of FDA-approved MC inhibitors with AAT might be a suitable approach to increase efficacy of AAT in the clinic.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 555-555
Author(s):  
Dennis Sgroi ◽  
Yi Zhang ◽  
Catherine A. Schnabel

555 Background: Identification of N+ breast cancer patients with a limited risk of recurrence improves selection of those for which chemotherapy and/or extended endocrine therapy (EET) may be most appropriate to reduce overtreatment. BCIN+ integrates gene expression with tumor size and grade, and is highly prognostic for overall (0-10yr) and late (5-10yr) distant recurrence (DR) in N1 patients. Clinical Treatment Score post-5-years (CTS5) is a prognostic model based on clinicopathological factors (nodes, age, tumor size and grade) and significantly prognostic for late DR. The current analysis compares BCIN+ and CTS5 for risk of late DR in N1 patients. Methods: 349 women with HR+, N1 disease and recurrence-free for ≥5 years were included. BCIN+ results were determined blinded to clinical outcome. CTS5 was calculated as previously described (Dowsett et al, JCO 2018; 36:1941). Kaplan-Meier analysis and Cox proportional hazards regression for late DR (5-15y) were evaluated. Results: 64% of patients were > 50 years old, 34% with tumors > 2cm, 79% received adjuvant chemotherapy and 64% received up to 5 years of ET. BCIN+ stratified 23% of patients as low-risk with 1.3% risk for late DR vs those classified as high-risk with 16.1% [HR 12.4 (1.7-90.4), p = 0.0014]. CTS5 classified patients into 3 risk groups: 29% of patients as low-risk (4.2% DR), 37% as intermediate-risk (10.6% DR), and 34% as high-risk (22.1% DR) [HR intermediate vs. low: 2.3 (0.7-7.0), p = 0.16; high vs. low: 5.3 (1.8-15.5), p = 0.002]. In a subset of patients who completed 5 years of ET (N = 223), BCIN+ identified 22% of patients as low-risk with a late DR rate of 2.1%, while CTS5 identified 29% and 37% of patients as low- and intermediate-risk with late DR rates of 5.2% and 10.3%, respectively. Conclusions: BCIN+ classified N1 patients into binary risk groups and identified 20% patients with limited risk of late DR ( < 2%) that may be advised to forego EET and its attendant toxicities/side effects. In comparison, CTS5 classified patients into 3 risk groups, with low- and intermediate-risk of late DR of 4-5% and 10%, wherein the risk-benefit profile for extension of endocrine therapy is less clear.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e18155-e18155 ◽  
Author(s):  
Drew Carl Drennan Murray ◽  
Shruti Bhandari ◽  
Phuong Ngo ◽  
Sarah Mudra ◽  
Rachana Shirish Lele ◽  
...  

e18155 Background: Black (B) women after early stage of diagnosis have been shown to have double the risk of white (W) women for failing to receive adjuvant chemotherapy. Despite lower incidence of breast cancer in B patients, they are more likely to die of the disease. Worse outcomes in B populations have been related to clinical and socioeconomic factors. However, the determination of improved access and its effects on survival in black patients remains uncertain. Methods: 1042844 patients diagnosed between 2004 and 2014 with stage I-III breast cancer were identified in the NCDB. Only W and B races were analyzed with established risk factors of age, stage, comorbidity score, and insurance status. Data was analyzed using univariable and multivariable logistic and Cox proportional hazards regression models. Odds Ratio (OR) for binary outcome, Hazard Ratio (HR) for time-to-event (survival) outcome along with 95% confidence interval (95% CI) are reported. Results: Among the total population 85.5% were W, 10.6% B, and 3.9% other. B were more likely to be uninsured (OR: 1.66; 95% CI: 1.59 - 1.72; p < 0.0001), or have Medicaid (OR: 2.01; 95% CI: 1.96 - 2.07; p < 0.0001). B were also diagnosed at later stage (stage 3 OR: 1.59; 95% CI: 1.57 - 1.63; p < 0.0001) with higher co-morbidities (OR: 2.49; 95% CI: 2.34 - 2.67; p < 0.0001) consistent with prior studies. B were more likely to experience delayed treatment (OR: 2.15; 95% CI: 2.10 - 2.20; p < 0.0001). B race remained an independent factor associated with higher likelihood of death compared to W patients (HR: 1.32; 95% CI: 1.3 - 1.34; p < 0.0001) in multivariable analysis. Conclusions: This large database study demonstrates that even when controlling for established risk factors such lack of insurance or Medicaid, higher comorbidities, and later stage at diagnosis, B patients were more likely to experience delays in treatment initiation and worse overall survival. This suggests race remains an independent risk factor for poor outcome even when clinical factors are matched. Further analysis including tumor biology should be examined to better understand this persistent disparity.


2005 ◽  
Vol 23 (34) ◽  
pp. 8597-8605 ◽  
Author(s):  
John J. Doyle ◽  
Alfred I. Neugut ◽  
Judith S. Jacobson ◽  
Victor R. Grann ◽  
Dawn L. Hershman

Purpose Adjuvant chemotherapy, especially with anthracyclines, is known to cause acute and chronic cardiotoxicity in breast cancer patients. We studied the cardiac effects of chemotherapy in a population-based sample of breast cancer patients aged ≥ 65 years with long-term follow-up. Patients and Methods In the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, we analyzed treatments and outcomes among women ≥ 65 years of age who were diagnosed with stage I to III breast cancer from January 1, 1992 to December 31, 1999. Propensity scores were used to control for baseline heart disease (HD) and other known predictors of chemotherapy, and Cox proportional hazards models were used to estimate the risk of cardiomyopathy (CM), congestive heart failure (CHF), and HD after chemotherapy. Results Of 31,748 women with stage I to III breast cancer, 5,575 (18%) received chemotherapy. Chemotherapy was associated with younger age, fewer comorbidities, hormone receptor negativity, multiple primary tumors, and advanced disease. Patients who received chemotherapy were less likely than other patients to have pre-existing HD (45% v 55%, respectively; P < .001). The hazard ratios for CM, CHF, and HD for patients treated with doxorubicin (DOX) compared with patients who received no chemotherapy were 2.48 (95% CI, 2.10 to 2.93), 1.38 (95% CI, 1.25 to 1.52), and 1.35 (95% CI, 1.26 to 1.44), respectively. The relative risk of cardiotoxicity among patients who received DOX compared with untreated patients remained elevated 5 years after diagnosis. Conclusion When baseline HD was taken into account, chemotherapy, especially with anthracyclines, was associated with a substantially increased risk of CM. As the number of long-term survivors grows, identifying and minimizing the late effects of treatment will become increasingly important.


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