Prediction of Late Recurrence and Distant Metastasis in Early-stage Breast Cancer: Overview of Current and Emerging Biomarkers

2020 ◽  
Vol 21 (10) ◽  
pp. 1008-1025
Author(s):  
A. Gouri ◽  
B. Benarba ◽  
A. Dekaken ◽  
H. Aoures ◽  
S. Benharkat

Recently, a significant number of breast cancer (BC) patients have been diagnosed at an early stage. It is therefore critical to accurately predict the risk of recurrence and distant metastasis for better management of BC in this setting. Clinicopathologic patterns, particularly lymph node status, tumor size, and hormonal receptor status are routinely used to identify women at increased risk of recurrence. However, these factors have limitations regarding their predictive ability for late metastasis risk in patients with early BC. Emerging molecular signatures using gene expression-based approaches have improved the prognostic and predictive accuracy for this indication. However, the use of their based-scores for risk assessment has provided contradictory findings. Therefore, developing and using newly emerged alternative predictive and prognostic biomarkers for identifying patients at high- and low-risk is of great importance. The present review discusses some serum biomarkers and multigene profiling scores for predicting late recurrence and distant metastasis in early-stage BC based on recently published studies and clinical trials.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 594-594
Author(s):  
Yi Zhang ◽  
Catherine A. Schnabel ◽  
Brock Schroeder ◽  
Piiha-Lotta Jerevall ◽  
Rachel Catherine Jankowitz ◽  
...  

594 Background: Breast Cancer Index (BCI) is a continuous risk index based on the combination of HOXB13:IL17BR (H:I) and the Molecular Grade Index (MGI) that estimates the individual risk of recurrence in ER+, LN- breast cancer patients. In the current study, a modified BCI model was developed using untreated breast cancer patients in order to evaluate its pure prognostic value, and to better optimize BCI for both early and late risk assessment. Methods: A model was built by linearly combining H:I and MGI weighted by their corresponding Cox regression coefficients using ER+ LN- patients from the untreated arm of the prospective Stockholm trial (N=283). Validation was performed in 2 independent ER+, LN- cohorts: the TAM arm of the Stockholm trial (N=317), and a multisite cohort of TAM-treated patients (N=358). Correlation of BCI with distant metastasis was evaluated by Kaplan-Meier analysis using the log rank test, and multivariate analysis adjusting for standard prognostic factors was performed using Cox proportional hazards. Results: The BCI linear model was significantly associated with risk of cumulative (0-10y), early (<5y) and late (≥5y) distant metastasis. Based on pre-specified cutpoints, BCI classified 64% and 55% patients as low-, 21% and 22% as intermediate-, and 16% and 23% as high-risk, with 10-y rates of distant recurrence (95% CI) of 4.8% (1.7-7.8%) and 6.6% (2.9–10.0%), 11.7% (3.1–19.5%) and 23.3% (12.3-33.0%), 21.1% (18.5–32.0%) and 35.8% (24.5–45.5%), in the Stockholm TAM and multisite cohort, respectively. Conclusions: BCI demonstrated significant prognostic performance beyond clinicopathological factors to predict cumulative, early and late risk of recurrence in early stage breast cancer patients. Use of BCI at diagnosis should enable clinicians to identify patients who are at high risk of late recurrence and may benefit from an additional 5y of hormonal therapy. [Table: see text]


2011 ◽  
Vol 29 (32) ◽  
pp. 4266-4272 ◽  
Author(s):  
Alistair Ring ◽  
Ivana Sestak ◽  
Michael Baum ◽  
Anthony Howell ◽  
Aman Buzdar ◽  
...  

Purpose The Arimidex, Tamoxifen Alone or in Combination (ATAC) study was a double-blind randomized trial in which postmenopausal women with early-stage breast cancer were assigned to receive anastrozole, tamoxifen, or the combination. We have conducted a retrospective analysis to examine the effects of comorbidities and age on treatment received, breast cancer–related mortality, and competing causes of mortality. Patients and Methods The current analyses were based on 10-year median follow-up data in the two monotherapy arms (anastrozole, n = 3,092; tamoxifen, n = 3,094) of the ATAC study. Baseline comorbidities and tumor and treatment characteristics were compared between women age less than 70 years and women age ≥ 70 years. The cumulative incidence of breast cancer–related and non–breast cancer–related mortality was assessed according to age and comorbidities. Results One thousand six hundred sixty-two patients (27%) were age ≥ 70 years at study entry. Older women were more likely to undergo mastectomy (odds ratio [OR], 1.92; 95% CI, 1.71 to 2.16) and less likely to receive radiotherapy (OR, 0.49; 95% CI, 0.44 to 0.55) or chemotherapy (OR, 0.24; 95% CI, 0.18 to 0.29). Women age ≥ 70 years had an increased risk of recurrence compared with women age less than 70 years (hazard ratio [HR], 1.21; 95% CI, 1.08 to 1.37) and a substantially increased risk of death without recurrence (HR, 4.13; 95% CI, 3.53 to 4.83). The risk of death without recurrence increased with comorbidity score (10-year estimates of 8.4%, 20.0%, and 30.4% for Satariano score 0, 1, and 2+, respectively; P < .001). Conclusion Age influences the risk of recurrence, and age and comorbidities significantly influence the risk of death without recurrence. Formal assessment of comorbidities should be incorporated into decisions regarding adjuvant therapies.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Jose G. Bazan ◽  
Sachin R. Jhawar ◽  
Daniel Stover ◽  
Ko Un Park ◽  
Sasha Beyer ◽  
...  

AbstractIn the modern era, highly effective anti-HER2 therapy is associated with low local-regional recurrence (LRR) rates for early-stage HER2+ breast cancer raising the question of whether local therapy de-escalation by radiation omission is possible in patients with small-node negative tumors treated with lumpectomy. To evaluate existing data on radiation omission, we used the National Cancer Database (NCDB) to test the hypothesis that RT omission results in equivalent overall survival (OS) in stage 1 (T1N0) HER2+ breast cancer. We excluded patients that received neoadjuvant systemic therapy. We stratified the cohort by receipt of adjuvant radiation. We identified 6897 patients (6388 RT; 509 no RT). Patients that did not receive radiation tended to be ≥70 years-old (odds ratio [OR] = 3.69, 95% CI: 3.02–4.51, p < 0.0001), to have ≥1 comorbidity (OR = 1.33, 95% CI: 1.06–1.68, p = 0.0154), to be Hispanic (OR = 1.49, 95% CI: 1.00–2.22, p = 0.049), and to live in lower income areas (OR = 1.32, 95% CI: 1.07–1.64, p = 0.0266). Radiation omission was associated with a 3.67-fold (95% CI: 2.23–6.02, p < 0.0001) increased risk of death. While other selection biases that influence radiation omission likely persist, these data should give caution to radiation omission in T1N0 HER2+ breast cancer.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10549-10549
Author(s):  
Jennifer A. Ligibel ◽  
Lori J. Pierce ◽  
Catherine M. Bender ◽  
Tracy E Crane ◽  
Christina Marie Dieli-Conwright ◽  
...  

10549 Background: Obesity and related factors are increasingly associated with increased risk of developing and dying from cancer. The American Society of Clinical Oncology (ASCO) conducted a survey of cancer patients to assess their experience in receiving recommendations and referrals related to weight, diet and exercise as a part of their cancer care. Methods: An online survey was distributed to potential participants between March and June 2020 via ASCO channels and patient advocacy organizations, with an estimated reach of over 25,000 individuals. Eligibility criteria included being 18 years, living in the US, and having been diagnosed with cancer. Logistic regression was used to determine factors associated with recommendation and referral patterns. Results: In total, 2419 individuals responded to the survey. Most respondents were female (75.5%), 61.8% had an early-stage malignancy, 38.2% had advanced disease, and 49.0% were currently receiving treatment. Breast cancer was the most common cancer type (36.0%). Average BMI was 25.8 kg/m2. The majority of respondents consumed £2 servings of fruits and vegetables per day (50.9%) and exercised £2 times per week (50.4%). Exercise was addressed at most or some oncology visits in 57.5% of respondents, diet in 50.7%, and weight in 28.4%. Referrals were less common: 14.9% of respondents were referred to an exercise program, 25.6% to a dietitian and 4.5% to a weight management program. In multiple regression analyses, racial and ethnicity minority respondents were more likely to receive advice about diet (Odds Ratio [OR] 1.92, 95% CI 1.56-2.38) and weight (OR 1.64, 95% CI 1.23-2.17) compared to non-Hispanic whites, individuals diagnosed with cancer in the past 5 yrs (vs > 5 yrs) were more likely to receive advice about exercise (OR 1.48, 95% CI 1.23-1.79), and breast cancer patients were more likely to receive advice about exercise (OR 1.37, 95% CI 1.11-1.68) and weight (OR 1.46, 95% CI 1.03-2.07) than other cancer patients. Overall, 74% of survey respondents had changed their diet or exercise after cancer diagnosis. Respondents reporting that their oncologist spoke to them about increasing exercise or eating healthier foods were more likely to report a change in behavior than those whose oncologists did not (exercise: 79.6% vs 69.0%, P < 0.001; diet 81.1% vs 71.4%, P < 0.001). Respondents whose oncologist had spoken to them about exercise were more likely to exercise > 2 times per week compared to respondents whose oncologists did not address exercise (53.5% vs 44.1%, P < 0.001). Conclusions: In a national survey of oncology patients, slightly more than half of respondents reported attention to diet and exercise during oncology visits. Provider recommendations for diet and exercise were associated with positive changes in these behaviors. Additional attention to diet and exercise as part of oncology visits is needed to help support healthy lifestyle change in cancer patients.


2017 ◽  
Vol 13 (5) ◽  
pp. e463-e473 ◽  
Author(s):  
Laura C. Pinheiro ◽  
Stephanie B. Wheeler ◽  
Katherine E. Reeder-Hayes ◽  
Cleo A. Samuel ◽  
Andrew F. Olshan ◽  
...  

Purpose: Endocrine therapy (ET) underuse puts women at increased risk for breast cancer (BC) recurrence. Our objective was to determine if health-related quality of life (HRQOL) subgroups were associated with underuse. Methods: Data came from the third phase of the Carolina Breast Cancer Study. We included 1,599 women with hormone receptor–positive BC age 20 to 74 years. HRQOL was measured, on average, 5 months postdiagnosis. Subgroups were derived using latent profile (LP) analysis. Underuse was defined as not initiating or adhering to ET by 36 months postdiagnosis. Multivariable logistic regression models estimated adjusted odds ratios (ORs) between HRQOL LPs and underuse. The best HRQOL LP was the reference. Chemotherapy- and race-stratified models were estimated, separately. Results: Initiation analyses included 953 women who had not begun ET by their 5-month survey. Of these, 154 never initiated ET. Adherence analyses included 1,114 ET initiators, of whom 211 were nonadherent. HRQOL was not significantly associated with noninitiation, except among nonchemotherapy users, with membership in the poorest LP associated with increased odds of noninitiation (adjusted OR, 5.5; 95% CI, 1.7 to 17.4). Membership in the poorest LPs was associated with nonadherence (LP1: adjusted OR, 2.2; 95% CI, 1.2 to 4.0 and LP2: adjusted OR,1.9; 95% CI, 1.1 to 3.6). Membership in the poorest LP was associated with nonadherence among nonchemotherapy users (adjusted OR, 2.1; 95% CI, 1.2 to 5.1). Conclusion: Our results suggest women with poor HRQOL during active treatment may be at increased risk for ET underuse. Focusing on HRQOL, a modifiable factor, may improve targeting of future interventions early in the BC continuum to improve ET initiation and adherence and prevent BC recurrence.


Breast Care ◽  
2017 ◽  
Vol 12 (3) ◽  
pp. 146-151 ◽  
Author(s):  
Ivana Sestak

Postmenopausal women with early oestrogen receptor-positive breast cancer who have received 5 years of endocrine therapy are at increased risk of developing a recurrence. An important clinical question is how to identify women who are at highest (or lowest) risk of a recurrence. The use of prognostic biomarkers allows individualised breast cancer therapy but correct identification of patients who will benefit most from extended endocrine therapy is essential. Several multigene assays have been developed to determine the likelihood of overall recurrence but so far none exist specifically for the prediction of late recurrence. Recent results from large clinical trials have shown that biomarker assays that include clinical information in their tests might be useful to predict and risk stratify patients for late recurrence. However, further research is needed to specifically offer multigene assays for the identification of late recurrence and thus justify routine use of these tests in the clinical setting.


2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Kazem Nejati ◽  
Sedigheh Fekri Aval ◽  
Mohammadreza Alivand ◽  
Abolfazl Akbarzadeh ◽  
AmirAhmad Arabzadeh

Context: Breast cancer (BC) is the most common cancer in women worldwide. Hereditary susceptibility created by mutations in autosomal dominant genes is responsible for 5 to 10% of all BC cases in women. Recent studies have identified genes associated with increased risk for aggressive BC, providing the basis for better risk management. Evidence Acquisition: The latest information in National Center for Biotechnology Information (NCBI), Google Scholar, ScienceDirect, and Scopus were the main databases for finding articles. A combination of keywords of ‘metastasis’, ‘invasion’, ‘aggressive breast cancer’, ‘prognostic factor’, ‘mutation’, and ‘cancer treatment’ was searched in the databases to identify related articles. Titles and abstracts of the articles were studied to choose the right articles. Results: Mutations in breast cancer type 1 susceptibility protein (BRCA1) and breast cancer type 2 susceptibility protein (BRCA2) genes are two central players related to the high risk of BC. Mutation in tumor protein p53 (TP53) is another important mutation that leads to triple-negative BC. Although the majority of BC types are not associated with high-throughput mutant genes such as BRCA1, BRCA2, and TP53, they are associated with low-throughput genes, including DNA repair protein Rad50 (RAD50), Nijmegen breakage syndrome gene (NBS1), checkpoint kinase 2 (CHEK2), BRCA1-interacting protein 1 (BRIP1), E-cadherin gene (CDH1) and PALB2, UCHL1, aldehydedehydrogenase1A3 (ALDH1A3), androgen receptor (AR), 5-bisphosphate 3-kinase (PIK3CA), phosphatidylinositol-4, and luminal gene expression that are generally mutated in the global population. High tumor mutational burden (TMB) was associated with improved progression-free survival. Conclusions: The lymph node status, early tumor size, ER, PR, human epidermal growth factor receptor-2 (HER2), and Ki-67 are conventional prognostic factors for BC. However, these factors cannot exactly predict the aggressive behavior of BC. Hence, in this review, we discussed new prognostic factors of aggressive BCs that are useful for the treatment of patients with BC.


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