scholarly journals The Heterogeneity of Breast Cancer Metabolism

2021 ◽  
pp. 89-101
Author(s):  
Jessica Tan ◽  
Anne Le
Keyword(s):  
Breast Cancer ◽  
Cancer Metabolism ◽  
Survival Rates ◽  
Specific Treatment ◽  
Hormone Receptor Status ◽  
Malignant Potential ◽  
Tumor Evolution ◽  
Clinical Behavior ◽  
Cancer Heterogeneity ◽  
Surface Molecules

AbstractDespite advances in screening, therapy, and surveillance that have improved patient survival rates, breast cancer is still the most commonly diagnosed cancer and the second leading cause of cancer mortality among women [1]. Breast cancer is a highly heterogeneous disease rooted in a genetic basis, influenced by extrinsic stimuli, and reflected in clinical behavior. The diversity of breast cancer hormone receptor status and the expression of surface molecules have guided therapy decisions for decades; however, subtype-specific treatment often yields diverse responses due to varying tumor evolution and malignant potential. Although the mechanisms behind breast cancer heterogeneity is not well understood, available evidence suggests that studying breast cancer metabolism has the potential to provide valuable insights into the causes of these variations as well as viable targets for intervention.

scholarly journals Trends in 5-year survival rates among breast cancer patients by hormone receptor status and stage

2014 ◽  
Vol 147 (3) ◽  
pp. 609-616 ◽  
Author(s):  
Lu Chen ◽  
Hannah M. Linden ◽  
Benjamin O. Anderson ◽  
Christopher I. Li
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Hormone Receptor ◽  
Survival Rates ◽  
Hormone Receptor Status ◽  
Breast Cancer Patients ◽  
Receptor Status

4D radiomic biomarker of functional tumor heterogeneity to predict breast cancer recurrence in pretreatment dynamic FDG-PET.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e12573-e12573
Author(s):  
Rhea Chitalia ◽  
Varsha Viswanath ◽  
Austin R. Pantel ◽  
Lanell Peterson ◽  
Eric Cohen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Size ◽  
Hormone Receptor ◽  
Fdg Pet ◽  
Tumor Heterogeneity ◽  
Hormone Receptor Status ◽  
Receptor Status ◽  
Cancer Heterogeneity ◽  
C Statistic ◽  
Discriminatory Capacity

e12573 Background: Breast cancer heterogeneity is thought to be associated with adverse outcomes. Dynamic molecular imaging modalities, including PET, permit 4-D sampling of tumor biologic properties and can therefore capture functional heterogeneity revealed by the temporal dimension of the dynamic tracer uptake. With the goal of improved non-invasive characterization of in vivo tumor biology, we have developed and tested a novel radiomic biomarker that characterizes 4-D functional tumor heterogeneity (FTH). We hypothesize subclonal populations are spatially contiguous regions of shared physiologic behavior that drive breast cancer heterogeneity and can be quantified. We describe an initial application of this approach to FDG PET imaging of breast cancer. Methods: We retrospectively analyzed data from a study of 50 patients with locally advanced breast cancer. Patients underwent 60-minute dynamic FDG PET over the chest prior to neoadjuvant chemotherapy and breast surgery and were followed for disease recurrence (DFS). A 3-D region bounding each tumor was identified by a radiologist and a novel Markov Random Field based 4-D segmentation paradigm segmented each tumor into three spatially constrained sub-regions with distinct time activity curve dynamics. From each tumor, an FTH imaging signature was extracted characterizing cluster compactness and separation. FTH imaging signatures were z-score normalized across all patients. Time-to-event analysis was used to assess the prognostic value of the FTH imaging signatures in predicting DFS. Discriminatory capacity compared to a baseline model of established prognostic factors (age, hormone receptor status, baseline tumor size) and standard PET uptake and kinetics markers (SUV, K1, and Ki) shown to be predictive of DFS (Dunnwald, J Clin Oncol 26:4449, 2008) was evaluated using the c-statistic and the log-likelihood statistical test. Results: 17 of 50 women (34%) had recurrence events. Adding FTH imaging signatures to the baseline model of age, baseline tumor size, and hormone receptor status improved a cross validated c-statistic from 0.51 to 0.74 (p < 0.05), and demonstrated higher discriminatory capacity over a model of age, tumor size, hormone receptor status, and standard PET measures (c-statistic = 0.59). Conclusions: Imaging biomarkers of 4-D metabolic tumor heterogeneity may add prognostic value in predicting recurrence-free survival in breast cancer and merit further study.

scholarly journals Clinical behavior and outcomes of breast cancer in young women with germline BRCA pathogenic variants

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Matteo Lambertini ◽  
Marcello Ceppi ◽  
Anne-Sophie Hamy ◽  
Olivier Caron ◽  
Philip D. Poorvu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Hormone Receptor ◽  
Young Patients ◽  
Disease Free Survival ◽  
Distant Recurrence ◽  
Hormone Receptor Status ◽  
Second Primary ◽  
Clinical Behavior ◽  
Receptor Status ◽  
The Impact

AbstractYoung breast cancer (BC) patients carrying a germline BRCA pathogenic variant (mBRCA) have similar outcomes as non-carriers. However, the impact of the type of gene (BRCA1 vs. BRCA2) and hormone receptor status (positive [HR+] vs. negative [HR−]) on clinical behavior and outcomes of mBRCA BC remains largely unknown. This is an international, multicenter, hospital-based, retrospective cohort study that included mBRCA patients diagnosed, between January 2000 and December 2012, with stage I–III invasive early BC at age ≤40 years. From 30 centers worldwide, 1236 young mBRCA BC patients were included. Among 808 and 428 patients with mBRCA1 or mBRCA2, 191 (23.6%) and 356 (83.2%) had HR+tumors, respectively (P < 0.001). Median follow-up was 7.9 years. Second primary BC (P = 0.009) and non-BC malignancies (P = 0.02) were more frequent among mBRCA1 patients while distant recurrences were less frequent (P = 0.02). Irrespective of hormone receptor status, mBRCA1 patients had worse disease-free survival (DFS; adjusted HR = 0.76, 95% CI = 0.60–0.96), with no difference in distant recurrence-free interval (DRFI) and overall survival (OS). Patients with HR+ disease had more frequent distant recurrences (P < 0.001) and less frequent second primary malignancies (BC: P = 0.005; non-BC: P = 0.18). No differences in DFS and OS were observed according to hormone receptor status, with a tendency for worse DRFI (adjusted HR = 1.39, 95% CI = 0.94–2.05) in patients with HR+ BC. Type of mBRCA gene and hormone receptor status strongly impact BC clinical behavior and outcomes in mBRCA young patients. These results provide important information for patients’ counseling on treatment, prevention, and surveillance strategies.

scholarly journals Amino Acid Transporters on the Guard of Cell Genome and Epigenome

Cancers ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 125
Author(s):  
Uğur Kahya ◽  
Ayşe Sedef Köseer ◽  
Anna Dubrovska
Keyword(s):  
Amino Acid ◽  
Cancer Metabolism ◽  
Tumor Imaging ◽  
Redox Homeostasis ◽  
Amino Acid Uptake ◽  
Metabolic Reprogramming ◽  
Tumor Evolution ◽  
Amino Acid Transporters ◽  
Acid Uptake ◽  
Growth And Survival

Tumorigenesis is driven by metabolic reprogramming. Oncogenic mutations and epigenetic alterations that cause metabolic rewiring may also upregulate the reactive oxygen species (ROS). Precise regulation of the intracellular ROS levels is critical for tumor cell growth and survival. High ROS production leads to the damage of vital macromolecules, such as DNA, proteins, and lipids, causing genomic instability and further tumor evolution. One of the hallmarks of cancer metabolism is deregulated amino acid uptake. In fast-growing tumors, amino acids are not only the source of energy and building intermediates but also critical regulators of redox homeostasis. Amino acid uptake regulates the intracellular glutathione (GSH) levels, endoplasmic reticulum stress, unfolded protein response signaling, mTOR-mediated antioxidant defense, and epigenetic adaptations of tumor cells to oxidative stress. This review summarizes the role of amino acid transporters as the defender of tumor antioxidant system and genome integrity and discusses them as promising therapeutic targets and tumor imaging tools.

scholarly journals Age-Related Biology of Early-Stage Operable Breast Cancer and Its Impact on Clinical Outcome

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1417
Author(s):  
Binafsha M. Syed ◽  
Andrew R. Green ◽  
Emad A. Rakha ◽  
David A.L. Morgan ◽  
Ian O. Ellis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Stage ◽  
Histological Grade ◽  
Survival Rates ◽  
Growth Factor Receptor ◽  
Progesterone Receptors ◽  
Biological Characteristics ◽  
Cancer Specific Survival ◽  
Age Related ◽  
Significant Difference

As age advances, breast cancer (BC) tends to change its biological characteristics. This study aimed to explore the natural progression of such changes. The study included 2383 women with clinically T0-2N0-1M0 BC, managed by primary surgery and optimal adjuvant therapy in a dedicated BC facility. Tissue micro-arrays were constructed from their surgical specimens and indirect immunohistochemistry was used for analysis of a large panel (n = 16) of relevant biomarkers. There were significant changes in the pattern of expression of biomarkers related to luminal (oestrogen receptor (ER), progesterone receptors (PgR), human epidermal growth factor receptor (HER-2), E-cadherin, MUC1, bcl2 CK7/8, CK18 and bcl2) and basal (CK5/6, CK14, p53 and Ki67) phenotypes, lymph node stage, histological grade and pathological size when decade-wise comparison was made (p < 0.05). The ages of 40 years and 70 years appeared to be the milestones marking a change of the pattern. There were significantly higher metastasis free and breast cancer specific survival rates among older women with ER positive tumours while there was no significant difference in the ER negative group according to age. Biological characteristics of BC show a pattern of change with advancing age, where 40 years and 70 years appear as important milestones. The pattern suggests <40 years as the phase with aggressive phenotypes, >70 years as the less aggressive phase and 40–70 years being the transitional phase.

scholarly journals Challenges and Perspectives on Breast Cancer Survivorship: The Journey Continues

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 96-96
Author(s):  
Victoria Raveis ◽  
Simona Kwon
Keyword(s):  
Breast Cancer ◽  
Quality Of Life ◽  
Cancer Survivor ◽  
Breast Cancer Survivors ◽  
Cancer Survival ◽  
Survival Rates ◽  
Extended Period ◽  
Health Issues ◽  
Age Related

Abstract Women have a 1-in-8 lifetime risk of breast cancer. Earlier diagnosis and treatment advances have improved 15- and 20-year survival rates. Increased survival can mean coping with the effects of cancer and its treatment over an extended period of time, while experiencing age-related changes in functioning and the emergence of other health issues. To explore breast cancer survivors’ perspectives on their issues and concerns across the life-course, focus groups were conducted with a culturally diverse sample (N=18) of survivors (72% white, 28% Black, 11% Hispanic). Participants were 44-82 years old. Most, 83% were 50 and older, 56% were 60 and older. The majority (83%) were diagnosed in their 40’s and 50’s. Two were diagnosed in their early 30’s and one at age 68. Participants reaffirmed the necessity, as a breast cancer survivor, of being a life-long health advocate on their own behalf, and the importance of being self-informed. As one woman commented: “Knowledge is power”. Survivors shared that their emergent health issues were complicated by their cancer history, and, that, as a cancer survivor, “I never stop worrying”. A widespread concern was not knowing if the health issues and co-morbidities they experienced (such as joint pain, neuropathy, tendinitis, heart disease), were age-related, a consequence of their cancer, or a late treatment effect. An overriding sentiment expressed was that clinicians have not recognized the importance of quality of life in cancer survival. As a survivor succinctly stated: “We are living longer, but we need to live long with quality of life.”

scholarly journals Comparison of survival in non-metastatic inflammatory and other T4 breast cancers: a SEER population-based analysis

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Dechuang Jiao ◽  
Jingyang Zhang ◽  
Jiujun Zhu ◽  
Xuhui Guo ◽  
Yue Yang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cox Model ◽  
Survival Rates ◽  
Tumor Grade ◽  
Population Based ◽  
Rank Test ◽  
Breast Cancers ◽  
Significant Independent Predictor ◽  
Cancer Specific Survival ◽  
7Th Edition

Abstract Background Previous studies have reported poor survival rates in inflammatory breast cancer (IBC) patients than non-inflammatory local advanced breast cancer (non-IBC) patients. However, until now, the survival rate of IBC and other T4 non-IBC (T4-non-IBC) patients remains unexplored. Methods Surveillance, Epidemiology, and End Results (SEER) database was searched to identify cases with confirmed non-metastatic IBC and T4-non-IBC who had received surgery, chemotherapy, and radiotherapy between 2010 and 2015. IBC was defined as per the American Joint Committee on Cancer (AJCC) 7th edition. Breast Cancer-Specific Survival (BCSS) was estimated by plotting the Kaplan-Meier curve and compared across groups by using the log-rank test. Cox model was constructed to determine the association between IBC and BCSS after adjusting for age, race, stage of disease, tumor grade and surgery type. Results Out of a total of 1986 patients, 37.1% had IBC and mean age was 56.6 ± 12.4. After a median follow-up time of 28 months, 3-year BCSS rate for IBC and T4-non-IBC patients was 81.4 and 81.9%, respectively (log-rank p = 0.398). The 3-year BCSS rate in HR−/HER2+ cohort was higher for IBC patients than T4-non-IBC patients (89.5% vs. 80.8%; log-rank p = 0.028), and in HR−/HER2- cohort it was significantly lower for IBC patients than T4-non-IBC patients (57.4% vs. 67.5%; log-rank p = 0.010). However, it was identical between IBC and T4-non-IBC patients in both HR+/HER2- (85.0% vs. 85.3%; log-rank p = 0.567) and HR+/HER2+ (93.6% vs. 91.0%, log-rank p = 0.510) cohorts. After adjusting for potential confounding variables, we observed that IBC is a significant independent predictor for survival of HR−/HER2+ cohort (hazards ratio [HR] = 0.442; 95% CI: 0.216–0.902; P = 0.025) and HR−/HER2- cohort (HR = 1.738; 95% CI: 1.192–2.534; P = 0.004). Conclusions Patients with IBC and T4-non-IBC had a similar BCSS in the era of modern systemic treatment. In IBC patients, the HR−/HER2+ subtype is associated with a better outcome, and HR−/HER2- subtype is associated with poorer outcomes as compared to the T4-non-IBC patients.

scholarly journals Comparison of clinicopathological features and long-term prognosis between mixed predominantly differentiated-type and pure differentiated-type early gastric cancer

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yutaka Okagawa ◽  
Tetsuya Sumiyoshi ◽  
Hitoshi Kondo ◽  
Yusuke Tomita ◽  
Takeshi Uozumi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Early Gastric Cancer ◽  
Vascular Invasion ◽  
Survival Rates ◽  
Malignant Potential ◽  
Clinicopathological Features ◽  
Node Metastasis ◽  
Group 5 ◽  
Long Term Prognosis

Abstract Background Recent studies have shown that mixed predominantly differentiated-type (MD) early gastric cancer (EGC) might have more malignant potential than pure differentiated-type (PD) EGC. However, no study has analyzed all differentiated-type EGC cases treated endoscopically and surgically. This study aimed to compare the differences in clinicopathological features and long-term prognosis between MD- and PD-EGC. Methods We evaluated all patients with differentiated-type EGCs who were treated endoscopically and surgically in our hospital between January 2010 and October 2014. The clinicopathological features and long-term prognosis of MD-EGC were compared with those of PD-EGC. Results A total of 459 patients with 459 lesions were evaluated in this study; of them, 409 (89.1%) and 50 (10.9%) were classified into the PD and MD groups, respectively. Submucosal invasion was found in 96 (23.5%) patients of the PD group and in 33 (66.0%) patients of the MD group (p < 0.01). The rates of positive lymphatic and vascular invasion and ulceration were significantly higher in the MD group than in the PD group (p < 0.01). The proportion of patients with lymph node metastasis was also significantly higher in the MD group than in the PD group (5 (10%) vs 6 (1.5%), p < 0.01). The 5-year overall and EGC-specific survival rates in the PD group were 88.3 and 99.5%, respectively, while they were 94.0 and 98.0% in the MD group, respectively. Conclusions MD-EGC has more malignant potential than PD-EGC. However, the long-term prognosis of MD-EGC is good and is not significantly different from that of PD-EGC when treated appropriately.

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