Iodine Map Radiomics in Breast Cancer: Prediction of Metastatic Status

Dual-energy CT (DECT) iodine maps enable quantification of iodine concentrations as a marker for tissue vascularization. We investigated whether iodine map radiomic features derived from staging DECT enable prediction of breast cancer metastatic status, and whether textural differences exist between primary breast cancers and metastases. Seventy-seven treatment-naïve patients with biopsy-proven breast cancers were included retrospectively (41 non-metastatic, 36 metastatic). Radiomic features including first-, second-, and higher-order metrics as well as shape descriptors were extracted from volumes of interest on iodine maps. Following principal component analysis, a multilayer perceptron artificial neural network (MLP-NN) was used for classification (70% of cases for training, 30% validation). Histopathology served as reference standard. MLP-NN predicted metastatic status with AUCs of up to 0.94, and accuracies of up to 92.6 in the training and 82.6 in the validation datasets. The separation of primary tumor and metastatic tissue yielded AUCs of up to 0.87, with accuracies of up to 82.8 in the training, and 85.7 in the validation dataset. DECT iodine map-based radiomic signatures may therefore predict metastatic status in breast cancer patients. In addition, microstructural differences between primary and metastatic breast cancer tissue may be reflected by differences in DECT radiomic features.

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Prognostic Role of Hedgehog-GLI1 Signaling Pathway in Aggressive and Metastatic Breast Cancers

Current Drug Metabolism ◽

10.2174/1389200221666200122120625 ◽

2020 ◽

Vol 21 (1) ◽

pp. 33-43 ◽

Cited By ~ 1

Author(s):

Prasuja Rokkam ◽

Shailender Gugalavath ◽

Deepak Kakara Gift Kumar ◽

Rahul Kumar Vempati ◽

Rama Rao Malla

Keyword(s):

Breast Cancer ◽

Signaling Pathway ◽

Neural Development ◽

Splice Variants ◽

Metastatic Breast ◽

Basic Function ◽

Breast Cancers ◽

Breast Cancer Patients ◽

Aberrant Expression ◽

Cellular Processes

Glioma-associated oncogene homolog 1 (GLI1) is reported as an amplified gene in human glioblastoma cells. It is a krupple like transcription factor, belonging to the zinc finger family. The basic function of GLI1 is normal neural development at various stages of human. The GLI1 gene was first mapped on the chromosome sub-bands 12q13.3-14.1. Further, single nucleotide polymorphism is mostly observed in translating a region of 5’ and 3’- UTR of GLI1 gene in addition to two post-transcriptional splice variants, GLIΔN and tGLI. Additionally, it also regulates a plethora of gene which mediates crucial cellular processes like proliferation, differentiation, oncogenesis, EMT, and metastasis. It also regulates tumor tolerance, chemoresistance, and radioresistance. Aberrant expression of GLI1 predicts the poor survival of breast cancer patients. GLI1 is an essential mediator of the SHH signaling pathway regulating self-renewal of stem cells, angiogenesis, and expression of FOXS1, CYR61. GLI1 mediated HH pathway can induce apoptosis. Hence, GLI1 can be a future diagnostic, prognostic marker, and as well as a potent target of therapeutics in breast cancer.

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MMTV Prevalence in Breast Cancer Samples in Romania - Do Major Geographical Differences Exist in The World Population?

10.21203/rs.3.rs-682741/v1 ◽

2021 ◽

Author(s):

Zsolt Fekete ◽

Bristena Octavia Terțan ◽

Lajos Ráduly ◽

Dan Tudor Eniu ◽

Rares Buiga ◽

...

Keyword(s):

Breast Cancer ◽

Dna Sequences ◽

Mus Musculus ◽

Breast Tissue ◽

Neoadjuvant Treatment ◽

Metastatic Breast ◽

Radical Mastectomy ◽

Cancer Tissue ◽

World Population ◽

Breast Cancer Patients

Abstract Background Breast cancer, although the most frequently diagnosed malignant tumor in humans, has a less clear etiology compared to other frequent cancer types. Mouse-mammary tumor virus (MMTV) is involved in breast cancer in mice and dogs and might play a role in the etiology of some breast cancers in humans, since it has been identified in 20-40% of breast cancer samples in Western Europe, USA, Australia and some other parts of the world’s population. The purpose of our study was to identify MMTV DNA sequences in breast tissue samples from breast cancer patients who underwent curative surgery in our regional center in Romania, EU. MethodsWe selected 75 patients with non-metastatic breast cancer treated surgically with curative intent, which did not undergo any neoadjuvant treatment. Out of these patients, 50 underwent radical lumpectomy and 25 modified radical mastectomy. We searched using PCR the MMTV-like DNA env sequence in the breast cancer tissue and normal breast tissue obtained from the same patients. ResultsNone of the examined samples was positive for MMTV-like target sequences on PCR.ConclusionsWe could not prove that MMTV plays a role in the etiology of breast cancer in our patient group. This finding is similar to publications of other geographically related research groups and might be due to the fact that only the Mus musculus domesticus mouse species was proven to carry infectious MMTV, but not the Mus musculus musculus species, which is specific to South-Eastern Europe (including Romania) and some parts of Asia.

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Clinical significance of serum PSA in breast cancer patients

BMC Cancer ◽

10.1186/s12885-019-6256-2 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 2

Author(s):

Toru Hanamura ◽

Koichi Ohno ◽

Shinya Hokibara ◽

Hideki Murasawa ◽

Toshitsugu Nakamura ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Tumor Biology ◽

Specific Antigen ◽

Metastatic Breast ◽

Serum Testosterone ◽

Biological Properties ◽

Cancer Tissue ◽

Breast Cancer Patients ◽

Post Menopausal

Abstract Background Recent preclinical data suggest that androgen receptor (AR) signaling plays a significant role in subsets of breast cancer. Clinical trials testing AR-targeting therapies in breast cancer have been conducted. Assessment of AR-signal in breast cancer tissue maybe useful for treatment selections. Prostate specific antigen (PSA) is the product of an androgen-responsive gene. Serum PSA (sPSA) can be detected in women by a highly sensitive assay although the concentration is much lower than that observed in males. We investigated if sPSA reflects tumor biology, including AR signaling in breast cancer patients. Methods In this study, 132 healthy controls and 144 breast cancer patients were enrolled. sPSA was evaluated by the chemiluminescent enzyme immunoassay (CLEIA) method. Correlations between sPSA and the various clinicopathological factors were analyzed. Results In post-menopausal state, sPSA detection rate was significantly higher in breast cancer patients compared with controls (27.4% vs 11.3%: p = 0.0090), but not in the whole cohort (29.2% vs 25.8%: p = 0.5265) or pre-menopausal subgroup (37.0% vs 42.6%: p = 0.6231). In post-menopausal breast cancer cases, higher sPSA value was associated with clinic-pathological factors including the expression of AR protein in primary legion. In a correlation analysis of quantitative data limited to post-menopausal metastatic breast cancer (MBC), sPSA was positively, albeit weakly correlated with clinic-pathological features including serum testosterone levels and AR positivity. Conclusions Our data suggest that sPSA may reflect tumor biological properties including AR activity in post-menopausal breast cancer.

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Methallotionein expression and outcome in patients with metastatic breast cancer (MBC).

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.1085 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 1085-1085

Author(s):

Jorge Arturo Rios-Perez ◽

Sameem Abedin ◽

Margaret Quinn Rosenzweig ◽

Su Yon Jung ◽

Rohit Bhargava ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Metastatic Breast ◽

Progression Free Survival ◽

Breast Cancer Diagnosis ◽

Rank Test ◽

Cancer Tissue ◽

Breast Cancer Patients ◽

Development Of Resistance ◽

Bivalent Metal Ions

1085 Background: Platinum-based agents are important components of therapy of metastatic breast cancer (MBC) and triple negative breast cancer. Their use can be limited by development of resistance. Metallothioneins (MT) are low molecular weight proteins believed to bind bivalent metal ions such as platinum and zinc. MT expression has been associated with decreased survival in breast cancer patients. A proposed mechanism confers resistance to platinum-based agents by their inactivation or limitation of their activity by MT binding. Methods: MT expression in 99 women with MBC (selected at random from our database of 800 women with MBC) was determined from primary breast cancer tissue (n=80) or metastatic tissue n=19). MT expression was determined by immunohistochemistry, and graded as negative, weak, moderate or strong. Clinical data was obtained through our database and supplemented by chart review. Overall survival from breast cancer diagnosis (OS), progression free survival for first metastastic regimen (PFS), and time from first metastasis to death or last update (metastatic survival, MS), were calculated through December 2011 using the log rank test. Results: Consistent with prior studies, moderate to strong MT expression was associated with decreased 5-year OS (p=.03). There was no correlation between MT expression and PFS or MS in this cohort. Surprisingly, MT expression at any degree was strongly associated with better MS in patients with MBC that received carboplatin-based regimens in the first line (n=25, p=.0005) or at any line (n=41, p=.0437). Conclusions: Consistent with prior studies, MT expression was associated with decreased survival in patients with MBC. Surprisingly, MT expression was associated with longer MS in patients with MBC that received carboplatin. These findings are inconsistent with the hypothesis that MT expression causes chemoresistance to platinum based agents in patients with metastatic breast cancer. Further studies are needed to elucidate the mechanisms behind these findings.

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The predictive potential of the spatial signature of lymphocytes in breast cancer patients.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.530 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 530-530

Author(s):

Nora Balint-Lahat ◽

Chen Mayer ◽

Noa Ben-Baruch ◽

Ady Yosepovich ◽

Kira Sacks ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Early Stage ◽

Principal Component ◽

Treatment Decision ◽

High Ratio ◽

Luminal Breast Cancer ◽

Breast Cancers ◽

Breast Cancer Patients ◽

Validation Set

530 Background: Tumor-infiltrating lymphocytes in breast cancer have emerged as both a prognostic and a potentially predictive immunotherapy biomarker. Advancements in artificial intelligence can extract pathology-based spatial immune fingerprints for use as treatment decision support tools. Methods: We examined 908 primary breast cancer patients with whole slide images (WSI) available from TCGA database. Digital structuring of WSIs included automated detection of lymphocytes, tumor and tumor adjacent stroma, using deep learning-based semantic segmentation. Prognosis was defined as progression free interval (PFI). A Cox Survival analysis was used to detect prognostic spatial features. We used principal component analysis (PCA) to reduce and decorrelate significant features. The resulting PCA features were used to fit the final model. The model was then validated on an independent database of WSI of breast lumpectomies, from two tertiary hospitals in Israel. Results: The analysis included 908 WSI. The average age was 58.4 years old, with a majority of early stage breast cancer (76.7%, stage I and II). The detection performance for tumor area and lymphocytes reached F1 scores of 99% and 97% respectively, in comparison to human annotation. In the Kaplan Meier (KM) analysis of 414 early stage luminal breast cancers, a high number of lymphocyte clusters (LC) and a high ratio between stromal lymphocyte density and tumor lymphocyte density (LD-S/LD-T) were significantly associated with longer PFI (p = 0.005 and p = 0.038, respectively). Based on these features, two continuous PCA features were added to the multivariate model, and remained significantly associated with PFI after adjusting for age (HR = 1.19, 95% CI 1.05-1.35; HR = 1.26 95% CI 1.03-1.55). The validation set was underpowered (n = 79) and data is still being collected. In a preliminary KM analysis of 37 early stage luminal breast cancer cases from the validation set, LD-S/LD-T was significantly associated with longer PFI (p = 0.046). Conclusions: In our study, LC and LD-S/LD-T, presumably surrogate measures of peritumoral lymphocytes, were found significantly associated with longer PFI.

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Metastatic male breast cancer (mMBC): Prognosis and survival of 35 patients

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e12001 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e12001-e12001

Author(s):

R. Foerster ◽

F. G. Foerster ◽

D. Baaske ◽

B. Schubotz ◽

V. Wulff ◽

...

Keyword(s):

Breast Cancer ◽

Male Breast Cancer ◽

Systemic Therapy ◽

Metastatic Breast ◽

Male Breast ◽

Tumor Characteristics ◽

Breast Cancers ◽

Breast Cancer Patients ◽

Radio Therapy

e12001 Background: Only about 1% of breast cancers occur in men, respectively 400–500 new cases per year in Germany. Clinical studies on breast cancer in men are limited for case studies or retrospective analysis. In the recent years no studies have been published on the clinical course of mMBC. Therefore we here present a retrospective cohort study on this topic. Methods: Clinical and pathological tumor characteristics and the follow-up of male breast cancer patients with metastatic disease diagnosed in the region Chemnitz/Zwickau in the state of Saxony between 1995 and 2007 were documented and statistically evaluated. Results: 35 men (median age 64.7 years) were diagnosed with mMBC; 10 (28.6%) of them with primary metastasis. Median survival time: 37 months. 85.7% (n = 30) had an invasive-ductile carcinoma. Most common localizations of metastasis: bones (n = 19), lungs (n = 19), liver (n = 7). Tumor characteristics at the point of diagnosis: 63.9% (n = 22) T2-T4, 38.7% (n = 12) G3, 48.4% (n = 15) N+, 79.3% (n = 23) ER+, 72.4% (n = 21) PgR+, 12.5% (n = 3) HER-2+, 13.8% (n = 4) triple negatives, and 69.2% (n = 9) AR+. The therapy in the metastatic state was very heterogeneous and consisted of systemic endocrine therapy in 45.5% (n = 10), systemic chemo therapy in 9% (n = 2) or a combination of both in 45.5% (n = 10). In 14 (40%) cases a palliative radio therapy was administered. The initial tumor characteristics like tumor size, nodal state and grading were not of any prognostic relevance on a future development of metastasis. Prognostic unfortunate were a negative hormone receptor state (p < 0.001) and triple negative receptor state (n.s.). Patients with primary metastasis showed a tendency towards worse survival than patients who developed the metastasis during follow up (n.s.). If a systemic therapy was given the prognosis was significantly improved (p < 0.005). Conclusions: Patients suffering from metastatic male breast cancer had a comparatively good prognosis and showed significant benefit from systemic therapy in this study. In patients with negative receptor state and without systemic therapy the prognosis was especially worsened. Our data suggest that an up-to-date adequate systemic therapy is capable of improving survival in men with metastatic breast cancer. No significant financial relationships to disclose.

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Real-World Data on Apatinib Efficacy - Results of a Retrospective Study in Metastatic Breast Cancer Patients Pretreated With Multiline Treatment

Frontiers in Oncology ◽

10.3389/fonc.2021.643654 ◽

2021 ◽

Vol 11 ◽

Author(s):

Zhaoyun Liu ◽

Jing Shan ◽

Qian Yu ◽

Xinzhao Wang ◽

Xiang Song ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Cancer Patients ◽

Real World ◽

Metastatic Breast ◽

Breast Cancers ◽

Breast Cancer Patients ◽

Real World Data ◽

Significant Treatment ◽

Nccn Guidelines

ObjectivesThe NCCN guidelines recommend that the addition of bevacizumab should be considered in metastatic breast cancers in some circumstances, but there are no recommendations for the similar antiangiogenic drug apatinib. The aim of this study was to evaluate the safety and efficacy of apatinib in metastatic breast cancer patients pretreated with multiline treatment in a real-world setting.Materials and MethodsMetastatic breast cancer patients pretreated with multiline treatment who had apatinib treatment initiated from September 2015 to August 2019 at Shandong Cancer Hospital and Institute were included. The primary endpoints included PFS and OS, and the secondary endpoint was treatment-related toxicity.ResultsA total of 66 patients with metastatic breast cancer received apatinib treatment after failure of multiline chemotherapy in this study. The median PFS and OS of all 66 patients were 6.0 months and 10.0 months, respectively. The clinical beneficial rate was 40.9%. All patients tolerated treatment well, and no patients died of toxicity. The common toxicities of apatinib were hand and foot syndrome, secondary hypertension and fatigue events. The number of prior chemotherapy regimens was significantly associated with DFS and OS. Capecitabine may be a better choice for combination with a longer median OS of 19 months, while apatinib combined with other drugs was 9 months, and the apatinib monotherapy was 10 months.ConclusionApatinib produced moderate efficacy in metastatic breast cancer patients pretreated with multiline treatment with no significant treatment-related adverse events. Apatinib might be a choice for women as a maintenance salvage therapy following multiline chemotherapy failure.

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Effects of improved hypoallergenic fabrics in medical wigs in patients with breast cancer with chemotherapy-induced alopecia: a randomised clinical trial

BMJ Supportive & Palliative Care ◽

10.1136/bmjspcare-2020-002309 ◽

2021 ◽

pp. bmjspcare-2020-002309

Author(s):

Nao Tamai ◽

Takeo Minematsu ◽

Mari Ikeda ◽

Yuko Mugita ◽

Hiromi Sanada

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Intervention Group ◽

Metastatic Breast ◽

Randomised Clinical Trial ◽

Controlled Study ◽

Control Group ◽

Breast Cancers ◽

Breast Cancer Patients ◽

Barrier Functions

PurposeChemotherapy causes changes in appearance in patients with cancer. Therefore, to have a normal life, it is necessary for patients to wear a wig. However, wearing a wig may strain an already sensitive scalp during chemotherapy. This study aimed to assess the effects of a hypoallergenic medical wig in breast cancer patients with chemotherapy-induced alopecia (CIA).MethodsA randomised, single-blind, controlled study was conducted from January 2015 to July 2017 in Tokyo, Japan. Women with non-metastatic breast cancers were enrolled. Participants were provided a hypoallergenic medical wig or a traditional medical wig. The primary endpoint was incidence of scalp dermatitis, including erythema, rash and erosion. The secondary endpoints were incidence of scalp symptoms, alterations in scalp barrier functions and quality of life (QOL). Patients were followed at the start of the first chemotherapy administration and at 13th week.ResultsFifty-nine women were included in the analysis. At 13th week, the incidence of erythema was 44.8% among patients in the intervention group and 86.7% among patients in the control group, in the intention-to-treat analysis (p<0.01). The incidence of erosion tended to decrease in the intervention group at the 13th week (p=0.09). The incidence of scalp symptoms, alterations in scalp barrier functions and QOL were not significantly different between the groups.ConclusionsThe incidence of dermatitis, including erythema, rash and erosion, decreased when wearing the new hypoallergenic medical wig. The gentle hypoallergenic medical wig is useful in improving erythema in cancer patients with CIA.Trial registration number UMIN000021289.

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Neuregulin Expression Modulates Clinical Response to Trastuzumab in Patients With Metastatic Breast Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2006.08.6850 ◽

2007 ◽

Vol 25 (19) ◽

pp. 2656-2663 ◽

Cited By ~ 45

Author(s):

Enrique de Alava ◽

Alberto Ocaña ◽

Mar Abad ◽

Juan Carlos Montero ◽

Azucena Esparís-Ogando ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Early Stage ◽

Metastatic Breast ◽

Breast Cancers ◽

Breast Cancer Patients ◽

Event Free Survival ◽

Mcf7 Cells ◽

Free Survival ◽

Her 2

Purpose Human epidermal growth factor receptor 2 (HER-2) overexpression has been associated with the genesis and progression of a subset of breast cancers. The function of HER-2 may be upregulated by overexpression or by the availability of neuregulins (NRGs), a group of transmembrane growth factors. Transmembrane NRGs strongly activated HER-2 and cell proliferation in breast cancer cells that did not overexpress HER-2, and treatment with trastuzumab prevented the proliferative action of transmembrane NRG. This raised the relevant clinical question of whether patients considered as HER-2 negative, but expressing transmembrane NRG, may benefit from treatment with trastuzumab. Patients and Methods MCF7 cells expressing transmembrane NRG (MCF7-NRGα2c) were injected into mice, and their sensitivity to trastuzumab was assessed. A retrospective study of 124 patients with early-stage or metastatic breast cancer was conducted. Expression of transmembrane NRG was evaluated by immunohistochemistry. In 11 patients, Western blot for NRGs was also carried out. Statistics were performed to analyze possible correlations between NRG expression and response to trastuzumab-based therapies, event-free survival, and overall survival (OS). Results Trastuzumab inhibited tumor growth in mice injected with MCF7-NRGα2c cells. Transmembrane NRG was frequently expressed in breast cancer patients. Overexpression of transmembrane NRG significantly correlated with a longer event-free survival and OS in patients with low or normal HER-2 expression who were treated with trastuzumab-based therapies but not in patients with HER-2 overexpression. Conclusion We suggest that the spectrum of patients who may benefit from trastuzumab-based therapies may be widened to include patients with metastatic breast cancer without HER-2 amplification but who express transmembrane NRGs.

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Differences in plasma microRNA content impair microRNA-based signature for breast cancer diagnosis in cohorts recruited from heterogeneous environmental sites

Scientific Reports ◽

10.1038/s41598-021-91278-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Jeanne P. Uyisenga ◽

Ahmed Debit ◽

Christophe Poulet ◽

Pierre Frères ◽

Aurélie Poncin ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Diagnosis ◽

Breast Cancer Diagnosis ◽

Circulating Microrna ◽

Cancer Tissue ◽

Healthy Controls ◽

Breast Cancers ◽

Breast Cancer Patients ◽

Cancer Subtypes ◽

Plasma Microrna

AbstractCirculating microRNAs are non-invasive biomarkers that can be used for breast cancer diagnosis. However, differences in cancer tissue microRNA expression are observed in populations with different genetic/environmental backgrounds. This work aims at checking if a previously identified diagnostic circulating microRNA signature is efficient in other genetic and environmental contexts, and if a universal circulating signature might be possible. Two populations are used: women recruited in Belgium and Rwanda. Breast cancer patients and healthy controls were recruited in both populations (Belgium: 143 primary breast cancers and 136 healthy controls; Rwanda: 82 primary breast cancers and 73 healthy controls; Ntot = 434), and cohorts with matched age and cancer subtypes were compared. Plasmatic microRNA profiling was performed by RT-qPCR. Random Forest was used to (1) evaluate the performances of the previously described breast cancer diagnostic tool identified in Belgian-recruited cohorts on Rwandan-recruited cohorts and vice versa; (2) define new diagnostic signatures common to both recruitment sites; (3) define new diagnostic signatures efficient in the Rwandan population. None of the circulating microRNA signatures identified is accurate enough to be used as a diagnostic test in both populations. However, accurate circulating microRNA signatures can be found for each specific population, when taken separately.

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