Proteomics of Grade 3 infiltrating ductal carcinoma in Malaysian Chinese breast cancer patients

Abstract Background Breast cancer is the most common cancer among women in China. Amplification of the Human epidermal growth factor receptor type 2 (HER2) gene is present and overexpressed in 18–20% of breast cancers and historically has been associated with inferior disease-related outcomes. There has been increasing interest in de-escalation of therapy for low-risk disease. This study analyzes the cost-effectiveness of Doxorubicin/ Cyclophosphamide/ Paclitaxel/ Trastuzumab (AC-TH) and Docetaxel/Carboplatin/Trastuzumab(TCH) from payer perspective over a 5 year time horizon. Methods A half-cycle corrected Markov model was built to simulate the process of breast cancer events and death occurred in both AC-TH and TCH armed patients. Cost data came from studies based on a Chinese hospital. One-way sensitivity analyses as well as second-order Monte Carlo and probabilistic sensitivity analyses were performed.The transition probabilities and utilities were extracted from published literature, and deterministic sensitivity analyses were conducted. Results We identified 41 breast cancer patients at Hangzhou First People’s Hospital, among whom 15 (60%) had a partial response for AC-TH treatment and 13 (81.25%) had a partial response for TCH treatment.No cardiac toxicity was observed. Hematologic grade 3 or 4 toxicities were observed in 1 of 28 patients.Nonhematologic grade 3 or 4 toxicities with a reverse pattern were observed in 6 of 29 patients. The mean QALY gain per patient compared with TCH was 0.25 with AC-TH, while the incremental costs were $US13,142. The incremental cost-effectiveness ratio (ICER) of AC-TH versus TCH was $US 52,565 per QALY gained. Conclusions This study concluded that TCH neoadjuvant chemotherapy was feasible and active in HER2-overexpressing breast cancer patients in terms of the pathological complete response, complete response, and partial response rates and manageable toxicities.

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Anemia Requiring Transfusion in Breast Cancer Patients on Dose-dense Chemotherapy: Prevalence, Risk Factors, Cost and Effect on Disease Outcome.

10.21203/rs.3.rs-990324/v1 ◽

2021 ◽

Author(s):

Parth Sharma ◽

Josh Thomas Georgy ◽

Anand George Andrews ◽

Ajoy Oommen John ◽

Anjana Joel ◽

...

Keyword(s):

Breast Cancer ◽

Risk Factors ◽

Cancer Patients ◽

Transfusion Requirement ◽

Low Grade ◽

Breast Cancer Patients ◽

Factors Associated ◽

Grade 3 ◽

Dose Dense ◽

Delay In Treatment

Abstract Purpose: Dose dense chemotherapy improves survival but also increases toxicity and treatment related cost. Here we report the prevalence of anemia, understand the risk factors of chemotherapy related anemia and determine the cost and time-delay associated with transfusion requirement in Indian non-metastatic breast cancer patients on dose dense preoperative chemotherapy.Methods: In this study, 116 triple negative breast cancer (TNBC) patients were treated preoperatively with Docetaxel and Cyclophosphamide alternating with Epirubicin and Cisplatin every 2-weekly. Patients were evaluated for anemia pre- and post-chemotherapy. We examined trends in the cell counts, transfusion requirement, time to transfusion as well as risk factors associated with transfusion during treatment, along with delay in treatment due to anemia and the additional cost incurred.Results: One hundred and sixteen women with high-risk non-metastatic TNBC were treated. Median age was 44.5 years. 56.1% had stage III disease. Delivery of 6/8 planned doses was achieved in 98.3% of patients, and all 8 doses in 86% patients. Anemia was detected at baseline in 54(46.5%) patients with mild(10-12g/dl) anemia in 42(36.2%) patients and moderate(8-10g/dl) in 12(10.3%) patients. Forty-four patients (37.9%) required transfusion during chemotherapy with 55(47.4%) patients having grade 1-2 anemia and 40(34.5%) patients having grade 3 anemia. The factors associated with transfusion were low grade of tumor (OR 2.48 (95% CI 1.08 - 5.68), p = 0.025), hemoglobin post 2 cycles of chemotherapy (OR 1.74 (95% CI 1.21- 2.51), p = 0.003), thrombocytopenia grade 3 or 4 (OR 4.35 (95% CI 1.062-17.827), p = 0.034) and drop in hemoglobin after 2 cycles (OR 1.65 (95% CI 1.09-2.48), p = 0.017). Nearly one fourth of the study population had a delay between two cycles of chemotherapy due to anemia. A median additional cost of Rs 7000 (IQR-Rs 7000 – Rs 14000) was incurred on transfusion.Conclusion: Anemia is a common toxicity associated with dose dense chemotherapy during curative breast cancer treatment leading to delay in treatment and increased cost. Low grade tumor, grade 3 or 4 thrombocytopenia and Grade 2 or higher anemia after 2 cycles of chemotherapy are risk factors for blood transfusions during treatment.

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CLINICAL AND SUBCLINICAL CHARACTERISTICS ON BREAST CANCER PATIENTS TREATED WITH ANTHRACYCLINES

Tạp chí Y học Cộng đồng ◽

10.52163/vjcm.v62i5.131 ◽

2021 ◽

Vol 62 (5) ◽

Author(s):

Bui Dang Minh Tri ◽

Doan Thanh Truc ◽

Tri Kim Ngoc ◽

Vo Van Cuong

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Ductal Carcinoma ◽

Nipple Discharge ◽

Medullary Carcinoma ◽

Unknown Boundary ◽

Age Group ◽

Breast Cancer Patients ◽

Research Subjects ◽

Tubular Carcinoma

Objective: Describing the clinical and subclinical characteristics on breast cancer patients treated with Anthracyclines at Thong Nhat hospital.Subjects and methods: a prospective descriptive study on 43 patients with breast cancer was treated with Anthracyclines with 4 to 6 cycles as determined by clinical doctor at Thong Nhat hospital. Results: Average age: 49.2 ± 3.2 years old. The age group accounted for the largest proportion in the study object was the 50-60 age group (48.84%). The percentage of patients who self-examined the tumor was the highest with 79.07%. There were 9.30% of patients with pain symptoms, 11.63% of patients with nipple discharge. Tumor position in the upper-external quadrant accounted for the largest percentage with 55.81%. The average size of tumors was 2.56 ± 1.2 (cm). The main form of lesions detected on ultrasound was the local lesion with over 80% with an unknown boundaryfeature (81.40%) and predominantly invasive (76.74%). The histopathological type accounted for the highest percentage was the invasive tubular carcinoma (79.07%), the medullary carcinoma andmucinous carcinoma body accounted for the lowest rate with 2.33% and 0%, respectively. The histological degree accounted for the highest percentage among the research subjects was degree 2with 50.18%. Stage III accounted for the highest rate with 46.51%.Conclusion: The most common age group for breast cancer was 50-60 years old, the main symptom was self-examination with breast tumors, breast cancer were mainly local tumor at the upper-externalposition. On ultrasound, the lesions were the local, unknown boundary, and invasive lesions. Breast cancer was mainly invasive ductal carcinoma, histologic degree 2.

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Imaging breast cancer using hyperpolarized carbon-13 MRI

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1913841117 ◽

2020 ◽

Vol 117 (4) ◽

pp. 2092-2098 ◽

Cited By ~ 20

Author(s):

Ferdia A. Gallagher ◽

Ramona Woitek ◽

Mary A. McLean ◽

Andrew B. Gill ◽

Raquel Manzano Garcia ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Lobular Carcinoma ◽

Hypoxia Inducible Factor ◽

Breast Cancer Patients ◽

Signal Ratio ◽

Tumor Subtypes ◽

Treatment Naïve ◽

Grade 3 ◽

Metabolic Heterogeneity

Our purpose is to investigate the feasibility of imaging tumor metabolism in breast cancer patients using 13C magnetic resonance spectroscopic imaging (MRSI) of hyperpolarized 13C label exchange between injected [1-13C]pyruvate and the endogenous tumor lactate pool. Treatment-naïve breast cancer patients were recruited: four triple-negative grade 3 cancers; two invasive ductal carcinomas that were estrogen and progesterone receptor-positive (ER/PR+) and HER2/neu-negative (HER2−), one grade 2 and one grade 3; and one grade 2 ER/PR+ HER2− invasive lobular carcinoma (ILC). Dynamic 13C MRSI was performed following injection of hyperpolarized [1-13C]pyruvate. Expression of lactate dehydrogenase A (LDHA), which catalyzes 13C label exchange between pyruvate and lactate, hypoxia-inducible factor-1 (HIF1α), and the monocarboxylate transporters MCT1 and MCT4 were quantified using immunohistochemistry and RNA sequencing. We have demonstrated the feasibility and safety of hyperpolarized 13C MRI in early breast cancer. Both intertumoral and intratumoral heterogeneity of the hyperpolarized pyruvate and lactate signals were observed. The lactate-to-pyruvate signal ratio (LAC/PYR) ranged from 0.021 to 0.473 across the tumor subtypes (mean ± SD: 0.145 ± 0.164), and a lactate signal was observed in all of the grade 3 tumors. The LAC/PYR was significantly correlated with tumor volume (R = 0.903, P = 0.005) and MCT 1 (R = 0.85, P = 0.032) and HIF1α expression (R = 0.83, P = 0.043). Imaging of hyperpolarized [1-13C]pyruvate metabolism in breast cancer is feasible and demonstrated significant intertumoral and intratumoral metabolic heterogeneity, where lactate labeling correlated with MCT1 expression and hypoxia.

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Serum ANGPTL2 Levels Reflect Clinical Features of Breast Cancer Patients: Implications for the Pathogenesis of Breast Cancer Metastasis

The International Journal of Biological Markers ◽

10.5301/jbm.5000080 ◽

2014 ◽

Vol 29 (3) ◽

pp. 239-245 ◽

Cited By ~ 22

Author(s):

Motoyoshi Endo ◽

Yutaka Yamamoto ◽

Masahiro Nakano ◽

Tetsuro Masuda ◽

Haruki Odagiri ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Clinical Features ◽

Cancer Progression ◽

Breast Cancer Cells ◽

Cancer Metastasis ◽

Ductal Carcinoma ◽

Breast Cancer Metastasis ◽

Breast Cancer Patients

Introduction Breast cancer is a leading cause of cancer-related death in women worldwide, and its metastasis is a major cause of disease mortality. Therefore, identification of the mechanisms underlying breast cancer metastasis is crucial for the development of therapeutic and diagnostic strategies. Our recent study of immunodeficient female mice transplanted with MDA-MB231 breast cancer cells demonstrated that tumor cell-derived angiopoietin-like protein 2 (ANGPTL2) accelerates metastasis through both increasing tumor cell migration in an autocrine/paracrine manner, and enhancing tumor angiogenesis. To determine whether ANGPTL2 contributes to its clinical pathogenesis, we asked whether serum ANGPTL2 levels reflect the clinical features of breast cancer progression. Methods We monitored the levels of secreted ANGPTL2 in supernatants of cultured proliferating MDA-MB231 cells. We also determined whether the circulating ANGPTL2 levels were positively correlated with cancer progression in an in vivo breast cancer xenograft model using MDA-MB231 cells. Finally, we investigated whether serum ANGPTL2 levels were associated with clinical features in breast cancer patients. Results Both in vitro and in vivo experiments showed that the levels of ANGPTL2 secreted from breast cancer cells increased with cell proliferation and cancer progression. Serum ANGPTL2 levels in patients with metastatic breast cancer were significantly higher than those in healthy subjects or in patients with ductal carcinoma in situ or non-metastatic invasive ductal carcinoma. Serum ANGPTL2 levels in patients negative for estrogen receptors and progesterone receptors, particularly triple-negative cases, reflected histological grades. Conclusions These findings suggest that serum ANGPTL2 levels in breast cancer patients could represent a potential marker of breast cancer metastasis.

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Gemcitabine and docetaxel combination regimen in metastatic breast cancer (MBC)

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.1107 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 1107-1107

Author(s):

D. Karacetin ◽

O. Maral ◽

O. Aksakal ◽

B. Okten ◽

B. Yalçın ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Cancer Patients ◽

Response Rate ◽

Menopausal Status ◽

Metastatic Breast ◽

Complete Response ◽

Combination Regimen ◽

Breast Cancer Patients ◽

Grade 3

1107 Background: No standart chemotherapy regimen has been estabilished for the treatment of patients with metastatic breast cancer. The gemcitabine and docetaxel combination has been shown to be synergistic . This study is conducted to verify the clinical efficacy and safety of gemcitabine and docetaxel combination therapy in metastatic breast cancer. Methods: 27 metastatic breast cancer patients were treated with gemcitabine-docetaxel combination . Gemcitabine 1,250 mg/m2 IV infusion, on day 1 and 8, and docetaxel 70 mg/m2 on day 1 in 21 day cycles. 4–6 cycles of chemotherapy were repeated every 3 weeks. The primary endpoint was response rate, and survival. Results: The median age was 50 years (range,32–77). Performans status (ECOG) was 0–1. Hormone receptor status: ER+/ER-; 11/16, PR+/PR-; 14/13. Menopausal status were: 11 premenopausal, 16 postmenopausal. Of the 27 evaluable patients, there were 11 (40.7%) partial responses and no complete response. Overall response rate was 40.7%. Median time to progression was 7 months, and median survival was 14 months. Toxicities included grade 3–4 neutropenia in 9 (30%), thrombocytopenia in 6 (22%), anemia in 3(9%). There were no treatment releated deaths Conclusions: The combination of gemcitabine and docetaxel has shown favorable toxicity profile and promising activity in metastatic breast cancer patients. No significant financial relationships to disclose.

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Clinical outcome of node-negative (NN) breast cancer (BC) patients

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.11102 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 11102-11102

Author(s):

G. Atalay Basaran ◽

D. Cabuk ◽

F. Dane ◽

M. Teomete ◽

S. Iyikesici ◽

...

Keyword(s):

Breast Cancer ◽

Adjuvant Chemotherapy ◽

Cancer Patients ◽

Treatment Decision ◽

Breast Conserving Surgery ◽

Breast Cancer Patients ◽

Prognostic Information ◽

Treatment Decision Making ◽

Group 5 ◽

Grade 3

11102 Background: Breast cancer patients (pts) with NN disease have diverse clinical outcomes. An optimal treatment decision- making tool has not been defined for this heterogeneous group. Methods: We identified pts with NN disease who have been treated between 1998–2006 in our department. We recorded the clinical/pathological, treatment characteristics and analyzed their survival outcome. High risk (HR) was defined as having at least one of the following features: age<35 yr-old, pts with grade 3 tumors (tms), ER and PR negative tms, tm size >2 cm. Results: Out of 597 early BC pts, 275 pts with NN disease were identified, 190 pts with HR, 85 with low risk (LR) features.The median age was 51 (26–83). The median follow up was 40 months (4–120 months). 47% pts were premenopausal. 31% pts had breast conserving surgery (BCS).58/29% pts had grade 2/3 tms. 34% pts with BCS or T3 tms received adjuvant radiotherapy. All receptor positive pts received adjuvant endocrine therapy (ET). In the HRNN group, 5% pts had tms>5cm, 51/40% pts had grade 2/3 tms, 43% pts had ER/PR negative tms. In the LRNN group 25/74% pts had grade 1/2 tms, no pt had receptor negative tm. 86%/51% pts received adjuvant chemotherapy (CT) in the HR and LRNN groups. 12%/48% pts received adjuvant ET alone in the HR and LRNN groups. 5pt in the HR and 1 pt in the LR group received no adjuvant systemic therapy due to their comorbidities and/or negative receptor status. So far, 14 pts had relapsed (8 from the HR, 6 from the LR group) and 3 pts died due to BC (1 from the HR, 2 from LR group). The 5-yr DFS was %94 in the HR and was %90 in the LR groups. HRNN pts had %98 and LRNN pts had %95 5-yr OS. Conclusion: It seems that prognostic information based merely on clinical/pathological characteristics might not accurately quantify the risk of recurrence and death, so that the decisions about adjuvant chemotherapy in NN breast cancer patients. Prospective evaluation of the performance of the new genomic prognostic tools compared to traditional prognostic factors is needed in order to more clearly define the HR vs LR subsets of NNBC pts. No significant financial relationships to disclose.

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Early-stage male breast cancer: A 10-year experience

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e11630 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e11630-e11630

Author(s):

N. Gercovich ◽

E. Gil Deza ◽

M. Russo ◽

C. Garcia Gerardi ◽

C. Diaz ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Male Breast Cancer ◽

Ductal Carcinoma ◽

Early Stage ◽

Male Breast ◽

Stage I ◽

Stage Ii ◽

Breast Cancers ◽

Breast Cancer Patients

e11630 Introduction: Male breast cancer is very rare, representing only between 0.7% and 1% of all breast cancers, and only half of them are early stage cases. Objective: The present study has been designed with the aim of studying retrospectively the clinical onset and evolution of male invasive breast cancer patients (stages I and II) treated at IOHM between 1997 and 2008. Methods: The records of 3,000 breast cancer cases followed between 1997 and 2008 were searched, looking for male stage I and II breast cancer patients. A database was designed following the recommendations of the Directors of Surgical Pathology of the USA. The information registered encompassed: adjuvant treatments, recurrence date and date of final consultation or death. Results: Twelve pts were identified. Mean age (range)= 66 yo (50–89 yo). Tumoral type= Invasive Ductal Carcinoma 12 pt. Tumoral subtype= NOS 9 pt (75%) Apocrine 2 pt (17%) Micropapillar 1 pt (8%). Nottingham´s grade= Grade 2: 8 pt, Grade 3: 3 pt, N/A=1 pt. Stage= I= 6 pt, II=6 pt. ER (Positve= 9 pt, Negative=1 pt, N/A= 2 pt). PR (Positve= 8 pt, Negative= 2 pt, N/A=2 pt). Her2neu (0+= 3 pt, 1+= 3 pt, 2+= 2 pt, N/A= 4 pt). Surgery= Mastectomy= 11 pt, Lumpectomy 1= pt. Radiotherapy=5 pt. Adjuvance= No=2 pt, Hormonotherapy (HT)= 3 pt, Chemotherapy (CHT) = 3 pt, CHT+HT= 4 pt. Recurrence= Yes= 2 pt, No= 10 pt. Survival: Dead= 1 pt, Alive =11 pt. Mean Time To Progression= Stage I =66 months, Stage II =42 months. Global survival: Stage I =66 months, Stage II =52 months. Conclusions: 1. Twelve stage I and II male breast cancer patients were identified out of 3000 (0.4%) breast cancer cases diagnosed and followed in the past 10 years at the IOHM. 2. Mastectomy was the surgical procedure in 11 of the 12 cases 3. Ten pt underwent adjuvant treatment. 4. With a mean follow up time of 60 months, all stage I patients are alive and there were no recurrences. Two of the 6 stage II pts progressed and one died. No significant financial relationships to disclose.

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