ChemInform Abstract: Immune Manipulation of Advanced Breast Cancer: An Interpretative Model of the Relationship Between Immune System and Tumor Cell Biology

Background. Breast cancer is the highest prevalence of malignancy for women in Indonesia and important national health problem. Estimated 2 million women developed breast cancer in 2018 with a mortality rate of 14.1 in every 100,000 women. Regarding the relationship between subtypes and breast cancer recurrence Several studies on gene expression have shown several subtypes of breast cancer, including the two most important subtypes, estrogen receptor (ER) positive (Luminal A and Luminal B) and ER negative (Triple negative and Her2 positive). Based on the explanation above, currently there is no data in Soetomo Hospital that discusses the role of breast cancer subtypes as a prognostic factor in determining the recurrence rate in locally advanced breast cancer.Methods. The research design is an associative test using a retrospective cohort observational analytical study design, associating the relationship between tumor subtypes with recurrence in locally advanced breast cancer patients after mastectomy and has received additional therapy according to standard procedures at Dr. Soetomo Surabaya This study used secondary data from the medical records of the Oncology Polyclinic, RSUD Dr. Soetomo Surabaya from 2014 to 2019.Results. The research subjects who have been selected according to inclusion criteria are 214 people, with the proportion in the population of luminal A and luminal B subtypes of 107 people each. Based on this study, it was found that the subtype was positively correlated with recurrence in LABC patients who had undergonecmastectomy with a significance value of p = 0.000 (p <0.05; 99% CI).Conclusion. There is a relationship between the recurrence rate and the molecular subtype of breast cancer in locally advanced breast cancer (LABC) patients after mastectomy at Dr Soetomo Hospital.

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Perubahan Volume Tumor, Jumlah Trombosit dan Kadar D–dimmer pada Karsinoma Payudara Lanjut Lokal Setelah Kemoterapi Neoadjuvan

Jurnal llmu Bedah Indonesia ◽

10.46800/jibi-ikabi.v43i1.70 ◽

2014 ◽

Vol 43 (1) ◽

pp. 23-28

Author(s):

Fredy Rustomi Damanik ◽

Maman Abdurahman ◽

Kiki Akhmad Rizki

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Advanced Breast Cancer ◽

Tumor Volume ◽

Locally Advanced Breast Cancer ◽

Locally Advanced ◽

Advanced Breast ◽

Clotting Factors ◽

Platelet Level ◽

The Relationship

Background. Locally advanced breast cancer places approximately 40–60% from all the new cases of breast cancer in developing countries. And this kind of breast cancer requires a combined therapy, i.e. chemotherapy, surgery and radiotherapy. Nowadays, the response of chemotherapy is evaluated from the reduction in tumor volume. There is also another parameter. Since half of patients with breast cancer show abnormalities of routine blood clotting factors, D–dimmer which is a fibrin degeneration product from vascular endothelial growth factor (VEGF) is used. There is an increase of plasma D–dimmer level among 86% of breast cancer patients. There is a strong relationship amongst serum VEGF and platelets count in breast cancer patient. Method. To analyze the correlation, we did an evaluation of the tumor volume, platelets count, and plasma D– dimmer among patients with locally advanced breast cancer, before and after cyclophospamide, doxorubicin, 5–fluorouracil (FAC) combined neoadjuvant chemotherapy. This was a prospective study enrolling 36 subjects. The data is obtained from the history, physical examination, laboratory and or radiological exams as it found in medical record. To have a normal distribution of the subjects, a Shapiro–Wilk test was done. Pearson correlation test was applied in evaluation of the relationship of tumor volume, platelet count and plasma D–dimmer level after chemotherapy. Data was analyzed using the SPSS program ver.19. Results. Tumor volume decreases till 153.811 cm3, the platelet level decreased till 4,958.333/mm3 and the plasma D–dimmer level also decreased up to101.389 ng/ml after FAC regimen. A significant relationship was found in platelet counts and tumor volume after chemotherapy with r of 0,391 (p=0,018). The relationship amongst the change in platelet level and plasma D–dimmer level showed a plateau which is quiet high with the value of r=0,473 (p=0,024). Conclusion. There is a positive correlation of the tumor volume, the platelet level, and plasma D–dimmer level after combined FAC neoadjuvant chemotherapy

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Modeling of pharmacodynamic (PD) biomarkers (BM) related to CDK4/6 inhibition and exploratory BM-response (progression free survival [PFS]) analyses in patients with advanced breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e14528 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e14528-e14528

Author(s):

Yanke Yu ◽

Yuan Liu ◽

Diane Dan Wang

Keyword(s):

Breast Cancer ◽

Advanced Breast Cancer ◽

Time Course ◽

Small Sample Size ◽

Phase 1 ◽

Small Sample ◽

Advanced Breast ◽

Longitudinal Change ◽

Indirect Response Model ◽

The Relationship

e14528 Background: Palbociclib (PAL) is an oral inhibitor of cyclin-dependent kinase 4 and 6 (CDK4/6) approved for advanced breast cancer (ABC). In a clinical trial, the expression levels of PD BMs related to PAL effect, including thymidine kinase (TK) in serum and phosphor-Rb (pRb) and Ki67 in skin tissues, were measured at both baseline and post-treatment in patients with ABC treated with PAL plus letrozole (LET). Pharmacokinetic (PK)/PD modeling was conducted previously to characterize the longitudinal change of pRb and Ki67. The PK/PD was further evaluated for TK and exploratory analyses were conducted to evaluate the relationship between PFS and all three BMs. Methods: The present analyses used data from a Phase 1 study evaluating the PK, PD, safety and efficacy of PAL plus LET in 26 Chinese women with ABC. A 2 compartment model was used to describe the PK of PAL. A precursor-dependent indirect response model was developed to describe the TK time course after PAL treatment. PAL effect was modeled as Imax inhibitory model. Cox proportional hazard model was used to assess the correlation of PFS with three BM metrics (baseline BM, simulated lowest BM and maximum BM change in Cycle 1). Results: The BM data included 194 TK observations from 26 patients. The PK/PD models adequately described the longitudinal change of TK, and showed PAL caused TK reduction. The estimated IC50 value was 49.5 ng/mL, similar to those for pRb and Ki67. The BM-response analyses for PFS showed that correlation was found for TK. There was a significant correlation between PFS and baseline TK (BTK) and minimum TK (MTK) in Cycle 1. A longer PFS was associated with lower BTK and lower MTK. A trend for longer PFS with higher maximum TK change in Cycle 1 was observed although the relationship was not statistically significant. Conclusions: PAL exposure had significant correlation with the reduction of all three BMs. Longer PFS was associated with lower BTK and MTK. Due to the small sample size (N = 26), this analyses result need to be confirmed in a larger study.

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