Introduction Neoadjuvant chemotherapy has become the standard form of treatment for locally advanced breast cancer. Chemoresistence is a problem that limits the effectiveness of chemotherapy. Therefore, predictive biomarkers are needed to choose the appropriate chemotherapy to the right patient. The role of NF-кb expression as a predictive biomarker of neoadjuvant chemotherapy response needs to be investigated in patients with locally advanced breast cancer who are treated with a regimen of cyclophosphamide-doxorubicin-5FU (CAF). Methods This observational study used the prospective cohort method to examine 62 samples. CAF was administered at 3-week intervals for 3 cycles of chemotherapy. The data utilized in this study include the positive and negative expression of NF-κB, ER, and HER2 overexpression. The cases were divided into groups that were responsive and non-responsive to the neoadjuvant chemotherapy. Results The average age in the youngest group was 26 years, and that in the oldest was 66 years. The highest age group was subjects in their 50s, which had 26 cases (41.9%). The majority of the cases were moderate grade with 38 cases (61.3%). The percentage of responsive subjects was higher in the groups with negative NF-κB expression (82.5%), positive HER2 status (85.7%), and negative ER status (71.9%). It was found that 37 cases (59.7%) were responsive to CAF, while 25 cases (40.3%) were non-responsive. There was a significant relationship between NF-κB expression and chemotherapy response (p < 0.05), and the percentage of responsive subjects was higher among those with negative NF-κB expression (82.5%) than positive NF-κB expression (18.2%). Conclusion NF-κB expression, ER status, and HER2 have a significant relationship with the response to anthracycline-based neoadjuvant chemotherapy for local advanced breast cancer, and NF-κB expression has the most significant relationship with the chemotherapy response. Therefore, NF-κB expression should be considered as a predictive biomarker for the response to CAF regimens.

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BACKGROUND: Breast cancer (BC) is the most common cancer among women worldwide and a leading cause of death in Indonesia. The primary treatment of locally advanced BC is neoadjuvant chemotherapy (NAC). The rapid proliferation of tumor cells in a neoplastic microenvironment is largely due to hypoxia, which also encourages the development of chemoresistant BC. The master regulator of the hypoxia response is hypoxia-inducible factor-1α (HIF-1α). The response evaluation criteria in solid tumors (RECIST) is an objective response metric that demonstrates the efficacy of a NAC based mostly on the size of the tumor. Ca15-3 is the protein product of the MUC1 gene and is the most widely used serum marker in BC. The purpose of this study is to investigate the relationship between HIF-1α and RECIST and between Ca15-3 and RECIST and to assess the relationship among all of them in BC. METHODS: This observational study used the prospective cohort method included 11 patients with histopathologically confirmed BC, specifically invasive ductal carcinoma. We evaluated the changes in HIF-1α and Ca15-3 serum levels using ELISA and measured tumor lesions with RECIST. The procedure was carried out twice. Serum levels were measured at baseline, and after receiving two cycles of NAC (5 weeks). RESULTS: Among the 11 patients included in this study, HIF-1α, Ca15-3, and RECIST decreased significantly after NAC. The changes in RECIST correlated with Ca15-3: each unit decrease in RECIST score was associated with a 0.3-unit decrease in Ca15-3 levels (p = 0.019). CONCLUSIONS: There was a decrease in HIF-1α, followed by a decrease in Ca15-3 and RECIST in response to chemotherapy. There was a statistically significant correlation between Ca15-3 and response to chemotherapy. This study evidences the relationship between factors that shape the local tumor microenvironment.

Tujuan: Untuk menganalisa hubungan kadar monosit sel darah tepi pada sebelum dan sesudah terapi pada penderita kanker payudara. Metode: Penelitian ini merupakan studi analitik observasional dengan pendekatan kohort prospektif, untuk menganalisa kadar monosit darah tepi sebelum dan sesudah terapi pada penderita kanker payudara. Kriteria inklusi penelitian ini, yaitu: pasien wanita dengan diagnosa kanker payudara stadium lanjut, umur 35-75 tahun dan pasien menyetujui untuk diikutsertakan dalam penelitian. Adapun kriteria eksklusinya adalah pasien wanita dengan diagnosa kanker payudara stadium dini, adanya keganasan atau kelainan hematologi sebelumnya, dan pasien yang meninggal selama waktu penelitian. Hasil: Pada penelitian ini didapatkan sebelum terapi median monosit adalah 5% (IQR 3-10%) dan sesudah pasien mendapatkan pengobatan mediannya turun menjadi 3% (IQR 1,0-7,7 menjadi lebih nyata dan bermakna (p<0,001). Analisis regresi linear dilakukan dalam analisis data orisinil dan data hasil resampling. Hasil estimasi perubahan kadar monosit menggunakan kedua data ini tidak berbeda jauh (-3,47 vs -3,63% masing-masing pada model dengan data orisinil dan resampling), yang menandakan penurunan monosit darah tepi setelah terapi. Perbedaanya adalah hasil analisis menggunakan data resampling menghasilkan interval estimasi yang lebih sempit (95% CI -4,23 hingga -3,03%) dengan nilai p<0,001 yang menandakan perhitungan yang bermakna secara statistik. Simpulan: Terdapat penurunan kadar monosit sel darah tepi pada pasien kanker payudara setelah dilakukan terapi.

Neoadjuvant chemotherapy is one of the therapeutic modalities used in the management of locally advanced breast cancer. Therapeutic response can be objectively assessed with RECIST and Ca 15-3 could be used to monitor response to breast cancer (BC) treatment. This study was aimed to prove the relationship between Ca 15-3 and response to neoadjuvant chemotherapy in locally advanced BC. The study was carried out at the Departement of Surgery Prof. Dr. R. D. Kandou Hospital Manado using a single-arm pre-post trial. Each patient would be performed Ca 15-3 test and clinical assessment (RECIST) pre and post chemotherapy for two sessions. There were 11 BC patients with invasive ductal carcinoma.  The average age was 60 years old and the majority had anemia and lymphocytopenia. There was a decrease in Ca 15-3 in each patient by a baseline of 21.8 U/mL pre-treatment and a decrease in the lesion size by 30.3 mm using RECIST. The results showed that changes in RECIST and Ca 15-3 level were correlated with each unit change in RECIST was associated with a decrease in Ca 15-3 level by 0.03 units (p=0.019). In conclusion, there was a decrease in Ca 15-3 level in response to chemotherapy, followed by a decrease in RECIST. There was a relationship between Ca 15-3 level and chemotherapy response assessed with RECIST after the second chemotherapy.Keywords: Ca 15-3, chemotherapy response, neoadjuvant chemotherapy, RECIST, breast cancer  Abstrak: Kemoterapi neoadjuvan masih merupakan pilihan utama terapi untuk kanker payudara (KPD) stadium lanjut local. Respon suatu kemoterapi dapat dinilai secara objektif dengan RECIST dan Ca 15-3 dapat digunakan untuk memantau respon terhadap pengobatan KPD. Penelitian ini bertujuan untuk membuktikan hubungan antara Ca 15-3 dengan respon kemoterapi neoadjuvan RECIST pada pasien KPD stadium lanjut lokal. Penelitian dilaksanakan di Bagian Bedah RSUP Prof. Dr. R. D. Kandou, Manado dengan menggunakan single-arm pre-post trial. Setiap individu yang terlibat akan diperiksa kadar Ca 15-3, serta penilaian RECIST sebelum dan sesudah mereka menerima kemoterapi selama dua sesi. Hasil penelitian mendapatkan 11 pasien KPD dengan karsinoma duktal invasif. Rerata usia 60 tahun, umumnya dengan anemia dan limfositopenia. Terdapat penurunan Ca 15-3 pada tiap pasien sebesar awal 21,8 U/mL pra pengobatan dan penurunan lesi 30,3 mm saat dinilai menurut RECIST. Didapatkan bahwa perubahan RECIST dan Ca 15-3 memiliki keterkaitan dengan setiap unit perubahan RECIST berhubungan dengan penurunan kadar Ca 15-3 sebesar 0,03 unit (p=0,019). Simpulan penelitian ini ialah terdapat hubungan antara kadar Ca 15-3 dengan respon kemoterapi setelah kemoterapi siklus ke dua.Kata kunci: Ca 15-3; respon kemoterapi; neoadjuvan kemoterapi; RECIST; kanker payudara