Role of clustered amplification as a marker for a special sensitivity to neoadjuvant anti-HER2 therapy with trastuzumab in patients with stage II-III breast cancer

Kolyadina, I. V.; Завалишина, Л Э; Ganshina, Inna P.; Andreeva, Yu Yu; Франк, Г. А.; Гордеева, О. О.; Zhukova, L.; Meshcheryakov, Andrey; Savelov, N.; Tuzova, Elena; Morozov, D. A.; Poddubnaya, I V

doi:10.17116/patol20198106156

Cited by 4 publications

(2 citation statements)

References 7 publications

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“…Human epidermal growth factor receptor 2 (HER-2) is a very important member of EGFR family. There are many studies on breast cancer and gastric cancer, and the conclusions are consistent [16][17][18][19] . HER-2 inhibitors have been used in the treatment of the above tumors [20,21] .…”

Section: Introductionmentioning

confidence: 66%

Clinic-pathological characteristics of MMR protein, KRAS-NRAS-BRAF gene mutation, HER-2 and PD-L1 status in 3822 Chinese colorectal cancer patients

Zhang¹,

Chen²,

Li³

et al. 2020

Preprint

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ObjectivesColorectal cancer is one of the most common cancers. It is a heterogeneous tumor. The aim of this study was to investigate MMR protein expression, KRAS-NRAS-BRAF gene mutation, HER-2 and PD-L1 status in large Chinese CRC patients. MethodsWe reviewed all CRC patients who underwent surgery in Peking University Cancer Hospital between 2010 and 2018 from a prospective collected medical database. We analyzed the clinic-pathological factors associated with immunohistochemistry profiles. We analyzed KRAS-NRAS-BRAF gene changes through ARMS-PCR. ResultsIn our study, d-MMR frequency of CRC was 8%. d-MMR was more common in poorly differentiated colorectal cancer (p = 0.000), and d-MMR was more likely to occur in stage T3 + T4( p = 0.026), and p-MMR was more likely to have lymph node metastasis(p = 0.000). d-MMR was more likely to occur in the right colon, and p-MMR patients usually occur in the rectum sigmoid colon(p = 0.000). p-MMR patients were more likely to have distant metastasis (p = 0.000). We analyzed all 3822 patients with-BRAF status available by IHC, the frequency of BRAF positive expression ration was 1.4%. A total of 1068 colorectal cancer patients had gene analysis by ARMS-PCR. 484 of them had KRAS gene mutation, 28 NRAS gene mutation, 20 BRAF mutation and 536 patients had no mutation. The percentage was 45%, 2.6%, 2%, and 50%, respectively. d-MMR patients usually had BRAF gene mutation (p < 0.001). KRAS and NRAS gene mutations were not associated with MMR status (p = 0.846, p = 0.438). PD-L1 expression was higher in the female group (p = 0.034), poorly differentiated adenocarcinoma group(p = 0.026), and d-MMR group (p = 0.005). The ratio of HER-2 3 + was 1.9%, and HER-2 3 + was usually found in p-MMR group(p = 0.043). ConclusionOur data can improve deeper understanding of colorectal cancer carcinogenic factors and future therapies for colorectal cancer.

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Section: Introductionmentioning

confidence: 66%

Clinic-pathological characteristics of MMR protein, KRAS-NRAS-BRAF gene mutation, HER-2 and PD-L1 status in 3822 Chinese colorectal cancer patients

Zhang¹,

Chen²,

Li³

et al. 2020

Preprint

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“…Therefore, targeted therapy for growth, proliferation, apoptosis, and metastasis of tumor cells has become an important research direction. Kolyadina et al [ 20 ] found that the occurrence and metastasis of many tumors were related to cell overproliferation caused by overexpression of specific oncogenes or receptor genes. Usually, HER2 protein is expressed only in the fetal period, and in a few tissues at a low level or not expressed in adulthood, but it is overexpressed in many tumor tissues.…”

Section: Discussionmentioning

confidence: 99%

Honokiol Suppression of Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Gastric Cancer Cell Biological Activity and Its Mechanism

Yan

Mao

2020

Med Sci Monit

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Clinical and morphological aspects of neoadjuvant chemotherapy efficacy in patients with aggressive luminal HER2-negative breast cancer

Morozov

Kolyadina

Poddubnaya

et al. 2022

Opuholi ženskoj reproduktivnoj sistemy

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Background. The role of neoadjuvant chemotherapy (NACT) in luminal HER2-negative breast cancer (BC) remains highly controversial due to the lack of reliable predictors of drug therapy efficacy.Objective: to evaluate the effectiveness of NACT in patients with aggressive luminal HER2-negative BC and to compare modern systems for assessing the pathomorphological response.Materials and methods. The tumor response to NACT regimens was assessed in 64 patients with aggressive luminal HER2-negative BC stage II–III. The median age of women was 46.5 years (range 31–76 years), 76.6 % had primary operable stages (cT1–3N0–1), locally advanced BC (cT4, cN2–3) – 23.4 % patients. The characteristics of BC were as follows: invasive ductal carcinoma (76.6 %), grade G2 and G3–54.7 % and 45.3 %, Ki-67 ranged from 20 % to 98 %, median 45 %. The ER expression level was low (1–10 %, ERlow) in 12.5 % and was more than 10 % in 87.5 % of cases. HER2 status corresponded to 0, 1+ and 2+ in the absence of gene amplification – in 50.0 %, 35.9 % and 14.1 % of patients, respectively. The rate of TILs <10 %, 10–20 % and >20 % was in 71.4 %, 10.7 % and 17.9 % of cases. After NACT with the inclusion of anthracyclines and taxanes ± platinum combinations (in BRCA mutated status), the patients underwent radical surgery (mastectomy or breast-conserving surgery) with an assessment of the pathological response.Results. 15.6 % of patients had a complete pathomorphological response (pCR) to treatment, which corresponded to the RCB-0 class and the pathomorphological stage ypT0N0. Residual tumor load with incomplete response was very significant – class RCB-I was noted in only 7.8 %, and RCB-II and RCB-III – in 39.1 % and 37.5 %, respectively. An increase in the size of the residual tumor and the number of affected lymph nodes were associated with an increase in the RCB class. Predictors of pCR achievement in luminal HER2-negative cancer were: grade G3, rare histological forms of BC (medullary, metaplastic), rate of TILs ≥30 %, low ER expression, and HER2 0 status.Conclusion. Assessment of Ki-67, tumor grade, ER and HER2 rate, and TILs before starting NACT will help identify a group of high sensitivity to chemotherapy and optimize the treatment strategy in aggressive luminal HER2-negative BC.

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Role of clustered amplification as a marker for a special sensitivity to neoadjuvant anti-HER2 therapy with trastuzumab in patients with stage II-III breast cancer

Cited by 4 publications

References 7 publications

Clinic-pathological characteristics of MMR protein, KRAS-NRAS-BRAF gene mutation, HER-2 and PD-L1 status in 3822 Chinese colorectal cancer patients

Clinic-pathological characteristics of MMR protein, KRAS-NRAS-BRAF gene mutation, HER-2 and PD-L1 status in 3822 Chinese colorectal cancer patients

Honokiol Suppression of Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Gastric Cancer Cell Biological Activity and Its Mechanism

Clinical and morphological aspects of neoadjuvant chemotherapy efficacy in patients with aggressive luminal HER2-negative breast cancer

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