Is there a correlation between HER2 gene amplification level and response to neoadjuvant treatment with trastuzumab and chemotherapy in HER2-positive breast cancer?

Antolín, Silvia; García‐Caballero, Lucía; Reboredo, Cristina; Molina, Aurea; Mosquera, Joaquín; Vázquez-Boquete, Ángel; Gallego, Rosalı́a; Santiago, Mari Paz; Concha, Ángel; Perez, E. Salgado; Calvo, Lourdes; García‐Caballero, Tomás

doi:10.1007/s00428-021-03104-7

Cited by 12 publications

(14 citation statements)

References 15 publications

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“…Overall, various anti-HER2 regimens were used as neoadjuvant chemotherapy. The anti-HER2 treatment used was trastuzumab monotherapy in six studies [ 33 , 34 , 35 , 36 , 37 , 38 ], and the combined treatment of trastuzumab and lapatinib in two studies [ 39 , 40 ]. For the study by Greenwell et al, there were no details about the type of anti-HER2 therapy.…”

Section: Resultsmentioning

confidence: 99%

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HER2 Amplification Level Predicts Pathological Complete Response in the Neoadjuvant Setting of HER2-Overexpressing Breast Cancer: A Meta-Analysis and Systematic Review

Gonullu

Angeli

Pamoukdjian

et al. 2023

IJMS

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Anti-HER2 therapies have dramatically improved the prognosis of human epidermal growth factor receptor 2 (HER2)-overexpressing cancers. However, the correlation between the HER2 copy number and the response rate to anti-HER2 remains unclear. Here, following the PRISMA method, we performed a meta-analysis in the neoadjuvant setting in breast cancer to study the association between the HER2 amplification level and the pathological complete response (pCR) to anti-HER2 therapies. Nine articles (four clinical trials, five observational studies) were retrieved after full-text screening, involving 11,238 women with locally advanced breast cancer in the neoadjuvant setting. The median HER2/CEP17 ratio cut-off value was 5.0 ± 5.0 (min-max = 1.0–14.0). For the overall population, the median pCR rate was 48% using the random effect model. The studies were categorized in quartiles as follows: ≤2 (Class 1); 2.1 to 5.0 (Class 2); 5.1 to 7.0 (Class 3); and >7.0 (Class 4). After grouping, the pCR rates were 33%, 49%, 57%, and 79%, respectively. When we excluded the study by Greenwell et al., which accounted for 90% of the patients, using the same quartiles, we still observed an increasing rate of pCR as the HER2/CEP17 ratio increased. This is the first meta-analysis demonstrating the relationship between the HER2 amplification level and the percentage of pCR in the neoadjuvant setting among women with HER2-overexpressing breast cancer, with potential therapeutic applications.

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Section: Resultsmentioning

confidence: 99%

“…“Total” refers to the total number of patients for the same HER2/CEP17 ratio. In this case, for the same study, several HER2/CEP17 ratio thresholds were considered [ 31 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 ].…”

Section: Figurementioning

confidence: 99%

HER2 Amplification Level Predicts Pathological Complete Response in the Neoadjuvant Setting of HER2-Overexpressing Breast Cancer: A Meta-Analysis and Systematic Review

Gonullu

Angeli

Pamoukdjian

et al. 2023

IJMS

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“…As one explanation, this patient had an exceptionally high HER2 copy number state, perhaps suggesting a component of oncogene addiction driven by a quantitative relationship between HER2 amplification and response in PDAC. Accordingly, prior literature in gastric cancer 40 , breast cancer with trastuzumab 46 and trastuzumab deruxtecan 47 support a positive correlation between HER2 gene copy number and response to anti-HER2 therapy. Conversely, loss of HER2 expression has been observed as a mechanism of resistance following anti-HER2 therapy in gastric cancer 48,49 .…”

Section: Discussionmentioning

confidence: 96%

Complete remission in a patient with widely metastatic HER2-amplified pancreatic adenocarcinoma following multimodal therapy informed by tumor sequencing and organoid profiling

King

Smith

Pineda

et al. 2021

Preprint

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This work, "Complete remission in a patient with widely metastatic HER2-amplified pancreatic adenocarcinoma following multimodal therapy informed by tumor sequencing and organoid profiling" highlights the power of multi-institution collaboration, combining strengths in organoid profiling (Kuo group at Stanford), personalized vaccine therapy (Gillanders group at WUSTL), in vitro drug testing and drug sensitivity (SEngine, MSK, and Mprobe), clinical trials (Dr Ari Baron at CPMC), and the Canopy Health learning network. Here, we demonstrate a complete clinical response achieved in a patient with HER2+ metastatic pancreatic ductal adenocarcinoma to a coordinated barrage of anti-HER2, personalized vaccine and checkpoint inhibition immunotherapy, radiation, and chemotherapy. Comprehensive organoid profiling with drug sensitivity screening and drug testing suggested a vulnerability to anti-HER2 directed therapy, facilitating personalized treatment selection for our patient, which contributed to her clinical benefit. Immune response monitoring following personalized vaccine, radiation and checkpoint inhibition showed a sustained increase in neoantigen specific T cell response.

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“…The results of treatment in patients with abnormal processes of the same localization with the same distribution, histological structure and degree of cell 123 22/ Том XXVII / 2 differentiation can differ significantly [29]. That is why it is essential to identify tissue and molecular markers in the tissues of the studied organs, which determine the specific phenotype of the disorder and provide important diagnostic and prognostic information about the status of the disease and its biological properties [30,31].…”

Section: Expression Of Epidermal Growth Factor Hormone Receptors Stan...mentioning

confidence: 99%

Triple-negative transformation of the endometrium, cervix and mammary gland on the background of immunodeficiency

Lytvynenko

Gargin

2022

Med. perspekt.

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Precancerous processes of the female reproductive system continue to be an issue that is being actively studied, despite the successes of recent years. One of the key prognostic factors is the characterization of the receptor set, primarily the mammary gland and endometrium, namely estrogen (ER), progesterone (PR), epidermal growth factor-2 (HER2) receptors. Purpose – to identify the features of the distribution of estrogen, progesterone and epidermal growth factor receptors in the tissues of the endometrium, cervix and mammary gland with a combination of HIV infection and alcohol abuse. Fifty women of reproductive age from 20 to 40 years were studied. After routine conduction and immunohistochemical staining, ER and PR expression were determined by a modified D.Allred scale. HER2 expression was determined by a semi-quantitative method. The obtained digital data were statistically processed. A morphometric study indicates that the combination of HIV infection and alcohol abuse significantly affects the distribution of receptors in the female reproductive system. To a greater extent, the overall score is reduced by reducing the number of cellular elements with the expression of ER and PR. HER2 receptor expression is significantly reduced in the endometrium and mammary gland. These changes may be facilitated by atrophic changes in these organs, which occurs in immunodeficiency. According to the D.Allred scale, the mean score decreases from 5.45±0.63 to 3.10±0.88 in the endometrium, from 4.68±0.65 to 2.47±0.58 in the cervix, from 6.57±0.67 to 3.57±0.77 in the mammary gland (p<0.05). HER2 expression decreased from 3.24±0.47 to 2.21±0.23 in the endometrium, from 3.43±0.66 to 2.36±0.32 in the mammary gland (p<0.05). The development of immunodeficiency is characterized by the restructuring of female reproductive organs with a change in the receptor set of the endometrium, cervix and mammary gland and a decrease in both the qualitative and quantitative composition of the receptors, which may serve as a prerequisite for the development of a triple-negative phenomenon in tumors of these organs.

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Is there a correlation between HER2 gene amplification level and response to neoadjuvant treatment with trastuzumab and chemotherapy in HER2-positive breast cancer?

Cited by 12 publications

References 15 publications

HER2 Amplification Level Predicts Pathological Complete Response in the Neoadjuvant Setting of HER2-Overexpressing Breast Cancer: A Meta-Analysis and Systematic Review

HER2 Amplification Level Predicts Pathological Complete Response in the Neoadjuvant Setting of HER2-Overexpressing Breast Cancer: A Meta-Analysis and Systematic Review

Complete remission in a patient with widely metastatic HER2-amplified pancreatic adenocarcinoma following multimodal therapy informed by tumor sequencing and organoid profiling

Triple-negative transformation of the endometrium, cervix and mammary gland on the background of immunodeficiency

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