Cutaneous Toxicities in Breast Cancer Patients Receiving Chemotherapy and Targeted Agents––An Observational Clinical Study

Anoop, T.M.; P, Rona Joseph; Pn, Mini; Kp, Pranab; Gopan, Gayatri; Chacko, Steffi

doi:10.1016/j.clbc.2021.01.009

Cited by 7 publications

(9 citation statements)

References 43 publications

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“…Cutaneous toxicity is the side effect of certain drugs on skin, which is often observed in patients treated with EGFR inhibitors including lapatinib. The clinical manifestations of lapatinib-induced cutaneous toxicity mainly include rash, generalized xerosis and pruritus (Anoop, Joseph, Pn, Kp, Gopan & Chacko, 2021;Morita et al, 2021). Severe cutaneous toxicity could cause a reduction in the dosage or even withdrawal, eventually worsen the survival quality and psychological health of patients.…”

Section: Discussionmentioning

confidence: 99%

Reduced HMGB1 expression contributed to lapatinib-induced cutaneous injury

Jiang

Zeng

et al. 2022

Preprint

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Background and Purpose Lapatinib, a widely-used dual inhibitor of EGFR/ERBB1 and HER2/ERBB2 effectively targeting HER2 positive breast cancer, has been seriously limited due to cutaneous toxicity. However, the specific mechanism of lapatinib-induced cutaneous toxicity has not been clarified, leading to a lack of effective strategy targets to improve clinical safety. Here, we aimed to identify molecular mechanism occurs in this process and strive for effective intervention strategies against lapatinib-induced cutaneous side effects. Experimental and Approach C57BL/6 mice were subjected to lapatinib via intragastric administration, serum was used for ELISA assay, skin tissue was collected and performed with histopathological analysis. Apoptotic assay was analyzed in HaCaT and NHEK cell lines, comet assay was conducted to measure the damage of DNA, real-time PCR was used to assess the level of HMGB and inflammatory factors. Key Results We found that lapatinib could induce mitochondrial dysfunction, lead to DNA damage and finally cause apoptosis of keratinocytes. In addition, we found that lapatinib could induce aberrant immune response and promote the release of inflammatory factors in vitro and in vivo. Mechanistically, downregulated expression of HMGB1 played a critical role in these toxic reaction processes. Delightfully, we found that saikosaponin A could significantly rescue the reduced HMGB1 transcription, which could alleviate lapatinib-induced DNA damage, inhibit keratinocyte apoptosis and further prevent toxicity of lapatinib in mice. Conclusion and Implications Our study provided molecular mechanism of lapatinib-induced cutaneous toxicity, and shed new light on the prevention of cutaneous adverse drug reactions induced by EGFR inhibitors.

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Section: Discussionmentioning

confidence: 99%

Reduced HMGB1 expression contributed to lapatinib-induced cutaneous injury

Jiang

Zeng

et al. 2022

Preprint

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“…Dermatology Review/Przegląd Dermatologiczny 2021/4 concLusions Nail plate hiperpigmanetation, including longitudinal melanonychia are common adverse events of breast cancer therapy [11].…”

Section: Conflict Of Interestmentioning

confidence: 99%

“…Przebarwienia płytki paznokciowej, w tym podłużna melanonychia, należą do najczęstszych dermatologicznych objawów niepożądanych chemioterapii raka piersi [11].…”

Section: Conflict Of Interestunclassified

Longitudinal melanonychia and distal onycholysis associated with 5-fluorouracil/adriamycin/cyclophosphamide chemotherapy for breast cancer

Żywno¹,

Terlikowska-Brzósko²,

Owczarek³

et al. 2021

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Introduction: Longitudinal melanonychia presents with pigmented longitudinal streaks of the nail plate. It results from an increased activity of melanocytes or melanocytic hyperplasia in the nail matrix or nail bed and is associated with increased melanin deposition in the nail plate. Distal onycholysis is characterized by separation of the distal part of the nail plate from the nail bed. Objective: To present a case of longitudinal melanonychia and distal onycholysis associated with 5-fluorouracil/adriamycin/cyclophosphamide chemotherapy. Case report: A 66-year-old woman, who received 5-fluorouracil/adriamycin/cyclophosphamide for breast cancer developed longitudinal melanonychia and distal onycholysis. After discontinuation of chemotherapy, nail changes improved significantly. Conclusions: Drug-induced longitudinal melanonychia and distal onycholysis are common adverse effects of breast cancer chemotherapy. This case shows that lesions may resolve after discontinuation of therapy.

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“…Além disso, duas toxicidades dermatológicas foram incluídas no cluster de TSS deste relato: alterações ungueais e hiperpigmentação. Em um padrão semelhante às gastrointestinais, investigações anteriores demonstraram frequências importantes de alterações ungueais e hiperpigmentação da pele (15,16) . Respectivamente em tais estudos, a frequência de alterações ungueais foi 77,9%, 34,0% e 45,20%%, enquanto a de hiperpigmentação foi 48,4% e 88,4% e 5,26%.…”

Section: Introductionunclassified

“…É digno de nota que as alterações ungueais resumem um conjunto de alterações específicas, enquanto a hiperpigmentação é uma alteração específica da pele. Por fim, além do impacto nos desfechos do tratamento oncológico previamente mencionados para toxicidades gastrointestinais, toxicidades dermatológicas também podem afetar a aparência e a autoestima, favorecendo o sofrimento psicológico das mulheres com câncer de mama (15)(16)(17)(18) .…”

Section: Introductionunclassified

Toxicidades Sistêmicas Simult Neas Relacionadas À Quimioterapia Do C Ncer De Mama: Um Relato Observacional E Prospectivo

Marinho

Barbosa-Lima

Santos

et al. 2022

Rev. Enferm. Atual In Derme

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Objetivo: avaliar quantitativamente um cluster de toxicidades sistêmicas relacionadas à quimioterapia em mulheres com câncer de mama ao longo do tratamento. Métodos: foi realizado um estudo observacional e prospectivo, de natureza quantitativa, envolvendo 140 mulheres com câncer de mama expostas à quimioterapia como modalidade de tratamento. A ocorrência de 14 toxicidades sistêmicas (baseadas no Common Terminology Criteria for Adverse Events, versão 4.03) foi avaliada nos prontuários médicos em dois segmentos: no ciclo intermediário e ao fim da quimioterapia. As frequências foram comparadas entre os dois segmentos do estudo, associando separadamente cada toxicidade e agrupando a quantidade de toxicidades simultâneas de cada paciente, considerando o nível de significância (p) de 5%. Resultados: observou-se que a maioria das toxicidades sistêmicas foram associadas entre os segmentos do estudo, bem como a maioria se manifestou com maior frequência ao final da quimioterapia. As toxicidades mais frequentes (considerando ambos os segmentos) foram vômito (90.7%), cefaleia (88.6%) e astenia (87.9%). As mais incomuns foram leucopenia (7.1%), neutropenia (13.6%) e parestesia (32.1%). Ao comparar a quantidade de toxicidades sistêmicas simultâneas entre os segmentos, observou-se um aumento significativo ao final da quimioterapia em relação ao ciclo intermediário (p <0.001). Conclusão: as mulheres com câncer de mama experimentaram uma quantidade maior de toxicidade sistêmicas simultâneas ao final da quimioterapia, bem como uma alta frequência de toxicidades sistêmicas ao longo do tratamento foi observada.

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Cutaneous Toxicities in Breast Cancer Patients Receiving Chemotherapy and Targeted Agents––An Observational Clinical Study

Cited by 7 publications

References 43 publications

Reduced HMGB1 expression contributed to lapatinib-induced cutaneous injury

Reduced HMGB1 expression contributed to lapatinib-induced cutaneous injury

Longitudinal melanonychia and distal onycholysis associated with 5-fluorouracil/adriamycin/cyclophosphamide chemotherapy for breast cancer

Toxicidades Sistêmicas Simult Neas Relacionadas À Quimioterapia Do C Ncer De Mama: Um Relato Observacional E Prospectivo

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