Letter to the Editor
Sarcoid-like reaction associated with HER2 treatment in patients with breast carcinoma
Reacción sarcoidea asociada a terapias anti-HER2 en pacientes con cáncer de mama
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A) First patient. Bilateral pulmonary nodules and bilateral mediastinal and hilar lymphadenopathies. B) Second patient. Single left hilar lymphadenopathy.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Antineoplastic therapy has evolved dramatically in recent decades, with the emergence of new therapeutic targets that have significantly changed the management and prognosis of many tumours.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Metastatic breast cancer is no exception. In less than 20% of breast tumours, cancer cells overexpress the HER2 (human epidermal growth factor receptor 2) protein on their surface, which promotes tumour cell growth, leading to increased aggressiveness and poorer prognosis. Treatments specifically targeting HER2 (HER2 inhibitor drugs) selectively block tumour growth and proliferation signals and this slows or stops the growth of HER2-positive breast cancer.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Trastuzumab is a humanised IgG1 monoclonal antibody directed against HER2, used in HER2+ breast cancer, which offers a significant survival advantage over patients who do not express HER2. The drug is generally well tolerated by most patients, although the most common side effect is fever or chills, but serious side effects are rare.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Cases of sarcoid-like reactions associated with antineoplastic immunotherapy have been reported, although they are usually related to the use of immune checkpoint inhibitors, mainly anti-PD1 (nivolumab, pembrolizumab) and anti-CTLA4 (ipilimumab).<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Sarcoid-like reactions associated with trastuzumab are much rarer, with very few cases reported in the literature.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2–4</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">We report 2 cases treated in our Systemic Autoimmune Diseases Unit at the Virgen de las Nieves Hospital in Granada, in collaboration with the Medical Oncology Service of the same centre.</p><p id="par0025" class="elsevierStylePara elsevierViewall">The first case is that of a 46-year-old patient who had been diagnosed with HER2+ infiltrating ductal carcinoma of the left breast 7 years earlier and had been treated with surgery, radiotherapy, chemotherapy, trastuzumab and hormone therapy who was in remission. While the patient was asymptomatic and with normal laboratory tests, bilateral pulmonary nodules and bilateral mediastinal and hilar lymphadenopathies were detected in a follow-up PET-CT scan (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A). Lymph node EBUS-FNAs were performed, reported as chronic non-necrotising granulomatous lymphadenitis. A lung biopsy ruled out neoplasm and described the lesion as a non-caseating granulomatous nodule. Microbiological stains and cultures were negative for bacteria, fungi and mycobacteria. Given the 6-year prior exposure to anti-HER2 therapy with trastuzumab, the findings were attributed to the treatment and the progressive reduction of the detected lesions was verified in follow-up imaging tests.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">The second case is that of a 47-year-old patient diagnosed 3 years earlier with HER2+ infiltrating ductal carcinoma of the left breast, treated with surgery, radiotherapy, chemotherapy and trastuzumab, who was also in remission. While the patient was also asymptomatic, a follow-up PET-CT scan showed a single left hilar lymphadenopathy with no other findings (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>B). Video-assisted thoracoscopy removal was performed. The pathological study described a non-necrotising granulomatous lymphadenitis. Having ruled out other causes of granulomatous disease (negative bacterial, fungal and mycobacterial cultures) and given previous exposure to trastuzumab, the development of this granuloma was associated with anti-HER2 therapy.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Sarcoid-like reactions have been reported in 4-14% of patients with malignancies. The main factors associated with their occurrence are the use of certain chemotherapy agents, immunotherapy and radiotherapy, as well as certain cell lines, such as carcinomas.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,3</span></a> These sarcoid-like reactions have been described up to several years after antineoplastic treatment.<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4,5</span></a> In the context of a neoplastic patient, it is complex to raise the suspicion of sarcoidosis in the differential diagnosis, which is why an individualised approach and multidisciplinary management are essential, the process of which should be directed towards the anatomopathological confirmation of the findings.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Ethical considerations</span><p id="par0040" class="elsevierStylePara elsevierViewall">Informed consent was obtained for imaging and subsequent publication.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Funding</span><p id="par0045" class="elsevierStylePara elsevierViewall">This paper has not received any funding.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Conflict of interest</span><p id="par0050" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Ethical considerations" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Funding" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "Conflict of interest" ] 3 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1027 "Ancho" => 1475 "Tamanyo" => 130247 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">PET-CT images. A) First patient. Bilateral pulmonary nodules and bilateral mediastinal and hilar lymphadenopathies. B) Second patient. Single left hilar lymphadenopathy.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mediastinal sarcoid-like reaction in cancer patients" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "C. Payá-Llorente" 1 => "A. Cremades-Mira" 2 => "M. Estors-Guerrero" 3 => "N. Martínez-Hernández" 4 => "A. Alberola-Soler" 5 => "J.M. 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