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- Publisher
- Hindawi Publishing Corporation
- Copyright
- Copyright © 2022 Akira Tsunoda et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
- ISSN
- 2090-6706
- eISSN
- 2090-6714
- DOI
- 10.1155/2022/2709062
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- See Article on Publisher Site
Abstract
Hindawi Case Reports in Oncological Medicine Volume 2022, Article ID 2709062, 4 pages https://doi.org/10.1155/2022/2709062 Case Report Atezolizumab-Induced Sarcoidosis-Like Reaction in a Patient with Metastatic Breast Cancer 1 1 2 3 4 Akira Tsunoda, Toshiro Mizuno , Shohei Iida, Katsunori Uchida, Masako Yamashita, 1 1 1 1 1 Koshi Sukeno, Hiroki Oka, Yasutaka Tono, Mikiya Ishihara, Kanako Saito, 1 2 1 Satoshi Tamaru, Keiichi Yamanaka , and Isao Tawara Department of Medical Oncology, Mie University Hospital, 2-174 Edobashi, Tsu, Mie Prefecture 514-8507, Japan Department of Dermatology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie Prefecture 514-8507, Japan Department of Oncologic Pathology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie Prefecture 514-8507, Japan Department of Breast Surgery, Mie Prefectural General Medical Center, Ohji-Hinaga 5450-132, Yokkaichi, Mie Prefecture 510-8561, Japan Correspondence should be addressed to Toshiro Mizuno; tomizuno@med.mie-u.ac.jp Received 15 November 2021; Accepted 17 January 2022; Published 27 January 2022 Academic Editor: Katsuhiro Tanaka Copyright © 2022 Akira Tsunoda et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Tumor-related sarcoidosis-like reactions (SLR) have been reported with the use of immune checkpoint inhibitors (ICIs). We report a case of 50-year-old woman who observed an enlarged lymph node in the right hilar region and the appearance of a subcutaneous mass in the extremities during chemotherapy with atezolizumab plus nab-paclitaxel for metastatic triple-negative breast cancer (TNBC). Skin biopsy revealed the formation of epithelioid granulation species with the Langhans giant cell. After discontinuing atezolizumab in the treatment procedure, the hilar lymph nodes and the subcutaneous mass were reduced. A pathological examination was effective in differentiating tumor exacerbation from SLR. Owing to limited information on ICI- related SLR in breast cancer, future studies are recommended to properly manage immune-related adverse effects during cancer treatment. 1. Introduction events (irAEs) during treatment remains a concern. Report- edly, irAEs occur in various parts of the body, causing endo- Triple-negative breast cancer (TNBC) constitutes 15–20% of crine and neurological disorders. One rare irAE is cases of breast cancer and is characterized by the absence of sarcoidosis-like reactions (SLR). Although tumor-related estrogen receptors (ER), progesterone receptors (PgR), and SLRs are sometimes reported with the extensive use of ICIs, overexpression or gene amplification of human epidermal their pathogenesis and etiology are not fully understood [3]. growth factor receptor type 2 (HER2) on the surface of can- We report a case of SLR during atezolizumab plus nab- cer cells [1, 2]. Recently, the results of IMpassion130 phase 3 paclitaxel ICI therapy for metastatic TNBC, with a literature clinical trial reported superiority in progression-free survival review on the mechanism of the said irAEs. of the anti-programmed death ligand 1 (PD-L1) monoclonal antibody atezolizumab plus nab-paclitaxel over placebo plus 2. Case Report nab-paclitaxel as a first-line treatment for patients with advanced or metastatic TNBC [2]. While therapeutic effec- A 50-year-old woman was diagnosed with breast cancer and tiveness of immune checkpoint inhibitors (ICIs) has been underwent right mastectomy with axillary lymph node dis- demonstrated, management of immune-related adverse section. The pathological findings revealed invasive ductal 2 Case Reports in Oncological Medicine Baseline After 6 months Figure 1: At baseline, computed tomography (CT) shows the appearance of the right subpectoral lymph node metastasis (3.6 cm diameter). After 6 months, CT showed further reduction of that lesion, while the right hilar lymph nodes are enlarged. 2 2 Table 1: Laboratory tests on nodule appearance. of epirubicin 90 mg/m plus cyclophosphamide 600 mg/m on day 1 every 3 weeks, followed by 12 cycles of paclitaxel Hematology 80 mg/m on day 1 every week [4, 5]. Two years after the WBC 4:75 × 10 μL surgery, an enlarged lymph node (φ 2.8 cm) in the right pec- RBC 4:06 × 10 μL toralis major muscle was observed (Figure 1). Cytology showed adenocarcinoma, indicating recurrence of breast Hb 11.9 g/dL cancer. The programmed death ligand 1 (PD-L1) expression Ht 37.7 % with SP 142 was positive (IC: 3) in the resected tissue. As a Plt 22:5×10 /μL first-line treatment, the patient received atezolizumab Immunology (840 mg) per body on days 1 and 15 plus nab-paclitaxel 100 mg/m on days 1, 8, and 15 every 28-day cycle [2]. With CRP 0.32 mg/dL the treatment, the lymph node metastases reduced. β-D glucan <2.8 pg/mL After 5 cycles of atezolizumab plus nab-paclitaxel, an sIL-2R 691 U/mL enlarged lymph node in the right hilar region, and appear- ACE 12.5 U/L ance of a subcutaneous mass in the extremities were Lysozyme 5.4 MCG/mL observed (Figure 1). Her vitals were stable, and the blood test Tuberculosis specific IFNγ Negative results showed no abnormalities (Table 1). Skin biopsy was Blood chemistry then performed on the subcutaneous mass, which showed formation of epithelioid granulation species with Langhans Total protein 7.6 g/dL giant cells (Figure 2). The skin tissue culture test did not Albumin 4.3 g/dL detect the presence of any organism that could be associated AST 19 IU/L with the appearance of the nodules. ALT 15 IU/L From these findings, we determined that SLR resulted LDH 231 IU/L from the use of atezolizumab. Atezolizumab was discontin- ALP 206 IU/L ued for the treatment of SLRs, while nab-paclitaxel mono- γ-GTP 16 IU/L therapy was continued. After the change in treatment, BUN 13.6 mg/dL there was a reduction in the size of the hilar lymph nodes and that of the subcutaneous mass. However, it was thought Cre 0.46 mg/dL that total 8 cycles of nab-paclitaxel became refractory due to Na 142 mEq/L the enlargement of the metastatic lesion just below the right K 4.0 mEq/L pectoral major muscle. Thereafter, chemotherapy such as Cl 104 mEq/L eribulin, capecitabine, and irinotecan for three to four cycles Ca 9.2 mg/dL each depending on metastatic TNBC progression has been Glucose 92 mg/dL administered [6–8]. The patient is currently undergoing car- boplatin plus gemcitabine, while the SLR-related lesions have remained reduced to date [9]. carcinoma, pT2 (3.0 cm) pN1a (3/22) cM0, and pStageIIB. The immunostaining confirmed ER negative, PgR negative, 3. Discussion and HER2 2+ (FISH: no amplification). She had no history of smoking, and none of her family members who lived with The use of immunotherapy in the field of oncology has rev- her were smokers. Her past medical history was unremark- olutionized treatment of cancer. However, with the applica- able. Adjuvant chemotherapy was performed with 4 cycles tion of ICIs, incidence of SLR as a type of irAE is also Case Reports in Oncological Medicine 3 Figure 2: Exploration of subcutaneous mass in the lower extremities. Hematoxylin and eosin stain shows epithelioid cell granuloma with Langhans giant cells. There are no necrotic tissue and no similarity to surgical specimens of breast cancer. Table 2: Published reports of SLR in patients with breast cancer. Subtype Authors Age (y) Treatment regimens References ER PgR HER2 Lafon M, et al. 69 0 0 Negative Nab-paclitaxel plus atezoliumab [15] Stoffaës L, et al. 62 95 70 Negative Palbocicurib plus anastrozole [16] Vieira H, et al. 71 90% 95% Positive Trasutuzumab plus anastrozole [17] Panagiotidis E, et al. 45 Negative Negative Positive Pertuzumab and trastuzumab [18] Shin HC, et al. 46 Positive Positve Negative TAM [19] . Bhattad PB, et al. 45 Positive Positive Negative TAM [20] 55 90% 90% Negative TAM [21] Martella S, et al. 53 90% 0% Negative TAM plus LHRHa [21] 53 90% 90% Negative TAM plus LHRHa [21] ER: estrogen receptors; PgR: progesterone receptors; HER2: human epidermal growth factor type 2; TAM: tamoxifen; LHRHa: luteinizing hormone-releasing hormone agonists. breast cancer requires further investigation through clinical increasing. According to a previous report, SLR is associated with 4.4% of malignant tumors. In terms of the frequency of case events. In this case, skin biopsy led to the diagnosis of malignant tumors by cancer type, it was commonly observed SLR, which could be appropriately treated with atezolizumab in melanoma, uterine carcinoma, lung cancers, and urethral withdrawal alone. Fluorodeoxyglucose-positron emission carcinoma [10]. The time to onset of SLR after initiating ICIs tomography (FDG-PET) was omitted because the lesions could be adequately identified by CT follow-up (Figure 1). has ranged from 3 weeks to almost 2 years, and there is no obvious ICI dose threshold for the development of ICI- TNBC behaves more aggressively with earlier relapses related SLR [10]. The mediastinal lymph node, lung, and and with poorer survival outcomes in comparison to other skin were common organs involved with ICI-related SLR. breast cancer subtypes [13]. If a new lesion is observed in Corticosteroid treatment or other antisarcoidosis treatment TNBC, it is important to immediately diagnose and assess was not required for all cases of ICI-related SLR [10]. the pathology to properly discern if changes in current treat- The mechanism of SLR during immunotherapy has been ment are necessary. If a lesion is found in a site characteristic previously described in several studies [10, 11]. It had been of SLR, as in the mediastinal lymph nodes, lung, or skin, it is shown that cytotoxic T-lymphocyte-associated protein 4 also important to perform a pathological examination to dif- (CTLA-4) blockade enhanced Th17 CD4+ cells in peripheral ferentiate between tumor exacerbation and SLR. blood, thus leading to an extended expression of proinflam- It has been suggested that the efficacy and safety of can- matory cytokines, such as IL-6 and TNF-α [11]. IL-2 secre- cer immunotherapy may be affected by the concomitant use tion by activated T cells is assumed to be involved in the of drugs such as antimicrobials, proton pump inhibitors, and pathogenesis of sarcoidosis [12]. However, information is steroids [14]. In this case, since there was no history of the limited regarding the development of SLR with PD-1 and use of any of the drugs mentioned above, it was inferred that PD-L1 checkpoint inhibitors than with CTLA-4 [10]. the combination treatment had little effect on immunother- Treatment-related SLR in breast cancer is not only apy and was not associated with the development of SLR. caused by ICIs but also caused by various drugs (Table 2). In conclusion, we herein report a case of a woman with SLR during atezolizumab plus nab-paclitaxel immunother- To date, only one case had been reported by ICI-related SLR. Whether SLR is a characteristic side effect of ICIs in apy in metastatic TNBC. Further evidence-based studies on 4 Case Reports in Oncological Medicine ICI-related SLR in breast cancer are recommended to effec- [12] M. Miyara, Z. Amoura, C. Parizot et al., “The immune paradox of sarcoidosis and regulatory T cells,” Journal of Experimental tively manage immune-related events during cancer Medicine, vol. 203, no. 2, pp. 359–370, 2006. treatment. [13] F. Kassam, K. Enright, R. Dent et al., “Survival outcomes for patients with metastatic triple-negative breast cancer: implica- tions for clinical practice and trial design,” Clinical Breast Can- Conflicts of Interest cer, vol. 9, no. 1, pp. 29–33, 2009. The authors declare that they have no conflicts of interest. [14] G. Rossi, A. Pezzuto, C. Sini et al., “Concomitant medications during immune checkpoint blockage in cancer patients: novel insights in this emerging clinical scenario,” Critical Reviews in Oncology/Hematology, vol. 142, pp. 26–34, 2019. References [15] M. Lafon, C. Blaye, M. 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Case Reports in Oncological Medicine – Hindawi Publishing Corporation
Published: Jan 27, 2022