Non-Response of Epstein–Barr Virus-Associated Breast Cancer after Primary Chemotherapy: Report of Two Cases
Abstract
:1. Introduction
2. Materials and Methods
2.1. Immunohistochemical Staining
2.2. EBV-Encoded RNA (EBER) In Situ Hybridization (ISH)
3. Results
3.1. Case 1
3.2. Case 2
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
BARF1 | BamHI-A rightward frame 1 |
BC | breast cancer |
BCL-2 | B-cell lymphoma 2 (Bcl-2) family |
EBER-1 | Epstein-Barr Early Ribonucleoprotein 1 |
EBNA1 | Epstein–Barr nuclear 8 antigen 1 |
EBV | Epstein–Barr virus |
EDTA | Ethylenediaminetetraacetic acid |
HER2 | human epidermal growth factor receptor 2 |
IHC | immunohistochemistry |
ISH | In situ hybridization (ISH) |
HRP | Horesradish-peroxidase |
IARC | International Agency for Research on Cancer |
LMP1 | Late-membrane protein 1 |
NACT | Neoadjuvant chemotherapy |
NST | Invasive breast cancer of no special type |
PD | Progressive disease |
PKR | Protein kinase R |
TNBC | triple-negative breast cancer |
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ONCOLOGIC EVENTS | THERAPEUTIC APPROACHES | |
---|---|---|
56-year-old female patient with the primary diagnosis of a well-differentiated, non-keratinizing, EBV-positive nasopharyngeal carcinoma with cervical lymph node metastases. Clinical tumor stage: cT2, cN3b, cM0, G1. | Induction therapy (3 cycles of cis-platin/ docetaxel/5-fluorouracil). Radiochemotherapy with cis-platin. Radiochemotherapy with cis-platin. | |
5 months a.p.d. * | Near-complete regression of the nasopharyngeal carcinoma and cervical cervical lymph node metastases. | |
9 months a.p.d. | Detection of right axillary lymph node metastases and bone metastases by PET-CT. | Treatment with 17 cycles of pembrolizumab as immunotherapy, without response. |
15 months a.p.d. | Detection of a hypermetabolic spherical mass of the right breast, right axillary lymph node, and bone metastases by CT. Histopathologic diagnosis on breast core needle biopsy: triple negative, poorly differentiated invasive breast cancer of no special type (NST, G3; ER-/PR-/HER2-). Clinical tumor stage: cT3, cN3, M1. | Systemic chemotherapy with paclitaxel/bevacizumab (3 cycles). |
16 months a.p.d. | Systemic progressive disease with the formation of diffuse bone metastases and cervical, axillary, infraclavicular, mediastinal, hilar, retroperitoneal, mesenteric, and retrocrural lymph node metastases. | |
18 months a.p.d. | Presentation of a mixed response concerning the generalized cancer disease in CT. | Systemic chemotherapy with 6 cycles of carboplatin/ gemcitabine. |
25 months a.p.d. | Mastectomy and axillary lymph node dissection performed as a debulking operation. Histopathologic tumor stage: ypT3, ypN2a (9/9), L1, R0. Positive result of the in situ-hybridizsation by EBER-ISH on the resected tumor tissue. | Systemic therapy by 6 cycles of carboplatin/gemcitabine. Experimental vaccination with two peptides of tumor-associated antigens Muc1 and TP53. |
Few months. | Death of the patient due to further progressive disease with a lack of response to chemotherapeutic approaches. |
ONCOLOGIC EVENTS | THERAPEUTIC APPROACHES | |
---|---|---|
49-year-old female patient with the diagnosis of an advanced, lymph node-positive moderately differentiated invasive breast cancer of no special type (NST, G2; immunohistochemically HER2-positive (3+). Clinical tumor stage: cT3, cN1, cM0. | Systemic neoadjuvant therapy with 6 cycles of docetaxel/carboplatin in combination with trastuzumab/ pertuzumab as neoadjuvant systemic therapy. | |
5 months a.p.d. * | Clinically stable disease. Pre-operative, post-neoadjuvant clinical tumor stage: ycT3(sat), ypN1. Tumor resection by quadrantectomy. Histopathologic tumor stage: ypT3, ypN1a(3/21), L1, R0. Due to the lack of clinical and pathological response to chemotherapeutic approach, EBV was tested, with serological detection of a highly positive status of latent EBV- infection. The in situ-hybridizsation by EBER-ISH on the resected tumor tissue was also positive. | Post-neoadjuvant systemic therapy with 6 cycles of trastuzumab emtansine. Further 8 cycles are planned for further months (ongoing). |
12 months a.p.d. | The patient is alive with stable disease. |
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Share and Cite
Gutjahr, E.; Fremd, C.; Arnscheidt, J.; Penzel, R.; Wacker, J.; Sinn, P. Non-Response of Epstein–Barr Virus-Associated Breast Cancer after Primary Chemotherapy: Report of Two Cases. Pathogens 2023, 12, 1387. https://doi.org/10.3390/pathogens12121387
Gutjahr E, Fremd C, Arnscheidt J, Penzel R, Wacker J, Sinn P. Non-Response of Epstein–Barr Virus-Associated Breast Cancer after Primary Chemotherapy: Report of Two Cases. Pathogens. 2023; 12(12):1387. https://doi.org/10.3390/pathogens12121387
Chicago/Turabian StyleGutjahr, Ewgenija, Carlo Fremd, Johanna Arnscheidt, Roland Penzel, Jürgen Wacker, and Peter Sinn. 2023. "Non-Response of Epstein–Barr Virus-Associated Breast Cancer after Primary Chemotherapy: Report of Two Cases" Pathogens 12, no. 12: 1387. https://doi.org/10.3390/pathogens12121387