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      EGFR-Mutated Breast Metastasis of Lung Adenocarcinoma: A Case Report


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          Breast metastasis from other primary carcinoma is very rare and could be difficult to identify despite immunohistochemistry analysis. Breast metastasis from lung adenocarcinoma can mimic triple-negative breast cancer. Given the prognosis and therapeutic challenges, a correct diagnosis appears essential, and molecular biomarkers could be useful. We report the case of a 52-year-old woman with a breast mass initially diagnosed as primary breast cancer and secondarily attached to breast metastasis from an EGFR-mutated lung adenocarcinoma. The same activating EGFR mutations were identified in both the primary lung carcinoma and the breast metastasis.

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          Most cited references11

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          The histological diagnosis of metastases to the breast from extramammary malignancies.

          Norman Lee (2007)
          This study aims to review histological and immunohistochemical features that are useful in the diagnosis of metastases to the breast. Histological features were compared between non-haematological metastases to the breast and 100 consecutive core biopsy specimens of primary invasive carcinomas of the breast. 18 non-haematological metastases to the breast were diagnosed over a 10-year period (0.3% of malignant mammary tumours). Elastosis and carcinoma in situ were seen only in primary mammary cancers. Two-thirds of tumours had features raising the possibility of metastasis, such as clear cell carcinoma suggestive of renal origin and small cell carcinoma suggestive of pulmonary origin. The features observed in haematological metastases are also described. Immunohistochemical panels to distinguish mammary carcinoma (oestrogen receptor, gross cystic fluid protein-15) from common metastases to the breast, including carcinoma of the lung (thyroid transcription factor-1), malignant melanoma (S100, HMB45, melan-A) and ovarian serous papillary carcinoma (Wilms' tumour 1), are discussed. The pathologist has a key role in considering the diagnosis of metastasis to the breast if the histological features are unusual for a primary mammary tumour. The clinical history is vital in some cases. Immunohistochemistry plays a useful supplementary role.
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            Mutations in the epidermal growth factor receptor (EGFR) gene in triple negative breast cancer: possible implications for targeted therapy

            Introduction Triple negative breast cancer is associated with poorer prognosis and unresponsiveness to endocrine and anti-HER2 directed agents. Despite emerging data supporting the use of polyADP-ribose polymerase (PARP) inhibitors, complete and durable responses are rare and exploration of additional targeted therapies is needed. Epidermal growth factor receptor (EGFR) is expressed in triple negative breast cancer and several clinical trials are testing the role of anti-EGFR directed therapy. However, the rate of EGFR mutations is poorly defined. We, therefore, sought to characterize EGFR mutations in triple negative breast cancers. Methods Seventy samples were randomly chosen from a cohort of 653 triple negative breast tumours for EGFR mutation analysis. These samples were immunostained for EGFR protein expression and consisted of negatively stained and positively stained cases. DNA was extracted from paraffin blocks and polymerase chain reaction was performed to amplify exon regions 18 to 21 of the EGFR gene. Direct sequencing of the purified PCR products was performed. Results EGFR mutations were found in 8 of 70 samples (11.4%). Mutations were predominantly exon 19 deletions (4 of 70 samples, 5.7%), which clustered in the region spanning codons 746 to 759 within the kinase domain of EGFR. Two types of exon 19 deletions were seen: a 15 nucleotide deletion (del E746-A750) (2 of 70 samples) and a 24 nucleotide deletion (del S752 - I759) (2 of 70 samples). Other exon 19 mutations observed were the inversion of the complementary strand (1 of 70 samples). Exon 21 mutations included missense substitution, L858R (1 of 70 samples) and T847I (2 of 70 samples). Mutations observed were independent of EGFR protein expression determined by immunohistochemical staining. Conclusions This study is among the first to document the presence and estimate the prevalence of EGFR mutations in triple negative breast cancer. These findings have potential implications for the design of clinical trials involving anti-EGFR directed therapy which currently do not select for patients based on presence of activating EGFR mutations, which may hence be underpowered to detect significant benefit in unselected populations. More complete sampling of EGFR mutation status in triple negative breast cancer is needed to determine the true mutation rate.
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              Epidermal growth factor receptor in breast carcinoma: association between gene copy number and mutations

              Background The epidermal growth factor receptor (EGFR) is an available target of effective anti-EGFR therapy for human breast cancer. The aim of this study was to assess the presence of EGFR gene amplification and mutations in breast cancer and to analyze the association between the statuses of these two gene alterations. Materials and methods EGFR gene amplification and mutations were investigated in formalin-fixed, paraffin-embedded tissues from 139 Chinese female patients with breast cancer by means of fluorescence in-situ hybridization (FISH) and fluorescently labeled real-time quantitative polymerase chain reaction (RT-PCR), respectively. Results EGFR gene amplification was observed in 46/139 (33.1%) of cases by FISH. Based on RT-PCR, 2/139 (1.4%) samples had EGFR gene mutations. Overall, only 1 (0.7%) of the cases was identified with both whole gene amplification and mutation, and 92 (66.2%) of cases were negative for both. High gene copy numbers of EGFR had significant correlation with the occurrence of EGFR protein expressions (P = 0.002). Conclusion In this study, EGFR mutations were presented in only two samples, indicating that EGFR mutations should not be employed in future trials with anti-EGFR therapies for breast cancer. However, EGFR whole gene amplification is frequently observed in patients with breast cancer. It will be of significant interest to investigate whether EGFR gene copy number is a suitable screening test for EGFR-targeted therapy for breast cancer.

                Author and article information

                Case Reports in Oncology
                S. Karger AG
                January – April 2015
                14 March 2015
                : 8
                : 1
                : 164-168
                aDépartement de Cancérologie Générale, bDépartement de Sénologie, cUnité de Pathologie Morphologique et Moléculaire, and dUnité d'Oncologie Moléculaire Humaine, CLCC Oscar Lambret, and eService de Chirurgie Thoracique, Hôpital Calmette, fPlateforme Régionale CHRU-COL de Génétique Moléculaire des Cancers, and gCentre de Pathologie, CHRU Lille, Lille, France
                Author notes
                *Dr. Eric Dansin, Département de Cancérologie Générale, CLCC Oscar Lambret, 3 rue Fréderic Combemale, FR-59020 Lille (France), E-Mail e-dansin@o-lambret.fr
                381014 PMC4386146 Case Rep Oncol 2015;8:164-168
                © 2015 S. Karger AG, Basel

                Open Access License: This is an Open Access article licensed under the terms of the Creative Commons Attribution-NonCommercial 3.0 Unported license (CC BY-NC) ( http://www.karger.com/OA-license), applicable to the online version of the article only. Distribution permitted for non-commercial purposes only. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 4, References: 12, Pages: 5
                Published: March 2015

                Oncology & Radiotherapy,Pathology,Surgery,Obstetrics & Gynecology,Pharmacology & Pharmaceutical medicine,Hematology
                Lung adenocarcinoma,Breast metastasis,EGFR tyrosine kinase inhibitors,EGFR mutation,Triple-negative breast cancer


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