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ABC1 - G. Viale - Role of pathology in the management of advanced breast cancer
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ABC1 - G. Viale - Role of pathology in the management of advanced breast cancer

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  • Gong Y, et al: Comparison of HER-2 status determined by fluorescence in situ hybridization in primary and metastatic breast carcinoma. Cancer. 2005 May 1;103(9):1763-9. Simon R, et al: Patterns of her-2/neu amplification and overexpression in primary and metastatic breast cancer. J Natl Cancer Inst. 2001 Aug 1;93(15):1141-6. Gancberg D, et al: Comparison of HER-2 status between primary breast cancer and corresponding distant metastatic sites. Ann Oncol. 2002 Jul;13(7):1036-43. Zidan J, et al: Comparison of HER-2 overexpression in primary breast cancer and metastatic sites and its effect on biological targeting therapy of metastatic disease. Br J Cancer. 2005 Sep 5;93(5):552-6.
  • Transcript

    • 1. Role of pathology in the management of advanced breast cancer Beppe Viale European Institute of Oncology University of Milan Milan, Italy
    • 2. The role of the pathologist
      • Confirm the metastatic nature of the lesion
      • Identify the breast as the primary site
        • Occult (unknown) primary
        • Distant relapse
      • Evaluate (re-evaluate) the biological features of the tumour
    • 3. The role of the pathologist
      • Confirm the metastatic nature of the lesion
        • Nonneoplastic lesions (e.g., tubercolosis)
        • Second primaries (e.g. lung carcinoma)
    • 4. Second primaries
    • 5. The role of the pathologist
      • Confirm the metastatic nature of the lesion
      • Identify the breast as the primary site
        • Occult (unknown) primary
        • Distant relapse
      • Evaluate (re-evaluate) the biological features of the tumour
    • 6. Carcinoma of unknown primary
      • CUP is not a rare event: 2-7% of all human malignancies (7th to 8th most frequent type of cancer)
      • Primary tumors remain unknown in some 20-45% of the patients
      • Median survival time is only a few months
      • CUP is the 4th commonest cause of cancer death both in men & women.
    • 7. CUP sites
      • Lymph nodes 42%
      • Liver 33%
      • Bone 29%
      • Lung 26%
      • Pleura 11%
      • Peritone um 9%
      • Brain, Adrenal, Skin,
      • Bone marrow 19%
    • 8. A biopsy will tell us where it is coming from (!)
      • Fine needle aspiration cytology
      • Core biopsy
      • Surgical biopsy
      • Avoid short-cuts : “… after a complete history and physical examination have been carried out along with basic laboratory, radiologic and endoscopic studies ”
    • 9. … but not always!
      • Primary identified with biopsy: 25%
      • Primary identified at autopsy: 30-55%
      • Primary remains unknown: 20-45%
    • 10. Metastasis from a second primary
    • 11. Metastasis from a second primary
    • 12. ER Breast carcinoma metastatic to bone
    • 13. ER Breast carcinoma metastatic to the stomach
    • 14. The role of the pathologist
      • Confirm the metastatic nature of the lesion
      • Identifythe breast as the primary site
        • Occult (unknown) primary
        • Distant relapse
      • Evaluate (re-evaluate) the biological features of the tumour
    • 15. Do tumors change?
      • 3-28% of metastatic lesions will either loose or acquire ER expression
      • 3-25% of the cases will either loose or acquire HER2 overexpression or amplification
    • 16. Why do tumours change?
      • Intratumoral heterogeneity?
        • Changes in primary and synchronous lymph node metastases
      • Therapy-induced changes?
        • Changes in primary and distant relapses
          • PgR down-regulation by endocrine therapy
          • Acquired resistance to endocrine treatments with HER2 over-expression
          • (Re-)Induction of ER expression by trastuzumab
          • Extensive degradation of HER2 protein by trastuzumab
    • 17. Intratumoral heterogeneity
    • 18. … also in the metastases
    • 19.  
    • 20. Why do tumours change?
      • Intratumoral heterogeneity?
        • Changes in primary and synchronous lymph node metastases
      • Therapy-induced changes?
        • Changes in primary and distant relapses
          • PgR down-regulation by endocrine therapy
          • Acquired resistance to endocrine treatments with HER2 over-expression
          • (Re-)Induction of ER expression by trastuzumab
          • Extensive degradation of HER2 protein by trastuzumab
    • 21. 1250 liver biopsies from 1999-2009; 255 identified as BC metastases
    • 22. But our assays are not “perfect”
      • Up to 20% false-negative assessments of ER status
      • Some 15% false-positive assessments of PgR status
      • Up to 15% false-positive assessments of HER2 status
    • 23. Real status - unknown!- (N) ER- (200) ER+ (800) 190 Sensitivity p + = 0.95 Tumor N 10 40 760 180 Metastasis N 10 9 1 2 38 38 722 Specificity p - = 0.95 Changed status from T to M 95/1000 = 9.5% + p + = 0.95 p - = 0.05 p + = 0.95 p - = 0.05 p + = 0.95 p - = 0.05 p - = 0.95 p + = 0.05 p + = 0.05 p + = 0.05 - + + - - + - - + - + p - = 0.95 p - = 0.95 Do tumours change?
    • 24. What to do?
      • Tell your pathologist you are in troubles
        • Start/stop a treatment
      • Double check HR & HER2 status
        • Re-stain simultaneously both the primary and the recurrence in the same run
        • Use an alternative assay (e.g., FISH)
    • 25. If discordance is confirmed
      • “ Good” for the patient: appearance of a target for therapy
      • “ Bad” for the patient: disappearance of a target for therapy
        • Would you deny a targeted treatment because a single core biopsy (or FNAC) of one of several metastases has shown ER or HER2 negative disease?
    • 26.  
    • 27.  
    • 28. Il sugo di tutta la storia (A. Manzoni, I Promessi Sposi)
      • The Pathologists’ role in the treatment of patients with advanced breast cancer includes:
        • confirmation of the metastatic nature of the lesion
        • identification of the breast as the site of origin
        • assessment or re-assessment of the predictive parameters
      Be nice to your fellow pathologists!

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