Positive Bone Marrow Biopsy is Associated with a Decreased Disease-Free Survival in Patients with Operable Breast Cancer

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1 Positive Bone Marrow Biopsy is Associated with a Decreased Disease-Free Survival in Patients with Operable Breast Cancer L Fortunato (*), A Mascaro (*), A Baldi ( ), M Farina (*), MAmini(**) ), C Vitelli (*) Department of Surgery (*), and Pathology (**) San Giovanni-Addolorata Hospital, Rome, Department of Biochemistry ( ), Second University of Naples ITALY SSO Annual Symposium Phoenix, AZ - March 7th,

2 Background Staging of breast cancer patients is essential, but our ability to predict relapse is imprecise 30% of node negative patients will relapse 40% of node positive patients will survive long term Further prognostic factors are urgently needed SSO

3 Review To date, at least 28 studies involving 6202 patients 18 of them have shown a correlation with DFS/OS Often, BM independent prognostic factor Lack of standardization and wide range of positivity Only few studies have employed RT-PCR SSO

4 Aim of Study Bone Marrow: Since 2000 Peripheral blood: Since 2002 RT-PCR: CEA and Mammaglobin Primary end point: Secondary end point: disease-free survival overall survival correlation with Microarray SSO

5 Methods Test was considered positive if any RT-PCR was positive All patients signed an informed consent Results remained unavailable to both patients and clinicians SSO

6 Results 274 patients were enrolled BM biopsy was unsuccessful in 9 patients RT-PRC technically not feasible in 18 patients 247 patients t available for results Only one patient was lost to follow-up (0.4%) SSO

7 Results RT-PCR Test was positive in 110/247 patients (45%) At a median F/U of 60 months 31 events (13%) have occurred 13 deaths due to disease 15 systemic recurrences 3 regional recurrences SSO

8 Positive Test and Tumor Characteristics N BM + % p Age < > Diameter 0.87 < 1 cm cm > 2 cm Histology 0.93 Ductal Non Ductal Nodal Status N N Hormonal status 0.66 Positive Negative C-Erb B Positive Negative Molecular Type 0.31 Luminal like Non Luminal Like SSO

9 Positive Test and Stage STAGE I STAGE II STAGE III P = SSO

10 Disease free survival Univariate i analysis Hazard Ratio Lower 95% CI Upper 95% CI P Age Menopausal status Histology Tumor diameter Nodal status Grade Hormonal status C-Erb B RT-PCR Test SSO

11 Disease free survival Univariate i analysis Hazard Ratio Lower 95% CI Upper 95% CI P Age Menopausal status Histology Tumor diameter Nodal status Grade Hormonal status C-Erb B RT-PCR Test SSO

12 Disease free survival Multivariate Analysis Hazard Ratio Lower 95% CI Upper 95% CI P RT-PCR Test Nodal status Interaction Test / Nodal status SSO

13 Disease free survival According to RT-PCR test and Nodal status P< P=

14 Bone Marrow and Peripheral blood Disease-free survival P = P =

15 CEA and Mammaglobin Disease free survival P < P =

16 5 year Disease-free survival N- / BM - N- / BM + N+ / BM - N+ / BM+ P= SSO

17 Re-staging? N- /BM- N- /BM+ N+ /BM- N+ /BM+ SSO

18 Conclusions Positive RT-PCR of the BM for Mammaglobin is associated with a four-fold increased risk of death or relapse RT-PCR of the PB is not associated with DFS Patients N-/BM- are almost certainly cured Patients N+/BM+ need more aggressive strategies SSO

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20 Review Author Year N Method Compart Positive (%) DFS OS Multivariate Porro IHC Bone Marrow N/A Harbeck IHC Bone Marrow Diel IHC Bone Marrow Landys IHC Bone Marrow N/A Untch IHC Bone Marrow N/A Mansi IHC Bone Marrow Braun IHC Bone Marrow Gerber IHC Bone Marrow Gebauer IHC Bone Marrow Solomayer IHC Bone Marrow Wiedswang IHC Bone Marrow Wong IHC Bone Marrow Pierga IHC Bone Marrow Ooka RT-PCR BoneMarrow Stathopoulou RT-PCR Peripheral Farmen RT-PCR Bone Marrow Apostolaki RT-PCR Peripheral

21 C+ BM- BM- BM+ BM+ 21

22 Comparison of the power to identify tumor cells between tests H/H IHC RT-PCR 22

23 Eventi sistemici e Decessi / Eventi sistemici 7 / 112 Decessi 10 2 / 99 2 / MIDOLLO POSITIVO MIDOLLO NEGATIVO Eventi: P= Sopravvivenza p=

24 RT-PCR Genomic DNA Primer 1 Primer 1 Primer 3 Exon 1 Exon 2 Exon 3 Primer 4 Primer 2 cdna Primer 1 Primer 3 Exon 1 Exon 2 Exon 3 Primer 4 Primer 2 24

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26 Sensitivity of Molecular testing by RT-PCR MAMM PIP PSE CEA CK19 MUC1 Gillanders WE, et al: Ann Surg 2004; 239:

27 Comparazione tra la capacità di identificazione delle cellule tumorali E/E IHC RT-PCR 27

28 Tipo di test effettuato MIDOLLO + PERIFERICO SOLO PERIFERICO SOLO MIDOLLO Pazienti sono state considerate negative in assenza di positività in tutti i test (Midollo/periferico CEA/Mammolobina) 28