1. Gli eventi cardiovascolari diversi dall’ischemia e dallo scompenso cardiaco dopo terapia con tamoxifene o letrozolo adiuvanti sono più frequenti con 1.Tamoxifene 2.Letrozolo 3.Nessuna differenza tra i due agenti ormonali EdiVoteStartEdiVoteStop 000 Standard 010

2. Dopo un follow-up mediano di 100 mesi, lo studio ATAC ha evidenziato che l’anastrozolo è superiore al tamoxifene in termini di riduzione di 1.Recidive locoregionali 2.Metastasi a distanza 3.Incidenza di tumori mammari controlaterali 4.Tutte le precedenti 25% EdiVoteStartEdiVoteStop 000 Standard 010

3. Secondo la WHO, per osteoporosi si intende un T-score 1.< -2.5 2.Tra -2.5 e -1 3.< -3.0 EdiVoteStartEdiVoteStop 000 Standard 010

4. Il Carcinoma Mammario nella paziente molto anziana Lazzaro Repetto ASL 1 Imperiese Ospedale G. Borea, Sanremo

5. Cancer in Senior Adults: unsolved questions - Most of elderly patients are 70 to 85 yrs. - At the best, we have evidence based treatment only for patients up to 75 yrs. - After 75 yrs, >50% of the pts do not received standard treatment or treatment at all, due to the fear of toxicity. - Available clinical data are at best, transferable to healthy senior patients only.

6. Giordano et al. JCO 2005 ……Undertreated population

7. Bastiaannet E. et al, Breast Cancer Res Treat (2010) 124:801–7 Qualsiasi trattamento sistemico p.<0.001

8. Proportional benefits by time period ER poor disease Recurrences are concentrated in the time period 0-4 (±80% vs. ±20% in the time period 5+) Most of the proportional benefit is concentrated within the time period 0-4 ER positive disease Recurrences are distributed over time (±60% in 0-4 vs. ±40% in 5+) Proportional benefit tends to be maintained over time (0-4 vs. 5+)

9. From “age” to “biology” “When analyzed by age, the reason for the previously reported lower impact of chemotherapy in older age was that many more women in the older age group had tumors with low or intermediate recurrence scores than the younger population. If only those older patients with high recurrence scores were analyzed, they derived a similar benefit from chemotherapy” K Albain. St Gallen 2005

10. CT adiuvante nelle anziane: quale regime? Senza Antracicline Con Antracicline Poli CT Con Taxani CMF x 6 Doc sett x 6 Epi x 4+CMF x 4 AC x 4-6 q3w FAC/FEC x 6 q3w 4 AC q3w + 4 Paclitax q3w (?) 3 FEC q3w + 3 Doc (?) 4 TC q3w Parliamo di pazienti con alto rischio di ricaduta: ER neg; N pos; ecc.

11. The “old” CMF……… CMF is the most frequently used adjuvant treatment regimen for elderly breast cancer patients, but reasonable concern exists on its use in this population

13. The “new” DOCETAXEL….. Docetaxel, is among most active drugs in breast cancer and it is effective in the adjuvant setting However, the standard 3-weekly schedule produces relevant side effects, that could be not tolerable for elderly patients The weekly schedule of docetaxel is less toxic Weekly docetaxel has shown promising activity and excellent tolerability also in elderly advanced breast cancer patients

14. Una schedula attiva… Hainsworth et al. The Oncologist 9, 2005

15. The ELDA study Adjuvant CMF (CTX 600 mg/m2, MTX 40 mg/m2, 5-FU 600 mg/m2 on days 1 and 8, every 4 weeks) Adjuvant Docetaxel (35 mg/m2 on days 1, 8,15 every 4 weeks) To demonstrate the superiority of weekly docetaxel over CMF as adjuvant treatment in terms of disease-free survival of elderly breast cancer patients RANDOM Both groups receive: 4 cycles followed by hormone therapy, if ER or PgR positive 6 cycles, if ER and PgR negative Aim of the ELDA study CROH 2010

16. ELDA:Conclusions The results of our safety analysis: – confirm the good tolerability of weekly docetaxel as adjuvant chemotherapy of elderly breast cancer patients – demonstrate a better compliance and safety profile of weekly docetaxel as compared to CMF, in particular for hematological toxicity Final results of ELDA trial must be awaited to draw definite conclusions on efficacy of adjuvant weekly docetaxel for elderly early breast cancer patients CROH 2010

18. Docetaxel 75 mg/m2 IV Cyclophosphamide 600 mg/m2 IV Doxorubicin 60 mg/m2 IV Cyclophosphamide 600 mg/m2 IV 4 x AC 4 x TC Design R Postoperative XRT and Tamoxifene were administered after the completion of CT, for appropriate patients N=1 106 Stratification  Nodes: 0 / 1-3 / 4+  Age: < 50 or ≥ 50 Every 3 weeks USO 9735 Stephen Jones: J Clin Oncol 27. © 2009

19. AC vs TC Risultati a 7 aa: TC (Docetaxel-Ciclofosfamide) vs AC (Doxorubicin-Ciclofosfamide) Jones S, et al. J Clin Oncol. 2009;27(8):1177-1183

20. Conclusions At 7 years, 4 cycles of TC compared with 4 cycles of AC was associated with – Superior DFS (P =.033) – Superior OS (P =.032) – Efficacy in HER2+ as well as HER2- disease (limited sample) – Efficacy established in “older” as well as younger patients USO 9735

21. What do we know from anthracycline (A)-based regimens? Associated with a 47% ten-year cardiac failure rate for women aged 66 to 70 years compared with 33% for CMF recipients and 28% for no adjuvant chemotherapy controls1 Associated with an increased risk of acute myeloid leukemia (HR 2.17) in patients aged ≥ 66 years (overall 10-year risk of AML after any adjuvant chemo vs nil = 1.72)2 1Giordano et al. ASCO 2006; 2Patt et al. ASCO 2006

22. ● Trastuzumab ● Lapatinib  Limited data  Selection bias related to study entry criteria  Data, at best, transferable to healthy patients  No data for the oldest old

23. Independent adjudication of symptomatic heart failure with the use of AC  trastuzumab adjuvant therapy Russel et al. J Clin Oncol 2010 ……………………………. …………………………………………………………Independent predictors for cardiac events were age older than 50 years, a low ejection fraction at the start of paclitaxel treatment*, and trastuzumab treatment. * Only at the univariate analysis

24. Crown et al. Breast Cancer Res Treat. 2008 ● Median age 55 years (range 19 - 87) ● Diarrhea events in elderly patients (≥70 years) had similar severity, onset, and resolution compared with diarrhea events in patients <70 years, although some minor differences existed.. …. Elderly patients with breast cancer experienced more grade 3 events (33% vs. 19% in patients <70 years)

25. Anti-HER2 therapy: conclusions ● Limited data ● Anti-HER2 therapy should not be denied to elderly BC patients ● Single agent trastuzumab or anti-HER2 treatment in combination with endocrine-therapy (if ER+) is an option when chemotherapy is not appropriate ● If in doubts, prescribe trastuzumab and avoid anthracyclines

26. In the absence of cardiac contraindications, adjuvant trastuzumab should be offered to older patients with ERBB2-positive breast cancer when chemotherapy is indicated, but cardiac monitoring is essential Lancet Oncol 2007

27. Gli eventi cardiovascolari diversi dall’ischemia e dallo scompenso cardiaco dopo terapia con tamoxifene o letrozolo adiuvanti sono più frequenti con 1.Tamoxifene 2.Letrozolo 3.Nessuna differenza tra i due agenti ormonali EdiVoteStartEdiVoteStop 000 Standard 010

28. Dopo un follow-up mediano di 100 mesi, lo studio ATAC ha evidenziato che l’anastrozolo è superiore al tamoxifene in termini di riduzione di 1.Recidive locoregionali 2.Metastasi a distanza 3.Incidenza di tumori mammari controlaterali 4.Tutte le precedenti 25% EdiVoteStartEdiVoteStop 000 Standard 010

29. Secondo la WHO, per osteoporosi si intende un T-score 1.< -2.5 2.Tra -2.5 e -1 3.< -3.0 EdiVoteStartEdiVoteStop 000 Standard 010

30. grazie