Il Trattamento del Carcinoma della Mammella Operabile: stato dell arte e pratica clinica Roma, 28 Novembre 2008

1. Il Trattamento del Carcinoma della Mammella Operabile:stato dell�arte e pratica clinica Roma, 28 Novembre 2008 Maria Sofia Rosati UOC Oncologia A - Policlinico �Umberto I�, Universit� di Roma �Sapienza�

2. CASO CLINICO ID paziente: PS Data di nascita: 23/03/1955 Professione: avvocato Anamnesi familiare per neoplasia: Padre fumatore deceduto a 73 aa per k polmone Menarca: 11 aa Mestruazioni: regolari Parti: 2 (et� prima gravidanza 23 aa) Anamnesi patologica remota : 1998 ( 43 aa) Isterectomia per fibromatosi diffusa sintomatica (non annessiectomia) 2004: Contusione del rachide dorso-lombare per incidente stradale

3. ANAMNESI PATOLOGICA ONCOLOGICA Et� alla prima diagnosi (2005): 50 aa (post-menopausa ?) 03-05-2005 Riscontro occasionale di nodulo QSE mammella dx durante Rx mammografia di screening Alla diagnosi: Ca 15-3: 88 U/mL (vn < 39), Ca 125 e CEA nei limiti 09-05-2005 CH: Mastectomia radicale dx e contestuale posizionamento espansore EI: carcinoma duttale infiltrante con residua componente intraduttale cribriforme e figure di cancerizzazione lobulare; 3/25 linfonodi sede di ripetizione neoplastica; pT1cN1biM0, G3 01-06-2005: TC TB: negativa per patologia in atto 05-06-2005: Scintigrafia ossea TB: iperfissazione del radiofarmaco in L1 da riferire a trauma

5. CHEMIOTERAPIA 15-06-2005: CHT adiuvante: 4EC?4 Paclitaxel Ca 15-3 post-CHT: 16 U/mL CEA, Ca 125 e OSTASE nei limiti

6. ORMONOTERAPIA 30-11-2005 esegue dosaggi ormonali: Progesterone 0.4 ng/mL - menopausa LH 180 mlU/mL (vr 35-200) - menopausa FSH 179 mlU/mL (vr 4-200)- menopausa 05-12-2005 Inizia terapia ormonale con letrozolo 28-12-2005/04-02-2005 esegue RT sulla fossa sovraclaveare

8. La paziente esegue una RM del rachide dorso-lombare per dolore persistente (post-traumatico?): reperto di lesione secondaria in L2

9. TC TB (08/08/2007)

10. 18F-FDG PET-TC: AGOSTO 2007

11. Settembre 2007: esegue RT su L2 Ca 15-3, Ca 125, CEA nei limiti Prosegue letrozolo e acido zoledronico

12. Follow-up Ottobre 2008 (PFS: 3 aa) : negativo per nuove localizzazioni scheletriche o d�organo La paziente presenta ECOG PS 0, ottima compliance al trattamento e non ha mai interrotto la propria attivit� lavorativa.

13. ANALISI A POSTERIORI Valutazione dello stato menopausale della paziente Classificazione del rischio AI upfront o switch? Adiuvante o I linea?

14. ANALISI A POSTERIORI Valutazione dello stato menopausale della paziente Classificazione del rischio AI upfront o switch? Adiuvante o I linea?

15. BREAST CANCER:Pamela J. Goodwin, Marguerite Ennis, Kathleen I. Pritchard, Maureen Trudeau, and Nicky HoodRisk of Menopause During the First Year After Breast Cancer DiagnosisJ. Clin. Oncol., Aug 1999; 17: 2365. 

16. Journal of Clinical Oncology, Vol 19, Issue 14 (July), 2001: 3303-3305 EDITORIAL Menopause and Breast Cancer: Addressing the Secondary Health Effects of Adjuvant Chemotherapy Patricia A. Ganz, Gail A. Greendale University of California, Los Angeles Schools of Public Health and Medicine, Jonsson Comprehensive Cancer Center, Los Angeles, CA IN RECENT YEARS there has been a significant decrease in breast cancer mortality.1 The reasons for this welcome improvement in survival are probably multifactorial, reflecting the more widespread utilization of mammography as well as the successful dissemination and utilization of adjuvant therapy. According to the recommendations of the National Institutes of Health Consensus Conference on Adjuvant Therapy of Breast Cancer,2 chemotherapy should be considered in all women with invasive breast cancer, and women with hormone receptor�positive tumors should be receiving adjuvant tamoxifen for 5 years� duration. The value of such therapy in very small tumors is being actively debated3,4 and will not be discussed further in this editorial. Although the relative and absolute survival benefits of adjuvant chemotherapy and adjuvant endocrine therapy are well documented in the serial reports from the Oxford Overview,5,6 few data are available on other noncancer health effects from such treatments. For example, few individual randomized treatment trials have prospectively examined the incidence of oligomenorrhea or menopause after adjuvant therapy,7 both of which may have other health effects, such as premature bone loss and increased risk of subsequent fractures. These late health effects take on increasing importance, given the long-term survival expected for most women with early-stage breast cancer.

17. ANALISI A POSTERIORI Valutazione dello stato menopausale della paziente Classificazione del rischio AI upfront o switch? Adiuvante o I linea?

19. St Gallen 2007 Il panel ha espresso chiara preferenza per lo switch da TAM a AI dopo 2-3 anni L�utilizzo upfront degli AI deve essere preferito nelle pazienti ad alto rischio o in donne HER2 (+) L�extended con AI dopo TAM � consigliato fortemente nelle pazienti N(+) dopo 5 anni di TAM L�utilizzo degli AI � da preferire nelle pazienti che utilizzano antidepressivi SSRI

20. ANALISI A POSTERIORI Valutazione dello stato menopausale della paziente Classificazione del rischio AI upfront o switch? Adiuvante o I linea?

23. ANALISI A POSTERIORI Valutazione dello stato menopausale della paziente Classificazione del rischio AI upfront o switch? Adiuvante o I linea?

24. Letrozole vs Tamoxifen Overall Survival Femara demonstrated a significant early survival advantage over tamoxifen 1 and 2-year survival rates were significantly greater with Femara than with tamoxifen What this means in clinical practice is that if you treat 100 patients, at 1 year, 8 more patients would be alive if they started on Femara thanif they started on tamoxifen 99% of patient crossed over by 36 months, which is also about the time the curves converge. This suggests that crossover may have contributed to the convergence of the curves Note: An analysis of survival at every 6 month interval was not prescribed in the initial protocol but was predetermined prior to database lock (September 2001) Femara demonstrated a significant early survival advantage over tamoxifen 1 and 2-year survival rates were significantly greater with Femara than with tamoxifen What this means in clinical practice is that if you treat 100 patients, at 1 year, 8 more patients would be alive if they started on Femara thanif they started on tamoxifen 99% of patient crossed over by 36 months, which is also about the time the curves converge. This suggests that crossover may have contributed to the convergence of the curves Note: An analysis of survival at every 6 month interval was not prescribed in the initial protocol but was predetermined prior to database lock (September 2001)

25. Letrozole vs Tamoxifene: Tempo alla CHT For patients who are treated with endocrine therapy for metastatic breast cancer, the switch to chemotherapy has negative quality-of-life and economic impact implications.Consequently, switching to chemotherapy should be delayed as long as possible. In the randomized, crossover, first-line, phase III clinical trial of letrozole vs tamoxifen in postmenopausal women with hormone receptor�positive or �unknown advanced breast cancer, patients who progressed rapidly with initial endocrine therapy were switched to chemotherapy. Patients who crossed over to the alternate endocrine therapy were switched to chemotherapy at second progression. Median time to chemotherapy was significantly longer with letrozole than with tamoxifen (16 months vs 9 months, respectively; P=0.005). For patients who are treated with endocrine therapy for metastatic breast cancer, the switch to chemotherapy has negative quality-of-life and economic impact implications.Consequently, switching to chemotherapy should be delayed as long as possible. In the randomized, crossover, first-line, phase III clinical trial of letrozole vs tamoxifen in postmenopausal women with hormone receptor�positive or �unknown advanced breast cancer, patients who progressed rapidly with initial endocrine therapy were switched to chemotherapy. Patients who crossed over to the alternate endocrine therapy were switched to chemotherapy at second progression. Median time to chemotherapy was significantly longer with letrozole than with tamoxifen (16 months vs 9 months, respectively; P=0.005).