La personalizzazione terapeutica: quanto influisce l età PierFranco Conte University of Padova Department of Surgery, Oncology and Gastroenterology IOV Istituto Oncologico Veneto I.R.C.C.S.
Breast Cancer in Young Women - Outline Epidemiology Biology of breast cancer in young patients Implications for local treatment Adjuvant therapy in young women: - Efficacy - Tolerability - Needs
Nuovi casi di tumore maligno stimati in Veneto nel 2014. Distribuzione per fasce di età e sesso Dati registro tumori Veneto
I tumori più frequenti in età 20-39 anni. Femmine. Casi annui stimati in Veneto nel 2014 e % sul tot. tumori 20-39 anni. SEDE Casi/anno tot tumori % Mammella 188 31.3% Cute melanomi 97 16.2% Tiroide 84 14.0% Utero 36 5.9% Linfoma di Hodgkin 29 4.9% Totale (eccetto cute non melanoma) 599 100% Dati registro tumori Veneto
Trend di incidenza 1990-2008 Le sedi più frequenti nelle femmine. Età 20-39 anni Dati registro tumori Veneto
Sopravvivenza relativa dei casi di tumore in età 20-39 anni. Casi incidenti nel periodo 2004-2007. Le sedi più frequenti nelle femmine Dati registro tumori Veneto
Breast Cancer in Young Women - Outline Epidemiology Biology of breast cancer in young patients Implications for local treatment Adjuvant therapy in young women: - Efficacy - Tolerability - Needs
Proportion of breast cancer subtypes among California women by age group, 2005-2009. BC patients diagnosed 2005-2009. Data from the California Cancer Registry: n=112,256 (5,605 aged 15-39, 19,776 aged 40-49, and 86,875 older than 50). HR-/HER2+ HR+/HER2+ TN HR+/HER2- Keegan et al, Breast Cancer Research 2012
Disease Free Survival by age Anders C. K. Et al. JCO 2008
Reasons for worse outcome for young breast cancer patients - diagnostic delay (no screening) - association with aggressive features - POSH Prospective observational study of BC pts <40yrs: n=2956, ductal histology 86.5%, G III 58.9%, N+ 50.2% - enrichment with aggressive subtypes - More TN and HER2+ - different tumor biology in young vs older? Keegan et al, Breast Cancer Research 2012
Breast Cancer in Young Women - Outline Epidemiology Biology of breast cancer in young patients Implications for local treatment Adjuvant therapy in young women: - Efficacy - Tolerability - Needs
Young BC patients have a higher risk of local relapse
Benefit from post-mastectomy RT 3131 pn+ pts with mastectomy + AND Any first recurrence (yrs 0-9) BC mortality <40yrs 40-49yrs 50-59yrs +60yrs <40yrs 40-49yrs 50-59yrs +60yrs 1314 pn1-3 pts with mastectomy + AND Any first recurrence (yrs 0-9) BC mortality <40yrs 40-49yrs 50-59yrs +60yrs <40yrs 40-49yrs 50-59yrs +60yrs EBCTCG, Lancet 2014
Breast Cancer in Young Women: implications for local treatment Young age, although correlated to a higher risk of local relapse, is not a contraindication to BCS Relevance of clear margins Benefit from post-mastectomy RT in N1-3 positive nodes Genetic factors influence treatment decision
Breast Cancer in Young Women - Outline Epidemiology Biology of breast cancer in young patients Implications for local treatment Adjuvant therapy in young women: - Efficacy - Tolerability - Needs
Overall survival in young (<35yrs) vs older (35-50yrs) pts according to tumor biology n tot=9885 (young n=1444); Diagnosis 1992-2001 All HR- HR unknown HR+ Ahn J Clin Oncol 2007
HR+ EBC: Upfront Adjuvant Endocrine Therapy Definitive local treatment PRE & PERIMENOPAUSE? POST- MENOPAUSE Tamoxifen 5y Tam 5y + OFS 5y Still standard of care 5y DFS % Tam 84.7 Tam+OS 86.6 HR 0.83 (95% CI 0.66-1.04) p = 0.10 Francis PA et al NEJM 2015
SOFT TRIAL: SELECTED AES AE Tamoxifen (N 1006) Tamoxifen + OS (N 1005) any G % G > 3 % any G % G > 3 % Hot flushes 79.8 7.6 93.4 13.2 depression 46.6 3.8 51.9 4.4 sweating 48.3-61.8 - insomnia 46.3 2.9 57.2 4.6 hypertension 17.2 5.4 23.2 7.5 muscoskeletal 69.0 6.3 75.1 5.5 osteoporosis 12.3 0.1 20.0 3.0 Vaginal dryness 41.8-49.8 - Decreased libido 42.4-47.5 - Glucose intolerance 1.8 0.3 3.5 1.4 Any AE 95.3 23.7 98.4 31.3 Francis PA et al NEJM 2015
TEXT and SOFT joint analysis TEXT trial (n=2672) Tamoxifen + OFS x 5y Exemestane + OFS x 5y SOFT trial (n=3066) Tamoxifen x 5y Joint Analysis (n=4690) median FU 5.7 y Tamoxifen + OFS x 5y Exemestane + OFS x 5y Tamoxifen + OFS x 5y Exemestane + OFS x 5y Primary endpoint: DFS Secondary endpoints: BCFI, DRFI, OS Pagani O, NEJM 2014
HR+ EBC: Upfront Adjuvant Endocrine Therapy Definitive local treatment PRE & PERIMENOPAUSE? POST- MENOPAUSE TEXT and SOFT joint analysis: results Tamoxifen 5y Tam 5y + OFS 5y Still standard of care AI 5y + OFS 5y Contraindication to Tam (endometrial hyperplasia or cancer, DVT, PE) High risk patients Pagani O, NEJM 2014
TEXT and SOFT joint analysis: selected AEs Pagani O, NEJM 2014
HR+ EBC: Ongoing Endocrine Therapy 5-ys TAM in PRE & PERIMENOPAUSE? 5-ys TAM in POSTMENOPAUSE 5 ys AI in POSTMENOPAUSE Stop TAM TAM up to 10y Trial Experimental arm pts # DFS Δ HR ATLAS 1 10y TAM 6,846 3.7% 0.75 attom 2 10y TAM 6,953 4% 0.85 1 Davies et al, Lancet 2013; 2 Gray et al, ASCO 2013
HR+ EBC: Ongoing Endocrine Therapy 5-ys TAM in PRE & PERIMENOPAUSE? 5-ys TAM in POSTMENOPAUSE 5 ys AI in POSTMENOPAUSE Stop TAM TAM up to 10y High risk patients Risk of endometrial cancer and PE Symptoms & sexuality Endometrial cancers Continue (3470) Stop (3486) P value 102 47 <0.0001 Endometrial cancer deaths 31 23 0.27
LHRHa during chemotherapy to preserve ovarian function Del Mastro L, 2014
Prevention Of Early Menopause Study: POEMS n= 118 Primary endpoint: Ovarian failure at 2 years Secondary endpoint: Pregnancy outcome Ovarian disfunction 1,2 yrs Exploratory: DFS/OS Moore H, NEJM 2015
Prevention Of Early Menopause Study: POEMS CHT CHT+Goserelin p OF 2yrs 22% 8% 0.04 Achieved pregnancy 11% 21% 0.03 DFS OS Moore H, NEJM 2015
Breast Cancer in Young Women Peculiar biological features Worse prognosis (even in case of HR+ disease) More efficacious endocrine therapies are available (OFS + exemestane; 10 y Tamoxifen) but side effects may be troblesome Sexuality and fertility are often overlooked by clinicians If chemotherapy is needed, OFS can preserve ovarian function and fertility