Breast cancer (screening) in older individuals: the oncologists - PowerPoint PPT Presentation

Breast cancer (screening) in older individuals: the oncologist’s viewpoint for the geriatrician Hans Wildiers Medical oncologist, Leuven, Belgium Past chairman of the EORTC elderly task force President-elect of SIOG (international society of geriatric oncology) Based on SIOG recommendations: Lancet Oncol 2007 p1101 and 2012 e148

CONFLICT OF INTEREST DISCLOSURE I have the following potential conflict(s) of interest to report - Research grant (to institute): Roche - Lecture fee (to institute): Roche, Amgen, Novartis, Celldex, Pfizer, PUMA - Travel support: Roche, Pfizer, PUMA

Median age at diagnosis: 62y INCIDENCE  30% occurs ≥70y of age • Age specific incidence • Percent of new breast cancer cases by Age group increases with age Incidence rate per 100,000 451 447 424 418 350 340 263 225 189 122 60 27 9 1 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 85+ Age (years) SEER database 2009-2013 females

Types of breast cancer 3 important classes: - Hormone sensitive (HER2 negatief) - HER2 positive - Triple negative estrogeen ER celkern Her2 ER = estrogeen receptor Her2 in 20% of breast cancers in 80% of breast cancers PR Tumor cel ER = estrogeen receptor PR = progesteron receptor

Slightly more favourable TUMOR BIOLOGY (in general) ≥ 70y compared to younger • IHC studies: biology slightly more favorable: – More ER + – Less HER2+ – Lower grade • Intrinsic subtype (PAM50) IHC = immunohistochemistry Mol Oncol 2014 de Kruijf Oncologist 2014 Jenskins

LESS TREATMENT with increasing age SEER database ; 49616 women with stage I/II breast cancer ≥67y Initial treatment for stage II breast Treated with chemotherapy if ER+, cancer by age N+ stage I/II breast cancer BCS = breast conserving surgery ; XRT = radiotherapy JCO 2010 Schonberg

Prognosis MORE breast cancer deaths UNDERTREATMENT! Substudy from TEAM trial (adjuvant exemestane) Age 65 – 74y Age <65y Age >=75y Cause specific death Breast cancer mortality Other cause mortality • Univariate HR 1.66 (95% CI 1.34-2.06), p<0.001 • Multivariable HR 1.63 (95% CI 1.23-2.16), p<0.001 Schonberg JCO 2010 ; Van de Water JAMA 2012

Prognosis OVERTREATMENT if treated identically to younger pts ! • A sizeable proportion of elderly with operable breast cancer die of NON-CANCER-related causes N = 14048 new early breast cancer, ≥50y, FUP 4,7y • Absolute benefit of surgery and adjuvant (chemo/radio)therapy is lower Ali Br J Cancer 2011

Regional differences in treatment and outcome! OVERTREATMENT ! • Large population based study, early breast cancer ≥70y • 6 European countries, n=214,673 Multivariate Relative Excess Risk of death adjusted for age, year of diagnosis, grade, morphology Stage I , 70-79y Treatments given Radiotherapy 57% Endocrine R/ 86% Endocrine R/ 18% Relative survival ± 100% (compared to non-breast cancer population) Courtesy to Marloes Derks and EURECCA

Regional differences in treatment and outcome! UNDERTREATMENT ! • Large population based study, early breast cancer ≥70y • 6 European countries, n=214,673 Multivariate Relative Excess Risk of Death adjusted for age, year of diagnosis, grade, Stage III , 70-79y morphology Treatments given * * * Relative survival (compared to non- Chemotherapy 53% Chemotherapy 17% breast cancer population) Belgium 71% Netherlands 61% England 58% Courtesy to Marloes Derks and EURECCA

Evolution of breast cancer outcome 1990-2007 UNDERTREATMENT : OVERTREATMENT : Worse outcome Competing cause of death Relative to 1990, the rate of breast cancer death in the general population decreased by 2.0 to 2.5%/yr for women age <75 years an 1.1%/yr for women age ≥75 years Yearly decrease in breast cancer death rates for the US population from 1990 to 2007 JCO 2011 Smith et al

Breast cancer screening in general population Benefits Harms - Better survival: - False positive results regular screening - Overdiagnosis and can reduce the risk of overtreatment dying from breast cancer - Cost - False reassurance Breast cancer mortality - Pain at examination declined 30% over last 20y: - Due to early detection? - Due to better treatment?

Breast cancer screening programs • Belgium: • screening mammography every 2y • between age 50 and 69 y • Netherlands: • screening mammography every 2y • Between age 50 to 70y till 1998 • Between age 50 to 75y since 1998 • Quality control !

Breast cancer screening in general population • 1000 women 50y receive annual mammography during 10y • 25 develop breast cancer • 4 die from breast cancer WITH screening • 5 die from breast cancer WITHOUT screening • 1 (0,3 – 3) lifes saved: breast cancer deaths 20% • 400 false positive mammographies (echo needed) • 80 receive biopsy • 7 operations for in situ carcinoma Trials rarely included women >68y !

Impact of screening on early versus late stage breast cancer in women ≥40y Example Bleyer, NEJM 2012

Impact of screening on early versus late stage breast cancer in older women Breast cancer incidence in women aged 70-75 years, the Netherlands. Incidence before screening -> after screening per 100,000 Early stage 249 363 Advanced stage 59 52 Nienke A de Glas et al. BMJ 2014;349

Conclusion breast cancer screening in older women • Screening in older women leads to a large proportion of overdiagnosis • Older patients are at risk of adverse events of breast cancer treatment • Increased risk of competing mortality with increasing age  even if breast cancer is diagnosed in an earlier stage this will possibly result in a very small survival benefit • Tremendous health expenditure with few beneficial effects

Conclusion breast cancer screening in older women (2) • Personalized screening based on • Remaining life expectancy • Breast cancer risk • Patients’ preferences: screening is a choice, not a public health imperative … • Improve treatment strategies in older patients, rather than implementing mass screening programs in older women

Tumor biology Tumor extent Luminal A T (tumor size) Luminal B HER2 neg N (nodal status) Triple negative Her2+ Tumor Therapy choice depends on … Host General health status Patient preference Geriatric assessment - Estimate life-expectancy - Predict treatment toxicity

Personalized medicine Today Tomorrow Tumor (e.g. breast) Tumor (e.g. breast) genetic alterations proliferation chemotherapy individualized gene expression signat. ER hormonal therapy epigenetic alterations targeted therapy HER2 targeted therapy protein/receptor: ILGF, AR, HER3, EGFR, mTOR, PTEN, RAS, ... Host Host functionality: ADL, IADL falls comorbidity: DM, aHT, ... individualized age comedication ? geriatric ECOG malnutrition (comorbidity) interventions cognition depression social support

Breast surgery Upfront surgery generally preferred But can be delayed for specific reasons Breast surgery or primary endocrine therapy alone? Study n F.U. (Mo) Results Surg+Tamoxifen vs Tamoxifen CRC 381 151 Local relapse HR 0,25 (0,19 – 0,32) 40% of control group received surgery OS HR 0,78 (0,63 – 0,96) 474 80 Local relapse HR 0,38 (0,25 – 0,57) GRETA OS HR 0,98 (0,77 – 1,25) Nottingham2 147 60 Not reported OS HR 0,80 (0,28 – 2,32) • Cochrane review: surgery + tamoxifen vs tamoxifen HR for PFS 0,65 (p 0,0001) HR for OS 0,86 (p 0,06) Cochrane review 2008 Hind

Radiotherapy Less relapse with ageing But still significant benefit from RT Breast irradiation after Breast Conserving Surgery ≥70y <50y 5y local recurrence after BCS 33% 13%* 5y local recurrence risk reduction of RT 22% 11%* BCS = breast conserving surgery; RT = radiotherapy Lancet Oncol 2007 Wildiers, derived from EBCTCG (n=42000)

Breast Radiotherapy RT could should be omitted in this population (small tumors, after breast conserving surgery N-, ER+) Study n Inclusion F.U. Local relapse Overall survival criteria (y) (at 10y and 5y) ≥70y Local/regional recurrence CALGB 636 RT: 67% 9343 RT: 2% T ≤2 cm, N - 12,6 13/166 died from BC No RT: 10% ER+ No RT: 66% 8/168 died from BC 1326 ≥65y PRIME Ipsilateral BC recurrence RT: 94% II RT: 1% T ≤3 cm, N - 4/40 died from BC 5 No RT: 94% No RT: 4% ER+ 8/49 died from BC ER+ = estrogen receptor positive ; RT = radiotherapy; Hughes JCO 2013 ALND = axillary lymph node dissection ; BC = breast cancer Kunkler Lancet Oncol 2015

Adjuvant hormone and chemotherapy • Antihormone therapy more beneficial than chemotherapy in older women derived from EBCTG 2005 (n=42000), numbers derived from Lancet Oncol 2007 Wildiers