are we overtreating dcis?
TRANSCRIPT
Are We Over-Treating DCIS?
Deanna J. Attai MD FACSAssistant Clinical Professor of Surgery
David Geffen School of Medicine UCLA
24 June 2016
No Disclosures
What Is DCIS?
• Malignant cell appearance• Non-obligate precursor • Without surgery 15-50%
progress to invasive cancer• ~20% upgrade rate• 15% autopsies women 20-56
Wood JOP 2016 12;4;309-311Cowell Mol Oncol 2013 7;5:859-869
Presentation / Incidence
• Typical presentation – mammographic calcifications
• Occasionally presents as palpable mass
• ~60,000 / year in US
2009 NIH Consensus Conferencehttps://consensus.nih.gov/2009/dcisstatement.htm
Diagnosis Rare Before Mammography
Vernig et al 2009http://www.ncbi.nlm.nih.gov/books/NBK32570/
Treatment Options• Surgery
• Mastectomy, Lumpectomy• SNB not routine unless mastectomy
• Radiation Therapy• Radiation reduced I-IBTR 19.4% ->8.5% (B17)• Other studies show I-IBTR 14-25% without RT
• Tamoxifen (B24)• Addition tamoxifen to L + RT reduced I-IBTR 32% vs. placebo• I-IBTR associated with increased risk of death HR 1.75• Recurrence of DCIS no increased risk of death
• Aromatase Inhibitors (B35, IBIS-II DCIS)
Predictors of Recurrence
Euhus D Gen Surg Newshttp://www.generalsurgerynews.com/Web-Only/Article/04-16/Better-
Prognostic-Tools-Are-Needed-for-DCIS/36064/ses=ogst
Treatment Effect / Risk of Invasive BC
Euhus D Gen Surg Newshttp://www.generalsurgerynews.com/Web-Only/Article/04-16/Better-
Prognostic-Tools-Are-Needed-for-DCIS/36064/ses=ogst
DCIS / Metastatic Disease
• MDA 2011 0.14% of 2123 patients
• 34% no locoregional recurrence• Narod et al 500/100,000
metastatic without locoregional recurrence
Roses et al Ann Surg Oncol (2011) 10:10; 2873-2878
Narod et al JAMA Oncol2015:1(7);888-896
Why the Confusion?• DCIS is not one disease• Hard to determine if over treating if we
don’t agree on endpoint• Overall survival• Breast cancer specific survival• Invasive vs. in-situ recurrence
• Breast cancer specific survival approaches 100% regardless of treatment choice
Moran M December 2015 ASCO Posthttp://www.ascopost.com/issues/december-25-2015/ductal-carcinoma-in-situ-and-relevant-
endpoints-for-omission-of-standard-treatments-are-we-there-yet/
How To Decide• Treatment decisions require tradeoffs
• Current treatment may compromise options if recurrence develops
• What endpoint most important to patients – local recurrence, toxicity from treatment, survival, others
• Difficult (impossible?) to have evidence based shared decision making when natural history of individual patient’s disease unknown
Van Nuys Prognostic Index
SilversteinAm J Surgery186;4:337-343
• 4,5,6: excision alone• Lack of consistent
external validation – limits clinical utility
Rudloff U, et alJ Clin Oncol
28;23;2762-3769
Patient Prognostic Score
Sagara et al 2016J Clin Onco 34:1190-1196
• Predict local recurrence, magnitude of benefit of RT
• Survival improvements in RT group only seen w/high grade, younger age, larger tumor size.
• Magnitude of survival difference with RT correlated with score
“As an oncology community we must be cognizant of overtreatment for this disease process that has low breast cancer mortality”
MSKCC Nomogram – Ipsilateral Recurrence
http://nomograms.mskcc.org/breast/DuctalCarcinomaInSituRecurrencePage.aspx
Rudloff U, et alJ Clin Oncol 28;23;2762-3769
Oncotype Dx DCIS
• Predicts risk of local recurrence after lumpectomy• Validated in:
• Grade 1-2 DCIS, ≤2.5cm or grade 3 ≤1cm; ≥3mm margin• 97% ER+, 29% treated with tamoxifen
• Complement to traditional clinical / pathology features
Solin LJ et alJ Natl Cancer Inst2013 105:701-710
Decision Aids• Majority of patients over-estimate
their risk of recurrence • Differing degrees of risk tolerance • Ideal: tailor treatment to individual
risk of recurrence• Decision aids increase knowledge,
reduce decisional conflict, decisions aligned with goals and values
Ozanne EM, et alBreast Cancer Res Treat
(2015) 154:181-190
OnlineDeCISion.orgNot yet validated for clinical use
OnlineDeCISion.orgNot yet validated for clinical use
OnlineDeCISion.orgNot yet validated for clinical use
Clinical Trials• Alliance NCT01439711
• Letrozole x 6 months• MRI at baseline, 3, 6 months• Surgical excision
• Alliance COMET• Standard vs. observational therapy +/- endocrine therapy
• UK LORIS• Low risk DCIS• Surgery vs. active surveillance (annual mammogram)
• EORTC LORD • Standard treatment vs. active surveillance
The Future
• Imaging• Core biopsy• Biomarkers • Tailored / precision therapy• ?No therapy for some• ?Intraductal therapy
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Are We Over-Treating DCIS?• It depends…
• In some cases: yes• Discussion of risks, unknowns• Decision tools• Incorporate patient preferences• Support clinical trials
•Don’t forget lifestyle counseling