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

21

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