DCIS. Treatment Options in DCIS. DCIS Incidence Rates DCIS: Surgical Treatment. Mastectomy Excision + RT Excision. ± Endocrine Therapy

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1 North American Menopause Society Orlando, FL DCIS 6 October 2016 DCIS: Surgical Treatment Monica Morrow, MD Chief, Breast Surgery Service Anne Burnett Windfohr Chair of Clinical Oncology Memorial Sloan Kettering Cancer Center DCIS Incidence Rates Treatment Options in DCIS Rate per 100, years years years Mastectomy Excision + RT Excision ± Endocrine Therapy Ward E, CA Cancer J Clin 2015;65:481 Year of diagnosis

2 Outcome of Surgical Treatment in DCIS Outcome of Surgical Treatment in DCIS Narod et al, JAMA Oncol 2015 SEER Study DCIS n = 108,196 Mean f/u 7.5 yrs (0-24) Worni et al, J Natl Cancer Inst 2015 SEER Study DCIS n = 121,080 Breast Cancer Specific Mortality 3.3% (95% CI %) Narod S, JAMA Oncol 2015;1:888 Worni M, J Natl Cancer Inst 2015;107:djv263 Outcome of Surgical Treatment in DCIS SEER9 Age Adjusted Incidence Rate of Breast Cancer by Stage ( ) Sagara et al, J Clin Oncol 2016 SEER Study DCIS n = 32,144 BCS ± RT Mean f/u 8.0 yrs 10 yr Breast Cancer Specific Mortality 1.8% RT n = 20, % no RT n = 11,815 Incidence rate (per 100,000) Sagara Y, J Clin Oncol 2016;34:1190

3 DCIS Factors Influencing Patient Decisions Do excellent outcomes with treatment translate to excellent outcomes with less or no treatment? Mortality is not a useful endpoint low with all treatments Local recurrence varies with treatment and is important to patients 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% greatly moderately not/slightly 0% recurrence radiation recovery body/sexuality Katz S, J Clin Oncol 2005;23:5526 Why Do We Perform Surgery in DCIS? Exclude the presence of invasive cancer at diagnosis Reduce the risk of future development of invasive cancer Presence of Invasive Cancer After Core Needle Biopsy of DCIS All Cases n = 7350 Underestimate: 25.9% (95% CI ) 14g vs 11g Bx Palpable Mammographic mass Predictors High nuclear grade Size > 20mm Low Risk Lesions Low/Int grade Underestimate n = % (15.4, 28.3) Size on imaging 20mm n = % (12.3, 31) Brennan M, Radiology 2011;260:119

4 Metaanalysis of Long Term Outcomes of Local Therapy for DCIS 5 prospective, 21 retrospective studies Follow up 10 yrs n = 9404 Treatment 10 yr LR 95% CI Mastectomy 2.6% BCS + RT 13.6% BCS 25.5% Metaanalysis of Long Term Outcomes of Local Therapy for DCIS Treatment 10 yr LR BCS 25.1% BCS + Tam 24.7% BCS + RT 14.1% BCS + RT + Tam 9.7% Stuart K, BMC Cancer 2015;15:890 Stuart K, BMC Cancer 2015;15:890 DCIS Excision Alone in Favorable DCIS: ECOG-ACRIN E5194 Is the outcome of excision alone in selected, low risk DCIS patients good enough that we should consider eliminating excision? Cohort 1 Cohort 2 Low/int grade High grade 2.5 cm 1 cm n = 561 n = 104 Median f/u 12.3 years * Protocol specified 3 mm or greater margin Solin L, J Clin Oncol 2015;33:3938

5 LR After Excision Alone for DCIS 12 Year Results of ECOG-ACRIN E5194 Margins and LR: ECOG-ACRIN E5194 Low/Int grade High grade Cohort 1: Low/int grade T 2.5 cm n = 561 Margin Width, mm 12 yr IBTR % % > % p =.87 Solin L, J Clin Oncol 2015;33:3938 Solin L, J Clin Oncol 2015;33:3938 What Is the Risk of Invasive Recurrence After Excision Alone in Low Risk DCIS? ECOG 5194 Impact of Invasive Recurrence on Mortality NSABP B17/B24 EORTC Breast Cancer Mortality Invasive DCIS Invasive Years since IBTR Solin L, J Natl Cancer Inst 2013;105:701 Wapnir I, JNCI 2011;103:1 Donker M, J Clin Oncol 2013;31:4054

6 RTOG 9804: RT vs Observation in Good Risk DCIS n = 629 low/int grade < 2.5 cm size margins 3 mm Modern molecular biology should be able to identify a truly low risk subset of DCIS patients Local Failure (%) True, but that hasn t happened yet Time Since Random Allocation (years) McCormick B, J Clin Oncol 2015;33:709 DCIS Score Comparison of Ontario Cohort to E5194 Cohort: KM 10yr Estimates of Risk of Local Recurrence ECOG E5194 Ontario DCIS Cohort Local Recurrence Risk (%) Local Recurrence Risk (%) Solin L, J Natl Cancer Inst 2013;105:701 Rakovitch E, SABCS 2014 Solin L, J Natl Cancer Inst 2013;105:701

7 Treatment With Excision Alone Surgery vs Active Monitoring for Low Risk DCIS (LORIS) Treatment with excision alone, regardless of margin width, is associated with substantially higher rates of IBTR than treatment with excision and WBRT, even in pre-defined low risk patients Level 1 evidence Eligibility Age > 46 years Screen detected calcifications 11g VAB Non-high grade DCIS Core Bx Excision + margins R A N D O M I Z E Surgery Observation Annual Mammogram Endpoint: Development of invasive cancer at 5 years Enrollment: 932 patients over 6 years PI: Adele Francis What Is the Risk of Invasive Cancer in Patients Meeting LORIS Eligibility Criteria? Results Rate of Upgrade to Invasive Carcinoma Surgical excision for DCIS diagnosed by core-needle biopsy Total Population n = 296 Meeting all clinical and pathologic LORIS criteria 296 patients (approx 16% of DCIS) Upgrade to invasive carcinoma n = 58 (20%) No Upgrade at surgical excision n = 238 (80%) Pilewskie M, Ann Surg Oncol 2016 (Epub) Pilewskie M, Ann Surg Oncol 2016 (Epub)

8 Results Tumor Characteristics of Cases with an Upgrade Stage IA (pn0) 54 (93%) T1a 26 (45%) T1b 14 (24%) Final Invasive Stage n = 58 Stage IB 1 (2%) Stage IIA 3 (5%) 26/58 T1mic = 45% have T1N1mi tumor pathology T1N1 13 (22%) that warrants genomic 1 (2%) profiling 2 (3%) or consideration for chemotherapy T2N0 1 (2%) Results Treatment Recommendations of Upgraded Cases Invasive upgrades (n = 57)* Proportion % Radiation therapy 27/30 90% Endocrine therapy 48/54 89% Chemotherapy** 10/57 18% Adjuvant treatment recommended 53/57 93% *treatment information missing for one patient **indications for chemotherapy: High/intermediate recurrence score, node positive or HER2 overexpressing disease, triple negative, high-risk tumor features T1c 1 (2%) Pilewskie M, Ann Surg Oncol 2016 (Epub) Pilewskie M, Ann Surg Oncol 2016 (Epub) Mastectomy Use Based on Who Made the Surgery Decision Conclusions % Surgeon Shared Patient Survival outcomes are excellent in DCIS regardless of treatment, but risk of LR varies significantly Good outcomes with treatment do not necessarily mean good outcomes without treatment 5 0 White Adjusted for age, marital status, # surgeons visited, comorbidity, tumor size, grade, SEER site Observation without excision is not warranted outside of a clinical trial Katz S, J Clin Oncol 2005;23:5526

9 Conclusions Patients are major drivers of radical treatment in DCIS Surgeons can reduce overtreatment by avoiding SN biopsies in BCT patients and re-excisions for margins > 2 mm