Balancing Evidence and Clinical Practice in the Treatment of Localized Breast Cancer May 5, 2006

Transcription

1 Balancing Evidence and Clinical Practice in the Treatment of Localized Breast Cancer May 5, 2006 Deborah Hamolsky MS, RN : DCIS Carol Franc Buck Breast Care Center UCSF Comprehensive Cancer Center Jane Armer PhD, RN : Lymphedema University of Missouri - Columbia School of Nursing Deena Dell MSN, RN, AOCN, BC : Moderator Decision Tools/Session Moderator Fox Chase Cancer Center

2 Ductal Carcinoma in Situ (DCIS): Controversies in Care Confinement of malignant cells within the natural basement membrane of duct Intraductal, non-invasive, non-infiltrating, stage 0 breast cancer (breastcancer.org) Artist: Mary Kelso Bryson

3 DCIS: Increasing Prevalence, Earlier Detection 2005 Statistics: DCIS 58, DCIS 2.8% of cases 1995 DCIS 15% of cases 2005 DCIS 24% of cases ~20% of breast cancers detected by mammography (NCI SEER data 2005; ACS, 2005) Decreasing incidence of palpable masses Increasing incidence of detection of DCIS with non-palpable disease Mammographic detection of calcifications Improved pathological detection

4 DCIS Controversies Surgery Lumpectomy (BCS) vs. Mastectomy? Sentinel Lymph Node (SLN) Bx? Radiation therapy None whole breast (WBR) vs. partial (PBR) Rx recommendation problems: DCIS heterogeneous, no uniform grading Inaccuracy of size measurement and limitations of imaging Long natural history (Sanders et al, 2005) Limited published clinical trial data

5 DCIS Classification: Predicting Outcomes, Matching Treatment Van Nuys Prognostic Index Tumor size Nuclear grade (low, intermediate, high) Margin width Presence, absence of comedonecrosis USC/VNPI Addition of age as variable (Silverstein, Mel 2003)

6 DCIS and Mastectomy Recurrence with mastectomy 1-2% 1 2% Mastectomy high cure rate; can be seen as prophylactic prevents invasive ca Mast vs. BCS meta- analysis 6 trials mastectomy decreases recurrence, no mortality benefit (Jatoi & Proshan,, 2005) How to decide? -? risk of recurrence -? risk of systemic disease and mortality -? surgical risks and emotional outcomes of mastectomy with, without reconstruction (Fisher, 1998; Jatoi & Proshan,, 2005 Personal communication L. Margolis, UCSF, 2006)

7 Breast Conserving Surgery (BCS): Lumpectomy Alone Author # of Patients Mean f/u (months) Recurrence No. (%) Lagios (19) 53 Silverstein (21) 33 Schwartz (14) 18 Fisher B-06B (43) 56 Fisher B-17B (16) 50 Invasive Recurrence (%)

8 Lumpectomy and xrt Author # of Patients Mean f/u months Recurrence # (%) Silverstein (18) 53 Solin (15) 55 Forquet (16) 72 Fisher B-06B (7) 50 Fisher B-17B (7) 29 Invasive Recurrence %

9 Magnetic Resonance Imaging Grouping Geographic Distribution / Enhancement Pattern n = 8 n = 5 n = 14 Small, ER+ Ki67, grade CD68, comedo ER+ CD68, comedo Focal All Linear Ductal All Regional, Multiregional Heterogeneous n = 11 n = 8 n = 3 Large, ER- ER- Ki67, grade Regional, Multiregional Clumped Ki67, grade CD68, comedo Segmental Clumped Ki67, grade CD68, comedo Homogenous All (Laura Esserman UCSF, 2004)

10 Partial Breast Irradiation (PBI) Techniques: Brachytherapy - multi-catheter - balloon catheter - mammosite - intraoperative RT with linear accelerator or low energy x-raysx - 3D conformal RT DCIS multicentricity & recurrence 6 studies: 24% of 374 pts. (Margolis, L., UCSF, personal communication 2006) Not all pts. eligible for xrt receive it (pt. choice, access) (Rogers, 2004)

11 Sentinel Lymph Node Biopsy in DCIS: Balancing Benefit and Risk Risks: lymphedema, seroma, hematoma,, infection, nueropathic pain, decreased mobility, lengthened recovery time Benefit: identify rare subset of DCIS with occult invasion and positive lymph nodes (+ SLN systemic therapy controversial) 1+ SLN/102 DCIS pts. +SLN 5 institutions (Zavagno( et al, 2005) 108 / 371 DCIS pts 1+SLN; ALND in 139 of 371 DCIS pts; 3 pts with + LN s (Yang et al, 2005) High risk DCIS 9/76 had +SLN, 7/9 micromets (Klauber-DeMore et al, 2000) POSTMASTECTOMY MORTALITY RISK is 1%!

12 Conclusions: Surgery and Whole Breast Irradiation (WBR) Low grade, non-comedo comedo, <2.5cm tumor, detected by mammogram, negative margins High grade, comedo necrosis, >2.5cm tumor, palpable tumor, Negative margins, post excision Mammograms Positive margins after excision Diffuse microcalcifications OBSERVE RADIATION AFTER EXCISION MASTECTOMY (NSABP B-06,BB 06,B-17, EORTC 10853, JCRT-Harvard, ECOG ES914, NCCN Practice Guidelines v )

13 Conclusions: Partial Breast Irradiation (PBI) 1. Preference that patients be enrolled on protocol; continued insufficient evidence 2. Adequate surgeon training for technique utilization in intra- operative (IORT), balloon catheter, bead or seed implants, shortened (accelerated) courses of external beam 3. Selection Criteria (off trial) Age >50 IDC or DCIS Total tumor size 2cm Negative margins of at least 2mm SLN / ALND negative (The American Society of Breast Surgeons, 2003; NCCN Practice Guidelines v )

14 Conclusions: Criteria to Include Sentinel Lymph Node (SLN) Biopsy Biopsy SLN with mastectomy (cannot technically do later if occult invasive disease) Not generally recommended for DCIS with breast conserving surgery unless DCIS >5cm or microinvasion (controversial) Insufficient data to include SLN for specific biological markers (grade, histology) (ASCO Guidelines, 2005, Pendas et al, 2004; Jakub et al, 2004, NCCN Guidelines, 2006)

15 Future Directions and New Questions in DCIS Treatment Will surgical treatment always be necessary? The role of adjuvant, neoadjuvant,, therapy Ongoing data collection re SLN, radiation therapy Role of MRI in DCIS Prevention Neoadjuvant Therapy hormone (Letrozole( Letrozole) statin trials (Fulvestrant( Fulvestrant) NSABP B-35 B Anastrozole v. Tamoxifen RTOG 9804 xrt v. no xrt for low risk DCIS NSABP B-9 B WBI v. PBR (NSABP 2006, UCSF Trials Program, 2006)

16 Biopsies in the Future Should Define Disease Type, Treatment and Prevention Approach CR n= PR n= DCIS Cumulative Prop MR n=30 NC n=8 PD n=3 P = Disease-free survival (months) Define Disease Subtype And Predisposition (Laura Esserman MD UCSF, 2004) Tailor Treatment

17 DCIS and the Art of Supporting Informed Patient Decisions Diagnosis, grade, extent of disease, age DCIS treatment choices Recurrence risk Chance of invasive cancer Chance of cancer in contralateral breast Patient Preference How important is Keeping your breast? Minimizing chance of having to deal with breast cancer? Avoiding radiation?

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