When do you need PET/CT or MRI in early breast cancer?

Transcription

1 When do you need PET/CT or MRI in early breast cancer? Elizabeth A. Morris MD FACR Chief, Breast Imaging Service Memorial Sloan-Kettering Cancer Center NY, NY

2 Objectives What is the role of MRI in initial staging of breast cancer? How important is it to detect unsuspected ipsilateral or contralateral disease within the breast What is the role of FDG PET/CT in initial staging of breast cancer? How important is it to detect metastatic disease

3 The staging controversy Screening of both breasts in high risk patients Recommended annually by ACS in USA NICE in UK BUT once patient diagnosed with breast cancer - controversy about staging MRI

4 MRI detects additional disease in 17% in suspected unicentric cancer What is significant additional disease that won t be treated by RT/HT/CT?

5 Multicentric/multifocal disease is common in suspected unicentric cancer 282 mastectomies for unicentric cancer by mammography & physical 105 (37%) no additional cancer 56 (20%) within 2 cm 121 (43%) > 2 cm Holland et al 1985

6 MRI does not appear to decrease recurrence in retrospective study U Penn Early stage IC or DCIS treated with RT 756 patients 215 MRI 541 no MRI 8 year follow up MRI no MRI 3% recurrence 4% recurrence Not matched though age, margin status date of treatment use of systemic therapy documented Solin et al J Clin Oncol 2008

7 Preop MRI in early stage IC & DCIS matched surgeon/stage/age (n=174) 5 yr follow up Recurrence Contralateral ca Distant metastasis # surgical procedures MRI 6 (3.6%) 3(2.3%) 3(2.3%) 227 No MRI 9 (4.9%) 6(3.2%) 10 (5.3%) 252 p MRI group dense vs no MRI group (p<0.0001) MRI group dense imaging occult vs no MRI group (p<0.0003) Li J et al. MSKCC RSNA 2010

8 Fewer total surgical procedures with pre-operative MRI Grady I et al The Breast Journal 2012.

9 MRI reduces incomplete excision of IDC Primary tumor Incompletely excised disease MRI N=22 (13.8%) Non-MRI N=35 (19.4%) P-value IDC IDC 2 / 126 (1.6%) 11 / 136 (8.1%) 0.02 IDC in situ 12 / 126 (9.8%) 12 / 136 (8.6%) n.s. ILC ILC 6 / 26 (23.1%) 5 / 26 (19.2%) n.s. ILC in situ 1 / 26 (3.8%) 3 / 26 (11.5%) n.s. Others 1 / 7 (14.3%) 4 / 18 (21.4%) n.s. *One woman with incompletely excised IDC refused any further treatment IDC: invasive ductal carcinma; ILC: invasive lobular carcinoma Pengel KE et al. Breast Cancer Res Treat 2009; 116:161 9.

10 ACOSOG Z11101 / ACRIN 6694 RCT Pre-operative MRI will recruit patients at high risk for recurrence (Bedrosian/Comstock) ER or PR+, her2 (luminal A) ER or PR +, her2 + (luminal B) ER/PR -, her2 + (her2) ER/PR/ Her-2 (basal) LR rate at 5 years 0.8% 1.5% 8.4% 7.1% Primary LR rates at 5 years between the MRI and no MRI arm Secondary Rates of re-excision, including conversion to mastectomy Rates of re-excision in women undergoing MRI guided localization False positive MRI rates Time to local recurrence Overall survival Contralateral breast cancer rates Nguyen et al, JCO 2008

11 Does MRI decrease positive margin rate? UK COMICE Trial Initial Surgery MRI No MRI WLE, n (%) 750 (91.9) 787 (97.5) Mastectomy, n (%) 58 (7.1) 10 (1.2) Quadrantectomy and mini flap, n (%) 1 (0.1) 0 (0.0) Other, n (%) 2 (0.2) 0 (0.0) Multi-center, randomized, controlled, open, fixed-sample, parallel-group trial Equal randomization of women with primary breast cancer scheduled for WLE Turnbull L et al Lancet 2010

12 COMICE: Type of Re-operation MRI No MRI Further WLE, n (%) 85 (10.4) 90 (11.2) Mastectomy, n (%) 48 (5.9)* 61 (7.6) Other, n (%) 1 (0.1) 1 (0.1) Mastectomy at initial operation patient decision, n (%) 3 (0.4) 2 (0.2) *includes 16 patients with pre-op path verification of additional disease Turnbull L et al Lancet 2010

13 Issues with COMICE Underpowered/low recruiting centers Weighted to post-menopausal patients Not state of the art quality MRI MR biopsy available only at a few sites MR localization not used No centralized review 16 women underwent mastectomy without path proof included as pathologically avoidable and included in MRI analysis Morris EA Lancet 2010

14 Defining positive margin rate as an end point is foolish MRI may not decrease positive margins Surgeon dependent Positioning of patient different Ability to localize irregular margins difficult What we see on MR imaging is currently near impossible to translate to the OR

15 MONET Trial I multi-institutional RCT Endpoints pre-operative MRI Re-excision Conversion to mastectomy

16 Monet Trial Endpoint P value #/type of initial surgical procedures.776 # re-excisions for pos margins after 1 BCS higher in MRI group # conversions to mastectomy after 1 BCS lower in MRI group Rate of additional surgical intervention after 1 BCS.069 Surgical planning affected by MRI results Smaller excisions in MRI patients Peters NH et al Eur J Cancer. 2011

17 What is the argument against detecting contralateral cancer (CBC)? Low CBC rates U Penn/Solin data 6% at 8 y both MR/no MR MSKCC data 3% at 4-5 y both MR/no MR SEER data 3% at 5 y CBC treated by endocrine & chemotherapy Oxford Overview CBC risk decreased 50% after 5 yrs of tamoxifen decreased 20% after chemotherapy Morrow M J Clin Oncol 2008 Morrow MJ Morris EA Lancet 2012

18 Value of bilateral examination - Contralateral cancer only on MRI Rieber et al % Fischer et al % Woo et al % Liberman et al % Lehman et al % Earlier diagnosis of unsuspected contralateral primary Both cancers treated at same time

19 Where there is perhaps less controversy: Invasive Lobular Cancer No MRI (n=168) MRI (n=99) P value Re-excisions 25 (15) 5 (5).014 Initial mastectomies Final mastectomies 78 (46) 44 (45) (59) 48 (48).098 MRI decreases re-excisions and does not increase mastectomy rate Mann RM et al Breast Cancer Res treatment 2010

20 ASBS Guidelines for staging MRI JACS 2005;200:742

21 Should we dispense with MRI? Staging Subgroups not yet adequately evaluated? Young women / Dense breasts / Difficult to evaluate on conventional imaging Number of surgeries

22 Future trials should ask whether MRI results can spare interventions Do less rather than more Does MRI better triage patients to appropriate one step surgery? Are there patients who can be treated percutaneously? Do all patients require whole breast radiation?

23 Does every patient radiation therapy? PROSPECT Trial Mann B & Rose A. Melbourne Post-operative Radiotherapy Omission in Selected Patients with Early breast Cancer Trial

24 Are we helping this premenopausal patient by detecting multicentric disease? Palpable

25 When should MRI be used in early stage breast cancer? Optional per NCCN guidelines No data to support improved local recurrence or survival May be helpful to detect additional disease in dense breasts No data to support differential detection rates based on breast density type or tumor type False positive findings can occur - Surgical decisions should not be based solely on the MRI findings. Biopsy of areas of concern identified by breast MRI is necessary

26 Comment from Sir William Osler on individual variability. Hortobagyi G N The Oncologist 2012;17:

27 FDG PET/CT test of choice for restaging suspected recurrence Efficient for demonstrating local-regional recurrences chest wall, axilla, extra-axillary nodes and distant mets based on tumor markers/clinical findings/conventional imaging

28 2012 NCCN Recommendations for imaging in initial work up and staging for stage I IIB or operable stage III Routine staging not indicated in the absence of signs or symptoms of metastatic disease No role for PET/CT

29 FDG uptake depends on histology and biologic characteristics FDG uptake lower in ILC than IDC 15 patients with ILC (median SUVmax 3.4) 107 patients with IDC (median SUVmax 6.6) FDG uptake lower in PR+ than PR- tumors FDG uptake lower in ER+ than ER- tumors

30 FDG uptake depends on histology and biologic characteristics Prospective, 132 women with tumors >2 cm Median SUVmax 9.7 vs 4.8, P<.0001 Median SUVmax 9.2 vs 5.8, P=.0005

31 FDG PET/CT has no role in assessing T Stage and multifocality/centricity Limited spatial resolution of PET/CT May miss small tumors in other quadrants Difficult to assess chest wall & skin Less sensitivity and less accuracy than MRI Heusner TA et al, breast cancer patients underwent PET/CT and MRI MRI aided classification of T stage in 77% PET/CT aided classification of T stage in 54%

32 Studies evaluating FDG PET/CT for Staging Unknown Node Metastases = extraaxillary nodes

33 Involved Level III or extraaxillary nodes can alter the Stage, surgical and radiation planning

34 FDT PET/CT can alter N Stage T2N2 T2N3a

35 FDT PET/CT can alter N Stage T4NO T4N2

36 FDT PET/CT can alter M Stage

37 FDT PET/CT can alter M Stage PET/CT better than CT or bone scan for depicting Lytic osseous mets Mixed lytic/sclerotic Lesions entirely within marrow space PET can lack sensitivity for purely sclerotic bone mets (CT however can adequately detect)

38 FDG PET/CT superior to bone scanning for osteolytic or mixed lytic sclerotic metastases

39 FDT PET/CT can alter M Stage Marrow involvement at an early stage

40 Who should get FDG PET-CT at initial staging? Groheux D et al J Nucl Med 131 patients 36 clinical stage IIA: staging modified in 5.6% 48 clinical stage IIB: staging modified in 14.6% 47 clinical stage IIIA: staging modified in 27.6% T3N1 primary operable T2N2 T3N2

41 When should FDG PET/CT be used in early stage breast cancer? NCCN recommends FDG PET-CT only in initial staging of inflammatory breast cancer Does 15% detection of additional disease in stage II and operable stage IIIA justify use? Does subtyping matter - TN? Exact clinical stage where FDG PET/CT would be cost effective is uncertain

42 Thank you!