Evolving Concepts in Breast Surgery in Multidisciplinary Care

Transcription

1 Evolving Concepts in Breast Surgery in Multidisciplinary Care Tina J. Hieken MD, FACS Associate Professor of Surgery, Mayo Clinic 3rd Annual West Cancer Center Oncology Conference Memphis, Tennessee Friday October 27, 2017

2 Evolution of Surgery for Breast Cancer Technical advances Growing data on oncologic safety of new approaches Integrated multidisciplinary care

3 Outline Breast Conservation Decreasing reoperation rates Frozen section Advances in XRT Hypofractionated, APBI Surgery + APBI in 9 days Improving Mastectomy Aesthetics - Nipple Sparing Mastectomy Technical advances Node positive disease; recurrent cancer Limiting Axillary Surgery Shift from ALND to SLN surgery Avoiding SLN Individualized Cancer Care/Personalized Medicine

4 "I wish you pathologists would find a way to tell us surgeons whether a growth is cancer or not while the patient is still on the table." Dr William Mayo Spencer Automatic Freezing Microtime #880 Louis B. Wilson Dr Wilson's publication in the December 2, 1905, issue of The Journal of the American Medical Association (1905;45:1737).

5 Frozen Section Pathology All margins evaluated intraoperatively Close and positive margins re-excised intraoperatively Final pathology report in hours Contributes to quicker recovery time, time to adjuvant recommendations Reoperation rate for margin control after lumpectomy for breast cancer is 3%

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7 FS Impact on Patient Care 30-day reoperation rates following lumpectomy for cancer were lower at Mayo Clinic Rochester than in the national data 3.6% vs 13.2% (P<.001) 14% 12% Multivariable analysis 10% Patients in the national NSQIP data set were over four 8% times as likely to undergo reoperation as those at the FS institution. 6% Mayo NSQIP 4% 2% Adjusted Odds ratio = % Lumpectomy for Breast Cancer (p=<0.001) Mastectomy for Cancer (p=0.69) Boughey JC, Hieken TJ, Jakub JW, et al. Surgery. 2014;156(1):

8 FS Widespread Expansion Cost Analysis Baseline assumption 35% reoperation rate FS used in 20% cases Annual cost saving $18.2 million to payer $0.4 million providers FS used in 100% cases Annual cost saving $90.9 million to payer $1.8 million providers Boughey JC. J Oncol Pract. 2016;12(4):e413-e422.

9 Advances in XRT ASTRO 2011 guidelines endorse short course WBI for patients >50 years, T1-T2 ER+ tumors

10 Why Women Don t Choose BCS When given the option of BCS + WBI vs mastectomy, mastectomy chosen for (1) Convenience (2) Fear of radiation (3) Distance to RT facility A woman living 75 miles from RT facility would travel ~5000 miles to complete 33 fractions 85% of women who lived within 25 miles of a facility received RT following BCS vs 40% of women who lived over 100 miles away (4) Age (5) Cost (6) Side effects 15% to 45% of patients do not receive RT after BCS Smith GL. Cancer. 2010;116: McBride J. Women s Health. 2013;22: Pan IW. J Natl Cancer Inst. 2014;106:djt340.

11 Rationale for APBI Growing body of data supports favorable local control and cosmesis for selected patients Decrease time and inconvenience of BCT 5-6 weeks 4-5 days Improve utilization of BCT Potentially reduce acute and chronic toxicity WBI: Entire breast, overlying skin, lower axilla, heart, and lung, lower axilla APBI: Smaller volume & dose to normal tissue Improve patient quality of life

12 Whole-Breast RT Partial-Breast RT

13 APBI Early 1990s 2002 FDA 2010 RTOG 0319 Interstitial Catheter Brachytherapy Longest Experience Balloon/Strut Based Brachytherapy Single lumen multi-lumen strut-based 3D conformal external beam Most commonly employed modality in NSABP B-39

14 Comparison of Techniques SAVI MammoSite 3D EBRT Scanderberg D, et al. J Appl Clin Med Phys. 2010;11(1):

15 SAVI Multi-lumen strut-based device Better dosimetry Favorable toxicity profile Improved long-term cosmesis

16 Patient Selection Guidelines Criteria ABS ASBS ASTRO NSABP B39 Age (y) Histology IDC, DCIS IDC DCIS IDC IDC, DCIS T size (cm) N status (if +, 6 sampled) Margin Neg Neg 2 mm No tumor on ink Shah C, et al. Brachytherapy. 2013;12(4): Correa et al PRO

17 Mayo Clinic Selection Guidelines for APBI Inclusion 50 years 2 cm Margins: 0.2 cm ER (+) Infiltrating ductal, mucinous, tubular, colloidal Pure DCIS Negative axillary US Exclusion LVI Neoadjuvant therapy Prior ipsilateral RT Prior ipsilateral cancer Connective tissue disease Multicentric EIC, LCIS, ILC BRCA1/2

18 Work Flow OR (POD 0) WLE+SLN SAVI placement POD 1 Final Path confirmed Rad Onc CT simulation POD Gy BID

19 Work Flow POD 6 Explant SAVI Follow up 3 wk 3 mo 6 mo 12 mo 24 mo

20 Mayo Clinic Rochester Experience APBI with intraoperative SAVI catheter placement Surgery (Postop Day 0) Lumpectomy and SLN mapping Intraoperative pathology (~3% to 5% FN) Intraoperative brachytherapy applicator placement Radiation Oncology Postop Day 1: CT simulation Postop Day 2: Begin treatment Treatment completed within 9 days

21 Postop Day 0 BCS + SAVI Placement

22 Radiation Oncology Workflow (Postop Day 2-5: Imaging Verification and Treatment)

23 Intraoperative Pathology: Frozen Section Delayed positive SLN Convert to WBI (ie, ACOSOG Z11) Utilize brachytherapy as boost Delayed positive margin Re-excise and replace catheter Convert to WBI and utilize catheter as boost 123 patients prospectively registered 110 (90%) intraoperative catheter placement 13 excluded based on FS pathology 6 SLN+ 7 disease too extensive 1/110 delayed +SLN had APBI as boost

24 Mayo Clinic APBI Outcomes 30-day complication rate 6% (7 patients) SSI (2 patients) Hematoma (2 patients) Partial wound separation (1 patient) Moist desquamation (1 patient) Atrial fibrillation (1 patient) Cumulative complication rate 17% (14 patients) of 81 patients with 1 year of follow-up Correlated with device size but no patient or tumor variables SSI (5 patients) Symptomatic seroma (5 patients) Fat necrosis on mammogram (2 patients) Fistula, resolved with conservative treatment (1 patient) Hieken TJ, et al. Ann Surg Oncol. 2016;23(10):

25 Recurrence Mayo Clinic APBI Outcomes Two patients (2%) developed an IBTR in the same quadrant of the breast as the index tumor; one invasive in scar at 8 months, one DCIS at margin of treated field at 26 monthhs Both had negative margins of 0.5 cm at initial operation and received APBI of 34 Gy in 10 fractions over 5 days Both patients recurrence treated with mastectomy Hieken TJ, et al. Ann Surg Oncol. 2016;23(10):

26 Mayo Clinic APBI - Cosmesis Hieken TJ, et al. Ann Surg Oncol. 2016;23(10):

27 Pre-surgery 9/26/ /1/2012 3/6/2013 9/9/2013 9/11/2016 One Year Post-Rx Four Years Post-Rx

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29 Schedule BED: Early effects (α β = 10Gy) BED: Tumor control and late effects (α β = 3.5 Gy) 2.67 Gy x 15 (START B) Gy x 10 BID (RTOG 3DCRT) Gy x 10 BID (RTOG Brachy) Gy x 3 (Mayo Brachy)* Gy x 3 (Mayo 3DCRT)* Gy(RBE) x 3 (Mayo Proton)* Gy or 5.4Gy x 5 (Fast Forward) *Administered Daily

30 A Phase II Study O\of Accelerated 3 Fraction Photon and Proton Partial Breast External Beam Radiotherapy and Partial Breast Brachytherapy for Early Invasive and Noninvasive Breast Cancer 168 women Age 50, ER+, 2 cm, lumpectomy with negative margins Patient and physician elect APBI technique 1 0 objective: Evaluate cosmesis at 3 years SAVI brachytherapy 7 Gy x 3 daily Proton Therapy (IMPT) 7.3 Gy (RBE) x 3 External Beam 3DCRT 7.3 Gy x 3 Robert Mutter, MD, PI

31 Nipple Sparing Mastectomy

32 Why? Improved aesthetics of NSM have fueled patient demand PREOP POSTOP Bilateral NSM via IFM incisions

33 Potential Benefits of NSM Improved cosmesis with retention of the native nipple Eliminates the need for a second operation to reconstruct a nipple Facilitates one-stage reconstruction (direct to implant or flap)

34 Nipple Sparing Mastectomy Among patients undergoing mastectomy with immediate breast reconstruction, improved aesthetics have fueled increased patient demand for nipplesparing mastectomy (NSM) NCCN guidelines: The nipple should be removed for the majority of breast cancer patients However, NSM may be considered for patients with early stage, low grade, biologically favorable, node-negative and peripheral tumors at least 2 cm from the nipple

35 Current Practice 40% of mastectomies with IBR are NSMs

36 Complications Nipple Necrosis Requiring Nipple Excision Hieken (2015) Coopey (2013) Peled (2012) Spear (2011) Nipples Excised for Necrosis/NSMs (%) 5/566 (0.9%) 11/645 (1.7%) 10/657 (1.5%) 3/162 (1.9%)

37 Cancer Outcomes of NSM Year N* Median F/U (months) LR (%) NACR (%) Krajewski Eisenberg (mean) Sakurai Coopey Peled Spear (mean) 0 0 Kim Gerber (mean) Sakamoto Crowe Sacchini Studies with f/u 5 years LR rates 2% to 12%; NACR rates 1% to 4% *Number of breasts operated on for cancer

38 Shift in Philosophy Mastectomy with immediate breast reconstruction Can we spare the nipple-areolar complex? When do we need to remove it?

39 NSM for Cancer Contraindicated Inflammatory breast cancer Paget s disease Tumor in the nipple Physical examination Imaging Ca++s extending into the nipple Cancer presenting with nipple discharge

40 Variable NSM for LN+ Disease Jan 2009 to June scheduled NSMs cancers in 226 patients 58 LN+ cases compared to 182 LN- cases LN Positive N = 58 LN Negative N = 182 Total N = 240 P Value Age, median (IQR) 46 (41-52) 49 (45-56) 48.5 (43-54) 0.02 ER Positive ER Negative 50 (86%) 8 (14%) 155 (88%) 22 (12%) 205 (87%) 30 (13%) 0.79 HER-2 Positive HER-2 Negative 8 (14%) 48 (86%) 10 (9%) 99 (91%) 19 (11%) 147 (89%) 0.42 LVI present 21 (36%) 5 (4%) 26 (11%) Murphy B, Hieken TJ, et al. Am J Surg. 2017;213(4):

41 Results Nipple Excision for Atypia or Neoplasm Variable LN Positive N = 58 n (%) LN Negative N = 182 n (%) Total N = 240 n (%) P Value Intraoperative 5 (9%) 9 (5%) 14 (6%) 0.32 Postoperative 1 (2%) 4 (2%) 5 (2%) 0.82 Murphy B, Hieken TJ, et al. Am J Surg. 2017;213(4):

42 Results Success of NSM by Nodal Status 100% 90% % 70% Nipple removed for any reason 60% 50% 40% 30% 20% 10% 0% P = 0.73 LN + LN - Converted to SSM NSM Successful Murphy B, Hieken TJ, et al. Am J Surg. 2017;213(4):

43 Results Oncologic Outcomes 7 locoregional recurrences after 25 months median follow-up 5 in LN+ patients 3 skin/subcutaneous in flaps away from the nipple At 13, 30 and 46 months 2 ipsilateral supraclavicular and mediastinal LNs At 24 and 32 months 2 in LN- patients Nipple-areolar complex at 62 months Axillary nodes after negative SLN at 20 months Murphy B, Hieken TJ, et al. Am J Surg. 2017;213(4):

44 Results Oncologic Outcomes 3-year local regional disease-free survival for all invasive cancer patients LN-positive 87% (95% CI 75% to 100%) LN-negative 99% (95% CI 97% to 100%) P = year breast cancer-specific survival for all invasive cancer patients LN-positive 97% (95% CI 92% to 100%) LN-negative 99% (95% CI 98% to 100%) P = 0.40 Murphy B, Hieken TJ, et al. Am J Surg. 2017;213(4):

45 Summary Conversion from planned NSM to SSM did not differ significantly between node-positive and node-negative patients with cancer Nipple-areolar complex recurrences None in LN+ patients One in a LN- patient Short-term oncologic outcomes satisfactory NSM may be appropriate for carefully selected patients with LN+ breast cancer

46 Nipple-Sparing Mastectomy for the Management of Recurrent Breast Cancer ~246,000 patients will be diagnosed with breast cancer in the USA in % are treated with BCS 6% to 15% will have a local recurrence 21 patients at Mayo who underwent NSM for recurrent disease (1/2009-6/2016) Mean patient age Initial cancer diagnosis: 47.8 years Recurrence: 57.6 years Median time to recurrence: 102 months (range months) Siegel RL, et al. CA Cancer J Clin. 2016;66(1):7-30. Mahmood U, et al. Ann Surg Oncol. 2013;20(5): Kummerow KL, et al. JAMA Surg. 2015;150(1):9-16.

47 Percent Operations Performed for Recurrent Breast Cancer n = 89 n = 33 n = 21 NSM SSM Total Mastectomy Operation Murphy BL, Boughey JC, Hieken TJ. Clin Breast Cancer, 2017;17(4):e209-e213.

48 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Clinical Tumor Stage NSM SSM Total Mastectomy P = ct2 ct1 ct0/ctis Murphy BL, Boughey JC, Hieken TJ. Clin Breast Cancer, 2017;17(4):e209-e213.

49 100% Clinical Nodal Stage 95% P = % 85% cn3 cn2 cn1 cn0 80% 75% NSM SSM Total Mastectomy Murphy BL, Boughey JC, Hieken TJ. Clin Breast Cancer, 2017;17(4):e209-e213.

50 Outcomes Conversion to SSM: 2 (9.5%) 19 had prior whole breast radiation 1 recent smoker 4 patients underwent HBOT 1 pre-operative 2 pre and post-operative 1 post-operative >50% of cases used intraoperative SPY perfusion imaging Murphy BL, Boughey JC, Hieken TJ. Clin Breast Cancer, 2017;17(4):e209-e213.

51 Outcomes Complications Cellulitis: 2 (9.5%) Seroma: 2 (9.5%) Superficial skin necrosis: 1 (4.8%) Full thickness necrosis: 1 (4.8%) All 19 patients have retained their native nipple No recurrences Median follow-up 17.5 months Murphy BL, Boughey JC, Hieken TJ. Clin Breast Cancer, 2017;17(4):e209-e213.

52 NSM in Recurrent Breast Cancer NSM may be performed in highly selected patients with recurrent breast cancer Similar complication rates Satisfactory short-term oncologic outcomes

53 SPY Angiography Improves understanding flap perfusion Critical for high-risk patients

54 SPY Angiography Mayo Protocol Harless CA, Jacobson SR. Breast J. 2016;22(3):

55 SPY Angiography Post mastectomy, no reconstruction Post mastectomy, 300 ml fill Post mastectomy, 200 ml fill

56 Number of Cases SPY Angiography * * * Before LA-ICGA After LA-ICGA Comparison of Complications Before and After LA-ICGA *Denotes statistical significance Harless CA, Jacobson SR. Breast J. 2016;22(3):

57 Subcutaneous (Pre-Pectoral) Breast Reconstruction breast in 79 patients Expanders/implants wrapped in Alloderm Placed in subq space Improved aesthetic outcomes Decreased OR time Decreased postoperative pain Woo A, et al. Breast J. 2017;23(5):

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60 Methods National Cancer Database ( ) Mayo Rochester Database ( ) Inclusion Invasive breast cancer Women age 70+ HR positive cn0 disease Exclusion Neoadjuvant therapy Recurrent disease M1 disease Welsh JL, et al. Ann Surg Oncol Aug 1. [Epub ahead of print].

61 N = 125,554 N = 667 No axillary surgery 13.6% 8.8% Welsh JL, et al. Ann Surg Oncol Aug 1. [Epub ahead of print].

62 Rates of pn+ in Women 70+ Years With HR+ cn0 Invasive Disease Overall pn+ 18,586/125, % 95/ % Stratified by Clinical T stage T1mic 29/ % 0/9 0% T1a 358/7, % 0/39 0% T1b 1,657/24, % 21/ % T1c 5,045/35, % 42/ % T2 6,502/24, % 27/ % T3 749/1, % 3/8 37.5% T4 329/ % 2/ % Welsh JL, et al. Ann Surg Oncol Aug 1. [Epub ahead of print].

63 Rates of pn+ in Women 70+ Years With HR+ cn0 Invasive Disease Overall pn+ 18,586/125, % 95/ % Stratified by Clinical T stage T1mic 29/ % 0/9 0% T1a 358/7, % 0/39 0% T1b 1,657/24, % 21/ % T1c 5,045/35, % 42/ % T2 6,502/24, % 27/ % T3 749/1, % 3/8 37.5% T4 329/ % 2/ % Stratified by Grade I 3,766/39, % 31/ % II 9,807/60, % 57/ % III 4,148/18, % 7/ % Welsh JL, et al. Ann Surg Oncol Aug 1. [Epub ahead of print].

64 Influence of Combined T Stage and Grade on Nodal Positivity 30% HIGH 20% 10% 0% Grade 1 Grade 2 Grade 1 Grade 2 LOW

65 Nodal Positivity Rates in Low-Risk Group 7.3% 7.7% Low-risk criteria Grade 1 T1a-c Grade 2 T1a-b

66 Nodal Positivity Rates in High-Risk Group 21.8% 22.8% High-risk criteria Grade 3 tumors T2+ tumors Grade 2 T1c tumors

67 Clinical Implications 70+ HR+ Grade 1, T1a-c Grade 2, T1a-b Consider Omit SLN surgery All Grade 3 T2+ tumors Grade 2, T1c tumors Candidates for SLN surgery Consider comorbidities and impact of nodal staging on adjuvant treatment recommendations Welsh JL, et al. Ann Surg Oncol Aug 1. [Epub ahead of print].

68 Discussion Nodal status important for decision-making Radiation therapy Avoid radiation/ partial breast radiation Addition of nodal fields for N+ Endocrine therapy Relative benefit Extended therapy 5-10 years for N+ Patient adherence Model provides a tool for shared decision making when counseling on whether to omit SLN surgery Welsh JL, et al. Ann Surg Oncol Aug 1. [Epub ahead of print].

69 Evolution of Axillary Surgery Routine ALND SLN - cn0 SLN - BCT with 1-2 LN+ SLN - pnac cn+

70 Response to Neoadjuvant Chemotherapy Increasing pcr rates Anthracyclines 10% to 15% Anthracyclines + taxanes 25% to 30% Her2 positive disease: Trastuzumab + chemo 40% to 50% 2 anti-her2 agents + chemo 50% to 60% Nodal response rates (cn1 to ypn0) Anthracyclines 30% Anthracyclines + taxanes 40% HER2-positive disease up to 70% to 75%

71 ACOSOG Z1071 FNR in cn1 Patients With at Least 2 SLNs Examined FNR = 12.6% Mapping Agent Blue dye only Radiolabeled colloid only Both blue dye and radiolabeled colloid Number of SLN Examined patients P Value 2/9 (22.2%) 10/50 (20.0%) 27/251 (10.8%) 19/90 (21.1%) 7/78 (9.0%) 4/60 (6.7%) 9/82 (11.0%) P = P = Boughey JC, et al. JAMA ;;310(14):

72 Impact of Inclusion of Metastases <0.2mm on SLN FNR and pcr rate SLNs from 17 patients revealed disease 0.2mm in size 1 (0.5%) had disease 0.2 mm identified on H&E 16 additional cases had disease 0.2 mm identified on IHC Node positive definition SLN metastases >0.2 mm by H&E SLN metastasis including 0.2 mm on IHC or H&E N Residual disease identified in SLNs or ALND FNR 95% CI (64.0%) 11.3% (66.2%) 8.7% The pathologic complete response rate in the nodes changed from 36.0% to 33.8% with the inclusion of metastasis 0.2 mm Boughey JC, et al. Cancer Res. 2015;75(9 Suppl): Abstract P

73 Clip 170 of 525 (32.4%) patients with cn1 disease and 2+ SLNs removed had clip placed in LN at diagnosis N Nodal residual disease FNR 95% CI Clip placed and found in SLN % 1.9% to 16.5% Clip placed and found in ALND % 5.4% to 41.9% Clip placed, location not known % 3.0% to 36.3% Clip not placed % 9.1% to 18.8% Boughey JC, et al. Ann Surg. 2016;263(4):

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75 Resection of Clipped Node & SLN Targeted Axillary Dissection Remove SLNs and ensure removal of clipped node (node with biopsy proven disease at presentation) Localize clipped node prior to surgery MDACC experience: 85 patients underwent TAD and ALND 50 patients had residual nodal disease Evaluation of the clipped node in addition to the SLN(s) improved the FNR to 2.0% Caudle AS, et al. J Clin Oncol. 2016;34(10):

76 Pre-Treatment Nodal Staging 272 NAC Patients patients Axillary US Negative (61) Suspicious (211) FNA- (42) cn0 (103) FNA+ (169) cn+ (169) All available pre/post-nac imaging evaluated

77 % Patients LN+ at Operation Post-NAC by Post-NAC Imaging Results 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 80% 69% 43% P< % 100% 83% 69% 58% 39% P<0.001 P = 0.03 CR PR NR pnac US pnac MRI pnac PET- CT Hieken TJ, et al. Ann Surg Oncol. 2013;20(10):

78 Patients Node-Positive at Presentation ypn-stage by CR on All Post-NAC Imaging 60% 50% 40% 30% 20% 10% 0% 58% 3% Hieken TJ, et al. Ann Surg Oncol. 2013;20(10): Imaging CR on all modalities performed 30% 14% 20% 14% 9% 3% 7% 2% 27% 14% Residual abnormality on any imaging ypn0 ypn0i+ ypn1mi ypn1 ypn2 ypn3 P = 0.006

79 Evolution of Axillary Surgery for cn1ln+ Patients After NAC, Mayo Clinic Use of SLN surgery (+/- ALND) increased from 30% in 2009 to 74% in 2016 (P<0.001) Omission of ALND increased from 3% in 2009 to 26% in 2016 (P<0.001) Nguyen TT, Hoskin T, Day C, Hieken TJ, Boughey JC. Ann Surg Oncol. 2017;24(S1):S64.

80 Evolution of Axillary Surgery for cn1+ Patients After NAC, Mayo Clinic Nguyen TT, Hoskin T, Day C, Hieken TJ, Boughey JC. Ann Surg Oncol. 2017;24(S1):S64.

81 Breast Cancer Treatment Is a Multidisciplinary Effort Patient Selection Pathology Systemic Therapies Radiation Surgery

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83 Evolving Concepts in Breast Surgery in Multidisciplinary Care Tina J. Hieken MD, FACS Associate Professor of Surgery, Mayo Clinic 3rd Annual West Cancer Center Oncology Conference Memphis, Tennessee Friday October 27, 2017