PMRT for N1 breast cancer :CONS. Won Park, M.D., Ph.D Department of Radiation Oncology Samsung Medical Center

Transcription

1 PMRT for N1 breast cancer :CONS Won Park, M.D., Ph.D Department of Radiation Oncology Samsung Medical Center

2 DBCG 82 b & c Overgaard et al Radiot Oncol pln(+), 8 or more nodes removed Systemic therapy CMF 8-9cycles or TAM 30mg for 48 weeks Radiotherapy Gy in frs chest wall, RNI

3 DBCG 82 b & c Overgaard et al Radiot Oncol 2007

4 Ragaz et al J Natl Cancer Inst 2005 Breast cancer-free survival British Columbia Randomized trial All 318 patients pn1 183 patients Overall survival

5 Meta-analysis for 8135 women in 22 trials EBCTCG Lancet 2014

6 Meta-analysis for 8135 women in 22 trials EBCTCG Lancet 2014

7 Meta-analysis for 8135 women in 22 trials EBCTCG Lancet 2014

8

9 St Gallen International expert consensus Ann Oncol 2013 Post-mastectomy radiotherapy was considered indicated by almost all Panel members for patients with four or more positive nodes, while the majority would not advise postmastectomy irradiation for those with one to three positive nodes, except in the presence of adverse tumour pathology. The Panel was content to omit post-mastectomy radiotherapy with pathologic uninvolved nodes even when fewer than eight nodes had been examined and if the tumour was 5 cm. Two-thirds felt that radiation therapy should be given after mastectomy if positive sentinel nodes were not followed by axillary dissection. Other indications recommended by the Panel for postmastectomy radiotherapy included positive deep margins and, for two-thirds of the Panel, tumours greater than 5 cm regardless of the nodal status. However, the Panel strongly rejected needing radiotherapy solely based on Grade 3, lymphovascular invasion, HER2-positive status or triple negative disease. Areas to be irradiated following mastectomy and axillary dissection should not be influenced by any neoadjuvant systemic therapy or by the intrinsic subtype of the tumour. There was no clear agreement about the necessity to include the supraclavicular fossa, though trials have routinely included this area. Most Panel members would not include the internal mammary nodes and a strong majority felt that the axilla should not be radiated after dissection.

10 LRR after mastectomy in NSABP 5 RCTs Taghian et al JCO 2004 MRM, pln(+), No PMRT Anthracycline-based CTx:90.3%

11 LRR after mastectomy in NSABP 5 RCTs Taghian et al JCO 2004

12 LRR after mastectomy in NSABP 5 RCTs Taghian et al JCO 2004

13 LRR after mastectomy in NSABP 5 RCTs Taghian et al JCO 2004

14 LRR after mastectomy in IBCSG trials Premenopausal patients with LN(+) Postmenopausal patients with LN(+) LRF rate Low risk: 14% medium risk: 18% high risk: 27% Wallgren et al JCO 2003

15 pn1 breast cancer- risk groups, SMC Yu et al IJROBP Retrospective review, pn1 breast cancer treated with mastectomy no radiotherapy or BCS - no ENI -systemic therapy: 443 patients (98.9%) CMF regimen: 280 patients (63.2%) AC regimen: 126 patients (28.4%) FAC regimen: 37 patients (8.3%) Hormone therapy: 271 patients (60.5%)

16 Yu et al IJROBP 2010

17 88.1% 96.8% 78.7% 74.3% 51.2% 95.7% 96.8% 86.8% 72.9% Risk groups Low risk: one or no factors (369 pts, 82.4%) Intermediate risk: two factors (61 pts, 13.6%) High risk: three or more factors (18 pts, 4.1%) Yu et al IJROBP 2010

18 pn1 breast cancer- risk groups, SMC Yu et al Clin Breast Can 2015 accepted -Retrospective review, pn1 breast cancer, treated with modern systemic chemotherapy treated with mastectomy no radiotherapy BCS - no ENI -Follow up: 58 months (7 to 111 months) -systemic therapy: 735 patients (100%) AC-T regimen: 679 patients (92.4%) TAC regimen: 30 patients (4.1%) TC regimen: 26 patients (3.5%) Hormone therapy: 570 patients (77.6%) Targeted therapy: 106 patients, ¾ patients of HER-2(+) patients

19 pn1 breast cancer- risk groups, SMC Yu et al Clin Breast Can 2015 accepted Patterns of first site recurrence according to molecular subtype Total Luminal A Luminal B HER-2 enriched TNBC Site of first recurrence (n=735) (n=248) (n=323) (n=62) (n=102) P Local n (%) 8 (1.1) 0 (0.0) 2 (0.6) 4 (6.5) 2 (2.0) Regional n (%) Axilla 2 (0.3) 0 (0.0 ) 0 (0.0) 1 (1.6) 1 (1.0) Internal mammary 13 (1.8) 1 (0.4) 8 (2.5) 0 (0.0) 4 (3.9) Supraclavicular 13 (1.8) 2 (0.8) 5 (1.5) 1 (1.6) 5 (4.9) Total 21 (2.9) 2 (0.8) 10 (3.1) 2 (3.2) 7 (6.9) 0.02 Locoregional n (%) 27 (3.7) 2 (0.8) 12 (3.7) 5 (8.1) 8 (7.8) Distant n (%) 42 (5.7) 5 (2.0) 21 (6.5) 2 (3.2) 14 (13.7) <0.001 Total n (%) 55 (7.4) 6 (2.4) 28 (8.7) 6 (9.7) 15 (14.7) <0.001

20 pn1 breast cancer- risk groups, SMC Yu et al Clin Breast Can 2015 accepted -Significant prognostic factors of RFS 1) LVI 2) HG 3 3) Non-luminal A subtype 98.0% 95.4% 88.6% 81.7%

21 AC vs. AC + T in NSABP B-28 Mamounas et al JCO 2005

22 AC vs. AC + T in NSABP B-28 Society of Surgical Oncology, 66 th Annual Cancer Symposium Ann Surg Oncol year cumulative incidence in percentage of LRR according to 21-gene RS Category All patients (n=1065) Lumpectomy + breast RT (n=461) Mastectomy (n=604) 1-3(+) LN (n=722) 4 (+) LN (n=343) low RS 3.3 ( ) 3.0 ( ) 3.5 ( ) 3.2 ( ) 3.5 (1.1-8) intermediate RS 7.2 ( ) 8.7 ( ) 5.9 (3.1-10) 5.1 ( ) 11.6 ( ) high RS 12.3 ( ) 11.1 ( ) 13 ( ) 7.9 ( ) 20.3 ( ) Log-rank P-value P<0.001 P=0.022 P=0.004 P=0.12 P=0.001

23 PMRT in T1-2N1 breast cancer McBride et al IJROBP MDACC - 4 groups based on time of diagnosis and use of adjuvant PMRT 1) early cohort ( ) without PMRT 2) early cohort ( ) with PMRT 3) later cohort ( ) without PMRT 4) later cohort ( ) with PMRT - In later cohort, routine use of sentinel lymph node surgery, taxane chemotherapy, aromatase inhibitors

24 PMRT in T1-2N1 breast cancer McBride et al IJROBP 2014 Crude rate Total Early cohort no-pmrt Early cohort PMRT Later cohort no-pmrt Later cohort PMRT LRR 8% 13.8% 5.1% 3.9% 4.4% 96.7% 90.5%

25 pn1 high risk group comparison Yu JI Oncology Retrospective review, pn1 breast cancer at SMC and KNCC - two or more risk factors: LVI, more than 2 ALN, ECE, level II or higher ALN -Treated with mastectomy no radiotherapy vs. radiotherapy or BCS - no SCRT vs. SCRT -Systemic therapy: TAC regimen: 200 patients (80.0%) AC or FAC regimen: 41 patients (16.4%) CMF regimen: 9 patients (3.6%) Targeted therapy: 20/43 patients (46.5%)

26 pn1 high risk group comparison Yu JI Oncology 2013 No-SCRT (n=153) SCRT (n=97) P-value Median f/u (months) All recurrence 16.3% 7.2% LRR 11.8% 1.0% 0.001

27 PMRT in T1-2N1 breast cancer Yang et al IJROBP Retrospective study, Sun Yat-Sen Cancer Center, Taiwan , pt1-2n1, MRM 544 patients patients: PMRT 383 patients: no PMRT - Follow up: 40 months (2-178 months) - Systemic chemotherapy: 430 patients (79%) - Hormonal therapy: all patients with receptor (+)

28 PMRT in T1-2N1 breast cancer Yang et al IJROBP LRR: 7.4%

29 PMRT in T1-2N1 breast cancer Yang et al IJROBP 2010

30 PMRT in T1-2N1 breast cancer He et al PLoS One Retrospective study, Sun Yat-Sen University Cancer Center, China , pt1-2n1, MRM 697 patients - 79 patients: PMRT 618 patients: no PMRT - Follow up: 65 months (6-144 months) - Systemic chemotherapy: 667 patients (95.7%) anthracycline or taxane regimen: 618 patients (92.7%) CMF regimen: 49 patients (7.3%) - Hormonal therapy: all patients with receptor (+) - Targeted therapy: only 5 patients

31 PMRT in T1-2N1 breast cancer He et al PLoS One year LRFS: 90.1% LRR: 11.1% in no PMRT 1.3% in PMRT (P = 0.005) - 5-year DMFS: 81.2% - 5-year DFS: 78.3% - 5-year OS: 88.1%

32 PMRT in T1-2N1 breast cancer He et al PLoS One risk factor 2-3 risk factors

33 Lymph node ratio in pn1 patients Kim et al BJC 2013 Korean Breast Cancer Registry , 3477 T1/T2 and pn1 mastectomy patients - antracycline- and taxane-based chemotherapy - exclusion: dissected LN 10, neoadjuvant chemotherapy breast conserving surgery, DCIS, stage IV PMRT - chest wall and regional lymph node depending on physician s preference Gy with Gy per fraction Lymph node ration (LNR) - cutoff value of LNR: low and intermediate LNR: 3059 (88%) and 418 (12%)

34 Lymph node ratio in pn1 patients Kim et al BJC 2013 all patients Low LNR Intermediate LNR

35 Risk factors Age Tumor size Pathologic grade Dissected node number Involved node number Lymph node ratio Extracapsular extension Hormonal status Lymphovascular invasion Molecular markers..

36 SWOG 9927 d/t poor accrual

37 Selective Use of Postoperative Radiotherapy after Mastectomy (SUPREMO) Trial a Phase III randomised trial to assess the role of adjuvant chest wall irradiation in intermediate risk breast cancer after mastectomy Inclusion - pt1-2n1m0, pt2n0m0 if grade III and/or LVI, pt3n0m0. - Stage II histologically confirmed unilateral breast cancer following neoadjuvant systemic therapy and mastectomy, if the original clinical stage was ct1-2cn0-1m0 or ct1-2pn1(sn)m0 and with the following (yptnm) stages after neoadjuvant systemic therapy: ypt1-2n1m0, ypt2n0m0 if grade III and/or LVI, ypt0-1n0 or ypt0pn1, ypt2n0, if the original clinical stage was ct3n0. ypt3n0m0, if original clinical staging was ct1-3n0m0 or ct1-3pn0(sn)m0

38 Selective Use of Postoperative Radiotherapy after Mastectomy (SUPREMO) Trial a Phase III randomised trial to assess the role of adjuvant chest wall irradiation in intermediate risk breast cancer after mastectomy - Randomization 1) no irradiation 2) chest wall irradiation with no regional radiotherapy - started in June Close in April ,600 patients recruitment

39 Conclusion - All pn1 mastectomy patient should not need to PMRT. - Which patients need to PMRT in pn1 patients? still controversial low risk group: no PMRT high risk group: PMRT - SUPREMO trial will give us some answers, but not definitive guideline. - Prospective randomized trial should be needed according to risk group.