LIPOFILLING AND ONCOPLASTIC BREAST SURGERY : oncologic safety JY Petit IEO Milan December 13-15, 2012 29 th Annual New York Controversies, Problems & Techniques in Surgery SYMPOSIUM COURSE DIRECTORS Robert Michler, MD; Steven Libutti, MD; Peter Shamamian, MD Controversies, Problems & Techniques in Surgery NO DISCLOSURE This presentation is the intellectual property of the presenter. Contact him for permission to reprint and/or to distribute
Immediate remodelling after tumourectomy
Indications
Conservative surgery 40g AL
Conservative surgery 60 g AL
Conservative surgery 50 g AL
Implant BR 40g AL
Implant reconstruction 50 g AL
1,75 m 46 kil 55 g left breast
Breast volume augmentation scar improvement Coleman technique
90 y old women 40 years after abdominal radiation therapy and non healing sacral pressure sore Dr Sadanori Akita 90% cells to circular area around sore Immediate Pre-op Intraop after debridement 10% cells to sore itself Intra-op after Cell Tx 145 days 14 Days Post Op 25 Days Post Op 41 Days Post Op
1994 Osteosarcoma tt Clinical results 2006 lipofilling Local recurrence LR of osteosarcoma 13 y after TT 18 mths after lipofilling
Kotaro Yoshimura, M.D.
SAFETY OF LIPOFILLING IN BREAST CANCER PATIENTS From the lab to clinical results F.BERTOLINI I.MARTIN PADURA IEO Milan Review Adipose tissue cells, lipotransfer and cancer: A challenge for scientists, oncologists and surgeons Francesco Bertolini a, NOS DISCLOSURE
155 Samples FROM LIPOTRANSFER HAVE BEEN PURIFIED COLEMAN TECHNIQUE Abdominal or thigh Human WAT >150 samples F. BERTOLINI S LAB Stromal vascular fraction Enzymatic digestion Purified CD34+ WAT-derived cells Immunomagnetic separation
Transplant of a human breast cell line on the mammary gland of a imunodeficient mouse to develop a breast cancer mouse model NSG, Females, 8 weeks old cell suspension in matrigel +blu dye cells suspension injected in the fourth mammary fad pad directly though the nipple 10 6 breast cancer cells 10 6 breast cancer cells + 2x10 5 WAT cells Tumors are detectable at day 7 raise 800-1000 mm3 in 35-40 days
Tumor volume (mm3) Tumor volume (mm3) Adipose derived CD34+ cells promote breast tumor growth in vivo Tumors were bigger when co-transplanted with adipose cells.and this was true with two different breast cell lines.. 2500 2000 1500 1000 Breast cell line 1 (MDA-MB-436) CD34+ Unfractionated Control CD34+, no tumor 500 0 0 29 62 76 Days MDA-MB-436 MDA-MB-436 CD34 + WAT cells 250 200 150 100 Breast cell line 2 (HCC1937) Control 50 0 0 36 63 70 88 95 Days
Injection of CD34+WAT-derived cells increases lung metastases WAT cells axillary lympho node metastases primary tumor mastectomy Lung Metastases 30 25 20 15 10 5 0 Controls CD34- injected CD34+ injected lung metastases
2012 9/269 with oncologic FU Only 2/9 with a control group (Rigotti - Petit) Only 1 with a cohort study group (Petit)
Eur J Surg Oncol. 2012 May;38(5):382-9. Epub 2012 Mar 15. Prospective trial of adipose-derived regenerative cell (ADRC)-enriched fat grafting for partial mastectomy defects: the RESTORE- 2 trial. Pérez-Cano R, Vranckx JJ, Lasso JM, Calabrese C, Merck B, Milstein AM, Sassoon E, Delay E, Weiler-Mithoff EM No local recurrence No control group Very short follow up
Annals of Oncology 2011 may 24 321 breast cancer patients who subsequently underwent lipofilling: Coleman technique 642 matched-patients with similar characteristics who did not undergo a lipofilling.
Matching criteriae
+6 months Washing out period
BCT C Invasif mastectomy DCIS p< 0.001
CONCLUSION: Matched Cohort Control Study I 1. No evidence of increasing risk of LRR after Lipofilling on the whole population 2- Significant increase of local recurrence rate in the group of intra epithelial neoplasia (DCIS LCIS)
EVALUATION OF FAT GRAFTING SAFETY IN PATIENTS WITH INTRA EPITHELIAL NEOPLASIA : A MATCHED COHORT STUDY Jean Yves Petit 1 ; Mario Rietjens 1 ; Edoardo Botteri 2 ; Nicole Rotmensz 2 ; Francesco Bertolini 3 ; Annals of Oncology (in press) 59 IN SITU breast cancer patients who subsequently underwent lipofilling (Coleman technique) 118 IN SITU matched-patients with similar characteristics who did not undergo a lipofilling.
Lipofilling n (%) Controls n (%) All patients 59 118 Age at first surgery (years) Median (range) 46 (30-64) 47 (26-69) Age at baseline (years) Median (range) 49 (33-65) 50 (29-72) p Matching Variable Matching Variable Time to baseline from surgery 1 year 1. -2 years 2.1-3 years > 3 years 19 (32.2) 13 (22.0) 10 (17.0) 17 (28.8) 38 (32.2) 26 (22.0) 20 (17.0) 34 (28.8) Matching Variable Histology Year of surgery Type of surgery Estrogen receptor a Progesteron receptor a Grade a Ki-67 % a Her2/neu a Margin status a after quadrantectomy Hormone therapy Estrogen receptor positive Radiotherapy after quadrantectomy DIN LIN 00-03 04-06 07-10 Quadrantectomy Mastectomy Positive Negative Positive Negative 1 2 3 < 14 14 Not Overexpressed Overexpressed Negative ( 1mm) Close (< 1mm) Positive Any None Standard ELIOT No 57 (96.6) 2 (3.4) 7 (11.9) 30 (50.9) 22 (37.3) 12 (20.3) 47 (79.7) 44 (80.0) 11 (20.0) 41 (74.6) 14 (25.6) 11 (19.6) 28 (50.0) 17 (30.4) 25 (43.9) 32 (56.1) 34 (64.2) 19 (35.9) 7 (58.3) 3 (25.0) 2 (16.7) 28 (63.6) 16 (36.4) 4 (33.3) 3 (25.0) 5 (41.7) 114 (96.6) 4 (3.4) 18 (15.3) 65 (55.1) 35 (29.7) 24 (20.3) 94 (79.7) 88 (80.0) 22 (20.0) 83 (72.8) 31 (27.2) 17 (14.5) 75 (64.1) 25 (21.4) 55 (48.3) 59 (51.8) 74 (67.3) 36 (32.7) 18 (78.3) 4 (17.4) 1 (4.4) 55 (62.5) 33 (37.5) 6 (25.0) 8 (33.3) 10 (41.7) Matching Variable Matching Variable Matching Variable Matching Variable 0.81 0.21 0.59 0.69 0.38 0.90 0.91
Local recurrences characteristics Lipofilling Age at baseline Surgery for the primary Location of the primary Yes 46 QUAD QSI DIN Yes 45 QUAD QSE DIN Yes 62 SSM QSE DIN Yes 41 SSM QSI DIN Yes 39 TM QSE DIN Histology of the primary Comedo + Micropapillar y Cribriform + Necrosis Cribriform + Micropapillar y + Necrosis Cribriforme + Micropapillar y + Papillary + Necrosis Cribiforme + micropapillar y + Necrosis Grade Margin Surgery for the relapse Location of the relapse 3 N NSM QSI DIN 3 N NSM QSE DIN + IDC Histology of the relapse Solid + necrosis + comedo Solid + necrosis Grade Lipofilling (CC) Lipofilling location Time from primary surgery to local relapse Time from lipofilling to local relapse 3 64 QSI, QII 28 24 3 40 QSE 21 7 2 N WE QSE IDC NR NR 35 QSI,QSE 62 12 2 N WE QE DIN NR NR 90 QSI,QSE 48 5 2 N WE QSE IDC papillary 1 27 QSI 30 14 Yes 45 NSM QSI, QII DIN Cribiforme + Solid 3 N WE QSE DIN + IDC Solid + necrosis 3 37 QII,QIE 26 11 No 39 NSM QI DIN Cribriform + Necrosis 2 N WE Retro areolar DIN Micropapillar y 2 n\a n\a 48 n\a No 45 NSM QSI DIN Cribriform + Micropapillar y + Necrosis 2 N WE No 47 SSM QII DIN Papillary 2 N WE QE Retro areolar DIN DIN + IDC Cribriform + Micropapillar y + Necrosis 2 n\a n\a 65 n\a Cribriform 1 n\a n\a 56 n\a Quadrantectomy Mastectomy 12 (20.3) 47 (79.7) 24 (20.3) 94 (79.7)
RISK FACTORS OF LOCO REGIONAL EVENT IN THE LIPOFILLING GROUP At risk (%) Events (5-year cum inc %) All patients 59 6 (17.8) Age at lipofilling < 50 years 30 (50.8) 5 (23.1) 50 years 29 (49.2) 1 (4.7) Histology DIN 57 (96.6) 6 (19.0) LIN 2 (3.4) 0 (0.0) 1 year 19 (32.2) 4 (37.7) Time to baseline 1.1-2 years 13 (22.0) 1 (7.7) from surgery 2.1-3 years 10 (17.0) 1 (10.0) > 3 years 17 (28.8) 0 (0.0) Type of surgery Quadrantectomy 12 (20.3) 2 (16.7) Mastectomy 47 (79.7) 4 (18.4) Estrogen receptor Positive 44 (80.0) 5 (20.3) Negative 11 (20.0) 1 (9.1) Progesteron Positive 41 (74.6) 4 (14.0) receptor Negative 14 (25.6) 2 (53.6) Grade Ki-67 % Her2/neu Margin status after quadrantectomy Hormone therapy Estrogen receptor positive Radiotherapy after quadrantectomy 1 2 3 < 14 14 Not Overexpressed Overexpressed Negative ( 1mm) Close (< 1mm) Positive Any None Standard ELIOT No 11 (19.6) 28 (50.0) 17 (30.4) 25 (43.9) 32 (56.1) 34 (64.2) 19 (35.9) 7 (58.3) 3 (25.0) 2 (16.7) 28 (63.6) 16 (36.4) 4 (33.3) 3 (25.0) 5 (41.7) 0 (0.0) 3 (21.4) 3 (NA) 1 (4.0) 5 (32.9) 4 (20.0) 2 (10.5) 1 (14.3) 1 (33.3) 0 (0.0) 3 (16.4) 2 (30.0) 1 (25.0) 1 (33.3) 0 (0.0) p 0.07 0.55 0.09 0.40 0.99 0.54 0.06 0.13 0.03 a 0.75 0.84 0.83 0.46
Cumulative Incidence 0.5 0.4 P-value: 0.02 HR Lipo vs No lipo =4.5 (95% CI 1.1-18.2) 5-year cumulative incidence: Lipofilling: 18% No Lipofilling: 3% 0.3 LR 0.2 Lipofilling 18% 0.1 0.0 No Lipofilling 3% 0 1 2 3 4 5 Years from baseline At risk Lipofilling 59 57 40 30 18 4 No Lipofilling 118 117 107 78 44 16
Cumulative Incidence Cumulative Incidence Cumulative Incidence Cumulative Incidence Cumulative Incidence Cumulative Incidence Cumulative Incidence Cumulative Incidence Age at lipofilling < 50 years Age at lipofilling >= 50 years 0.5 0.4 0.3 P-value: 0.02 0.2 0.1 Lipofilling; n=30 No Lipofilling; n=53 0.5 0.4 0.3 0.2 0.1 P-value: 0.58 Lipofilling; n=29 No Lipofilling; n=65 0.0 0.0 0 1 2 3 4 5 Years from baseline 0 1 2 3 4 5 Years from baseline G1 and G2 G3 0.5 0.5 0.4 Lipofilling; n=39 Lipofilling; n=17 0.4 No Lipofilling; n=92 No Lipofilling; n=25 0.3 0.3 P-value: 0.23 0.2 0.2 P-value: 0.03 0.1 0.0 0.1 0.0 0 1 2 3 4 5 Years from baseline 0 1 2 3 4 5 Years from baseline Ki-67 < 14% Ki-67 >= 14% 0.5 0.4 0.3 0.2 Lipofilling; n=25 No Lipofilling; n=55 0.1 0.1 P-value: 0.0 0.89 0.0 P-value: <0.01 0.5 0.4 0.3 0.2 Lipofilling; n=32 No Lipofilling; n=59 0 1 2 3 4 5 0 1 2 3 4 5 Years from baseline Years from baseline Quadrantectomy Mastectomy 0.5 0.4 0.3 Lipofilling; n=12 No Lipofilling; n=24 0.5 0.4 0.3 Lipofilling; n=47 No Lipofilling; n=94 0.2 0.1 0.2 0.1 0.0 0.0 0 1 2 3 4 5 0 1 2 3 4 5 P-value: 0.04 P-value: 0.11 Years from baseline Years from baseline
CONCLUSION INCREASING RISK OF LOCAL RECURRENCES AFTER LIPOFILLING IN PATIENTS TREATED FOR NON INVASIVE BREAST CANCER Strength : matched cohort study But conclusion should be considered cautiously: small series short follow up
CONCLUSION FURTHER STUDIES ARE REQUIRED ESPECIALLY WITH LIPOFILLING USING STEM CELLS ENHANCEMENT assuming the increasing risk of cancer stimulation with an increasing concentration of stem cells