The document summarizes breast conservation therapy (BCT) experience at IRCH-AIIMS in New Delhi, India. It discusses the evolution and rationale for BCT, techniques used including oncoplastic surgery, indications and contraindications. The IRCH-AIIMS protocol for BCT involves lumpectomy, axillary dissection, whole breast radiotherapy with tumor bed boost. Of 272 BCT cases, 5-year disease-free and overall survival were 76% and 92%. BCT is underutilized but offers cosmetic and psychological advantages over mastectomy for early breast cancer when adequate infrastructure and multidisciplinary care is available.

1. Breast Conservation Therapy IRCH-AIIMS Experience Dr. Manish Varma, Dr. SVS Deo, Dr.NK Shukla, Dr. Vinod Raina*, Dr.GK Rath** Dept. of Surgical , Medical* and Radiation oncology**, IRCH, AIIMS, New Delhi

2. Evolution of Surgery for BC Ultra Radical Early 19 th Century Conservation, Reconstruction 20 th century Radical Late 19 th Century

3. Morbidity of Mastectomy Breast - Symbol of Femininity, Attractiveness and motherhood Loss of feminine attractiveness Altered body image perception Psycho sexual problems Painful reminder of cancer Depression

4. Evolution of Modern BCT Innovative Pilot studies - 1960-70 BCT promising intervention for EBC Retrospective comparative studies - 70s BCT Safer & effective option Prospective Randomized trials – 1980s MRM Vs BCT- comparable out come 20 yrs RCT Results - 2000 20 yrs FU, BCT vs MRM – No survival difference Scientifically studied & validated therapeutic intervention in Breast Cancer

5. Rationale of BCT Natural history Breast cancer is a systemic disease with hematogenous spread early in the disease process 20% of node negative patients develop distant metastases Limits of surgical efficacy Equivalent results of Radical and Modified radical mastectomy : More extensive surgery might not result in better cure rates

6. Rationale of BCT Surgery and Radiation as a combined modality Surgery alone- More failure at margins Radiotherapy alone- More failure at the epicenter Using surgery to remove grossly visible tumor with a small margin and moderate-dose radiotherapy to treat the larger volume of tissue that may harbor residual disease

7. Surgery and Radiation as combined modality First used as an adjuvant after mastectomy to eradicate sub clinical disease in internal mammary,supraclavicular and axillary nodes and chest wall BCT uses Radiation for control of sub clinical disease in the residual breast tissue in addition to the above mentioned sites

8. Randomized Trials - BCT vs MRM Group No 10 Yr Survival (%) Loc. Rec(% ) BCT - MRM BCT - MRM NSABP 2105 62 - 62 10 - 8 French 179 78 - 79 7 - 9 Milan 701 71 - 69 4 - 2 EORTC 903 75 - 75 13 - 9 Danish 905 79 - 82 3 - 4 NCI 237 77 - 75 17 - 9

9. Randomized Trials - BCT vs MRM 20 Year Follow up Milan Trial – NEJM 2002 Local Relapse – 8 % vs 2.3 % (BCT vs MRM) OS – 59 % vs 59% (BCT vs MRM) NCI Trial - Cancer 2003 DFS – 64 % vs 67 % (BCT vs MRM) OS – 54 % vs 58% (BCT vs MRM)

10. NCI Consensus Conference - EBC In early breast cancer breast conservation treatment is not only equivalent to mastectomy but also preferable as it preserves the breast with all the attendant psychological and breast image advantages there by enhancing quality of life.

11. BCT - Multidisciplinary approach Surgical Oncologist Radiation Oncologist Medical Oncologist Radiologist Pathologist

12. Goals of Breast Conservation Acceptable cosmetic outcome Minimal local recurrence Uncompromised - DFS and OS Good quality of life

13. Breast Conservation Therapy Patient Selection Indications for BCT Patient motivation Stage I & II B.C (Tumor < 5 cm) Availability of adequate infrastructure Mammography Radiotherapy good pathology services Reliability regarding Rx compliance & Follow up

14. Contraindications to BCT Absolute High probability of recurrence Multicentric disease Positive surgical margins (EIC) High probability of complications from irradiation CVD Prior irradiation to chest wall Early pregnancy

15. Contraindications to BCT Relative High probability of subsequent breast cancers BRCA1 and BRCA2 mutations Poor cosmetic results Unfavorable tumor-breast ratio Oncologically necessary removal of nipple-areola complex Large medial lesions Personal preference of the patient

16. BCT Surgical Margins Ideal margin – No consensus 3D excision with minimum of 1 cm gross margin(0.5 to 2 cm) Local Relapse - Quadrantectomy vs Tumerectomy Milan study - 5 % vs 13% Fine balance between cosmesis and margins India - Main fear is local relapse - Wide margins

17. Breast Conservation Surgery Indications for Re-excision EIC & Margin + ve > focal microscopic margin +ve Uncertain resection margins Residual microcalcification

18. Breast Conservation Therapy Radiotherapy Integral part of BCT With in 4 to 6 weeks of BCS To control Microscopic residual disease WBRT – 50Gy / 25 Fr / 5 weeks Linac / Cobalt Tumor Bed Boost - 15 Gy Electron beam Brachytherapy

19. Breast Conservation Therapy Tumor Bed Boost

20. Breast Conservation Therapy Tumor Bed Boost

21. Breast Conservation Therapy: Radiotherapy Meta analysis “ Vinh Hung et al”, JNCI, 2004 Pooled data from all trials on BCT with and with out RT 8.6 % survival benefit apart Decreased local relapse Definite role in eradicating microscopic tumor foci . Group No. Local Failure (%) - RT + RT NSABP '92 1141 39 12 Ontario '92 837 26 6 Milan '93 567 9 0.3 Sweden '94 381 20 3

22. BCT- Recent Advances Accelerated Partial Breast Irradiation (APBI) 80- 90 % recurrences after BCT occur around tumor bed APBI - R.T . Limited area of Breast over short duration Accelerated Partial Breast Irradiation equivalent to WBRT Advantages – Short duration of treatment Limited Breast Irradiation Several phase I & II Studies – Promising results Technique – Mammosite / IORT / Brachytherapy / IMRT

23. BCT- Recent Advances Surgery - Oncoplastic Techniques – BCS Recent data – 1 cm tumor free margin is more important than absolute tumor size BCT > 5 cm tumor is not an absolute CI for BCT Volume loss > 30% Central quadrant tumors Cavity – RT – Fibrosis Deformities Skin loss – Breast Asymmetry To Improve Cosmesis - Oncoplastic Techniques – BCS

24. BCT- Recent Advances Surgery - Oncoplastic Techniques – BCS Aims Improving Cosmetic outcome, limiting deformity, and reduce scarring Types of Oncoplasty – BCT Volume Displacement Procedures Volume Replacement Method - Mini LD Flap Reconstruction (MLDF) Anderson B et al , Lancet Oncology 2005

25. Oncoplastic Techniques for BCS : Volume Displacement

26. Oncoplastic Techniques for BCS : Volume Replacement -Mini Latissimus Dorsi flap (MLDF) Latissmus Dorsi Flap – Skin / Muscle / Fat Popular flap BR – Tansini - 1906 Proximity to defect/Long pedicle Minimal functional impairment & donor site morbidity Volume Replacement - Mini LD Flap - BCT Noguchi et al 1996 & Raja et al 1997 Improved Cosmetic Results following BCT + MLDF Gendy et al 2003 , BJS

27. Mini Latissimus Dorsi flap (MLDF)

28. Mini Latissimus Dorsi flap (MLDF)

29. BCT- Recent Advances MRI in BCT Dense Breast on Mammogram Post Surg & RT – Breast Unknown primary with Axillary node Indeterminate Mammogram

30. BCT- Recent Advances MRI in BCT

31. BCT- Recent Advances MRI in BCT

32. BCT – Pushing Frontiers Family H/O Breast cancer Not a contraindication of BCT. Chabner et al 2004 Lobular carcinoma Not a contraindication for BCT. C arolin et al , Breast J, 2004 EIC Not a contraindication as long as margin status is taken care of. Smith et al , Cancer 1999 Young age (< 40 yrs) Not a contraindication for BCT

33. BCT – Pushing Frontiers Expanded indications of BCT BCT for Central tumors & Pagets Disease Central segmentectomy with Nipple Areola Complex removal with negative margins is feasible . Pierce et al, Cancer 1999 in subset of patients Multifocal BC and BCT 6 studies > 200 patients acceptable LR Tumors encompassed in a single margin –ve resection Cosmetically acceptable lumpectomy

34. BCT – Pushing Frontiers BCT for Non Palpable lesions Mammo guided wire localization and lumpectomy feasible Recently “Radio Guided Occult Lesion localization” ROLL is increasingly being used

35. Mammo guided wire localization and lumpectomy

36. BCT – Pushing Frontiers BCT in LABC Neo Adjuvant Chemotherapy BCT NSABP -18 Trial 1500 pts Increased BCT in T3 group Higher Local recurrences but no effect on overall survival Unresolved issues Method of response assessment Tumor Localization in responders Pre chemo titanium clip placement ? Extent of resection

37. BCT in LABC post NACT Better Chemotherapeutic drugs Response rates in over 2/3 rd patients CR Rates –upto 1/3 rd Progression on chemotherapy – 2-3% Attempted in Non-inflammatory LABC

38. Increased likelihood of loco-regional recurrence Large tumor size Advanced nodal disease Multifocal pattern of residual disease after NACT LVI Chen et al. Journal of clinical oncology, 2004 BCT in LABC post NACT

39. Contraindications to BCT after NACT Residual tumor size >5 cm Residual skin edema or direct skin involvement Chest wall fixation Diffuse microcalcification on post NACT mammography Multicentric disease Chen et al. Journal of clinical oncology, 2004 BCT in LABC post NACT

40. Nearly half of these patients can undergo successful breast conservation with acceptable long term disease free and overall survivals William G et al. Annals of Surgery 2002. ( Univ of North Carolina, USA ) Allen M. Chen et al.J of Clinical Oncology 2004 ( M.D.Anderson, Texas, USA) Viswambharan JK et al. Indian J Cancer. 2005 (JIPMER, India) Asoglu O. Acta Chir Belg. 2005 ( Istanbul, Turkey) Merajver SD. J Clin Oncol. 1997 (Univ of Michigan, USA) Beriwal S, et al. Breast J. 2006 Drexel University College of Medicine, Philadelphia, USA Shen J, et al. Ann Surg Oncol. 2004 ( University of Texas M. D. Anderson Cancer Center, Houston, USA ) BCT in LABC post NACT

41. BCT Rates Recent survey 2002 USA - NCDB BCT- Grossly underutilized option BCT rates – 10 to 45 % in USA in EBC Factors for low BCT Age - young age > BCT Place of treatment- Urban vs Rural, North & east USA Socioeconomic factors ? Low reimbursement for BCT

42. Breast conservation therapy IRCH –AIIMS Current BCT rate – 30 % of EBC Reasons for refusing BCT Fear of recurrence in residual breast Family members not keen for BCT Second opinion- Physician bias

43. Breast Conservation Therapy: IRCH Treatment Protocol SURGERY Initial phase - Quadrantectomy Subsequently - Wide excision - 1.5 cm, 3 dimensional tumor free margins Previous lumpectomy patients - Re-excision of scar and lumpectomy cavity Re-excision of tumor bed after lumpectomy - specimens sent separately as medial, lateral, superior, inferior and deep margins Titanium clips placed in tumor bed

44. Breast Conservation Therapy: IRCH Treatment Protocol SURGERY All patients - complete axillary lymph node dissection (level I-III) Incision - single or double - S ingle incision for selected UOQ tumors - two incisions in remaining tumors - one for lumpectomy and other for axillary dissection A single drain in axilla and no drains in the tumor bed

45. RADIOTHERAPY Whole breast radiotherapy (WBRT) 45 Gy EBRT - 25 #, 5weeks 3-4 weeks after surgery Tumor bed boost Using Electrons or low dose rate peri-operative brachytherapy Peri-operative brachytherapy Single or two plane nylon catheters implant in tumor bed after lumpectomy Inter-catheter distance 1 cm Breast Conservation Therapy: IRCH Treatment Protocol

46. RADIOTHERAPY Boost delivered through nylon catheters using iridium-192 wires or seeds by remote controlled after loading technique 2-3 days after surgery Electron boost After completion of WBRT Using a linear accelerator The boost dose - 15 to 20 Gy RT to axilla – EBRT if Involvement of >3 nodes Extra nodal spread Breast Conservation Therapy: IRCH Treatment Protocol

47. SYSTEMIC THERAPY Adjuvant Chemotherapy - All high-risk patients Pre-menopausal status Tumor size >1 cm, Node positive ER/PR negative High grade tumors Lymphovascular invasion Six cycles of DEC/CEF/CMF - depending upon the risk factors and economic status Breast Conservation Therapy: IRCH Treatment Protocol

48. SYSTEMIC THERAPY No adjuvant chemotherapy – Post menopausal women with < 1 cm ER/ PR positive tumor Neo-adjuvant chemotherapy - 3 cycles anthracycline based for patients with > 4 cm tumor keen for BCT Hormonal therapy - ER/PR positive Tamoxifen/ AIs for 5 years Breast Conservation Therapy: IRCH Treatment Protocol

49. FOLLOW UP After completion of treatment in breast cancer clinic First 2 years - every 3 monthly and thereafter 6 monthly Clinical examination and SAP at each follow up Chest X-ray – 6 monthly Annual bilateral mammogram Cosmesis Assessed at the end of one year Graded - good, average and poor - JCRT criteria Breast Conservation Therapy: IRCH Treatment Protocol

50. IRCH –AIIMS Experience Study period - 1998 -2007 No. of BCT - 272 Mean Age – 44.2 yrs (23-66 yrs) Premenopausal- 37.4% Receptor +ve – 33% -ve – 45% Unknown – 22% Positive family history– 8.9%

51. IRCH –AIIMS Experience 50% 14.7% 20.5% 6.3% 6.8% Site

52. IRCH –AIIMS Experience Post op Radiotherapy EBRT - 92.6% Brachytherapy – 44.2% Stage distribution EBC – 93.7% LABC – 6.3%

53. IRCH –AIIMS Experience Histo-pathology Margin +ve – 2.1% Pathological Node +ve - 29% Extranodal spread – 7.9% Recurrence (Total 33 patients, 12%) Local - 2.6% Systemic – 8.4% Local+Systemic – 1.1%

54. IRCH –AIIMS Experience 5 yr DFS – 76%

55. IRCH –AIIMS Experience 5 yr OS – 92%

56. Conclusions BCT most scientifically evaluated surgical treatment modality for EBC Cosmetic and psychological advantages Grossly under-utilized treatment option Need to educate patients and physicians Recent advances – Expand indications for BCT NACT increases the BCT rates in LABC, but may have a higher risk of local recurrence

57. Thank You Dr. Manish Varma MS, DNB, MNAMS Department of Surgical Oncology BRA-IRCH, All India Institute of Medical Sciences New Delhi