1. Hon-chi Yip Department of Surgery North District Hospital

2.  Definition  Multifocal (MF) – multiple tumors in same quadrant (>5cm apart)  Multicentric (MC) – multiple tumors in different quadrants  Not based on anatomy of breast  Increasingly detected due to the widespread use of MRI breast

3. 1. Monoclonal proliferation of a single mammary carcinoma 2. Multiple independent synchronous tumors in the same breast

4.  Wide local excision + radiotherapy  Established treatment modality for early stage breast cancer  No difference in overall, disease-free survival  Improved body image and lifestyle score  National Institutes of Health (NIH) Consensus Conference statement 1990  BCT as preferred surgical treatment of women with early stage breast cancer NIH Consensus Conference. JAMA 1991;265(3):391-5

5.  Traditionally contraindicated for BCT  Landmark trials for BCT – NSABP B-06, EORTC, Milan etc  Exclusion criteria – Multifocal or multicentric disease  Increased difficulty to obtain negative margin  Potential increase risk of recurrence Fisher B et al. N Engl J Med 2002;347:1233–1241. Veronesi U et al. N Engl J Med 2002;347:1227–1232. van Dongen JA et al. J Natl Cancer Inst 2000;92:1143–1150.

6.  Allow wide excision for BCT without compromising the natural shape of the breast  Integration of plastic surgery techniques for immediate breast reshaping  Oncologic efficacy (margin status & recurrence) compare favorably with traditional BCT  Results of 298 OPS treated breast cancer ▪ 5 year overall survival 94.6%, DFS 93.7%  Recent enthusiasm on BCT in MF / MC disease Staub G et al. Ann Chir Plast Esthet. 2007;53(2):124–34.

7. 1. Oncological considerations  Effect on overall survival  Effect on disease recurrence, esp. locoregional 2. Technical considerations  Complete excision, negative margin  Satisfactory cosmetic result

8.  Lack of level 1 evidence  What are the available evidence in the literature?  Medline and PubMed search – keywords:  ‘‘Multifocal’’ or ‘‘Multicentric’’ or ‘‘Breast Conservation’’ or ‘‘Mastectomy’’  ‘‘Breast Cancer’’ or ‘‘Ductal Carcinoma In-Situ (DCIS)’’

10. Study, yearMF or MCPatients, nLocal recurrence, %Median FU, months Leopold, 1989MF & MC104064 Kurtz, 1990MF & MC612571 Wilson, 1993MF132572 Hartsell, 1994MC273.753 Nos, 1999MF561160 Cho, 2002MF & MC15076 Kaplan, 2003MF & MC36345 Okumura, 2004MF & MC34058 Oh, 2006MF & MC97666 Gentillini, 2008MF & MC476573 Lim, 2009MF147259 Chung, 2012MF1646.1112 Yerushalmi, 2012MF & MC3005.595

11. Study, yearMF or MCPatients, nLocal recurrence, %Median FU, months Leopold, 1989MF & MC104064 Kurtz, 1990MF & MC612571 Wilson, 1993MF132572  Resection margins not routinely evaluated  Surgery involved gross excision of suspicious masses only  No fixed protocol for adjuvant therapy

12. Study, yearMF or MCPatients, nLocal recurrence, %Median FU, months Leopold, 1989MF & MC104064 Kurtz, 1990MF & MC612571 Wilson, 1993MF132572 Hartsell, 1994MC273.753 Nos, 1999MF561160 Cho, 2002MF & MC15076 Kaplan, 2003MF & MC36345 Okumura, 2004MF & MC34058 Oh, 2006MF & MC97666 Gentillini, 2008MF & MC476573 Lim, 2009MF147259 Chung, 2012MF1646.1112 Yerushalmi, 2012MF & MC3005.595

14. Weissenbacher et al. Breast Cancer Res Treat 2010;122:27-34 Overall survival Chung et al. J Am Coll Surg 2012;215:137-147

15. Ustaalioglu BO et al. Am J Clin Oncol 2012;36:580-586

16.  MF/MC not associated with inferior survival on multivariate analysis Yerushalmi et al. Annals of Oncology 2012;23:876-881

17.  No comparative survival data on BCT vs mastectomy in MF / MC disease

18.  Excision of multifocal / multicentric tumors without resulting in significant breast distortion  Careful preoperative assessment required

19.  Routine use of MRI breast in preoperative staging for early CA breast is controversial  Meta-analysis showed that MRI could identify additional multifocal / multicentric foci that preclude breast conservation  Possibility of false positive finding, unnecessary mastectomy  RCT showed no improvement in reoperation rate L Turnbull et al. Lancet 2010;375:563-71 Houssami et al. J Clin Oncol 2008;26:3248-58

20.  Possible role in confirmed MF / MC disease to rule out additional tumor foci and define extent of disease?

21.  Size, location and distribution of the lesions  Breast volume, ptosis  Surgeon preference  Single vs multiple wide local excisions  Choice of breast restoration  Oncoplastic surgical techniques

22.  When considering BCT, the following factor is contraindication:

23.  BCT is not absolutely contraindicated in cases of multifocal or multicentric breast cancers  Acceptable recurrence rate and survival can be obtained with adequate tumor excision and adjuvant therapy  Therapeutic strategy should be individualized based on the feasibility of wide local excision with negative margins and patient’s preference

25. 1. Monoclonal proliferation of a single mammary carcinoma 2. Multiple independent synchronous tumors in the same breast  One small scale series found near identical morphologic and immunohistochemical pattern in 32 multicentric tumor specimens  75% cases had evolutionary related cytogenetically abnormal clone in different tumor lesions from same breast  Another study of 24 cases only showed 10 cases of identical histological and immunohistochemical pattern Middleton LP et al.Cancer. 2002 Apr 1;94(7):1910-6. Dawson PJ et al. Hum Pathol. 1995;26:965–969 Texieira MR et al. Br J Cancer 1994;70:922-927

26.  Excision volume  >20% of volume excised – significant risk of deformity  OPS allow for significantly greater excision volumes while preserving natural breast shape  Tumor location  Zones of high risk / low risk of deformity  Glandular density  Lower risk of necrosis in mobilizing dense glandular breast versus low density breast with major fatty composition

27.  Level 1  <20% breast volume excised  Level 2  20-50% breast volume excised

28.  Glandular mobilization  Intra-mammary flap reconstruction  NAC reposition

29.  Only posterior undermining leaving skin attached  Mammoplasty techniques

30.  St. Gallen International Breast Cancer Conference, Switzerland, Mar 2013  Treatment recommendation after reviewing latest evidence