BCT for multifocal multicentric breast cancer - Is it contraindicated?

1. Hon-chi Yip Department of Surgery North District Hospital BCT for multifocal multicentric breast cancer -Is it contraindicated?

2. Multifocal / multicentric breast cancer • 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. Pathophysiology of multifocality and multicentricity • Monoclonal proliferation of a single mammary carcinoma • Multiple independent synchronous tumors in the same breast

4. Breast conservation therapy • 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. Multifocal / multicentric breast cancer • 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. Development of oncoplastic surgery (OPS) • 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. Important issues • Oncological considerations • Effect on overall survival • Effect on disease recurrence, esp. locoregional • Technical considerations • Complete excision, negative margin • Satisfactory cosmetic result

8. Oncological considerations • 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)’’

9. Local recurrence

10. Studies on LR in BCT for MF / MC disease

11. Early studies • Resection margins not routinely evaluated • Surgery involved gross excision of suspicious masses only • No fixed protocol for adjuvant therapy

12. Studies on LR in BCT for MF / MC disease

13. Unifocalvs multifocal CA breastPrognostic implication

14. Unifocalvs MF/MC – recurrence and survival Overall survival Weissenbacher et al. Breast Cancer Res Treat 2010;122:27-34 Chung et al. J Am Coll Surg 2012;215:137-147

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

16. Unifocalvs MF / MC – population based study • MF/MC not associated with inferior survival on multivariate analysis Yerushalmi et al. Annals of Oncology 2012;23:876-881

17. MF / MC breast cancer – survival • No comparative survival data on BCT vs mastectomy in MF / MC disease

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

19. Role of MRI breast in preoperative assessment • 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 Houssami et al. J Clin Oncol 2008;26:3248-58 L Turnbull et al. Lancet 2010;375:563-71

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

21. Choice of approach • 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. St GallenConsensus 2013 • When considering BCT, the following factor is contraindication:

23. Conclusion • 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

24. The end

25. Pathophysiology of multifocality and multicentricity • Monoclonal proliferation of a single mammary carcinoma • 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. Texieira MR et al. Br J Cancer 1994;70:922-927 Dawson PJ et al. Hum Pathol. 1995;26:965–969

26. Selection criteria • 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. Bilevel classification of OPS • Level 1 • <20% breast volume excised • Level 2 • 20-50% breast volume excised

28. Level 1 OPS • Glandular mobilization • Intra-mammary flap reconstruction • NAC reposition

29. Level 2 OPS • Only posterior undermining leaving skin attached • Mammoplasty techniques

30. Expert opinion - St. Gallen Consensus 2013 • St. Gallen International Breast Cancer Conference, Switzerland, Mar 2013 • Treatment recommendation after reviewing latest evidence