bct for multifocal multicentric breast cancer - is it contraindicated?

Hon-chi YipDepartment of SurgeryNorth District Hospital

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

1. Monoclonal proliferation of a single mammary carcinoma

2. Multiple independent synchronous tumors in the same breast

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 cancerNIH Consensus Conference. JAMA 1991;265(3):391-5

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.

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.

1. Oncological considerations Effect on overall survival Effect on disease recurrence, esp. locoregional

2. Technical considerations Complete excision, negative margin Satisfactory cosmetic result

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)’’

Study, year MF or MC Patients, n Local recurrence, %

Median FU, months

Leopold, 1989 MF & MC 10 40 64

Kurtz, 1990 MF & MC 61 25 71

Wilson, 1993 MF 13 25 72

Hartsell, 1994 MC 27 3.7 53

Nos, 1999 MF 56 11 60

Cho, 2002 MF & MC 15 0 76

Kaplan, 2003 MF & MC 36 3 45

Okumura, 2004 MF & MC 34 0 58

Oh, 2006 MF & MC 97 6 66

Gentillini, 2008 MF & MC 476 5 73

Lim, 2009 MF 147 2 59

Chung, 2012 MF 164 6.1 112

Yerushalmi, 2012 MF & MC 300 5.5 95

Study, year MF or MC Patients, n Local recurrence, %

Median FU, months

Leopold, 1989 MF & MC 10 40 64

Kurtz, 1990 MF & MC 61 25 71

Wilson, 1993 MF 13 25 72

Resection margins not routinely evaluated Surgery involved gross excision of suspicious masses only No fixed protocol for adjuvant therapy

Study, year MF or MC Patients, n Local recurrence, %

Median FU, months

Leopold, 1989 MF & MC 10 40 64

Kurtz, 1990 MF & MC 61 25 71

Wilson, 1993 MF 13 25 72

Hartsell, 1994 MC 27 3.7 53

Nos, 1999 MF 56 11 60

Cho, 2002 MF & MC 15 0 76

Kaplan, 2003 MF & MC 36 3 45

Okumura, 2004 MF & MC 34 0 58

Oh, 2006 MF & MC 97 6 66

Gentillini, 2008 MF & MC 476 5 73

Lim, 2009 MF 147 2 59

Chung, 2012 MF 164 6.1 112

Yerushalmi, 2012 MF & MC 300 5.5 95

Weissenbacher et al. Breast Cancer Res Treat 2010;122:27-34

Overall survival

Chung et al. J Am Coll Surg 2012;215:137-147

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

MF/MC not associated with inferior survival on multivariate analysis

Yerushalmi et al. Annals of Oncology 2012;23:876-881

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

Excision of multifocal / multicentric tumors without resulting in significant breast distortion

Careful preoperative assessment required

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 rateL Turnbull et al. Lancet 2010;375:563-71

Houssami et al. J Clin Oncol 2008;26:3248-58

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

Size, location and distribution of the lesionsBreast volume, ptosisSurgeon preference

Single vs multiple wide local excisionsChoice of breast restoration

Oncoplastic surgical techniques

When considering BCT, the following factor is contraindication:

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

1. Monoclonal proliferation of a single mammary carcinoma2. 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

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

Level 1 <20% breast volume excised

Level 2 20-50% breast volume excised

Glandular mobilization Intra-mammary flap reconstructionNAC reposition

Only posterior undermining leaving skin attached

Mammoplasty techniques

St. Gallen International Breast Cancer Conference, Switzerland, Mar 2013

Treatment recommendation after reviewing latest evidence