1. Jackie Osland, M.D. September 11, 2010 oslandjs@wsspa.com

2.  Nothing to disclose

3.  Oncoplastic Surgery  MRI Indications  Nipple sparing mastectomy  Management of the Axilla-ACOSOG Z-11 trial

4.  Based upon integration of plastic surgery techniques for immediate reshaping after wide excision for breast cancer  Techniques range from simple reshaping and mobilization of breast tissue to more advanced mammoplasty techniques

5.  Excision volume  Tumor location  Glandular density

6.  Single most predictive factor for breast deformity  Once 20% is excised, clear risk of deformity  Advanced mammoplasty techniques can allow resection of up to 50% of the breast volume

7.  Upper outer quadrant-most favorable location for an optimal cosmetic result  Lower pole, upper inner quadrant are less favorable  Bird’s beak deformity-after excision of tumors from the lower pole

8.  Based on mammography or clinical exam  Density predicts ability to undermine without the complication of fat necrosis  Low density breast tissue  Higher risk of fat necrosis  Limit undermining, perform only posterior undermining

9.  Clough 2010 Annals of Surgical Oncology  American Society of Breast Surgeons annual meeting  Breast3 meeting February 2011

10.  Ideal patient-young patient with dense breast tissue, medium-sized lumpectomy required  6 steps  Skin incision  Undermining of the skin and NAC  Full thickness glandular excision  Closure of the glandular defect  NAC repositioning if necessary

11.  Allow for enbloc excision of the cancer without fragmentation  Allow for extensive undermining to facilitate reshaping  Follow Kraissl’s lines to limit scarring  If tumor adjacent to NAC, use edge of NAC with possible radial extension towards the tumor

12.  Key factors-extensive subcutaneous undermining  Easier to undermine the skin before excising the lesion  Follow the mastectomy plane  Facilitates tumor resection and glandular redistribution  Reduce undermining if risk factors for fat necrosis present  Smoking  Fatty replaced breast

13.  Extensive resections lead to NAC deviation towards the excised area  First step-completely transect the terminal ducts and separate the NAC from the underlying breast tissue  Maintain 0.5-1 cm of tissue behind the NAC  May reduce NAC sensitivity

14.  Excision in a fusiform pattern oriented towards the NAC  Facilitates reapproximation of the gland

15.  Mobilize tissue from lateral positions or central portion of the breast  Suture the glandular flaps together

16.  NAC will deviate toward the excision site after an extensive resection  Deepithelialize a crescent of skin opposite the defect, resuture the NAC

17.  MRI for screening  MRI for treatment selection

18.  Mammography screening credited with up to half of the reduction in breast cancer mortality in the USA  10-15% of breast cancers are not visible to mammography  22% of cancers in women under age 50 yrs  10% of cancers in women over age 50 yrs  BRCA mutation carriers High percentage of cancer being indentified in the interval between annual mammograms

19.  Detects increased vascularity  Sensitivity not altered by breast density  High cost  Lack of specificity

20.  No prospective randomized trials  11 prospective series comparing outcome of screening with MRI to mammography  Warner 2008 published a meta-analysis of these series  Sensitivity- Mammo 32% MRI 75% Combined 84%

21.  In several of the studies, the sensitivity of mammography was superior to that of MRI for the detection of DCIS  In all of the studies, the specificity of mammography was higher than the specificity of MRI  Recall rate- MRI-10.7% Mammo-3.9%  Biopsy rate-MRI- 3.1% Mammo-1.3%  Whether the increased sensitivity of MRI over mammography offers a survival advantage is uncertain however high risk women screened with MRI have smaller tumors and less nodal involvement at diagnosis

22.  Most of the data involve FMH as the factor  LCIS and ADH  Port 2007 reported on a retrospective group of patients who had LCIS and ADH Cancer -1% of 478 MRI’s 25% recommended to have a biopsy 50% had at least 1 MRI requiring short-term follow-up  Favorable results of screening with MRI in women at genetic risk may not be duplicated to other high-risk groups

23.  Recommend annual screening based on evidence  BRCA mutation carrier or untested first-degree relative of a carrier  Lifetime risk of 20-25% or >, as defined by models largely dependent on FMH www.cancer.gov/bcrisktool/  Recommend annual MRI screening based on expert consensus  XRT to chest between age 10-30yrs  Li-Fraumeni and first degree relatives  Cowden syndrome and first-degree relatives  Insufficient evidence to recommend for or against  LCIS, ADH, dense tissue, personal history of breast cancer  Recommend against MRI screening-<15% lifetime risk

24.  Subclinical tumor foci are present in significant numbers of women with clinically localized breast cancer  P/E and mammo finds multicentricity in <10%  Pathology sectioning finds multifocality or multicentricity in 21-63%  BCT offers equivalent survival to mastectomy with 10-year rates of local recurrence less than 10%, considerably lower than the incidence of multifocality/multicentricity in pathology studies

25.  Houssani 2008  2610 patients  Additional cancer found by MRI in 16%  Mann 2008  Meta-analysis of 18 studies and 450 cases of lobular cancer  Additional cancer found by MRI in 32% It seems as if MRI identifies some, but not all, of the tumor foci identified by serial sectioning

26.  Sardanelli 2004  Performed MRI on 90 cancer patients prior to mastectomy Sensitivity -81% 89% for invasive cancer 40% for DCIS Out of the 90 patients, MRI failed to detect disease in 19 patients, incorrectly identified disease in 30, correctly identified extent of disease in 50

27.  Mayo clinic study of 5405 patients  2003 to 2006 they increased their use of MRI from 10% to 26% of new cancers  Women who had a MRI had a 1.7 times higher rate of having a mastectomy

28.  COMICE trial  UK prospective randomized trial  Designed to detect improved outcomes of BCT patients who underwent MRI  1623 patients randomized to MRI or not  MRI group-7.1% underwent mastectomy based on MRI findings  Conversion to mastectomy-no difference  13% mastectomy rate in the MRI group  8.8% mastectomy rate in the non-MRI group

29.  NCCN guidelines  Use of MRI to evaluate women considering breast- conserving therapy is optional  If MRI imaging is performed, it should be done with a dedicated breast coil, with consultation with the multidisciplinary team by a team capable of performing MRI-guided biopsy  Limitations include a high % of false positives  Should generally be considered in the staging of breast cancer for patients whose breasts cannot be imaged adequately with mammography and ultrasound  Patients should not be denied the option of breast conservation therapy based upon MRI findings alone in the absence of tissue sampling

30.  Well-informed patients suffer less distress when false-positive findings necessitate additional biopsies or prolong the pre-surgical workup  MRI supported for determining extent of disease in patients with breast cancer and associated conventional imaging difficulties (dense tissue, invasive lobular)  Since the negative predictive value of MRI is unknown,for lesions meeting criteria for biopsy by other modalities, it my be preferable to biopsy the lesion rather than obtain an MRI

31.  Growing number of series of nipple sparing mastectomies  In the aggregate, they provide significant evidence  Randomized trial unlikely to occur

32.  Hartman NEJM 1999  Retrospective review of 639 women at moderate- high risk for breast cancer  Bilateral prophylactic mastectomy 575 had a nipple sparing mastectomy (NSM), 64 had a simple mastectomy (SM)  14 yrs of follow-up 1.2% (NSM) vs 0% (SM) developed breast cancer 6 tumors at the chest wall, one subject with bone metastases No patients developed breast cancer in the residual NAC

33.  Sacchini 2006  Multi-institutional review of 192 NSMs 64 cases of DCIS or invasive cancer  All tumors peripherally located, >1 cm from NAC  Follow-up of 100 weeks 4 patients with local recurrence, 2 with invasive cancer, 2 with risk factors only  All recurrences were distant from the NAC 3 in the upper-outer quadrant, one in the axillary tail

34.  Crowe 2008  149 NSM’s 73% with cancer, 27% for prophylaxis  6% conversion to NAC removal due to intraoperative frozen section  No disease seen at NAC at 164 weeks of follow-up  2 local recurrences, 2 distant recurrences

35.  Karolinska 2008  Sweden in the late 1980’s  216 patients, 184 NSM’s  676 weeks of follow-up  Patients with large tumors and extensive axillary metastases  High local recurrence rate-24%  No recurrences at the NAC

36.  At least 8 published series, 2000 cases

37.  Technical considerations  Remove major ducts from behind the nipple and send as a separate specimen  Relative contraindications Large, pendulous breasts Unilateral mastectomy  Contrary to some belief, BRCA mutations are not a contraindication

38.  Incision planning  Lateral radial  Circumareolar with lateral extension  Inframammary crease Best suited for small breast cup size, little ptosis, manageable distance between the incision site and the upper portions of the breast (20 cm or so)

39.  Creating skin flaps  Skin flaps are longer, and therefore more vulnerable than standard mastectomy flaps  Flap loss rates are related to traction time  Patient education  Intraoperative findings may necessitate removal of the NAC  Sensation at the NAC will be altered  Nipple necrosis

40.  Legendary Chinese curse  First of three curses of increasing severity  May you live in interesting times  May you come to the attention of those in authority  May you find what you are looking for

41.  Dr. Armando Guilano, MD  April 2010 American Surgical Association in Chicago  Presented the results of the ACOSOG Z-11 trial  Z-11 Trial Randomized, prospective controlled trial May 1999-2004 Her 2 neu testing became a standard 2006 Oncotype testing-2005 Failed to reach accrual target of 1900 patients

42.  One of the largest randomized trials studying axillary node dissection (AND)  NSABP B4 1971 1765 patients clinically node negative 3 groups RM, SM+XRT, SM 25 year follow-up –no difference in survival  Institut Curie, Paris 1982 658 patients-all had lumpectomy and breast XRT AND or axillary XRT No survival difference, better axillary control with AND

43.  T1 and T2 tumors  Clinically node negative  Excluded patients with matted nodes or 3 or more positive sentinel nodes  Lumpectomy and whole breast radiation  All had a positive SLN detected by H&E  Randomized to AND or no AND  58% had chemo, 46% had hormonal therapy

44.  Median follow-up of 6.3 years  AND group  4% locoregional recurrence  No AND groups  2.8% locoregional recurrence  This is the first large, randomized trial to show that completion AND offers no advantage with respect to locoregional recurrence with one or two positive sentinel nodes

45.  Paper not published yet  Does not mean all patients with positive nodes do not need an AND  Clinically node negative, T1, T2 Preop clinical stage Stage 1 or 2  All of the patients had lumpectomy with radiation

46.  Options in increasing order of “progressiveness”  Wait  Discuss with your local medical oncologist  If micrometastases found on postoperative pathology, do not take patient back for the AND  If macrometastases found on postoperative pathology, do not take patient back for AND if only one or two nodes positive in a T1 or T2 tumor undergoing lumpectomy and radiation

47.  Forgo AND in all patients with 1-2 positive SLN’s with T1/T2 tumors undergoing lumpectomy and radiation  Discontinue practice of intraoperative SLN analysis  Consent patient for SLN biopsy plus or minus portocath, rather than plus or minus AND  Forgo AND for mastectomy patients with T1/T2 tumors and and 1-2 positive nodes ???????????????????????????????????????????????????????