Jackie Osland, M.D. September 11, 2010

 Nothing to disclose

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

 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

 Excision volume  Tumor location  Glandular density

 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

 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

 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

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

 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

 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

 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

 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 cm of tissue behind the NAC  May reduce NAC sensitivity

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

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

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

 MRI for screening  MRI for treatment selection

 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

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

 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%

 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

 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

 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  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

 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

 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

 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

 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

 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

 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

 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

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

 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

 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

 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

 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

 At least 8 published series, 2000 cases

 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

 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)

 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

 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

 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 Her 2 neu testing became a standard 2006 Oncotype testing-2005 Failed to reach accrual target of 1900 patients

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

 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

 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

 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

 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

 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 ???????????????????????????????????????????????????????