Changes in Surgical Management of the Axilla Over 11 Years - Report on More Than 1500 Breast Cancer Patients Treated with Neoadjuvant Chemotherapy on the Prospective I-SPY2 Trial.

BACKGROUND: Axillary surgery after neoadjuvant chemotherapy (NAC) is becoming less extensive. We evaluated the evolution of axillary surgery after NAC on the multi-institutional I-SPY2 prospective trial. METHODS: We examined annual rates of sentinel lymph node (SLN) surgery with resection of clipped node, if present), axillary lymph node dissection (ALND), and SLN and ALND in patients enrolled in I-SPY2 from January 1, 2011 to December 31, 2021 by clinical N status at diagnosis and pathologic N status at surgery. Cochran-Armitage trend tests were calculated to evaluate patterns over time. RESULTS: Of 1578 patients, 973 patients (61.7%) had SLN-only, 136 (8.6%) had SLN and ALND, and 469 (29.7%) had ALND-only. In the cN0 group, ALND-only decreased from 20% in 2011 to 6.25% in 2021 (p = 0.0078) and SLN-only increased from 70.0% to 87.5% (p = 0.0020). This was even more striking in patients with clinically node-positive (cN+) disease at diagnosis, where ALND-only decreased from 70.7% to 29.4% (p < 0.0001) and SLN-only significantly increased from 14.6% to 56.5% (p < 0.0001). This change was significant across subtypes (HR-/HER2-, HR+/HER2-, and HER2+). Among pathologically node-positive (pN+) patients after NAC (n = 525) ALND-only decreased from 69.0% to 39.2% (p < 0.0001) and SLN-only increased from 6.9% to 39.2% (p < 0.0001). CONCLUSIONS: Use of ALND after NAC has significantly decreased over the past decade. This is most pronounced in cN+ disease at diagnosis with an increase in the use of SLN surgery after NAC. Additionally, in pN+ disease after NAC, there has been a decrease in use of completion ALND, a practice pattern change that precedes results from clinical trials.

Area Deprivation Index in Patients with Invasive Lobular Carcinoma of the Breast: Associations with Tumor Characteristics and Outcomes.

BACKGROUND: Although investigators have shown associations between socioeconomic status (SES) and outcomes in breast cancer, there is a paucity of such data for invasive lobular carcinoma (ILC), the second most common type of breast cancer. Herein we evaluated the relationship between SES with tumor features and outcomes in stage I to III patients with ILC. METHODS: We analyzed a prospectively maintained institutional ILC database and utilized the area deprivation index (ADI) to determine neighborhood adversity, an indicator of SES. We used Cox proportional hazards models in Stata 17.0 to evaluate relationships between ADI quintile (Q), race, body mass index (BMI), clinicopathologic features, treatment type, and event-free survival (EFS). RESULTS: Of 804 patients with ILC, 21.4% lived in neighborhoods classified as ADI Q1 (least resource-deprived) and 19.7% in Q5 (most resource-deprived). Higher deprivation was significantly associated with larger tumor size (3.6 cm in Q5 vs. 3.1 cm in Q1), increased presence of lymphovascular invasion (8.9% in Q5 vs. 6.7% in Q1), and decreased use of adjuvant endocrine therapy (67.1% in Q5 vs. 73.6% in Q1). On multivariable analysis, tumor size, receptor subtypes, and omission of adjuvant endocrine therapy were associated with reduced EFS. CONCLUSIONS: These data show that patients with ILC and higher ADI experience more aggressive tumors and differences in treatment. More data evaluating the complex relationships between these factors is needed to optimize outcomes for patients with ILC, regardless of SES. IMPACT: ADI is associated with differences in patients with ILC.

Association of Residual Ductal Carcinoma In Situ With Breast Cancer Recurrence in the Neoadjuvant I-SPY2 Trial.

Importance: Pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) in breast cancer strongly correlates with overall survival and has become the standard end point in neoadjuvant trials. However, there is controversy regarding whether the definition of pCR should exclude or permit the presence of residual ductal carcinoma in situ (DCIS). Objective: To examine the association of residual DCIS in surgical specimens after neoadjuvant chemotherapy for breast cancer with survival end points to inform standards for the assessment of pathologic complete response. Design, Setting, and Participants: The study team analyzed the association of residual DCIS after NAC with 3-year event-free survival (EFS), distant recurrence-free survival (DRFS), and local-regional recurrence (LRR) in the I-SPY2 trial, an adaptive neoadjuvant platform trial for patients with breast cancer at high risk of recurrence. This is a retrospective analysis of clinical specimens and data from the ongoing I-SPY2 adaptive platform trial of novel therapeutics on a background of standard of care for early breast cancer. I-SPY2 participants are adult women diagnosed with stage II/III breast cancer at high risk of recurrence. Interventions: Participants were randomized to receive taxane and anthracycline-based neoadjuvant therapy with or without 1 of 10 investigational agents, followed by definitive surgery. Main Outcomes and Measures: The presence of DCIS and EFS, DRFS, and LRR. Results: The study team identified 933 I-SPY2 participants (aged 24 to 77 years) with complete pathology and follow-up data. Median follow-up time was 3.9 years; 337 participants (36%) had no residual invasive disease (residual cancer burden 0, or pCR). Of the 337 participants with pCR, 70 (21%) had residual DCIS, which varied significantly by tumor-receptor subtype; residual DCIS was present in 8.5% of triple negative tumors, 15.6% of hormone-receptor positive tumors, and 36.6% of ERBB2-positive tumors. Among those participants with pCR, there was no significant difference in EFS, DRFS, or LRR based on presence or absence of residual DCIS. Conclusions and Relevance: The analysis supports the definition of pCR as the absence of invasive disease after NAC regardless of the presence or absence of DCIS. Trial Registration: ClinicalTrials.gov Identifier NCT01042379.

Neoadjuvant T-DM1/pertuzumab and paclitaxel/trastuzumab/pertuzumab for HER2+ breast cancer in the adaptively randomized I-SPY2 trial.

HER2-targeted therapy dramatically improves outcomes in early breast cancer. Here we report the results of two HER2-targeted combinations in the neoadjuvant I-SPY2 phase 2 adaptive platform trial for early breast cancer at high risk of recurrence: ado-trastuzumab emtansine plus pertuzumab (T-DM1/P) and paclitaxel, trastuzumab and pertuzumab (THP). Eligible women have >2.5 cm clinical stage II/III HER2+ breast cancer, adaptively randomized to T-DM1/P, THP, or a common control arm of paclitaxel/trastuzumab (TH), followed by doxorubicin/cyclophosphamide, then surgery. Both T-DM1/P and THP arms 'graduate' in all subtypes: predicted pCR rates are 63%, 72% and 33% for T-DM1/P (n = 52), THP (n = 45) and TH (n = 31) respectively. Toxicity burden is similar between arms. Degree of HER2 pathway signaling and phosphorylation in pretreatment biopsy specimens are associated with response to both T-DM1/P and THP and can further identify highly responsive HER2+ tumors to HER2-directed therapy. This may help identify patients who can safely de-escalate cytotoxic chemotherapy without compromising excellent outcome.

Synchronous Detection of Circulating Tumor Cells in Blood and Disseminated Tumor Cells in Bone Marrow Predicts Adverse Outcome in Early Breast Cancer.

PURPOSE: We examined the prognostic impact of circulating tumor cells (CTCs) and disseminated tumor cells (DTCs) detected at the time of surgery in 742 untreated patients with early breast cancer. EXPERIMENTAL DESIGN: DTCs in bone marrow were enumerated using the EPCAM-based immunomagnetic enrichment and flow cytometry (IE/FC) assay. CTCs in blood were enumerated either by IE/FC or CellSearch. Median follow-up was 7.1 years for distant recurrence-free survival (DRFS) and 9.1 years for breast cancer-specific survival (BCSS) and overall survival (OS). Cox regressions were used to estimate hazard ratios for DRFS, BCSS, and OS in all patients, as well as in hormone receptor-positive (HR-positive, 87%) and HR-negative (13%) subsets. RESULTS: In multivariate models, CTC positivity by IE/FC was significantly associated with reduced BCSS in both all (n = 288; P = 0.0138) and HR-positive patients (n = 249; P = 0.0454). CTC positivity by CellSearch was significantly associated with reduced DRFS in both all (n = 380; P = 0.0067) and HR-positive patients (n = 328; P = 0.0002). DTC status, by itself, was not prognostic; however, when combined with CTC status by IE/FC (n = 273), double positivity (CTC+/DTC+, 8%) was significantly associated with reduced DRFS (P = 0.0270), BCSS (P = 0.0205), and OS (P = 0.0168). In HR-positive patients, double positivity (9% of 235) was significantly associated with reduced DRFS (P = 0.0285), BCSS (P = 0.0357), and OS (P = 0.0092). CONCLUSIONS: Detection of CTCs in patients with HR-positive early breast cancer was an independent prognostic factor for DRFS (using CellSearch) and BCSS (using IE/FC). Simultaneous detection of DTCs provided additional prognostic power for outcome, including OS.

Erratum: Author Correction: Surgical Standards for Management of the Axilla in Breast Cancer Clinical Trials with Pathological Complete Response Endpoint.

[This corrects the article DOI: 10.1038/s41523-018-0074-6.].

Surgical Standards for Management of the Axilla in Breast Cancer Clinical Trials with Pathological Complete Response Endpoint.

Advances in the surgical management of the axilla in patients treated with neoadjuvant chemotherapy, especially those with node positive disease at diagnosis, have led to changes in practice and more judicious use of axillary lymph node dissection that may minimize morbidity from surgery. However, there is still significant confusion about how to optimally manage the axilla, resulting in variation among practices. From the viewpoint of drug development, assessment of response to neoadjuvant chemotherapy remains paramount and appropriate assessment of residual disease-the primary endpoint of many drug therapy trials in the neoadjuvant setting-is critical. Therefore decreasing the variability, especially in a multicenter clinical trial setting, and establishing a minimum standard to ensure consistency in clinical trial data, without mandating axillary lymph node dissection, for all patients is necessary. The key elements which include proper staging and identification of nodal involvement at diagnosis, and appropriately targeted management of the axilla at the time of surgical resection are presented. The following protocols have been adopted as standard procedure by the I-SPY2 trial for management of axilla in patients with node positive disease, and present a framework for prospective clinical trials and practice.

Complications After Total Skin-Sparing Mastectomy and Expander-Implant Reconstruction: Effects of Radiation Therapy on the Stages of Reconstruction.

BACKGROUND: Many patients undergoing total-skin sparing mastectomy (TSSM) and 2-staged expander-implant (TE-I) reconstruction require postmastectomy radiation therapy (PMRT). Additionally, many patients undergoing TSSM for recurrent cancer have a history of lumpectomy and radiation therapy (XRT). Few studies have looked at the impact of XRT on the stages of TE-I reconstruction. METHODS: Patients undergoing TSSM and immediate TE-I reconstruction between 2006 and 2013 were identified from a prospectively maintained database. Rates of TE-I loss and severe infection requiring intravenous antibiotics were compared in patients with prior XRT (85 cases) and PMRT (133 cases). Complications were divided by stage of reconstruction: first stage (TSSM and TE placement) and second stage (TE-I exchange). RESULTS: Mean follow-up time was 2.5 years. Patients with prior XRT had more complications after the first stage of reconstruction than the second (TE-I loss: 15% vs 5%, P = 0.03; infection: 20% vs 8%, P = 0.04). Patients receiving PMRT had low complication rates after the first stage, when they had not yet received radiation (TE-I loss: 2%; infection: 5%). However, complication rates after TE-I exchange (TE-I loss, 18%; infection, 31%) were significantly higher, and nearly 4-fold higher than patients with prior XRT. CONCLUSIONS: Patients with prior XRT are at high risk for complications after the first stage of TE-I reconstruction after TSSM; however, the risk of complications at the second stage is comparable to patients without radiation exposure and significantly lower than patients receiving PMRT. Patients receiving radiation therapy should be given appropriate preoperative counseling regarding their risks.

Tissue Expander Reconstruction After Total Skin-Sparing Mastectomy: Defining the Effects of Coverage Technique on Nipple/Areola Preservation.

BACKGROUND: Total skin-sparing mastectomy (TSSM) has become increasingly frequent in recent years, as inclusion criteria continue to expand. Options for tissue expander coverage in these patients include complete submuscular tissue expander coverage and acellular dermal matrix (ADM)-assisted coverage. This study compares both techniques with regard to relevant outcomes, during a recent 1-year period at our institution. METHODS: All women undergoing TSSM and immediate expander placement between January 2012 and January 2013 were prospectively tracked. Patient demographics, expander coverage type, adjuvant treatment, length and characteristics of expansion, and incidence of complications were analyzed. RESULTS: In 1 year, 127 patients underwent TSSM on 202 breasts. Overall, 113 expanders underwent submuscular coverage, and 89 underwent ADM-assisted coverage. Mean intraoperative fill volume was 52 mL in the submuscular cohort and 205 mL in the ADM cohort (P = 0.0001). Mean tissue expander size was 404 mL in the submuscular cohort and 454 mL in the ADM cohort (P = 0.0002). χ analysis demonstrated no differences between the cohorts in incidence of complications, including partial/complete nipple necrosis. CONCLUSIONS: The use of ADM for expander coverage after TSSM allowed for greater initial expander fill. With large and ptotic breasts, this allows for reduced incidence of skin folds in the preserved breast skin pocket, and greater control over final nipple position, as the amount of loose, mobile skin is reduced by the greater initial fill. The safety profile of ADM use after TSSM is equivalent to that of submuscular coverage, with no differences in partial or complete nipple necrosis.

Expanding the Indications for Total Skin-Sparing Mastectomy: Is It Safe for Patients with Locally Advanced Disease?

BACKGROUND: Indications for total skin-sparing mastectomy (TSSM) continue to expand. Although initially used only for early-stage breast cancer, TSSM currently is offered in many centers to patients with locally advanced disease. However, despite this practice change, limited data on oncologic outcomes in this population have been reported. METHODS: A retrospective review of a prospectively collected database of all patients undergoing TSSM and immediate reconstruction from 2005 to 2013 was performed. The outcomes for patients with stage 2b and stage 3 cancer were included in the analysis. The primary outcomes included the development of locoregional or distant recurrences. RESULTS: Of 753 patients undergoing TSSM, 139 (18 %) presented with locally advanced disease. Of these 139 patients, 25 (18 %) had stage 2b disease, and 114 (82 %) had stage 3 disease. Most of the patients (97 %) received chemotherapy (77 % neoadjuvant, 20 % adjuvant), whereas 3 % received adjuvant hormonal therapy alone. Of the neoadjuvant patients, 13 (12 %) had a pathologic complete response (pCR) to treatment. During a mean follow-up period of 41 months (range 4-111 months), seven patients (5 %) had a local recurrence, 21 patients (15.1 %) had a distant recurrence, and three patients (2.2 %) had simultaneous local and distant recurrences. None of the local recurrences occurred in the preserved nipple-areolar complex skin. CONCLUSIONS: Patients with locally advanced breast cancer are most at risk for distant rather than local recurrence, even after TSSM. When used in conjunction with appropriate multimodal therapy, TSSM is not associated with an increased risk for local recurrence in this population, even in the setting of low pCR rates.

Negative Genetic Testing Does Not Deter Contralateral Prophylactic Mastectomy in Younger Patients with Greater Family Histories of Breast Cancer.

BACKGROUND: Increasing rates of contralateral prophylactic mastectomy (CPM) correlate with adoption of total skin-sparing mastectomy (TSSM). We aimed to characterize patients with unilateral breast cancer who underwent TSSM with CPM or without CPM (No CPM). METHODS: We reviewed all patients with unilateral breast cancer who underwent TSSM from 2006 to 2013. Trends in CPM and genetic testing were evaluated across time. Patient characteristics and complications were compared between CPM and No CPM groups. RESULTS: We identified 591 patients (293 No CPM and 298 CPM) with median follow-up of 25 (interquartile range [IQR] 13-52) months. All patients with deleterious mutations and 58% of those who tested negative for mutations underwent CPM. In patients who tested negative for mutations, CPM was correlated with younger patient age, greater family history, and younger age of relatives diagnosed with breast/ovarian cancer. CPM was associated with an increased risk of superficial nipple necrosis (relative risk [RR] 2.1, 95% confidence interval [CI] 1.12-4.0), wound breakdown (RR 1.62, 95% CI 1.04-2.5), and infections requiring oral antibiotics (RR 1.59, 95% CI 1.16-2.2). In patients with tissue expander/implant reconstruction, CPM was associated with an increased risk of implant exposure (RR 1.95, 95% CI 1.03-3.7) but did not affect the risk of implant loss (RR 0.91, 95% CI 0.56-1.48). CONCLUSIONS: Patients who choose CPM fit the profile of patients with higher risk of contralateral breast cancer (CBC), which may be due to polygenic risk factors that are currently under investigation. Physicians should address patients' fears of CBC, screening concerns, and the risk of complications when considering CPM.

Tumor Involvement of the Nipple in Total Skin-Sparing Mastectomy: Strategies for Management.

BACKGROUND: Despite a growing body of literature on oncologic and reconstructive outcomes after total skin-sparing mastectomy (TSSM), some questions related to this approach remain unanswered, including strategies for managing tumor involvement of the nipple while maintaining the aesthetic benefits of TSSM. METHODS: A prospectively maintained database of patients undergoing TSSM and immediate breast reconstruction from 2005 to 2013 was reviewed. Outcomes included tumor involvement of resected nipple tissue and subsequent management, recurrences after nipple involvement, and trends in management of involved nipple tissue. RESULTS: The study included 1176 breasts in 751 patients treated with TSSM. The follow-up period was 31.3 months. The nipple-areolar complex (NAC) of 32 breasts (2.7 %) had a positive margin or involvement of nipple tissue. Of these breasts, 56 % contained invasive cancer, and 44 % had in situ disease. Management included repeat excision (11 cases, 34 % of cases), radiation of the NAC (as part of the postmastectomy breast field) without further excision (5 cases, 16 %), complete NAC removal (8 cases, 25 %), and no further treatment (8 cases, 25 %). Management by complete NAC skin excision significantly decreased during the study period (p = 0.003). The overall local recurrence rate was 6.2 %. No patients had recurrence in the preserved NAC skin. CONCLUSIONS: Despite expanding indications for TSSM, it can be performed safely with low rates of nipple involvement. Over time, tumor involvement of the nipple has been treated with re-excision or other alternative approaches to NAC removal that preserve the aesthetic benefits of total skin-sparing approaches without an early adverse impact on local recurrence.

Immediate implant-based breast reconstruction following total skin-sparing mastectomy: defining the risk of preoperative and postoperative radiation therapy for surgical outcomes.

BACKGROUND: Radiation therapy is increasingly used in breast cancer therapy. With total skin-sparing mastectomy and nipple/areola complex preservation, defining the risks of various treatment regimens for morbidity is important, in the setting of immediate prosthetic reconstruction. The authors assessed the effects of premastectomy and postmastectomy radiation therapy on outcomes in total skin-sparing mastectomy and immediate prosthetic reconstruction. METHODS: All patients undergoing total skin-sparing mastectomy and immediate prosthetic reconstruction at the authors' institution between 2006 and 2012 were identified. Cohort 1 included patients undergoing total skin-sparing mastectomy and reconstruction with no radiation. Cohort 2 included patients with a prior history of radiation before total skin-sparing mastectomy and reconstruction. Cohort 3 included patients undergoing radiation after total skin-sparing mastectomy and reconstruction. RESULTS: A total of 580 patients underwent 903 breast reconstructions following total skin-sparing mastectomy. Cohort 1 included 727 breasts, cohort 2 included 63 breasts, and cohort 3 included 113 breasts. Any radiation delivery caused an increased rate of infection requiring antibiotics (21.6 percent, p = 0.00) and an increased risk of expander/implant loss (18.75 percent, p = 0.00). Cohort 2 had a higher risk of wound breakdown (p = 0.012). All cohorts showed similar low rates of nipple/areola necrosis. CONCLUSIONS: Both preoperative and postoperative radiation following total skin-sparing mastectomy and immediate prosthetic reconstruction result in higher, but acceptable, complication risks. Complications related to nipple/areola preservation are similar to those in nonradiated patients and in those undergoing skin-sparing mastectomy. Thus, nipple/areola complex preservation is safe in women undergoing radiation therapy. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Local recurrence rates are low in high-risk neoadjuvant breast cancer in the I-SPY 1 Trial (CALGB 150007/150012; ACRIN 6657).

BACKGROUND: Increasingly, women with stage 2 and 3 breast cancers receive neoadjuvant therapy, after which many are eligible for breast-conserving surgery (BCS). The question often arises as to whether BCS, if achievable, provides adequate local control. We report the results of local recurrence (LR) from the I-SPY 1 Trial in the setting of maximal multidisciplinary treatment where approximately 50 % of patients were treated with BCS. METHODS: We analyzed data from the I-SPY 1 Trial. Women with tumors ≥3 cm from nine clinical breast centers received neoadjuvant doxorubicin, cyclophosphamide and paclitaxel followed by definitive surgical therapy, and radiation at physician discretion. LR following mastectomy and BCS were analyzed in relation to clinical characteristics and response to therapy as measured by residual cancer burden. RESULTS: Of the 237 patients enrolled in the I-SPY 1 Trial, 206 were available for analysis. Median tumor size was 6.0 cm, and median follow-up was 3.9 years. Fourteen patients (7 %) had LR and 45 (22 %) had distant recurrence (DR). Of the 14 patients with LR, nine had synchronous DR; one had DR > 2 years later. Only four (2 % of evaluable patients) had LR alone. The rate of LR was low after mastectomy and after BCS, even in the setting of significant residual disease. CONCLUSIONS: Overall, these patients at high risk for early recurrence, treated with maximal multidisciplinary treatment, had low LR. Recurrence was associated with aggressive biological features such as more advanced stage at presentation, where LR occurs most frequently in the setting of DR.

Immediate implant-based breast reconstruction following total skin-sparing mastectomy in women with a history of augmentation mammaplasty: assessing the safety profile.

BACKGROUND: Preservation of the nipple-areolar complex with total skin-sparing mastectomy is becoming a popular mastectomy technique. As experience increases, the patient inclusion criteria for total skin sparing mastectomy expand. The authors assessed outcomes of total skin-sparing mastectomy and immediate prosthetic reconstruction in women with a prior history of augmentation mammaplasty. METHODS: Between 2005 and 2012, all women with a history of augmentation mammaplasty and implants in place, undergoing total skin-sparing mastectomy and immediate prosthetic reconstruction, were prospectively tracked. Patient demographics, expander coverage type, adjuvant treatment, and incidence of complications were analyzed. Outcomes in these patients were compared with those of patients undergoing the same operation, without prior augmentation history. RESULTS: Thirty-four women with prior augmentation underwent total skin-sparing mastectomy and immediate tissue expander placement on 51 breasts. Comparison to the nonaugmentation group showed similar rates of superficial nipple necrosis (0 percent, p=0.324), complete nipple necrosis (0 percent, p=0.324), and skin flap necrosis (4 percent, p=1.0). The prior augmentation group did have a higher rate of implant loss (10 percent, p=0.515), with all but one of these occurring in irradiated patients. CONCLUSIONS: Total skin-sparing mastectomy and immediate prosthetic reconstruction is a safe technique in women with a history of augmentation mammaplasty. The preferred reconstructive technique is immediate submuscular tissue expander placement. In the setting of no radiation history, this operation carries a safety profile similar to that of patients without a history of prior augmentation, and can be offered safely. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

Total skin-sparing mastectomy in BRCA mutation carriers.

BACKGROUND: Total skin-sparing mastectomy (TSSM) with preservation of the nipple-areolar complex skin has become increasingly accepted as an oncologically safe procedure. Oncologic outcomes after TSSM in BRCA mutation carriers have not been well-studied. METHODS: We identified 53 BRCA-positive patients who underwent bilateral TSSM for prophylactic (26 patients) or therapeutic indications (27 patients) from 2001 to 2011. Cases were age-matched (for prophylactic cases) or age- and stage-matched (for therapeutic cases) with non-BRCA-positive patients. Outcomes included tumor involvement of resected nipple tissue, the development of new breast cancers in patients who underwent risk-reducing TSSM, and local-regional recurrence in patients who underwent therapeutic TSSM. RESULTS: Outcomes from 212 TSSM procedures in 53 cases and 53 controls were analyzed. In patients undergoing TSSM for prophylactic indications, in situ cancer was found in one (1.9 %) nipple specimen in BRCA-positive patients versus two specimens (3.8 %) in the non-BRCA-positive cohort (p = 1). At a mean follow-up of 51 months, no new cancers developed in either cohort. In patients undergoing TSSM for therapeutic indications, in situ or invasive cancer was found in zero of the nipple specimens in BRCA-positive patients versus two specimens (3.7 %) in the non-BRCA-positive cohort (p = 0.49). At a mean follow-up of 37 months, there were no local-regional recurrences in the BRCA-positive cohort and 1 (3.7 %) in the non-BRCA-positive cohort. CONCLUSIONS: TSSM is an oncologically safe procedure in BRCA-positive patients. In patients undergoing TSSM as a risk-reducing strategy, 4-year follow-up demonstrates no increased risk of developing new breast cancers; longer-term follow-up is ongoing.

The effects of acellular dermal matrix in expander-implant breast reconstruction after total skin-sparing mastectomy: results of a prospective practice improvement study.

BACKGROUND: Neither outcome after total skin-sparing mastectomy and expander-implant reconstruction using acellular dermal matrix nor a strategy for optimal acellular dermal matrix selection criteria has been well described. METHODS: Prospective review of three patient cohorts undergoing total skin-sparing mastectomy with preservation of the nipple-areola complex and immediate expander-implant reconstruction from 2006 to 2010 was performed. Cohort 1 (no acellular dermal matrix) comprised 90 cases in which acellular dermal matrix was not used. Cohort 2 (consecutive acellular dermal matrix) included the next 100 consecutive cases, which all received acellular dermal matrix. Cohort 3 (selective acellular dermal matrix) consisted of the next 260 cases, in which acellular dermal matrix was selectively used based on mastectomy skin flap thickness. Complication rates were compared using chi-square analysis. RESULTS: The study included 450 cases in 288 patients. Mean follow-up was 25.5 months. Infection occurred in 27.8 percent of the no-acellular dermal matrix cases, 20 percent of the consecutive cases, and 15.8 percent of the selective cases (p = 0.04). Unplanned return to the operating room was required in 23.3, 11, and 10 percent of cases, respectively (p = 0.004). Expander-implant loss occurred in 17.8, 7, and 5 percent of cases, respectively (p = 0.001). Additional analysis of the odds ratios of developing complications after postmastectomy radiation therapy demonstrated a specific protective benefit of acellular dermal matrix in irradiated patients. CONCLUSIONS: Acellular dermal matrix use in expander-implant reconstruction after total skin-sparing mastectomy reduced major postoperative complications in this study. Maximal benefit is achieved with selected use in patients with thin mastectomy skin flaps and those receiving radiation therapy. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Outcomes after total skin-sparing mastectomy and immediate reconstruction in 657 breasts.

BACKGROUND: Total skin-sparing mastectomy (TSSM), a technique comprising removal of all breast and nipple tissue while preserving the entire skin envelope, is increasingly offered to women for therapeutic and prophylactic indications. However, standard use of the procedure remains controversial as a result oft concerns regarding oncologic safety and risk of complications. METHODS: Outcomes from a prospectively maintained database of patients undergoing TSSM and immediate breast reconstruction from 2001 to 2010 were reviewed. Outcome measures included postoperative complications, tumor involvement of the nipple-areolar complex (NAC) on pathologic analysis, and cancer recurrence. RESULTS: TSSM was performed on 657 breasts in 428 patients. Indications included in situ cancer [111 breasts (16.9%)], invasive cancer [301 breasts (45.8%)], and prophylactic risk-reduction [245 breasts (37.3%)]. A total of 210 patients (49%) had neoadjuvant chemotherapy, 78 (18.2%) had adjuvant chemotherapy, and 114 (26.7%) had postmastectomy radiotherapy. Nipple tissue contained in situ cancer in 11 breasts (1.7%) and invasive cancer in 9 breasts (1.4%); management included repeat excision (7 cases), NAC removal (9 cases), or radiotherapy without further excision (4 cases). Ischemic complications included 13 cases (2%) of partial nipple loss, 10 cases (1.5%) of complete nipple loss, and 78 cases (11.9%) of skin flap necrosis. Overall locoregional recurrence rate was 2% (median follow-up 28 months), with a 2.4% rate observed in the subset of patients with at least 3 years' follow-up (median 45 months). No NAC skin recurrences were observed. CONCLUSIONS: In this large, high-risk cohort, TSSM was associated with low rates of NAC complications, nipple involvement, and locoregional recurrence.

Evaluating the feasibility of extended partial mastectomy and immediate reduction mammoplasty reconstruction as an alternative to mastectomy.

OBJECTIVES: To assess the efficacy of using concurrent partial mastectomy and reduction mammoplasty for resection of a wide range of tumor sizes and compare oncologic outcomes and postoperative complications on the basis of tumor size. BACKGROUND: Although tumor size greater than 4 cm has been considered an indication for undergoing a mastectomy, this dictum may not apply in women with breast hypertrophy, where the ratio of tumor size to breast size may still permit breast conservation. We wished to evaluate whether an approach combining partial mastectomy with reduction mammoplasty could provide a safe oncologic procedure with immediate breast reconstruction that could technically be applied even for large (>4 cm) lesions. METHODS: A retrospective review of all patients undergoing partial mastectomy and concurrent reduction mammoplasty performed at our institution from 2000 to 2009. Clinical characteristics at presentation, pathologic data, and follow-up data were collected and analyzed. RESULTS: Eighty-five consecutive simultaneous partial mastectomy/reduction mammoplasty procedures were performed in 79 patients. Average tumor size was 2.8 cm for ductal carcinoma in situ (0.05-17.0 cm), 2.4 cm for invasive ductal carcinoma (IDC) (0.2-8.9 cm), 3.5 cm for lobular carcinoma (1.6-8.0 cm), and 5.7 cm for phyllodes tumors (3.7-7.6 cm). Twenty-five of 85 tumors (29.4%) were larger than 4 cm. Distribution for stage 0, I, II, III, and IV disease was 15, 12, 35, 19, and 2 tumors respectively, with an additional 2 phyllodes tumors. Median follow-up was 39 months (10-130 months). Seventy-five patients (94.9%) achieved successful breast conservation, whereas 4 patients (5.1%) went on to completion mastectomy. Thirteen patients (16.4%) required 1 reexcision to achieve clear margins, and 2 (2.5%) required multiple reexcisions. Two patients had a local recurrence during the follow-up period, one of whom underwent reexcision and the other underwent mastectomy. The overall complication rate was 14.1%, which included 4 major complications (4.7%) requiring an unplanned return to the operating room and need for hospital readmission, and 8 minor wound-related complications (9.4%). Neither recurrence nor complication rates were increased in patients with tumors greater than 4 cm when compared with tumors less than or equal to 4 cm. CONCLUSIONS: A partial mastectomy with concurrent reduction mammoplasty technique is a viable option for breast conservation even for larger tumors, combining a safe oncologic procedure with excellent cosmesis. A combined effort between breast surgeons and reconstructive surgeons has a high probability of success with low recurrence rates. In carefully selected patients, this approach may be preferable to mastecomy and breast reconstruction, particularly when postmastectomy radiation therapy is anticipated.