Local-Regional Recurrence After Neoadjuvant Endocrine Therapy: Data from ACOSOG Z1031 (Alliance), a Randomized Phase 2 Neoadjuvant Comparison Between Letrozole, Anastrozole, and Exemestane for Postmenopausal Women with Estrogen Receptor-Positive Clinical Stage 2 or 3 Breast Cancer.

BACKGROUND: The ACOSOG Z1031 trial addressed the ability of three neoadjuvant aromatase inhibitors (NAIs) to reduce residual disease (cohort A) and to assess whether switching to neoadjuvant chemotherapy (NCT) after 4 weeks of receiving NAI with Ki67 greater than 10% increases pathologic complete response (pCR) in postmenopausal women with estrogen receptor-enriched (Allred score 6-8) breast cancer (BC). METHODS: The study enrolled 622 women with clinical stage 2 or 3 estrogen receptor-positive (ER+) BC. Cohort A comprised 377 patients, and cohort B had 245 patients. The analysis cohort consisted of 509 patients after exclusion of patients who did not meet the trial eligibility criteria, switched to NCT or surgery due to 4-week Ki67 greater than 10%, or withdrew before surgery. Distribution of time to local-regional recurrence (LRR) was estimated using the competing-risk approach, in which distant recurrence and second primaries were considered to be competing-risk events. Patients who died without LRR, distant recurrence, or a second primary were censored at the last evaluation. RESULTS: Of the 509 patients, 342 (67.2%) had breast-conserving surgery (BCS). Of 221 patients thought to require mastectomy at presentation, 50% were able to have BCS. Five (1%) patients had no residual disease in the breast or nodes at surgery. Among 382 women alive at this writing, 90% have been followed longer than 5 years. The 5-year cumulative incidence rate for LRR is estimated to be 1.53% (95% confidence interval 0.7-3.0%). CONCLUSIONS: Rarely does NAI result in pCR for patients with stage 2 or 3 ER+ BC. However, a significant proportion will have downstaged to allow for BCS. Local-regional recurrence after surgery is uncommon (1.5% at 5 years), supporting the use of BCS after NAI.

NCCN Guidelines® Insights: Breast Cancer, Version 4.2023.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Breast Cancer address all aspects of management for breast cancer. The treatment landscape of metastatic breast cancer is evolving constantly. The therapeutic strategy takes into consideration tumor biology, biomarkers, and other clinical factors. Due to the growing number of treatment options, if one option fails, there is usually another line of therapy available, providing meaningful improvements in survival. This NCCN Guidelines Insights report focuses on recent updates specific to systemic therapy recommendations for patients with stage IV (M1) disease.

Oxidative stress inhibits distant metastasis by human melanoma cells.

Solid cancer cells commonly enter the blood and disseminate systemically, but are highly inefficient at forming distant metastases for poorly understood reasons. Here we studied human melanomas that differed in their metastasis histories in patients and in their capacity to metastasize in NOD-SCID-Il2rg(-/-) (NSG) mice. We show that melanomas had high frequencies of cells that formed subcutaneous tumours, but much lower percentages of cells that formed tumours after intravenous or intrasplenic transplantation, particularly among inefficiently metastasizing melanomas. Melanoma cells in the blood and visceral organs experienced oxidative stress not observed in established subcutaneous tumours. Successfully metastasizing melanomas underwent reversible metabolic changes during metastasis that increased their capacity to withstand oxidative stress, including increased dependence on NADPH-generating enzymes in the folate pathway. Antioxidants promoted distant metastasis in NSG mice. Folate pathway inhibition using low-dose methotrexate, ALDH1L2 knockdown, or MTHFD1 knockdown inhibited distant metastasis without significantly affecting the growth of subcutaneous tumours in the same mice. Oxidative stress thus limits distant metastasis by melanoma cells in vivo.

Differences in Re-excision Rates for Breast-Conserving Surgery Using Intraoperative 2D Versus 3D Tomosynthesis Specimen Radiograph.

BACKGROUND: Intraoperative specimen radiographs performed during breast conservation surgery for cancer reduces the need for re-excision for positive margins. We studied 2D versus 3D image-guided cavity margin excision and compared it to final pathology and need for additional surgery. METHODS: We conducted a retrospective review of 657 breast-conserving operations performed for cancer from 2013 to 2018. Procedures were performed by four surgeons at a single tertiary institution with access intraoperatively to 2D and 3D radiographs. Data collected included demographics, intraoperative margin assessment, final pathology, and re-excision rates. RESULTS: A total of 466 patients had 2D and 191 had 3D specimen imaging. The 2D group had a lower mean age and a higher body mass index and proportion of minority patients than the 3D group (P < 0.01). In the 3D group, there was a higher percentage of patients with mammographically denser breasts (P < 0.06); 58% of patients in the 3D group had additional imaging-directed cavity margins excised versus 32% of patients in the 2D group (P < 0.01). In the 2D group, 44 patients (9%) had positive final margins versus 8 patients (4%) in the 3D group (P = 0.02). No difference was found on total volume of excision (P = 0.56). The re-excision rate for the 2D group was 11% versus 5% for the 3D group (P = 0.02; adjusted odds ratio = 0.41, 95% confidence interval 0.19-0.86). CONCLUSIONS: Re-excision rates using both modalities are low. A lower re-excision rate is independently associated with 3D tomosynthesis. This allows surgeons to excise additional margins at the index operation, decreasing reoperations and anxiety/costs for patients.

Effect of Axillary Dissection vs No Axillary Dissection on 10-Year Overall Survival Among Women With Invasive Breast Cancer and Sentinel Node Metastasis: The ACOSOG Z0011 (Alliance) Randomized Clinical Trial.

Importance: The results of the American College of Surgeons Oncology Group Z0011 (ACOSOG Z0011) trial were first reported in 2005 with a median follow-up of 6.3 years. Longer follow-up was necessary because the majority of the patients had estrogen receptor-positive tumors that may recur later in the disease course (the ACOSOG is now part of the Alliance for Clinical Trials in Oncology). Objective: To determine whether the 10-year overall survival of patients with sentinel lymph node metastases treated with breast-conserving therapy and sentinel lymph node dissection (SLND) alone without axillary lymph node dissection (ALND) is noninferior to that of women treated with axillary dissection. Design, Setting, and Participants: The ACOSOG Z0011 phase 3 randomized clinical trial enrolled patients from May 1999 to December 2004 at 115 sites (both academic and community medical centers). The last date of follow-up was September 29, 2015, in the ACOSOG Z0011 (Alliance) trial. Eligible patients were women with clinical T1 or T2 invasive breast cancer, no palpable axillary adenopathy, and 1 or 2 sentinel lymph nodes containing metastases. Interventions: All patients had planned lumpectomy, planned tangential whole-breast irradiation, and adjuvant systemic therapy. Third-field radiation was prohibited. Main Outcomes and Measures: The primary outcome was overall survival with a noninferiority hazard ratio (HR) margin of 1.3. The secondary outcome was disease-free survival. Results: Among 891 women who were randomized (median age, 55 years), 856 (96%) completed the trial (446 in the SLND alone group and 445 in the ALND group). At a median follow-up of 9.3 years (interquartile range, 6.93-10.34 years), the 10-year overall survival was 86.3% in the SLND alone group and 83.6% in the ALND group (HR, 0.85 [1-sided 95% CI, 0-1.16]; noninferiority P = .02). The 10-year disease-free survival was 80.2% in the SLND alone group and 78.2% in the ALND group (HR, 0.85 [95% CI, 0.62-1.17]; P = .32). Between year 5 and year 10, 1 regional recurrence was seen in the SLND alone group vs none in the ALND group. Ten-year regional recurrence did not differ significantly between the 2 groups. Conclusions and Relevance: Among women with T1 or T2 invasive primary breast cancer, no palpable axillary adenopathy, and 1 or 2 sentinel lymph nodes containing metastases, 10-year overall survival for patients treated with sentinel lymph node dissection alone was noninferior to overall survival for those treated with axillary lymph node dissection. These findings do not support routine use of axillary lymph node dissection in this patient population based on 10-year outcomes. Trial Registration: clinicaltrials.gov Identifier: NCT00003855.

Locoregional Recurrence After Sentinel Lymph Node Dissection With or Without Axillary Dissection in Patients With Sentinel Lymph Node Metastases: Long-term Follow-up From the American College of Surgeons Oncology Group (Alliance) ACOSOG Z0011 Randomized Trial.

BACKGROUND AND OBJECTIVE: The early results of the American College of Surgeons Oncology Group (ACOSOG) Z0011 trial demonstrated no difference in locoregional recurrence for patients with positive sentinel lymph nodes (SLNs) randomized either to axillary lymph node dissection (ALND) or sentinel lymph node dissection (SLND) alone. We now report long-term locoregional recurrence results. METHODS: ACOSOG Z0011 prospectively examined overall survival of patients with SLN metastases undergoing breast-conserving therapy randomized to undergo ALND after SLND or no further axillary specific treatment. Locoregional recurrence was prospectively evaluated and compared between the groups. RESULTS: Four hundred forty-six patients were randomized to SLND alone and 445 to SLND and ALND. Both groups were similar with respect to age, Bloom-Richardson score, Estrogen Receptor status, adjuvant systemic therapy, histology, and tumor size. Patients randomized to ALND had a median of 17 axillary nodes removed compared with a median of only 2 SLNs removed with SLND alone (P < 0.001). ALND, as expected, also removed more positive lymph nodes (P < 0.001). At a median follow-up of 9.25 years, there was no statistically significant difference in local recurrence-free survival (P = 0.13). The cumulative incidence of nodal recurrences at 10 years was 0.5% in the ALND arm and 1.5% in the SLND alone arm (P = 0.28). Ten-year cumulative locoregional recurrence was 6.2% with ALND and 5.3% with SLND alone (P = 0.36). CONCLUSION: Despite the potential for residual axillary disease after SLND, SLND without ALND offers excellent regional control for selected patients with early metastatic breast cancer treated with breast-conserving therapy and adjuvant systemic therapy.

Factors affecting sentinel lymph node identification rate after neoadjuvant chemotherapy for breast cancer patients enrolled in ACOSOG Z1071 (Alliance).

OBJECTIVE: To evaluate factors affecting sentinel lymph node (SLN) identification after neoadjuvant chemotherapy (NAC) in patients with initial node-positive breast cancer. BACKGROUND: SLN surgery is increasingly used for nodal staging after NAC and optimal technique for SLN identification is important. METHODS: The American College of Surgeons Oncology Group Z1071 prospective trial enrolled clinical T0-4, N1-2, M0 breast cancer patients. After NAC, SLN surgery and axillary lymph node dissection (ALND) were planned. Multivariate logistic regression modeling assessing factors influencing SLN identification was performed. RESULTS: Of 756 patients enrolled, 34 women withdrew, 21 were ineligible, 12 underwent ALND only, and 689 had SLN surgery attempted. At least 1 SLN was identified in 639 patients (92.7%: 95% CI: 90.5%-94.6%). Among factors evaluated, mapping technique was the only factor found to impact SLN identification; with use of blue dye alone increasing the likelihood of failure to identify the SLN relative to using radiolabeled colloid +/- blue dye (P = 0.006; OR = 3.82; 95% CI: 1.47-9.92). The SLN identification rate was 78.6% with blue dye alone; 91.4% with radiolabeled colloid and 93.8% with dual mapping agents. Patient factors (age, body mass index), tumor factors (clinical T or N stage), pathologic nodal response to chemotherapy, site of tracer injection, and length of chemotherapy treatment did not significantly affect the SLN identification rate. CONCLUSIONS: The SLN identification rate after NAC was higher when mapping was performed using radiolabeled colloid alone or with blue dye compared with blue dye alone. Optimal tracer use is important to ensure successful identification of SLN(s) after NAC.

Tumor biology correlates with rates of breast-conserving surgery and pathologic complete response after neoadjuvant chemotherapy for breast cancer: findings from the ACOSOG Z1071 (Alliance) Prospective Multicenter Clinical Trial.

OBJECTIVE: To determine the impact of tumor biology on rates of breast-conserving surgery and pathologic complete response (pCR) after neoadjuvant chemotherapy. BACKGROUND: The impact of tumor biology on the rate of breast-conserving surgery after neoadjuvant chemotherapy has not been well studied. METHODS: We used data from ACOSOG Z1071, a prospective, multicenter study assessing sentinel lymph node surgery after neoadjuvant chemotherapy in patients presenting with node-positive breast cancer from 2009 through 2011, to determine rates of breast-conserving surgery and pCR after chemotherapy by approximated biologic subtype. RESULTS: Of the 756 patients enrolled on Z1071, 694 had findings available from pathologic review of breast and axillary specimens from surgery after chemotherapy. Approximated subtype was triple-negative in 170 (24.5%), human epidermal growth factor receptor 2 (HER2)-positive in 207 (29.8%), and hormone-receptor-positive, HER2-negative in 317 (45.7%) patients. Patient age, clinical tumor and nodal stage at presentation did not differ across subtypes. Rates of breast-conserving surgery were significantly higher in patients with triple-negative (46.8%) and HER2-positive tumors (43.0%) than in those with hormone-receptor-positive, HER2-negative tumors (34.5%) (P = 0.019). Rates of pCR in both the breast and axilla were 38.2% in triple-negative, 45.4% in HER2-positive, and 11.4% in hormone-receptor-positive, HER2-negative disease (P < 0.0001). Rates of pCR in the breast only and the axilla only exhibited similar differences across tumor subtypes. CONCLUSIONS: Patients with triple-negative and HER2-positive breast cancers have the highest rates of breast-conserving surgery and pCR after neoadjuvant chemotherapy. Patients with these subtypes are most likely to be candidates for less invasive surgical approaches after chemotherapy.

Fluorouracil, epirubicin, and cyclophosphamide (FEC-75) followed by paclitaxel plus trastuzumab versus paclitaxel plus trastuzumab followed by FEC-75 plus trastuzumab as neoadjuvant treatment for patients with HER2-positive breast cancer (Z1041): a randomised, controlled, phase 3 trial.

BACKGROUND: Neoadjuvant chemotherapy with trastuzumab for patients with HER2-positive breast cancer can produce a pathological complete response in the breast in 30-65% of patients. We investigated the effect of the timing of trastuzumab administration with anthracycline and taxane neoadjuvant chemotherapy. METHODS: This randomised trial was done at 36 centres in the USA and Puerto Rico. Women with operable HER2-positive invasive breast cancer were randomly assigned (1:1) with a biased coin minimisation algorithm, stratified for age, tumour size, and hormone receptor status. Neither patients nor investigators (except for a cardiac safety review panel) were masked to treatment assignment. Patients randomly assigned to sequential treatment received fluorouracil 500 mg/m(2), epirubicin 75 mg/m(2), and cyclophosphamide 500 mg/m(2) (FEC-75) on day 1 of a 21-day cycle for four cycles followed by paclitaxel 80 mg/m(2) and trastuzumab 2 mg/kg (after a 4 mg/kg loading dose) once per week for 12 weeks, while those randomly assigned to the concurrent treatment group received paclitaxel and trastuzumab once per week for 12 weeks followed by four cycles of FEC-75 (on day 1 of each 21-day cycle) and once-weekly trastuzumab, in the same doses as the sequential group. Surgery, including evaluation of the axilla, was done within 6 weeks of completion of neoadjuvant treatment. The primary outcome was the percentage of patients who had a pathological complete response in the intention-to-treat population. The study is registered with ClinicalTrials.gov, number NCT00513292. FINDINGS: From Sept 15, 2007, to Dec 15, 2011, 282 women were enrolled (140 in the sequential group, 142 in the concurrent group). Two patients in the sequential group withdrew consent before starting treatment. 78 of 138 (56·5%, 95% CI 47·8-64·9) patients who received sequential treatment had a pathological complete response in the breast versus 77 of 142 (54·2%, 95% CI 45·7-62·6) who received concurrent treatment (difference 2·3%, 95% CI -9·3 to 13·9). No treatment-related deaths occurred. The most common severe toxic effects were neutropenia (35 [25·3%] of 138 patients in the sequential group vs 45 [31·7%] of 142 patients in the concurrent group) and fatigue (six [4·3%] vs 12 [8·5%]). Left ventricular ejection fraction dropped below the institutional lower limit of normal at week 12 in one (0·8%) of 130 patients who received sequential treatment and four (2·9%) of 137 patients who received concurrent treatment; by week 24, it had dropped below this limit in nine (7·1%) of 126 patients and in six (4·6%) of 130 patients, respectively. INTERPRETATION: Concurrent administration of trastuzumab with anthracyclines offers no additional benefit and is not warranted. FUNDING: US National Cancer Institute.

Endocrine-Sensitive Disease Rate in Postmenopausal Patients With Estrogen Receptor-Rich/ERBB2-Negative Breast Cancer Receiving Neoadjuvant Anastrozole, Fulvestrant, or Their Combination: A Phase 3 Randomized Clinical Trial.

Importance: Adding fulvestrant to anastrozole (A+F) improved survival in postmenopausal women with advanced estrogen receptor (ER)-positive/ERBB2 (formerly HER2)-negative breast cancer. However, the combination has not been tested in early-stage disease. Objective: To determine whether neoadjuvant fulvestrant or A+F increases the rate of pathologic complete response or ypT1-2N0/N1mic/Ki67 2.7% or less residual disease (referred to as endocrine-sensitive disease) over anastrozole alone. Design, Setting, and Participants: A phase 3 randomized clinical trial assessing differences in clinical and correlative outcomes between each of the fulvestrant-containing arms and the anastrozole arm. Postmenopausal women with clinical stage II to III, ER-rich (Allred score 6-8 or >66%)/ERBB2-negative breast cancer were included. All analyses were based on data frozen on March 2, 2023. Interventions: Patients received anastrozole, fulvestrant, or a combination for 6 months preoperatively. Tumor Ki67 was assessed at week 4 and optionally at week 12, and if greater than 10% at either time point, the patient switched to neoadjuvant chemotherapy or immediate surgery. Main Outcomes and Measures: The primary outcome was the endocrine-sensitive disease rate (ESDR). A secondary outcome was the percentage change in Ki67 after 4 weeks of neoadjuvant endocrine therapy (NET) (week 4 Ki67 suppression). Results: Between February 2014 and November 2018, 1362 female patients (mean [SD] age, 65.0 [8.2] years) were enrolled. Among the 1298 evaluable patients, ESDRs were 18.7% (95% CI, 15.1%-22.7%), 22.8% (95% CI, 18.9%-27.1%), and 20.5% (95% CI, 16.8%-24.6%) with anastrozole, fulvestrant, and A+F, respectively. Compared to anastrozole, neither fulvestrant-containing regimen significantly improved ESDR or week 4 Ki67 suppression. The rate of week 4 or week 12 Ki67 greater than 10% was 25.1%, 24.2%, and 15.7% with anastrozole, fulvestrant, and A+F, respectively. Pathologic complete response/residual cancer burden class I occurred in 8 of 167 patients and 17 of 167 patients, respectively (15.0%; 95% CI, 9.9%-21.3%), after switching to neoadjuvant chemotherapy due to week 4 or week 12 Ki67 greater than 10%. PAM50 subtyping derived from RNA sequencing of baseline biopsies available for 753 patients (58%) identified 394 luminal A, 304 luminal B, and 55 nonluminal tumors. A+F led to a greater week 4 Ki67 suppression than anastrozole alone in luminal B tumors (median [IQR], -90.4% [-95.2 to -81.9%] vs -76.7% [-89.0 to -55.6%]; P < .001), but not luminal A tumors. Thirty-six nonluminal tumors (65.5%) had a week 4 or week 12 Ki67 greater than 10%. Conclusions and Relevance: In this randomized clinical trial, neither fulvestrant nor A+F significantly improved the 6-month ESDR over anastrozole in ER-rich/ERBB2-negative breast cancer. Aromatase inhibition remains the standard-of-care NET. Differential NET response by PAM50 subtype in exploratory analyses warrants further investigation. Trial Registration: ClinicalTrials.gov Identifier: NCT01953588.

Management of locoregional and systemic recurrence of breast cancer: to stage or not to stage and how.

The surveillance of breast cancer patients after potentially curative treatment may result in the identification of locoregional or distant recurrence. While many patients expect frequent imaging studies to monitor for recurrence, there are no data supporting aggressive imaging surveillance beyond mammography. However, when recurrent disease is suspected, it is appropriate to undertake re-staging to develop a rational management plan. The rationale and methods for appropriate surveillance and re-staging are discussed.

Sentinel lymph node surgery after neoadjuvant chemotherapy in patients with node-positive breast cancer: the ACOSOG Z1071 (Alliance) clinical trial.

IMPORTANCE: Sentinel lymph node (SLN) surgery provides reliable nodal staging information with less morbidity than axillary lymph node dissection (ALND) for patients with clinically node-negative (cN0) breast cancer. The application of SLN surgery for staging the axilla following chemotherapy for women who initially had node-positive cN1 breast cancer is unclear because of high false-negative results reported in previous studies. OBJECTIVE: To determine the false-negative rate (FNR) for SLN surgery following chemotherapy in women initially presenting with biopsy-proven cN1 breast cancer. DESIGN, SETTING, AND PATIENTS: The American College of Surgeons Oncology Group (ACOSOG) Z1071 trial enrolled women from 136 institutions from July 2009 to June 2011 who had clinical T0 through T4, N1 through N2, M0 breast cancer and received neoadjuvant chemotherapy. Following chemotherapy, patients underwent both SLN surgery and ALND. Sentinel lymph node surgery using both blue dye (isosulfan blue or methylene blue) and a radiolabeled colloid mapping agent was encouraged. MAIN OUTCOMES AND MEASURES: The primary end point was the FNR of SLN surgery after chemotherapy in women who presented with cN1 disease. We evaluated the likelihood that the FNR in patients with 2 or more SLNs examined was greater than 10%, the rate expected for women undergoing SLN surgery who present with cN0 disease. RESULTS: Seven hundred fifty-six women were enrolled in the study. Of 663 evaluable patients with cN1 disease, 649 underwent chemotherapy followed by both SLN surgery and ALND. An SLN could not be identified in 46 patients (7.1%). Only 1 SLN was excised in 78 patients (12.0%). Of the remaining 525 patients with 2 or more SLNs removed, no cancer was identified in the axillary lymph nodes of 215 patients, yielding a pathological complete nodal response of 41.0% (95% CI, 36.7%-45.3%). In 39 patients, cancer was not identified in the SLNs but was found in lymph nodes obtained with ALND, resulting in an FNR of 12.6% (90% Bayesian credible interval, 9.85%-16.05%). CONCLUSIONS AND RELEVANCE: Among women with cN1 breast cancer receiving neoadjuvant chemotherapy who had 2 or more SLNs examined, the FNR was not found to be 10% or less. Given this FNR threshold, changes in approach and patient selection that result in greater sensitivity would be necessary to support the use of SLN surgery as an alternative to ALND. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00881361.

Factors associated with local-regional recurrence after a negative sentinel node dissection: results of the ACOSOG Z0010 trial.

OBJECTIVE: To determine factors important in local-regional recurrence (LRR) in patients with negative sentinel lymph nodes (SLNs) by hematoxylin and eosin (H&E) staining. BACKGROUND: Z0010 was a prospective multicenter trial initiated in 1999 by the American College of Surgeons Oncology Group to evaluate occult disease in SLNs and bone marrow of early-stage breast cancer patients. Participants included women with biopsy-proven T1-2 breast cancer with clinically negative nodes, planned for lumpectomy and whole breast irradiation. METHODS: Women with clinical T1-2,N0,M0 disease underwent lumpectomy and SLN dissection. There was no axillary-specific treatment for H&E-negative SLNs, and clinicians were blinded to immunohistochemistry results. Systemic therapy was based on primary tumor factors. Univariable and multivariable analyses were performed to determine clinicopathologic factors associated with LRR. RESULTS: Of 5119 patients, 3904 (76.3%) had H&E-negative SLNs. Median age was 57 years (range 23-95). At median follow-up of 8.4 years, there were 127 local, 20 regional, and 134 distant recurrences. Factors associated with local-regional recurrence were hormone receptor-negative disease (P = 0.0004) and younger age (P = 0.047). In competing risk-regression models, hormone receptor-positive disease and use of chemotherapy were associated with reduction in local-regional recurrence. When local recurrence was included in the model as a time-dependent variable, older age, T2 disease, high tumor grade, and local recurrence were associated with reduced overall survival. CONCLUSIONS: Local-regional recurrences are rare in early-stage breast cancer patients with H&E-negative SLNs. Younger age and hormone receptor-negative disease are associated with higher event rates, and local recurrence is associated with reduced overall survival.

Volume of excision and cosmesis with routine cavity shave margins technique.

BACKGROUND: Cavity shave margin (CSM) removal is a surgical technique that reduces re-excision rates. One criticism of this technique has been that negative margins are obtained primarily as a result of higher volumes of tissue removed. This study evaluates the volume of tissue removed in a group that underwent CSM versus one that underwent standard partial mastectomy (SPM) and explores cosmetic outcomes. METHODS: Single-institution retrospective review identified 533 patients with a diagnosis of breast cancer who underwent PM. Matched pair analysis of 72 patients who had undergone PM with CSM versus 72 who had undergone SPM was performed. Volumes were calculated from dimensions in the pathology report. A subgroup was analyzed by a multidisciplinary panel for cosmetic outcome using the Harvard Breast Cosmesis Grading Scale. RESULTS: Mean tumor size in the CSM group was 1.52 versus 1.51 cm(3) in the SPM (P = 0.8073). Mean total volume of tissue excised with CSM was lower than that in the SPM group. Mean volume of excision with CSM was 80.66 and 165.1 cm(3) in the SPM group (P = 0.0005). Patients undergoing CSM required fewer re-excisions than the SPM group: 13 (18.1%) versus 25 (34.6%) (P = 0.03). Mean score for cosmesis was 2.3 in the CSM group and 3.0 for SPM (P = 0.0004). CONCLUSIONS: CSM decreases the need for re-excision. Total tissue volume excised is lower in patients who undergo CSM, and cosmetic results appear to be improved. This approach should be considered for all patients undergoing PM.

Evaluation of a hydrogel based breast biopsy marker (HydroMARK®) as an alternative to wire and radioactive seed localization for non-palpable breast lesions.

BACKGROUND AND OBJECTIVES: HydroMARK® is a newly available biopsy marker for image-guided needle biopsies of non-palpable breast lesions. Objective was to determine if the marker could be utilized independently for lesion localization using intra-operative ultrasound alone. METHODS: A single institution retrospective review identified patients who underwent surgical excision of breast lesions after placement of the HydroMARK®. Endpoints included intra-operative visualization of the marker, successful excision of the lesion, and presence of the marker on specimen radiograph. RESULTS: The study included 31 lesions in 25 patients. Twenty-nine (93.6%) HydroMARKSs® were adequately visualized by intra-operative ultrasound. Intra-operative ultrasound without pre-operative placement of a localizing device was successful for localization in six cases (19.4%). Intra-operative difficulties were encountered in 16 of 31 (51.6%) procedures. This included either extrusion of the marker when the biopsy tract was transected in 14 (45.2%) cases or migration of the marker prior to the procedure in two (6.4%) cases. The marker was visualized on specimen radiograph in 15 (48.4%) cases. CONCLUSIONS: While intraoperative sonographic visibility was excellent, a large number of excisions were associated with extrusion of the marker. Modifications are needed to improve acceptability of this marker for intra-operative localization independent of pre-operative wire or seed localization.

Aesthetic subunit of the breast: an analysis of women's preference and clinical implications.

Patient satisfaction in breast surgery is dependent on achieving a balance among all aesthetic subunits. The purpose of this study is to identify which subunit of the breast women consider important and correlate this clinically to improve patient satisfaction following breast surgery. A total of 313 subjects (ages, 20-80) were surveyed using a 25-point survey instrument collected via a telemedicine form. The data was analyzed to determine clinical significance. Of the subjects, 63% selected the upper inner quadrant as the most important subunit. Furthermore, 66% of the subjects indicated defects located in this region would lead them to seek operative intervention and this was consistent for all subgroups. Based on these results, defects in the upper inner quadrant of the breast are more likely to cause patient dissatisfaction. Patient outcomes following surgery can be enhanced by restoring volume and minimizing scars in this upper medial subunit of the breast.

ACR Appropriateness Criteria® Imaging of the Axilla.

This publication reviews the current evidence supporting the imaging approach of the axilla in various scenarios with broad differential diagnosis ranging from inflammatory to malignant etiologies. Controversies on the management of axillary adenopathy results in disagreement on the appropriate axillary imaging tests. Ultrasound is often the appropriate initial imaging test in several clinical scenarios. Clinical information (such as age, physical examinations, risk factors) and concurrent complete breast evaluation with mammogram, tomosynthesis, or MRI impact the type of initial imaging test for the axilla. Several impactful clinical trials demonstrated that selected patient's population can received sentinel lymph node biopsy instead of axillary lymph node dissection with similar overall survival, and axillary lymph node dissection is a safe alternative as the nodal staging procedure for clinically node negative patients or even for some node positive patients with limited nodal tumor burden. This approach is not universally accepted, which adversely affect the type of imaging tests considered appropriate for axilla. This document is focused on the initial imaging of the axilla in various scenarios, with the understanding that concurrent or subsequent additional tests may also be performed for the breast. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial.

CONTEXT: Sentinel lymph node dissection (SLND) accurately identifies nodal metastasis of early breast cancer, but it is not clear whether further nodal dissection affects survival. OBJECTIVE: To determine the effects of complete axillary lymph node dissection (ALND) on survival of patients with sentinel lymph node (SLN) metastasis of breast cancer. DESIGN, SETTING, AND PATIENTS: The American College of Surgeons Oncology Group Z0011 trial, a phase 3 noninferiority trial conducted at 115 sites and enrolling patients from May 1999 to December 2004. Patients were women with clinical T1-T2 invasive breast cancer, no palpable adenopathy, and 1 to 2 SLNs containing metastases identified by frozen section, touch preparation, or hematoxylin-eosin staining on permanent section. Targeted enrollment was 1900 women with final analysis after 500 deaths, but the trial closed early because mortality rate was lower than expected. INTERVENTIONS: All patients underwent lumpectomy and tangential whole-breast irradiation. Those with SLN metastases identified by SLND were randomized to undergo ALND or no further axillary treatment. Those randomized to ALND underwent dissection of 10 or more nodes. Systemic therapy was at the discretion of the treating physician. MAIN OUTCOME MEASURES: Overall survival was the primary end point, with a noninferiority margin of a 1-sided hazard ratio of less than 1.3 indicating that SLND alone is noninferior to ALND. Disease-free survival was a secondary end point. RESULTS: Clinical and tumor characteristics were similar between 445 patients randomized to ALND and 446 randomized to SLND alone. However, the median number of nodes removed was 17 with ALND and 2 with SLND alone. At a median follow-up of 6.3 years (last follow-up, March 4, 2010), 5-year overall survival was 91.8% (95% confidence interval [CI], 89.1%-94.5%) with ALND and 92.5% (95% CI, 90.0%-95.1%) with SLND alone; 5-year disease-free survival was 82.2% (95% CI, 78.3%-86.3%) with ALND and 83.9% (95% CI, 80.2%-87.9%) with SLND alone. The hazard ratio for treatment-related overall survival was 0.79 (90% CI, 0.56-1.11) without adjustment and 0.87 (90% CI, 0.62-1.23) after adjusting for age and adjuvant therapy. CONCLUSION: Among patients with limited SLN metastatic breast cancer treated with breast conservation and systemic therapy, the use of SLND alone compared with ALND did not result in inferior survival. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00003855.

Association of occult metastases in sentinel lymph nodes and bone marrow with survival among women with early-stage invasive breast cancer.

CONTEXT: Immunochemical staining of sentinel lymph nodes (SLNs) and bone marrow identifies breast cancer metastases not seen with routine pathological or clinical examination. OBJECTIVE: To determine the association between survival and metastases detected by immunochemical staining of SLNs and bone marrow specimens from patients with early-stage breast cancer. DESIGN, SETTING, AND PATIENTS: From May 1999 to May 2003, 126 sites in the American College of Surgeons Oncology Group Z0010 trial enrolled women with clinical T1 to T2N0M0 invasive breast carcinoma in a prospective observational study. INTERVENTIONS: All 5210 patients underwent breast-conserving surgery and SLN dissection. Bone marrow aspiration at the time of operation was initially optional and subsequently mandatory (March 2001). Sentinel lymph node specimens (hematoxylin-eosin negative) and bone marrow specimens were sent to a central laboratory for immunochemical staining; treating clinicians were blinded to results. MAIN OUTCOME MEASURES: Overall survival (primary end point) and disease-free survival (a secondary end point). RESULTS: Of 5119 SLN specimens (98.3%), 3904 (76.3%) were tumor-negative by hematoxylin-eosin staining. Of 3326 SLN specimens examined by immunohistochemistry, 349 (10.5%) were positive for tumor. Of 3413 bone marrow specimens examined by immunocytochemistry, 104 (3.0%) were positive for tumors. At a median follow-up of 6.3 years (through April 2010), 435 patients had died and 376 had disease recurrence. Immunohistochemical evidence of SLN metastases was not significantly associated with overall survival (5-year rates: 95.7%; 95% confidence interval [CI], 95.0%-96.5% for immunohistochemical negative and 95.1%; 95% CI, 92.7%-97.5% for immunohistochemical positive disease; P = .64; unadjusted hazard ratio [HR], 0.90; 95% CI, 0.59-1.39; P = .64). Bone marrow metastases were associated with decreased overall survival (unadjusted HR for mortality, 1.94; 95% CI, 1.02-3.67; P = .04), but neither immunohistochemical evidence of tumor in SLNs (adjusted HR, 0.88; 95% CI, 0.45-1.71; P = .70) nor immunocytochemical evidence of tumor in bone marrow (adjusted HR, 1.83; 95% CI, 0.79-4.26; P = .15) was statistically significant on multivariable analysis. CONCLUSION: Among women receiving breast-conserving therapy and SLN dissection, immunohistochemical evidence of SLN metastasis was not associated with overall survival over a median of 6.3 years, whereas occult bone marrow metastasis, although rare, was associated with decreased survival. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00003854.