ACOSOG Z0011 Trial Research Articles

The feasibility of the ACOSOG Z0011 criteria for omitting axillary lymph node dissection after positive sentinel lymph node biopsy in Chinese breast cancer patients: A multicenter study.

e12058 Background: The ACOSOG Z0011 trial has been described as practice-changing of sentinel lymph nodes (SLNs) positive breast cancers. This study was undertaken to examine current practice patte...

P024. Are patients diagnosed with breast cancer aged 70 and above receiving gold standard care?

(55/918). Of the 55 patients, 22 patients were excluded (Eleven patients had mastectomy, six had more than two nodes involved, four had neo adjuvant chemotherapy and one declined surgery) leaving 33 patients. Therefore 2.2% (33/1499) of the cohort met the inclusion criteria for the ACOSOG Z0011 trial. Conclusions: In this observational study, only 2.2% (33/1499) of the patients were identified as per the ZOO11 criteria. This means only a very few number of patients could be spared from axillary lymph node dissection. So clearly it is not a practice changing trial in the axillary surgical management of our cohort of patients.

P025. The efficacy of axillary ultrasound in nodal staging in symptomatic breast cancer

(55/918). Of the 55 patients, 22 patients were excluded (Eleven patients had mastectomy, six had more than two nodes involved, four had neo adjuvant chemotherapy and one declined surgery) leaving 33 patients. Therefore 2.2% (33/1499) of the cohort met the inclusion criteria for the ACOSOG Z0011 trial. Conclusions: In this observational study, only 2.2% (33/1499) of the patients were identified as per the ZOO11 criteria. This means only a very few number of patients could be spared from axillary lymph node dissection. So clearly it is not a practice changing trial in the axillary surgical management of our cohort of patients.

Abstract P2-01-17: Total tumoral load as a prediction tool of non-sentinel node metastases in patients with early breast cancer and positive sentinel lymph node assesed by OSNA

Abstract Background: Total tumoral load (TTL) in the sentinel lymph nodes (SLN) assessed by the OSNA assay is a new variable that is able to predict the likelihood of more axillary metastasis. Compared with the number of positive SLNs, the TTL is independent of the number of metastatic SLNs and a better predictor of further nodal metastasis. Although establishing specific cutoff-points of the TTL can be questionable because they may change in the future and increasingly become more patient specific, we have seen that TTL <15.000 could be a good cut off by its high negative predictive value (NPV). Changes in practice have been occurred after the ACOSOG Z0011 trial and nowadays, patients with ≤ 2 positive SLNs may spare an axillary lymph node dissection (ALND) with no impact on the oncological outcome. In the Z0011, 27% of patients had additional non-SLN metastasis in the cALND. The objective of this study was to compare two methods of SLN metastatic burden, the TTL and the number of positive SLNs, for predicting non-SLN metastasis in patients with positive SLNs by OSNA. Methods: This is a retrospective cohort study of 145 consecutive patients with cT1-T2 invasive breast cancer with ultrasonographically node-negative treated between April 2010 to April 2013, where there is at least one positive SLN assesed by OSNA. We design a prediction tool based on the TTL results determined by OSNA to calculate the likelihood of not finding more positive non-SLN (http://www.vhebron.net/es/calculadora-risc-metastasi-2). Our group have demonstrated that TTL=15.000 could be a good cut off by its high NPV and sensitivity, 85.5% and 76.7%, respectively. Results: A total 325 SLNs were removed with a mean of 2.24. The type of SLN metastasis were macrometastasis in 85 patients (58.6%) and micrometastasis in 60 patients (41.4%). When considering patients with number of positive SLNs, of 109 patients with ≤2 positives SLNs and an cALND, 17 patients (22%) had non-SLN metastasis; and of 5 patients with ≥3 SLN, four (80%) had non-SLN metastasis. Taking the TTL results, of 51 patients with TTL <15.000 copies/µL with cALND (90.2% with one positive SLN), 7 patients (14%) had non-SLN metastasis, were a media of 2.2 extra non-SLN metastasis. Of 55 patients with TTL ≥15.000 copies/µL (with 1 or 2 positives SLNs) with cALND, 20 patients (36%) had non-SLN metastasis and there were a media of 2.5 non-SLN metastasis (range 1-8). Of 34 patients (62%) with one positive SLN with TTL ≥15.000 copies/µL, 12 patients (35%) had non-SLN metastasis; and of 21 patients with two positive SLN with TTL ≥15.000 copies/µL, eight patients (38%) had non-SLN metastasis. Conclusion: The total tumor load obtained by OSNA predicts non-SLN metastasis independent of the number of positive SLNs. The assess of the TTL in our cohort of patients show that patients with one or two positives SLNs with high TTL had high likelihood of non-SLN metastasis greater than 27% of Z0011 criteria. Prospective studies are needed to determine the clinical impact of this variable in patients outcome in the management of patients with SLN assesed by OSNA. Citation Format: Martin Espinosa-Bravo, Francesc Pérez-Ceresuela, Sebastian Diaz-Botero, Vicente Peg, Isabel T Rubio. Total tumoral load as a prediction tool of non-sentinel node metastases in patients with early breast cancer and positive sentinel lymph node assesed by OSNA [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-01-17.

P341 Use of fibrin glue in the prevention of seroma formation after axillary lymphadenectomy

Goals: The ACOSOG Z0011 trial showed that an axillary lymph node dissection (ALND) may be safely omitted in selected patients with a positive sentinel lymph node biopsy (SNB). One of these eligible criteria has non palpable lymphadenopathy. However, the eligibility for patients with a suspicious Ultrasonography (US) is controversial. The purpose of this study was to evaluate the validity of the SNB for patients with suspicious lymph node (sN+) compared to clinical node negative patients (cN0). Methods: Patients with suspicious axillary lymph node positive breast cancer by preoperative assessed US or CT were performed fine needle aspiration (FNA) cytology between 2004 and 2014. Patients with a negative axillary US (cN0 group) or negative FNAC (sN+ group) result underwent SNB. All SNB positive patients underwent completion ALND. The number of positive nodes after ALND was compared cN0 group with sLN group. Results: 530/2683 patients (19.7%) had positive SNB. Ultrasoundaxilla was 49% sensitive and 84% specific in predicting SNB metastases. The positive (PPV) and negative predictive value (NPV) was 53% and 81% respectively. For suspicious group, this was 68.4% sensitive and 99.7% specific in detecting SNB metastases. PPV and NPV were 99.6% and 74.2% respectively. The number of metastasis lymph nodes is 1 (48%), 2 (19%), 3 (9%), more than 4 (54%) and N1mic (17%) in the cN0 group, and 1 (37%), 2 (14%), 3 (7%), more than 4 (10%) and N1mic (28%) in the cN1 suspicious group. Conclusion: These results suggest that patients with suspicious axillary metastases on ultrasound-guided biopsy have less involved nodes than SNB-positive patients with clinical negative node. Therefore, we conclude that SNB can be safely performed in patients with clinically suspicious lymph node on ultrasonography. Disclosure of Interest: No significant relationships.

Clinical Usefulness of One-Step Nucleic Acid Amplification Assay in the New Era of Sentinel Lymph Node Biopsy for Breast Cancer

SUMMARY According to the results of the ACOSOG Z0011 trial and IBCSG trial 23-01, rapid intraoperative examinations of the sentinel lymph nodes (SLN) are needed in only a limited number of breast cancer patients, including those with more than three sentinel nodes or who undergo mastectomy. In this new era of SLN biopsies, one-step nucleic acid amplification assay is a promising method for accurately assessing metastasis in the whole SLN, and which help to accurately select patients requiring axillary dissection and reliably evaluate the risk of recurrence. One-step nucleic acid amplification assay may therefore be an alternative to conventional pathology in detecting metastasis in the SLNs, when used for both intraoperative and postoperative examinations.

To do or not to do: axillary nodal evaluation after ACOSOG Z0011 Trial.

Methods of axillary evaluation in invasive breast cancer continue to evolve. The recent American College of Surgeons Oncology Group Z0011 Trial is a prospective, randomized, multicenter trial that compared the survival and locoregional recurrence rates after complete axillary lymph node dissection (ALND) versus sentinel node biopsy (SNB) alone in women with a positive sentinel node in an effort to avoid the complications associated with ALND. As the results of this trial are implemented clinically, affecting surgical management of axillary metastatic disease, radiologists may need to redefine their role in the preoperative assessment of the axilla. Before the Z0011 trial, breast imagers worked to identify axillary metastases preoperatively, allowing appropriate patients to proceed directly to ALND and avoiding the need for SNB. However, the Z0011 trial concluded that ALND may not be necessary in women with metastatic axillary disease who meet the trial criteria. In the Z0011 trial, after 6 years of median follow-up there was no difference in either locoregional recurrence or survival among the women who underwent SNB alone compared with those who underwent ALND, suggesting that ALND is unnecessary in a subset of women with a positive node at SNB. These results raise questions about how aggressively radiologists should pursue percutaneous sampling of axillary nodes, as some practitioners conclude that, in an otherwise eligible woman, positive results from imaging-guided percutaneous biopsy preclude a Z0011 trial-directed pathway. Debate about the best way to implement the results of the Z0011 trial into daily clinical practice exists. It is important for breast imagers to work closely with breast surgeons to provide the most appropriate treatment course for each patient.

Evolution of sentinel lymph node biopsy in breast cancer, in and out of vogue?

Sentinel lymph node biopsy (SLNB) was introduced 2 decades ago and thereafter validated for routine surgical management of breast cancer, including cases treated with neoadjuvant chemotherapy. As the number of lymph nodes for staging has decreased, pathologists have scrutinized SLN with a combination of standard hematoxylin and eosin, levels, immunohistochemistry (IHC), and molecular methods. An epidemic of small-volume metastases thereby arose, leading to modifications in the American Joint Committee on Cancer staging to accommodate findings such as isolated tumor cells (ITC) and micrometastases. With the goal of determining the significance of these findings, retrospective followed by prospective trials were performed, showing mixed results. The ACOSOG Z10 and NSABP B-32 trials both independently showed that ITC and micrometastases were not significant and thus discouraged the use of levels and IHC for detecting them. However, the Surveillance Epidemiology and End Results database showed that patients with micrometastases had an overall decreased survival. In addition, the MIRROR (Micrometastases and ITC: Relevant and Robust or Rubbish?) trial, showed that patients with ITC and micrometastases treated with adjuvant therapy had lower hazard ratios compared with untreated patients. Subsequently, the ACOSOG Z0011 trial randomized patients with up to 2 positive SLN to axillary lymph node dissection (ALND) or not, all treated with radiation and chemotherapy, showing no difference in survival or recurrence rates between the 2 groups and causing a shift from ALND. As the rate of ALND has declined, the necessity of performing levels, IHC, frozen section, and molecular studies on SLN needs to be revisited.

148. Management of micro-metastasis in sentinel lymph node biopsy during breast cancer operation

Background: According to the results of ACOSOG Z0011 trial, ASCO and NCCN guideline showed that women with one to two metastatic SLNs planning to undergo breast-conserving surgery with whole-breast radiotherapy should not undergo ALND (in most cases). However, some prudent surgeons are still undergo ALND if SLN positive in accordance with Z0011 criteria. We evaluated the cases with micrometastasis in sentinel lymph node (SLN) during operation in our hospital.

The role of ultrasound-guided lymph node biopsy in axillary staging of invasive breast cancer in the post-ACOSOG Z0011 trial era.

Axillary status in invasive breast cancer, established by sentinel lymph node biopsy (SLNB) or ultrasound-guided lymph node biopsy, is an important prognostic indicator. The ACOSOG Z0011 trial showed that axillary dissection may be redundant in selected sentinel node-positive patients, raising questions on the applicability of these conclusions on ultrasound positive patients. The purpose of this study was to evaluate potential differences in patient and tumor characteristics and survival between axillary node positive patients after ultrasound (US group) or sentinel lymph node procedure (SN group). Patients diagnosed with invasive breast cancer at the Máxima Medical Center between January 2006 and December 2011 were studied. In total, 302 node-positive cases were included: 139 and 163 cases in the US and SN groups, respectively. Patients in the US group were older at diagnosis (p<0.001), more often had palpable nodes (p<0.001), mastectomy (p<0.001), larger tumors (p<0.001), higher tumor grade (p=0.001), lymphovascular invasion (p=0.035), a positive Her2Neu (p=0.006), and a negative hormonal receptor status (p=0.003). Also, they were more likely to have more lymph nodes with macrometastases (p<0.001), extranodal extension (p<0.001), and involvement of level-III-lymph node (p<0.001). Finally, they showed a worse disease-free survival [hazard ratio (HR)=2.71; 95% confidence interval (CI)=1.49-4.92] and overall survival (HR=2.67; 95% CI=1.48-4.84) than the SN group. These results suggest that ultrasound-positive patients have less favorable disease characteristics and a worse prognosis than SN-positive patients. Therefore, we conclude that omitting an ALND is as yet only applicable, as concluded in the Z0011, in patients with a positive SLNB.

No Radiation-Delivery Bias in the Seminal ACOSOG Z0011 Trial

The ACOSOG Z0011 trial (NEJM JW Oncol Hematol Oct 12 2010) showed that axillary lymph node dissection (ALND) is unnecessary in patients with clinically axillary node-negative T1 or T2 breast cancer and one or two positive sentinel lymph nodes who undergo lumpectomy, radiotherapy, and systemic therapy. That practice-changing trial generated much discussion, debate, and angst among clinicians as the results were applied to clinical practice. One concern is …

Radiation field design in the ACOSOG Z0011 (Alliance) Trial.

ACOSOG Z0011 established that axillary lymph node dissection (ALND) is unnecessary in patients with breast cancer with one to two positive sentinel lymph nodes (SLNs) who undergo lumpectomy, radiotherapy (RT), and systemic therapy. We sought to ascertain RT coverage of the regional nodes in that trial. We evaluated case report forms completed 18 months after enrollment. From 2012 to 2013, we collected all available detailed RT records for central review. Among 605 patients with completed case report forms, 89% received whole-breast RT. Of these, 89 (15%) were recorded as also receiving treatment to the supraclavicular region. Detailed RT records were obtained for 228 patients, of whom 185 (81.1%) received tangent-only treatment. Among 142 with sufficient records to evaluate tangent height, high tangents (cranial tangent border ≤ 2 cm from humeral head) were used in 50% of patients (33 of 66) randomly assigned to ALND and 52.6% (40 of 76) randomly assigned to SLND. Of the 228 patients with records reviewed, 43 (18.9%) received directed regional nodal RT using ≥ three fields: 22 in the ALND arm and 21 in the SLND arm. Those receiving directed nodal RT had greater nodal involvement (P < .001) than those who did not. Overall, there was no significant difference between treatment arms in the use of protocol-prohibited nodal fields. Most patients treated in Z0011 received tangential RT alone, and some received no RT at all. Some patients received directed nodal irradiation via a third field. Further research is necessary to determine the optimal RT approach in patients with low-volume axillary disease treated with SLND alone.

Estrogen Receptor, Progesterone Receptor, and HER2 Status Predict Lymphovascular Invasion and Lymph Node Involvement

The ACOSOG Z0011 trial demonstrated that axillary dissection (ALND) is not necessary for local control or survival in women with T1/2cN0 cancer undergoing breast-conserving therapy. There is concern about applying these results to triple-negative (TN) cancers secondary to their high local-recurrence (LR) rate. We examined the frequency of lymphovascular invasion (LVI) and nodal metastases in TN cancers to determine whether ALND can be safely avoided in this subtype. Data were obtained from a database of patients with invasive breast cancer treated at Memorial Sloan Kettering Cancer Center from January 1998 to December 2010. A total of 11,596 tumors were classifiable into clinical surrogates for molecular subtype by immunohistochemical analysis: hormone receptor (HR)+/HER2+, HR+/HER2-, HR-/HER2+, and TN (HR-/HER2-). Multivariable logistic regression analysis (MVA) was used to determine associations between clinicopathologic variables and subtype. There were differences in age, tumor size, LVI, grade, and nodal involvement among groups. On MVA controlling for size, grade, and age, ER, PR, and HER2 status were significantly associated with LVI (p<0.0001). Relative to TN tumors, HR+/HER2-, HR+/HER2+, and HR-/HER2+ tumors had higher odds of demonstrating LVI of 1.8 (odds ratio 1.8; 95% confidence interval 1.6-2.1), 2.5 (2.5; 2.0-3.0), and 1.7 (1.7; 1.4-2.1), respectively. On MVA adjusting for size, grade, LVI, and age, TN tumors had the lowest odds of having any or high-volume nodal involvement (≥4 nodes, p<0.0001). LVI and nodal metastases were least frequent in TN cancers compared with other subtypes, despite the uniformly worse prognosis and increased LR rate in TN tumors. This suggests TN cancers spread via lymphatics less frequently than other subtypes and ALND may be avoided in TN patients meeting Z0011 eligibility criteria.

Coverage of regional lymphatic drainage in helical IMRT for breast cancer

Results of the ACOSOG Z0011 trial suggest that in patients with breast cancer, non-palpable lymphadenopathy and 1 – 2 metastatic sentinel lymph nodes, sentinel lymph node biopsy yields comparable results to axillary lymph node dissection if followed by tangential adjuvant radiotherapy of the breast. Tangential radiotherapy has thus been incorporated as a prerequisite for the abandonment of axillary lymph node dissection in these patients. The degree to which the axillary and other lymphatic drainage is covered by intensity-modulated radiotherapy has not been reported.

Patterns of nodal staging during breast conservation surgery in the medicare patient: will the ACOSOG Z0011 trial change the pattern of care?

ACOSOG Z0011 spares axillary dissection (AD) in breast conservation surgery (BCS) patients with T1/T2 tumors and 1-2 positive nodes. Current patterns of care and the impact of Z0011 on AD versus additional surgery rates for Medicare patients undergoing BCS are unknown. SEER data linked to Medicare claims for 1999-2005 were reviewed for women with invasive nonmetastatic breast cancer who underwent nodal staging on the same day as BCS. There were 3,280 women with T1/T2 tumors and positive nodes who underwent same-day nodal staging; 2,532 (77.2 %) of these women had 1-2 positive nodes. Assuming 25.7 % have extracapsular extension, 651 women would require AD. However, 1,881 women, or 57.4 % of those with T1/T2 tumors and positive nodes, would be spared AD. Meanwhile, among the 748 women having ≥ 3 positive nodes, 579 underwent same-day AD, but under Z0011, would now wait for permanent section. A total of 160 of these women underwent re-excision or completion mastectomy at a later date anyway, when delayed AD could be performed. The remaining 419 women with ≥ 3 positive nodes would require an additional surgery date for the sole purpose of completion AD. The Z0011 paradigm would consequently necessitate an additional surgery date for 1,070 (651 + 419) women, or 32.6 % of those with T1/T2 tumors and positive nodes. The Z0011 paradigm appears to increase the number of Medicare patients undergoing BCS who require an additional surgery date but decrease the number requiring AD to a greater extent. Future changes in the use of AD or axillary irradiation may yet modify that impact substantially.

Abstract P5-14-19: Radiation field design on the ACOSOG Z0011 trial

Abstract Purpose/Objective: The landmark ACOSOG Z0011 trial established that axillary lymph node dissection (ALND) is unnecessary in breast cancer patients with one or two positive sentinel lymph nodes (SLN) who undergo lumpectomy, radiation therapy (RT) and systemic therapy. At a median follow-up of 6.3 years there were no differences in overall survival or local-regional recurrences between patients receiving ALND or SLN biopsy alone. The protocol required whole breast RT using standard tangential fields, but the extent of RT coverage of the regional nodes in these patients has not previously been described. We sought to ascertain this information. Methods: The RT data on the ACOSOG Z0011 trial was collected from case report forms completed by enrolling providers 18 months after enrollment. The response options on the forms included breast, supraclavicular, &amp; other. We reviewed these data and, in 2011-2013, we attempted to identify and contact all treating radiation oncology practices to request detailed radiation treatment records for central review. RT data was sent to the Quality Assurance Review Center (QARC) and reviewed by two independent radiation oncologists, blinded regarding the arm to which the patients were randomized. Results: Of the 891 patients enrolled on Z0011, 35 withdrew consent prior to surgery, leaving 856 who were analyzed in the primary report on trial outcomes.1 Among the 605 of these patients with a completed adjuvant radiation therapy form, 89% were noted to receive whole breast RT. Of these, 89 patients (15%) were recorded as also receiving treatment to the supraclavicular region. Detailed RT records were received on 228 patients: 104/389 (26.7%) and 124/404 (30.7%) on the ALND and SLND arms, respectively. Of the 228 patients, 185 patients (81.1%) received tangent-only treatment. Among these 185 patients, there was sufficient data to evaluate tangent field height in 142 (76.8%). High tangent RT fields (with cranial tangent border within 2 cm of the humeral head) were used in 52.6% (40/76) patients randomized to the ALND arm and 50% (33/66) patients randomized to the SLND arm. Of the 228 patients with records reviewed, 43 (18.9%) received directed regional nodal RT using ≥3 fields: 22 in the ALND and 21 in the SLND arm. Those receiving directed nodal RT tended to have greater nodal involvement (p&amp;lt;0.001). Conclusions: Most patients treated on the Z0011 trial received tangential field RT alone, and some received no radiotherapy at all. Some patients received directed nodal irradiation via a third field. In a subgroup for whom detailed RT records were available, the highest rates of directed nodal irradiation were among those with multiple nodes involved. As survival rates and local-regional recurrences were similar in the study arms, no conclusions can be drawn from this analysis on whether this additional radiation treatment was necessary or beneficial. 1JAMA 2011; 305 (6): 569-575. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-14-19.

Abstract P1-01-19: Role of axillary clearance with tumor positive sentinel node in mastectomy group: Is the results of ACOSOG Z0011 trial adaptable to mastectomy patient?

Abstract Background: Recent data from ACOSOG Z0011 trial or AMAROS trial suggest that axillary lymph node dissection(ALND) may be unnecessary for patients with positive sentinel lymph node biopsy(SLNB) receiving breast conserving surgery(BCS) with irradiation. However, consensus statements and guidelines until recently recommended that patients with mastectomy and tumor positive sentinel node undergo completion ALND. In this preliminary study, we compared these patients who did not undergo ALND with the patients who received BCS with SLNB only and irradiation and we analyzed the locoregional recurrence rate to show no differences of outcomes between two groups. Method: We identified 6,163 women with invasive breast cancer who underwent surgical resection at the National Cancer Center (Goyang,Gyeonggi-do,Korea) between January 2000 to December 2011. Clinico-pathological data obtained from prospective collecting medical database of our institution were analyzed retrospectively. The mastectomy with positive SLNB group was 47 patients and BCS with positive SLNB and irradiation group was 172 patients. The primary end point was loco-regional recurrence rate. Result : Clinical and tumor characteristics were similar between two groups except T stage and receptor status. The mean tumor size was 5.5cm with mastectomy group and 3.5cm with BCS group. The median number of nodes removed was three. There was not a single case of locoregional recurrence in both groups. At a median follow-up of 53.5 months (last follow-up, May 2013), 5-year overall survival was 85.7% with mastectomy and 97.3% with BCS group. Conclusion : In our study, there was no case of locoregional recurrence as above. This results lend weight to the argument that SLNB without ALND may be reasonable management for selected patients with appropriate surgery and adjuvant systemic therapy. This study can be regarded as a preliminary study with a sufficient value despite of the prognosis showed some statistical differences between two groups. It resides in the difference of initial stage of patients of two groups. We will present additional data compared with the mastectomy with axillary clearance group at the meeting. Acknowledgement This work was supported by grant from the National Cancer Center Korea (1210331-2). Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-01-19.

Abstract AL-2: William L. McGuire memorial lecture – Local therapy in the molecular era: Relevant or relic?

Abstract Surgery has always been driven by disease burden; initially, to determine operability, and recently, to select patients for BCT. Systemic therapy also initially relied on disease burden (axillary nodes, tumor size), but gene profiles and molecular targets now predominate in selecting systemic therapy. Reliance on disease burden as a determinant of the intensity of local therapy is problematic as advanced imaging modalities and molecular pathology allow detection of increasingly smaller tumors. The application of management strategies proven beneficial for macroscopic tumor to subclinical disease has the potential for overtreatment as evidenced by increased mastectomy rates in patients undergoing preoperative MRI, and use of ALND and chemotherapy for sentinel node micrometastases. It is an appropriate time to ask how recognition of molecular subtypes and improvements in systemic therapy can be leveraged to improve local therapy outcomes and decrease the burden of therapy. Recognition that systemic therapy results in a major decrease in the rate of IBTR was the major impetus for SSO and ASTRO to commission a systemic review on margins for BCT in stage I and II breast cancer as the evidence base for a consensus conference. We concluded that evidence that margins more widely clear than no ink on tumor significantly improve local control was lacking and the routine practice of obtaining more widely clear margins is not indicated. Adoption of this approach has the potential to spare many women unnecessary surgery. The morbidity of ALND can also be avoided in many patients. The ACOSOG Z0011 trial showed no benefit to ALND for patients with 1 or 2 sentinel node metastases receiving WBRT and systemic therapy. There were many criticisms of this study, but 3 other prospective randomized trials (NSABP B04, NSABP B32, IBCSG 2013) demonstrate that residual axillary nodal disease does not translate to regional recurrence or a decrease in survival in a 1:1 ratio, and that systemic therapy greatly reduces the incidence of regional recurrence. In a prospective study of the applicability of Z0011 findings to an unselected population of women meeting study eligibility criteria, we found that only 16% of 287 consecutive patients had metastases in ≥3 sentinel nodes or matted nodes identified intraoperatively, sparing 84% ALND. These examples represent initial steps in reducing the morbidity of local therapy. Moving forward, it is appropriate to ask whether patients with favorable molecular profiles (luminal A), require the same local therapy as those with other molecular subtypes. More controversially, the success of HER2 blockade in improving survival raises the question of whether effective targeted therapy could allow a reduction in local therapy intensity. A major barrier to progress is the belief of many clinicians and patients that bigger surgery is better surgery. The full realization of multidisciplinary care will occur when improvements in outcomes with one modality result in studies examining the elimination of other treatments which may no longer be beneficial to patients. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr AL-2.

Outcomes of sentinel lymph node-positive breast cancer patients treated with mastectomy without axillary therapy.

53 Background: Early-stage breast cancer patients with minimal axillary disease identified by sentinel lymph node dissection (SLND) have a low rate of regional recurrence when treated with breast conserving surgery and radiation. Patients who fit criteria for the ACOSOG Z0011 trial are candidates to avoid completion axillary lymph node dissection (CLND). As the incidence of total mastectomy (TM) has increased, it has become important to characterize which TM patients with a positive SLN may not benefit from further axillary treatment, including CLND and/or radiation therapy (XRT). Methods: We utilized an institutional database to identify patients who were treated with a TM for invasive breast cancer and had a positive SLN from 1994-2010. CLND was defined as removal of 10 or more lymph nodes. Clinicopathologic factors were analyzed and the rate of regional recurrence as well as overall and disease-free survival were determined. Results: A total of 730 patients with invasive breast cancer and a positive SLN were treated with TM including 71 patients who did not have CLND or XRT and 27 patients who did not have CLND but did receive XRT. Median follow-up was 66 months. The 10-year actuarial rate of regional recurrence was not significantly different for patients who received no further axillary treatment when compared to those who underwent CLND and XRT (4.9% vs 3.1%) or to those who underwent CLND without XRT (4.9% vs 1.4%). Survival was not significantly different between patients who did not receive further axillary treatment compared to those who underwent CLND without XRT or those who underwent both CLND and XRT. Using a nomogram previously developed by our group, the predicted probability of additional non-SLN involvement was significantly lower for patients who did not undergo CLND compared to those who did (10% vs. 23%, p&lt;0.0001). Conclusions: In select patients with early stage breast cancer treated with mastectomy with a positive SLN, CLND may be avoided without adversely affecting recurrence or survival.

Life beyond Z11

The ACOSOG Z0011 (Z11) trial demonstrated the presence of a group of breast cancer patients with some residual axillary disease who did not benefit from axillary lymph node dissection (ALND) in the presence of whole breast radiotherapy and systemic therapy at short term follow-up. It is important that further long-term follow-up of this cohort continues. The outcomes of those patients fitting Z11 criteria who do not undergo ALND should be recorded on a prospective register to ensure close observation should any late divergence in overall survival develop. It is also essential that future studies are inclusive of groups excluded from Z11 rather than simply a re-hash of the trial.