Successful Use of a Cadaver Model to Teach Ultrasound-Guided Breast Procedures to Surgical Trainees.

INTRODUCTION: In academic breast surgery, ultrasound use tends to be limited to radiology departments, thus formal surgical resident training in breast ultrasound is sparse. Building on residents' ultrasound skills in our general surgery training program, we developed a novel curriculum to teach ultrasound-guided breast procedures (UGBPs), including core needle biopsy (CNB) and wire localization (WL). We hypothesized that learning UGBPs on cadavers would be preferred to learning with a breast phantom model using chicken breasts. METHODS: Residents received a 1-h lecture on breast CNB and WL followed by a 1-h hands-on laboratory session. Olives stuffed with red pimentos were used to replicate breast masses and implanted in chicken breasts and the breasts of lightly embalmed and unembalmed female cadavers. All residents practiced UGBPs with a course instructor on both models. Residents completed anonymous prelaboratory and postlaboratory surveys utilizing five-point Likert scales. RESULTS: A total of 35 trainees participated in the didactics; all completed the prelaboratory survey and 28 completed the postlaboratory survey. Participant clinical year ranged from 1 to 6. Residents' confidence in describing and performing CNBs and WLs increased significantly on postlaboratory surveys, controlling for clinical year (P < 0.001). Eighty-point seven percent preferred learning UGBPs on cadavers over phantoms most commonly citing that the cadaver was more realistic. CONCLUSIONS: Following a novel 2-h UGBP training curriculum using phantom and cadaveric models, resident confidence in describing and performing UGBPs significantly improved. Most favored the cadaveric model and reported that the course prepared them for real-life procedures.

Higher risk tumor features are not associated with higher nodal stage in patients with estrogen receptor-positive, node-positive breast cancer.

INTRODUCTION: Studies support omission of axillary lymph node dissection (ALND) for patients with sentinel node-positive disease, with ALND recommended for patients who present with clinically positive nodes. Here, we evaluate patient and tumor characteristics and pathologic nodal stage of patients with estrogen receptor-positive (ER +) breast cancer who undergo ALND to determine if differences exist based on nodal presentation. MATERIALS AND METHODS: Retrospective chart review from 2010 to 2019 defined three groups of patients with ER + breast cancer who underwent ALND for positive nodes: SLN + (positive node identified at SLN biopsy), cNUS (abnormal preoperative US and biopsy), and cNpalp (palpable adenopathy). Patients who received neoadjuvant chemotherapy or presented with axillary recurrence were excluded. RESULTS: Of 191 patients, 94 were SLN + , 40 were cNUS, and 57 were cNpalp. Patients with SLN + compared with cNpalp were younger (56 vs 64 years, p < 0.01), more often pre-menopausal (41% vs 14%, p < 0.01), and White (65% vs 39%, p = 0.01) with more tumors that were low-grade (36% vs 8%, p < 0.01). Rates of PR + (p = 0.16), levels of Ki67 expression (p = 0.07) and LVI (p = 0.06) did not differ significantly among groups. Of patients with SLN + disease, 64% had pN1 disease compared to 38% of cNUS (p = 0.1) and 40% of cNpalp (p = 0.01). On univariable analysis, tumor size (p = 0.01) and histology (p = 0.04) were significantly associated with pN1 disease, with size remaining an independent predictor on multivariable analysis (p = 0.02). CONCLUSION: Historically, higher risk features have been attributed to patients with clinically positive nodes precluding omission of ALND, but when restricting evaluation to patients with ER + breast cancer, only tumor size is associated with higher nodal stage.

SAVI SCOUT® localization of metastatic axillary lymph node prior to neoadjuvant chemotherapy for targeted axillary dissection: a pilot study.

PURPOSE: In clinically node-positive breast cancer, axillary staging after neoadjuvant chemotherapy (NAC) is optimized with targeted axillary dissection (TAD), which includes removal of the biopsy-proven metastatic lymph node (LN) in addition to sentinel lymph nodes (SLN). Localization of the clipped node is currently performed post-NAC; however, technical limitations can make detection and localization of the treated LN challenging. We prospectively evaluated the feasibility of localizing the metastatic LN with a SAVI SCOUT® reflector (SAVI) prior to NAC for targeted removal at surgery. METHODS: Twenty-five patients with stage 2/3 breast cancer underwent ultrasound-guided localization of the biopsy-proven LN with SAVI prior to NAC. After NAC, patients with clinical response underwent TAD. Primary outcome measures were rate of successful localization, days between insertion of SAVI and axillary surgery, frequency of retrieval of clipped node, and frequency of SAVI-LN as SLN. RESULTS: After NAC, 23/25 (92%) had clinical axillary down-staging and underwent TAD. Two patients with persistent palpable axillary disease underwent ALND for initial staging. Axillary surgery was performed at an average of 141 days post-SAVI insertion and the SAVI was successfully retrieved in all cases. Among 23 patients undergoing TAD, the SAVI was retrieved within a LN in all patients, whereas clip migration was observed in two patients. The median SLN removed was 4, and SAVI-LN was SLN in 22/23 patients. Axillary pCR rate was 44%. CONCLUSION: Localizing a metastatic LN with SAVI reflector prior to NAC for targeted removal at surgery is feasible and may provide technical and logistical advantages over axillary localization post-NAC. CLINICAL TRIAL REGISTRY: Clinical trials.gov identifier: NCT03411070.

Assessing the Burden of Nodal Disease for Breast Cancer Patients with Clinically Positive Nodes: Hope for More Limited Axillary Surgery.

BACKGROUND: Omission of axillary lymph node dissection (ALND) is accepted for patients with one or two positive sentinel nodes, and studies are focusing on clinically node-positive patients who have been downstaged with neoadjuvant chemotherapy (NAC). Evidence is lacking for patients with positive nodes who undergo surgery upfront. These patients are assumed to have a higher burden of nodal disease such that ALND remains the standard of care. METHODS: Patients who underwent ALND for breast cancer between 2010 and 2019 at the authors' institution were retrospectively identified. Those with clinical N1 disease were included in the study. Patients who received NAC and those who had surgery for sentinel node positive disease or axillary recurrence were excluded. Clinical and pathologic factors associated with nodal stage were evaluated. RESULTS: Of 111 patients who met the inclusion criteria, 61.3% had a palpable node on exam, and 41.4% ultimately had pN1 disease. Most of the tumors were estrogen receptor (ER)-positive (91.5%), and 21.7% of the tumors were invasive lobular cancers. Lobular histology, tumor size, and metastasis size were associated with higher nodal stage. In the multivariable analysis, the patients with nodal metastasis larger than 10 mm had significantly lower odds of having pN1 disease (odds ratio 0.12; 95% confidence interval 0.02-0.69; p = 0.02). In a subset analysis of patients with palpable nodes, tumor size and histology remained significantly associated with nodal stage. CONCLUSION: More than 40% of breast cancer patients with clinically positive nodes had minimal nodal disease (pN1) at surgery. Additionally, palpable nodes on exam did not predict higher nodal stage. A subset of patients with clinically positive nodes may be identified who can potentially be spared the morbidity of ALND.

"Going Flat" After Mastectomy: Patient-Reported Outcomes by Online Survey.

BACKGROUND: The Going Flat movement aims to increase awareness and acceptance of mastectomy alone as a viable option for patients. Little is known about motivations and satisfaction with surgical outcomes in this population. METHODS: An online survey was administered to 931 women who had a history of uni- or bilateral mastectomy for treatment of breast cancer or elevated breast cancer risk without current breast mound reconstruction. Satisfaction with outcome and surgeon support for the patient experience were characterized using 5-level scaled scores. RESULTS: Mastectomy alone was the first choice for 73.7% of the respondents. The top two reasons for going flat were desire for a faster recovery and avoidance of a foreign body placement. Overall, the mean scaled satisfaction score was 3.72 ± 1.17 out of 5. In the multivariable analysis, low level of surgeon support for the decision to go flat was the strongest predictor of a satisfaction score lower than 3 (odds ratio [OR], 3.85; 95% confidence interval [CI], 2.59-5.72; p < 0.001). Dissatisfaction also was more likely among respondents reporting a body mass index (BMI) of 30 kg/m2 or higher (OR, 2.74; 95% CI, 1.76-4.27; p < 0.001) and those undergoing a unilateral procedure (OR, 1.99; 95% CI, 1.29-3.09; p = 0.002). Greater satisfaction was associated with receiving adequate information about surgical options (OR, 0.48; 95% CI, 0.32-0.69; p < 0.0001) and having a surgeon with a specialized breast surgery practice (OR, 0.56; 95% CI, 0.38-0.81; p = 0.002). CONCLUSIONS: Most patients undergoing mastectomy alone are satisfied with their surgical outcome. Surgeons may optimize patient experience by recognizing and supporting a patient's decision to go flat.

A comparison of two non-radioactive alternatives to wire for the localization of non-palpable breast cancers.

PURPOSE: Multiple wire-free technologies for localization of non-palpable breast cancers have emerged as satisfactory alternatives to wire. However, no study has compared two non-radioactive wire-free approaches to one another. The purpose of this study was to compare outcomes among LOCalizer™ radiofrequency identification (RFID), SAVI Scout® (SAVI), and wire localization (WL). METHODS: This was a retrospective, cross-sectional cohort study of patients undergoing lumpectomy for non-palpable breast cancer at a single institution between August 2017 and February 2019. Patients were divided into three cohorts based on localization technique: RFID, SAVI or WL. Operative times and average tumor volumes were compared using one-way analysis of variance. Positive margin and re-excision rates were compared with Fisher's exact test. RESULTS: Among 104 patients who underwent lumpectomy for non-palpable breast cancer, 33 patients (31.7%) had RFID, 21 (20.2%) had SAVI, and 50 (48.0%) had WL. Operative times were 79 min for RFID, 81 min for SAVI, and 78 min for WL (p = 0.91). Volume of tissue resected was 36.3 cm3, 31.7 cm3, and 35.3 cm3 for RFID, SAVI, and WL, respectively (p = 0.84). Positive margin rates (RFID 3.0% vs SAVI 9.5% vs WL 8.0%, p = 0.67) and re-excision rates (RFID 6.1% vs SAVI 9.5% vs WL 10.0%, p = 0.82) were similar across groups. CONCLUSIONS: Wire-free localization technologies have been compared to WL demonstrating similar efficacy. Our study suggests that RFID and SAVI Scout also perform similarly to one another. Physicians and institutions may consider more nuanced features of each localization system rather than performance alone when choosing a wire-free alternative.

National Trends in Immediate Breast Reconstruction: An Analysis of Implant-Based Versus Autologous Reconstruction After Mastectomy.

BACKGROUND: Many factors affect access to immediate breast reconstruction (IR) after mastectomy. The present study was performed to assess trends, outcomes, and predictors of IR techniques using a nationally representative cohort. METHODS: The 2009-2014 National Inpatient Sample (NIS) was used to identify adult women who underwent inpatient mastectomy with IR. Patients were compared by type of reconstruction: implant-based IR versus autologous reconstruction (AR). AR was classified as a microsurgical or pedicled flap procedure. Incidence, outcomes, and predictors were assessed using Chi squared univariate tests and multivariable logistic regression analyses. RESULTS: Of 194,073 women who underwent IR, 136,668 (70.4%) received implant-based IR and 57,405 (29.6%) received AR. Of those who underwent AR procedures, 31,336 (54.6%) received microsurgical flaps and 26,680 (46.5%) received pedicled flaps. Utilization of deep inferior epigastric perforator (DIEP) flaps increased significantly (28.6-42.5% of AR, P < 0.001). Predictors of AR were Black race [adjusted odds ratio (AOR) = 1.46, P < 0.001], lower Elixhauser Comorbidity Index (AOR = 1.25, P < 0.001), private insurance (AOR = 1.07, P = 0.030), body mass index (BMI) ≥ 30 kg/m2 (AOR = 1.38, P < 0.001), urban teaching hospital designation (AOR = 1.77, P < 0.001), and high hospital volume (AOR = 3.11, P < 0.001). Similar factors were associated with the use of microsurgical flaps. AR and microsurgical flaps were associated with higher rates of acute inpatient complications, resource utilization and length of stay (LOS) compared with implant-based IR and pedicled flaps, respectively. CONCLUSION: Implant-based IR remains the most common type of IR, although rates of microsurgical AR are on the rise. Follow-up of complications, costs, and quality-of-life measures may show that AR provides long-term high-value care despite upfront morbidity, cost, and use of hospital resources.

Current Status of Contralateral Prophylactic Mastectomy: Investigating Structural Racial Disparity.

BACKGROUND: Contralateral prophylactic mastectomy (CPM) remains a personal decision, influenced by psychosocial factors, including cosmesis and peace of mind. Although use of CPM is disproportionately low among Black patients, the degree to which these disparities are driven by patient- vs hospital-level factors remains unknown. STUDY DESIGN: Patients undergoing mastectomy for nonmetastatic ductal or lobular breast cancer were tabulated using the National Cancer Database from 2004 to 2020. The primary endpoint was receipt of CPM. Multivariable logistic regression models were constructed with interaction terms between Black-serving hospital (BSH) status and patient race to evaluate associations with CPM. Cox proportional hazard models were used to evaluate long-term survival. RESULTS: Of 597,845 women studied, 70,911 (11.9%) were Black. After multivariable adjustment, Black race (adjusted odds ratio 0.65, 95% CI 0.64 to 0.67) and treatment at BSH (adjusted odds ratio 0.84, 95% CI 0.83 to 0.85) were independently linked to lower odds of CPM. Although predicted probability of CPM was universally lower at higher BSH, Black patients faced a steeper reduction compared with White patients. Receipt of CPM was linked to improved survival (hazard ratio [HR] 0.84, 95% CI 0.83 to 0.86), whereas Black race was associated with a greater HR of 10-year mortality (HR 1.14, 95% CI 1.12 to 1.17). CONCLUSIONS: Hospitals serving a greater proportion of Black patients are less likely to use CPM, suggestive of disparities in access to CPM at the institutional level. Further research and education are needed to characterize surgeon-specific and institutional practices in patient counseling and shared decision-making that shape disparities in access to CPM.

Impact of Safety-Net Hospital Status on Immediate Reconstruction Following Mastectomy: A Contemporary National Analysis.

INTRODUCTION: Immediate breast reconstruction (IBR) following mastectomy has been shown to improve quality of life and partially mitigate the adverse psychological impacts associated with the procedure. The present study examined hospital-based and patient-level disparities in utilization and outcomes of IBR following mastectomy. METHODS: All female adult hospitalizations with a diagnosis of breast cancer undergoing mastectomy were identified in the 2016 to 2020 National Inpatient Sample. Safety-net hospitals (SNH) were defined as those in the top quartile of all Medicaid or self-pay admissions. Patients who underwent mastectomy at SNH comprised the SNH cohort (others: Non-SNH). Multivariable models were developed to examine the impact of SNH status and patient factors on rates of IBR. RESULTS: Of an estimated 127,740 hospitalizations, 28,330 (22.2%) were treated at SNH. The proportion of patients receiving IBR increased from 46.7% in 2016 to 51.7% in 2020 (nptrend<.001). Compared to others, SNH were younger (57.9 ± 13.5 vs 58.3 ± 13.5 years) and less commonly White (45.6 vs 69.9%) (all P < .001). Additionally, SNH were more likely to receive unilateral mastectomy (67.1 vs 55.2%) but less frequently underwent IBR (37.7 vs 51.5%) (all P < .001). After adjustment, Black and Asian race, SNH, and bilateral mastectomy were associated with decreased odds of IBR. Increasing IBR hospital volume did not eliminate the observed racial disparity at non-SNH or SNH. CONCLUSION: There are disparities in rates of IBR following mastectomy attributable to SNH status. Future work is needed to ensure all patients have access to reconstructive care irrespective of payer status or the hospital at which they receive care.

Does surgeon-performed intraoperative wire localization allow for lower margin positivity rates compared to radiologist-performed preoperative localization in early breast cancer?

BACKGROUND: This study compares positive margin rates in breast conserving surgery (BCS) for early breast cancer using two localization techniques: surgeon-performed intraoperative ultrasound-guided wire localization (IOWL) versus radiologist-performed preoperative wire localization (POWL). METHODS: Patients with unifocal breast cancer undergoing BCS with follow-up at a single institution were retrospectively identified. Factors associated with positive margins were identified. RESULTS: 177 patients underwent IOWL (N â€‹= â€‹85) or POWL (N â€‹= â€‹92). There was a significantly lower rate of positive margins for IOWL vs. POWL (7.1 â€‹% vs. 23.9 â€‹%, p â€‹= â€‹0.002) and a corresponding lower rate of re-excision for IOWL vs. POWL (5.9 â€‹% vs. 18.5 â€‹%, p â€‹= â€‹0.011). Presence of DCIS was associated with positive margins (p â€‹= â€‹0.015). After adjusting for presence of DCIS, tumor size, and volume of tissue removed, the positive margin rate was significantly lower in the IOWL group compared to the POWL group (aOR 0.34, 95 â€‹% CI 0.13-0.93). CONCLUSIONS: In this study, adjusted analysis favored IOWL in achieving negative tumor margins. Prospective studies are needed to further explore the impact of IOWL on quality, cost-effectiveness, and patient experience.

National trends and predictors of mastectomy with immediate breast reconstruction.

PURPOSE: This study aimed to evaluate national trends in utilization, resource use, and predictors of immediate breast reconstruction (IR) after mastectomy. METHODS: The 2005-2014 National Inpatient Sample database was used to identify adult women undergoing mastectomy. IR was defined as any reconstruction during the same inpatient stay. Multivariable regression models were utilized to identify factors associated with IR. RESULTS: Of 729,340 patients undergoing mastectomy, 41.3% received IR. Rates of IR increased from 28.2% in 2005 to 58.2% in 2014 (NP-trend<0.001). Compared to mastectomy alone, IR was associated with increased length of stay (2.5 vs. 2.1 days, P < 0.001) and hospitalization costs ($17,628 vs. $8,643, P < 0.001), which increased over time (P < 0.001). Predictors of IR included younger age, fewer comorbidities, White race, private insurance, top income quartile, teaching hospital designation, high mastectomy volume, and performance of bilateral mastectomy. CONCLUSION: Mastectomy with IR is increasingly performed with resource utilization rising at a steady pace. Our study points to persistent sociodemographic and hospital level disparities associated with the under-utilization of IR. Efforts are needed to alleviate disparities in IR.

How patients experience endocrine therapy for breast cancer: an online survey of side effects, adherence, and medical team support.

PURPOSE: Many patients with hormone receptor-positive (HR+) breast cancer do not adhere to endocrine therapy (ET), and treatment-related side effects are often discussed by participants in online breast cancer forums. Our aim was to survey this unique group of patients about their ET-related experiences. METHODS: We partnered with patients active in breast cancer social media communities to develop a survey assessing ET-related side effects and medical team communication. Patients with a history of HR+ breast cancer who had received a recommendation to take ET were eligible to participate in the anonymous, online survey. RESULTS: Respondents included 2353 women and 54 men. Aromatase inhibitors were the most commonly used medication. Side effects were reported by 91.2%, were more often experienced by women than men (p < 0.001), and were primarily related to medication type. Approximately one-third of respondents discontinued therapy early. While most felt supported by their medical team, 31.5% reported that their side effects were dismissed or minimized. Survey respondents most frequently reported that a healthy diet and exercise, yoga/acupuncture, and vitamins/supplements were helpful in managing ET-related side effects. CONCLUSIONS: ET-related side effects are very common, and one-third discontinued treatment early. Lifestyle changes and complementary therapies can be important tools for side effect management. One-third of patients did not feel that their side effects were taken seriously. IMPLICATIONS FOR CANCER SURVIVORS: This is the largest survey of ET use by participants in online breast cancer communities. Further research is needed to identify strategies to improve treatment adherence and to better manage ET-related side effects.

Intratumor Heterogeneity of the Estrogen Receptor and the Long-term Risk of Fatal Breast Cancer.

Background: Breast cancer patients with estrogen receptor (ER)-positive disease have a continuous long-term risk for fatal breast cancer, but the biological factors influencing this risk are unknown. We aimed to determine whether high intratumor heterogeneity of ER predicts an increased long-term risk (25 years) of fatal breast cancer. Methods: The STO-3 trial enrolled 1780 postmenopausal lymph node-negative breast cancer patients randomly assigned to receive adjuvant tamoxifen vs not. The fraction of cancer cells for each ER intensity level was scored by breast cancer pathologists, and intratumor heterogeneity of ER was calculated using Rao's quadratic entropy and categorized into high and low heterogeneity using a predefined cutoff at the second tertile (67%). Long-term breast cancer-specific survival analyses by intra-tumor heterogeneity of ER were performed using Kaplan-Meier and multivariable Cox proportional hazard modeling adjusting for patient and tumor characteristics. Results: A statistically significant difference in long-term survival by high vs low intratumor heterogeneity of ER was seen for all ER-positive patients (P < .001) and for patients with luminal A subtype tumors (P = .01). In multivariable analyses, patients with high intratumor heterogeneity of ER had a twofold increased long-term risk as compared with patients with low intratumor heterogeneity (ER-positive: hazard ratio [HR] = 1.98, 95% confidence interval [CI] = 1.31 to 3.00; luminal A subtype tumors: HR = 2.43, 95% CI = 1.18 to 4.99). Conclusions: Patients with high intratumor heterogeneity of ER had an increased long-term risk of fatal breast cancer. Interestingly, a similar long-term risk increase was seen in patients with luminal A subtype tumors. Our findings suggest that intratumor heterogeneity of ER is an independent long-term prognosticator with potential to change clinical management, especially for patients with luminal A tumors.

Breast Cancer Screening in the Precision Medicine Era: Risk-Based Screening in a Population-Based Trial.

Ongoing controversy over the optimal approach to breast cancer screening has led to discordant professional society recommendations, particularly in women age 40 to 49 years. One potential solution is risk-based screening, where decisions around the starting age, stopping age, frequency, and modality of screening are based on individual risk to maximize the early detection of aggressive cancers and minimize the harms of screening through optimal resource utilization. We present a novel approach to risk-based screening that integrates clinical risk factors, breast density, a polygenic risk score representing the cumulative effects of genetic variants, and sequencing for moderate- and high-penetrance germline mutations. We demonstrate how thresholds of absolute risk estimates generated by our prediction tools can be used to stratify women into different screening strategies (biennial mammography, annual mammography, annual mammography with adjunctive magnetic resonance imaging, defer screening at this time) while informing the starting age of screening for women age 40 to 49 years. Our risk thresholds and corresponding screening strategies are based on current evidence but need to be tested in clinical trials. The Women Informed to Screen Depending On Measures of risk (WISDOM) Study, a pragmatic, preference-tolerant randomized controlled trial of annual vs personalized screening, will study our proposed approach. WISDOM will evaluate the efficacy, safety, and acceptability of risk-based screening beginning in the fall of 2016. The adaptive design of this trial allows continued refinement of our risk thresholds as the trial progresses, and we discuss areas where we anticipate emerging evidence will impact our approach.

Use of Molecular Tools to Identify Patients With Indolent Breast Cancers With Ultralow Risk Over 2 Decades.

IMPORTANCE: The frequency of cancers with indolent behavior has increased with screening. Better tools to identify indolent tumors are needed to avoid overtreatment. OBJECTIVE: To determine if a multigene classifier is associated with indolent behavior of invasive breast cancers in women followed for 2 decades. DESIGN, SETTING, AND PARTICIPANTS: This is a secondary analysis of a randomized clinical trial of tamoxifen vs no systemic therapy, with more than 20-year follow-up. An indolent threshold (ultralow risk) of the US Food and Drug Administration-cleared MammaPrint 70-gene expression score was established above which no breast cancer deaths occurred after 15 years in the absence of systemic therapy. Immunohistochemical markers (n = 727 women) and Agilent microarrays, for MammaPrint risk scoring (n = 652 women), were performed from formalin-fixed paraffin-embedded primary tumor blocks. Participants were postmenopausal women with clinically detected node-negative breast cancers treated with mastectomy or lumpectomy and radiation enrolled in the Stockholm tamoxifen (STO-3) trial, 1976 to 1990. EXPOSURES: After 2 years of tamoxifen vs no systemic therapy, regardless of hormone receptor status, patients without relapse who reconsented were further randomized to 3 additional years or none. MAIN OUTCOMES AND MEASURES: Breast cancer-specific survival assessed by Kaplan-Meier analyses and multivariate Cox proportional hazard modeling, adjusted for treatment, patient age, year of diagnosis, tumor size, grade, hormone receptors, and ERBB2/HER2 and Ki67 status. RESULTS: In this secondary analysis of node-negative postmenopausal women, conducted in the era before mammography screening, among the 652 women with MammaPrint scoring available (median age, 62.8 years of age), 377 (58%) and 275 (42%) were MammaPrint low and high risk, respectively, while 98 (15%) were ultralow risk. At 20 years, women with 70-gene high and low tumors but not ultralow tumors had a significantly higher risk of disease-specific death compared with ultralow-risk patients by Cox analysis (hazard ratios, 4.73 [95% CI, 1.38-16.22] and 4.54 [95% CI, 1.40-14.80], respectively). There were no deaths in the ultralow-risk tamoxifen-treated arm at 15 years, and these patients had a 20-year disease-specific survival rate of 97%, whereas for untreated patients the survival rate was 94%. Recursive partitioning identified ultralow risk as the most significant predictor of good outcome. In tumors "not ultralow risk," tumor size greater than 2 cm was the most predictive of outcome. CONCLUSIONS AND RELEVANCE: The ultralow-risk threshold of the 70-gene MammaPrint assay can identify patients whose long-term systemic risk of death from breast cancer after surgery alone is exceedingly low.