Novel hyaluronan formulation for preventing acute skin reactions in breast during radiotherapy: a randomized clinical trial.

PURPOSE: We conducted a randomized, double-blind, vehicle-controlled clinical trial to investigate the use of a new proprietary hyaluronan (HA) formulation for the prevention of acute skin toxicity in breast cancer patients undergoing radiotherapy (RT). METHODS: Thirty women with breast cancer undergoing whole breast RT were enrolled. Each patient was randomly assigned to HA formulation (study cream, S) on the medial or lateral half of the irradiated breast and the control cream (placebo, P) on the other half. The primary endpoint was physician's evaluation of skin symptoms at week 5 during RT and week 2 post-RT. We also collected patients' independent assessment of skin after RT, patient's product preference, and an independent physician panel assessment of skin reactions based on photographs. RESULTS: Twenty-eight patients were evaluable. On physician's evaluation, there was no significant difference in radiation dermatitis between S and P and no overall preference to either cream at week 5 during or week 2 post-RT. More patients preferred S in evaluating skin appearance and skin reactions, but this did not reach statistical significance. Univariate analysis showed that physicians had an overall preference to the S cream at week 2 post-RT in patients with larger breasts. On the independent panel assessment, 3 reviewers saw no significant difference in radiation toxicity, whereas one reviewer reported better skin outcome with S cream at week 5. CONCLUSIONS: We found a nonstatistically significant patient preference but overall no significant radioprotective effects for this HA formulation compared with placebo except in patients with larger breasts. TRIAL REGISTRATION: The study was registered at www.clinicaltrials.gov (NCT02165605).

Mammographic density changes in surgical weight loss-an indication for personalized screening.

BACKGROUND: Obesity and high radiologic breast density independently increase breast cancer risk. We evaluated the effect of surgical weight loss on mammographic density (MD). METHODS: Patients undergoing bariatric surgery and screening mammography (MG) were identified, data regarding demographics, comorbidities, calculated and genetic breast cancer risk was collected. Patients had a MG before and after surgery. Fellowship-trained breast radiologists assigned Breast Imaging Reporting and Data System density categories. RESULTS: Patients underwent sleeve gastrectomy (n = 56) or gastric bypass (n = 7), 78% had hypertension, 48% had diabetes. Four had deleterious BRCA mutations, four were calculated high risk. Mean weight loss = 28.7 kg. Mean initial BMI = 44.3 kg/m2 (range:33-77), final BMI = 33.6 kg/m2 (range:20-62;p < 0.01). Density was unchanged in 53, decreased in 1, increased in 9. Of these 9(14%), 5 changed from almost entirely fatty to scattered MD, and 4 changed from scattered MD to heterogeneously dense. Mean weight loss of the 9 with increased MD was greater than the cohort (37.7vs.28.7 kg;p < 0.01). CONCLUSIONS: Surgical weight loss increased MD in 14%. Increased MD masks malignancies, patients may benefit from additional screening based on calculated risk assessments that include MD.

Bracketed radioactive seed localization vs bracketed wire-localization in breast surgery.

Multiple localizers placed in a bracketed fashion facilitates excision of radiographically extensive breast lesions. In this study, bracketed radioactive seed localization (bRSL) was compared to bracketed wire localization (bWL). We hypothesized that bRSL would achieve adequate margins and decrease re-operation rates with similar or less specimen volumes (SV) than bWL. Retrospective review identified patients who underwent bracketed breast procedures at an academic medical center. Data collected included patient demographics, tumor features, treatment variables, and surgical outcomes. Wilcoxon rank-sum test and chi-square test were used to compare continuous and categorical data, respectively. A multivariable logistic regression model was used to evaluate the association between re-excision and localization technique after adjusting for clinically relevant variables. Patients who underwent bWL were 3.9 times more likely to undergo re-excision compared to patients in bRSL group (OR=3.9, 95% CI: 2.0-7.4). Initial and total SV did not significantly differ between the two groups (P=.4). Patients were significantly more likely to undergo a mastectomy in the bWL group than in the bRSL group (24% vs 7%; P<.01). For patients undergoing excision of radiologically extensive breast lesions, bRSL serves as an alternative to bWL. In this retrospective study, bRSL was associated with a decreased re-excision rate with similar SV and a lower rate of mastectomy when compared to bWL.

Genetic Ancestry using Mitochondrial DNA in patients with Triple-negative breast cancer (GAMiT study).

BACKGROUND: Triple-negative breast cancer (TNBC) lacks estrogen, progesterone, and human epidermal growth factor receptor 2 (HER2)/neu receptors, and is aggressive and therapeutically challenging. Genetic ancestry testing is an emerging medical field. Mitochondrial DNA (mtDNA), which is distinct from nuclear DNA, is maternally inherited and allows for origin determination. Patients with TNBC tend to be younger and are more likely to be African American, making this an ideal disease for mtDNA exploration. To the authors' knowledge, the current study is the first to perform mtDNA for self-described African American, White, and Hispanic patients with TNBC to identify mtDNA patterns. METHODS: Patients with TNBC who were at any stage of therapy/survivorship were included. Self-reported ethnicity was confirmed at the time of the prospective buccal swab. Haplogroup prediction was performed on sequencing of hypervariable region 1. Using sequence similarity scores and lineage databases, sequence patterns were determined. Data regarding presentation and treatment, tumor features, and outcomes was collected. RESULTS: A total of 92 patients were included: 31 self-described African American, 31 White, and 30 Hispanic individuals. Hispanic patients were found to have the largest tumor size (4.5 cm; P = .01) and youngest age (41 years; P<.0001). Eight patients were BRCA1/2 mutation carriers. There were no differences noted among groups with regard to surgery, lymph node metastases, or survival. Analysis revealed Nigerian, Cameroon, or Sierra Leone ancestry and haplogroups A, U, H, or B to be the most common mtDNA patterns. Twelve discordances (13%) between mtDNA analysis and self-described ethnicity were identified among the 92 patients. The highest discordance (26%; 8 patients) was noted in self-described Hispanic patients: 3 had Nigerian ancestry, and 1 individual demonstrated haplogroup K mtDNA (Ashkenazi Jewish ancestry). CONCLUSIONS: Discordance between self-reported ethnicity and mtDNA analysis was identified in 13% of patients with TNBC. The identification of mtDNA patterns with a predisposition toward TNBC may allow for risk stratification. Cancer 2017;107-113. © 2016 American Cancer Society.

Office ductoscopy for surgical selection in women with pathologic nipple discharge.

BACKGROUND: Pathologic nipple discharge (PND) is diagnosed clinically and managed by diagnostic duct excision (DDE). Mammary ductoscopy in the office setting may change this standard. We performed a prospective study to assess the utility of office ductoscopy for surgical selection in women with nipple discharge. METHODS: Women with nipple discharge meeting at least 2 of 3 criteria of PND (spontaneous, single duct, bloody or serous) underwent office ductoscopy. Those showing papillomatous lesions underwent DDE in the operating room (surgical group, n = 38); if no lesion was present, women were followed clinically (observation group, n = 21). RESULTS: A papillomatous lesion was identified in 79% of women with 3-criteria PND and in 21% with 2 criteria (P = .001). DDE yielded a proliferative lesion in 35 of 38 women (92%). Of the 38, 27 (71%) had papillomata, 2 (5%) had florid hyperplasia, and 6 (16%) had ductal carcinoma in situ (DCIS) on final pathology. Also, 11 women with papilloma and 1 with DCIS presented with 2-criteria PND. Ductoscopy findings were a better predictor of the presence of intraductal neoplasia (area under curve [AUC] 0.9, 95% confidence interval [95% CI] 0.8-0.98) compared with 3-criteria PND (AUC 0.7, 95% CI 0.6-0.8). The 21 women in the observation group did not develop signs of malignancy or need biopsy during a 48-month follow-up period. CONCLUSIONS: Our findings suggest that office ductoscopy provides accurate surgical selection of women with nipple discharge and should be considered for women with 2 criteria of PND, and those with negative ductoscopy can be safely observed. These findings need confirmation in a larger study with longer follow-up.

A Pilot and Feasibility Mobile Health Intervention to Support Healthy Behaviors in African American Breast Cancer Survivors.

African American breast cancer (AA BC) survivors are more likely to have cancer-related comorbidities compared with other women, ultimately putting them at higher risk for overall mortality and breast cancer-specific mortality. Survivorship care guidelines emphasize the importance of attention to obesity, weight management, and physical activity. Mobile technologies have been effective for improving health behaviors among cancer survivors, though few studies have focused on AA BC survivors. Creating Healthy Actions through Technology (CHAT) was a 4-week pilot intervention that employed an ecological momentary assessment (EMA) to improve survivors' physical activity and diet behaviors. We evaluated the acceptability, feasibility, and impact of a mHealth intervention for AA BC survivors. Participants (N = 22) were randomized to intervention (n = 13) or control (n = 9). All participants completed daily EMAs via smartphone for 4 weeks and wore accelerometers for seven consecutive days at baseline, 4, and 8 weeks. Intervention participants additionally received tailored health messages. Diet was measured using a self-reported questionnaire and physical activity with accelerometers. Participant engagement was high. Of 84 EMA assessments, the average response was 63 (SD 16.1). Participant accelerometer wear was at least 6 of the 7 days (SD 1.7) for each assessment. Eighty-five percent of participants reported the intervention helped change behaviors. Intervention participants reduced their sedentary time by 4.37 (SD = 7.14) hours/day versus controls (p = .05), reduced fast food intake by 1.5 servings (p = 0.008), and increased vigorous activity by 0.56 (SD = 28.10) minutes, which was non-significant (p = 0.959). Findings show feasibility and acceptability and potential of the intervention to positively impact physical activity among AA BC survivors.

Cosmetic Outcomes of a Phase 1 Dose Escalation Study of 5-Fraction Stereotactic Partial Breast Irradiation for Early Stage Breast Cancer.

PURPOSE: Our purpose was to evaluate cosmetic changes after 5-fraction adjuvant stereotactic partial breast irradiation (S-PBI). METHODS AND MATERIALS: Seventy-five women with in situ or invasive breast cancer stage 0, I, or II, with tumor size ≤3 cm, were enrolled after lumpectomy in a phase 1 dose escalation trial of S-PBI into cohorts receiving 30, 32.5, 35, 37.5, or 40 Gy in 5 fractions. Before S-PBI, 3 to 4 gold fiducial markers were placed in the lumpectomy cavity for tracking with the Synchrony respiratory tracking system. S-PBI was delivered with a CyberKnife robotic radiosurgery system. Patients and physicians evaluated global cosmesis using the Harvard Breast Cosmesis Scale. Eight independent panelists evaluated digital photography for global cosmesis and 10 subdomains at baseline and follow-up. McNemar tests were used to evaluate change in cosmesis, graded as excellent/good or fair/poor, from baseline to year 3. Wilcoxon signed rank tests were used to evaluate change in subdomains. Cohen's kappa (κ) statistic was used to estimate interobserver agreement (IOA) between raters, and Fleiss' κ was used to estimate IOA between panelists. RESULTS: Median cosmetic follow-up was 5, 5, 5, 4, and 3 years for the 30, 32.5, 35, 37.5, and 40 Gy cohorts. Most patients reported excellent/good cosmesis at both baseline (86.3%) and year 3 (89.8%). No dose cohort had significantly worsened cosmesis by year 3 on McNemar analysis. No cosmetic subdomain had significant worsening by year 3. IOA was fair for patient-physician (κ = 0.300, P < .001), patient-panel (κ = 0.295, P < .001), physician-panel (κ = 0.256, P < .001), and individual panelists (Fleiss κ = 0.327, P < .001). CONCLUSIONS: Dose escalation of S-PBI from 30 to 40 Gy in 5 fractions for early stage breast cancer was not associated with a detectable change in cosmesis by year 3. S-PBI is a promising modality for treatment of early stage breast cancer.

Hypermethylated genes as biomarkers of cancer in women with pathologic nipple discharge.

PURPOSE: In a pilot study of women with pathologic nipple discharge (PND) undergoing ductoscopy, we tested quantitative assessment of gene promoter hypermethylation using quantitative multiplex methylation-specific PCR (QM-MSP) to enhance detection of duct carcinoma in situ (DCIS). EXPERIMENTAL DESIGN: Women with PND underwent ductoscopy; ducts with significant lesions were surgically resected (36 ducts in 33 women) and those with minimal findings were not (28 ducts in 16 women). QM-MSP was done on ductoscopy cell samples. Results were compared with cytology and tissue histology. RESULTS: Cells from ducts with significant lesions on ductoscopy had significantly higher levels of methylation than those with minimal findings. Furthermore, cells from ducts with DCIS displayed higher levels of methylation than those with benign lesions such as papilloma (P = 0.006); or ducts with minimal findings on ductoscopy (P = 0.0001). Cumulative RASSF1A, TWIST1, and HIN1 gene methylation accurately distinguished ducts with cancerous versus benign lesions (100% sensitivity, 72% specificity, and area under the curve of 0.91 according to receiving operating characteristic analyses). QM-MSP analysis was more informative than cytology (100% versus 29% sensitivity, respectively), for detecting DCIS. In a validation set of paraffin-embedded DCIS and papilloma samples from women presenting with PND, QM-MSP was significantly higher in DNA from DCIS than papilloma sections (P = 0.002). CONCLUSION: The positive predictive value of ductoscopy was more than doubled (19% versus 47%) with the addition of QM-MSP, demonstrating the benefit of targeting ducts having both high methylation and significant abnormalities on ductoscopy for surgical excision. Future large-scale studies to validate this approach are needed.

Risk Factors for Fat Necrosis After Stereotactic Partial Breast Irradiation for Early-Stage Breast Cancer in a Phase 1 Clinical Trial.

PURPOSE: This study reports predictive dosimetric and physiologic factors for fat necrosis after stereotactic-partial breast irradiation (S-PBI). METHODS AND MATERIALS: Seventy-five patients with ductal carcinoma-in situ or invasive nonlobular epithelial histologies stage 0, I, or II, with tumor size <3 cm were enrolled in a dose-escalation, phase I S-PBI trial between January 2011 and July 2015. Fat necrosis was evaluated clinically at each follow-up. Treatment data were extracted from the Multiplan Treatment Planning System (Cyberknife, Accuray). Univariate and stepwise logistic regression analyses were conducted to identify factors associated with palpable fat necrosis. RESULTS: With a median follow-up of 61 months (range: 4.3-99.5 months), 11 patients experienced palpable fat necrosis, 5 cases of which were painful. The median time to development of fat necrosis was 12.7 months (range, 3-42 months). On univariate analyses, higher V32.5-47.5 Gy (P < .05) and larger breast volume (P < .01) were predictive of any fat necrosis; higher V35-50 Gy (P < .05), receiving 2 treatments on consecutive days (P = .02), and higher Dmax (P = .01) were predictive of painful fat necrosis. On multivariate analyses, breast volume larger than 1063 cm3 remained a predictive factor for any fat necrosis; receiving 2 treatments on consecutive days and higher V45 Gy were predictive of painful fat necrosis. Breast laterality, planning target volume (PTV), race, body mass index, diabetic status, and tobacco or drug use were not significantly associated with fat necrosis on univariate analysis. CONCLUSIONS: Early-stage breast cancer patients treated with breast conserving surgery and S-PBI in our study had a fat necrosis rate comparable to other accelerated partial breast irradiation modalities, but S-PBI is less invasive. To reduce risk of painful fat necrosis, we recommend not delivering fractions on consecutive days; limiting V42.5 < 50 cm3, V45 < 20 cm3, V47.5 < 1 cm3, Dmax ≤ 48 Gy and PTV < 100 cm3 when feasible; and counseling patients about the increased risk for fat necrosis when constraints are not met and for those with breast volume >1000 cm3.

Axillary management after sentinel lymph node biopsy in breast cancer patients.

According to the available data, sentinel lymph node (SLN) biopsy is proving to be an accurate staging technique with less post-surgical morbidity than standard axillary lymph node dissection (ALND). Survival benefits associated with SLN biopsy and, as well as the significance of IHC detected micrometastases have yet to be determined. The long term results of several multicenter trials are pending, yet preliminary results are in favor of abandoning ALND in favor of the less invasive alternative. Despite this, ALND remains the standard of care in breast cancer patients with clinically palpable axillary lymph nodes that are suspicious for metastatic disease. Although controversial, many clinicians believe that axillary metastases will precede systemic spread of disease. Therefore, axillary clearance of clinically palpable nodes could potentially quell the progression of metastases. Regardless of whether or not this theory is true, not many would argue against debulking suspicious nodal disease.

Preliminary Results of a Phase 1 Dose-Escalation Trial for Early-Stage Breast Cancer Using 5-Fraction Stereotactic Body Radiation Therapy for Partial-Breast Irradiation.

PURPOSE: To evaluate the tolerability of a dose-escalated 5-fraction stereotactic body radiation therapy for partial-breast irradiation (S-PBI) in treating early-stage breast cancer after partial mastectomy; the primary objective was to escalate dose utilizing a robotic stereotactic radiation system treating the lumpectomy cavity without exceeding the maximum tolerated dose. METHODS AND MATERIALS: Eligible patients included those with ductal carcinoma in situ or invasive nonlobular epithelial histologies and stage 0, I, or II, with tumor size <3 cm. Patients and physicians completed baseline and subsequent cosmesis outcome questionnaires. Starting dose was 30 Gy in 5 fractions and was escalated by 2.5 Gy total for each cohort to 40 Gy. RESULTS: In all, 75 patients were enrolled, with a median age of 62 years. Median follow-up for 5 cohorts was 49.9, 42.5, 25.7, 20.3, and 13.5 months, respectively. Only 3 grade 3 toxicities were experienced. There was 1 dose-limiting toxicity in the overall cohort. Ten patients experienced palpable fat necrosis (4 of which were symptomatic). Physicians scored cosmesis as excellent or good in 95.9%, 100%, 96.7%, and 100% at baseline and 6, 12, and 24 months after S-PBI, whereas patients scored the same periods as 86.5%, 97.1%, 95.1%, and 95.3%, respectively. The disagreement rates between MDs and patients during those periods were 9.4%, 2.9%, 1.6%, and 4.7%, respectively. There have been no recurrences or distant metastases. CONCLUSION: Dose was escalated to the target dose of 40 Gy in 5 fractions, with the occurrence of only 1 dose-limiting toxicity. Patients felt cosmetic results improved within the first year after surgery and stereotactic body radiation therapy. Our results show minimal toxicity with excellent cosmesis; however, further follow-up is warranted in future studies. This study is the first to show the safety, tolerability, feasibility, and cosmesis results of a 5-fraction dose-escalated S-PBI treatment for early-stage breast cancer in the adjuvant setting.

Ductal lavage for breast cancer risk assessment.

Ductal lavage is a minimally-invasive procedure that permits sampling of breast ductal fluids for cytopathologic analysis. The technique is performed with topical anesthesia and involves cannulation of any fluid-yielding nipple orifice with a specially-designed catheter for lavage and aspiration of the ductal system. The procedure is used for women who have clinical evidence of increased breast cancer risk; if atypia is detected, it may strengthen a woman's interest in committing to a risk-reducing strategy or a chemoprevention trial. The technology also is being used as a tool in ongoing translational research studies.

Impact of weight change during neoadjuvant chemotherapy on pathologic response in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is an uncommon but aggressive subtype of breast cancer. Obesity has been associated with an increased risk of breast cancer and worse prognosis. Some studies suggest that obese patients are less likely to achieve pathologic complete response (pCR) to neoadjuvant chemotherapy (NCT) and experience worse overall survival. Ki-67 is a proliferation marker that correlates with tumor aggressiveness. The goal of this study was to examine the impact of weight change during NCT for TNBC on pathologic response and Ki-67 reduction. Retrospective review identified 173 TNBC patients treated between 2004 and 2011. Data were collected on patient demographics, pre- and post-NCT body mass index (BMI), Ki-67, and pCR. Data analysis was performed using the two-tailed Student's t-test, analysis of variance (ANOVA), and Fisher's exact test. Sixty-six patients met final study criteria. Forty-three patients lost weight during chemotherapy and 23 gained weight. Patients in the weight gain group were significantly younger (P = 0.0013). There was no significant difference between the two groups in terms of Ki-67 reduction (P = 0.98) or pCR (P = 0.58). When patients were separated into normal weight (BMI<25 kg/m(2) ), overweight (BMI ≥ 25 and <30 kg/m(2) ), and obese (BMI ≥ 30 kg/m(2) ), there was no significant difference in Ki-67 among those groups either before or after NCT. The degree of obesity did not have a significant impact on Ki-67 reduction. Weight change during NCT does not appear to correlate with Ki-67 change or achieving pCR in TNBC. This may reflect the nature of this subtype of breast cancer that is less responsive to the hormonal effects that adipose tissue exerts on cancer cell proliferation.

Strategies for reducing cancer incidence and mortality in African American and Arab American and Chaldean communities in the Detroit metropolitan area.

OBJECTIVES: We studied the feasibility of implementing a community-based participatory process (CBPP) that addressed cancer education, prevention, and screening in 2 ethnic minority populations by evaluating the improvement in rates of cancer screening compared with historical benchmarks. METHODS: From 2003 to 2009, 2281 community members participated in CBPPs conducted by the Beaumont Cancer Institute in cooperation with the Arab American and Chaldean (AAC) Council, the National Cancer Institute, and the American Cancer Society. The study population consisted of 1067 individuals who completed a postcancer forum survey: 642 from the African American (AA) and 425 from the AAC forums. Data were collected on participants' screening history and participation in subsequent screening tests after the previous year's CBPP. RESULTS: Following attendance of at least one cancer forum the previous year, 329 (30.8%) of the 1067 participant respondents underwent some type of cancer screening, 32% in the AA forums and 28.9% in the AAC forums. Compared with published controls, the CBPPs led to a 38.6% increase in mammographic screening and a 28.7% increase in prostate-specific antigen screening; the AA cohort had 39.7% and 28.4% increases whereas the AAC cohort had 36.3% and 28.9% increases in mammographic and prostate-specific antigen screening, respectively. CONCLUSIONS: The results of this study suggest that implementing CBPPs are feasible in underscreened ethnic minority populations. Further studies need to be performed to determine the absolute benefit of CBPPs compared with baseline levels of screening within these ethnic minority populations.

Differences in disease presentation, management techniques, treatment outcome, and toxicities in African-American women with early stage breast cancer treated with breast-conserving therapy.

BACKGROUND: Data on patients who received breast-conserving therapy (BCT) for early stage breast cancer were examined to detect differences in disease presentation, management techniques, long-term treatment outcomes, and toxicities based on race. METHODS: Six hundred ninety-nine women with breast cancer (39 African-American [AA] women and 660 Caucasian [C] women) who received BCT were analyzed on race, clinical and pathologic characteristics at presentation, management techniques, treatment-related toxicities, recurrence, and survival. The median follow-up was 12.2 years. RESULTS: At diagnosis, AA women were younger (aged<50 years, 49% vs 29%; P=.002), had larger tumors (mean, 17.0 mm vs 13.9 mm; P=.032), had more estrogen receptor-negative tumors (56% vs 18%; P<.001), and higher nuclear grade tumors (grade 3, 52% vs 29%; P=.006). Compared with C women, AA women more frequently received adjuvant chemotherapy (59% vs 19%; P<.001) and lymph node irradiation (26% vs 13%; P=.033). No other significant treatment differences were observed. After treatment, AA women experienced more breast pain (P=.001), more arm edema (P=.046), and less excellent cosmetic results (P=.008), but there were no statistically significant differences in local recurrence (P=.232), distant metastasis (P=.263), overall survival (P=.131), or cause-specific survival (P=.092) based on race. CONCLUSIONS: The current results suggested that AA women present with larger and more aggressive breast tumors and, as a result, more frequently received adjuvant chemotherapy and lymph node irradiation. Small differences in treatment-related toxicities and cosmesis were observed, but no differences in efficacy were identified.

Clinicopathologic features associated with having four or more metastatic axillary nodes in breast cancer patients with a positive sentinel lymph node.

BACKGROUND: The survival benefit of a completion axillary lymph node dissection (ALND) in patients after removal of a metastatic sentinel lymph node (SLN) is uncertain and is under study in ongoing clinical trials. The completion ALND remains necessary, however, for the identification of cases with at least four metastatic lymph nodes, in which extended-field locoregional and/or postmastectomy radiation will be recommended. Our goal was evaluate clinicopathologic features that might serve as surrogates for determining which patients with a positive SLN are likely or unlikely to belong to this high-risk subset. METHODS: Records were reviewed for 285 patients from 2 comprehensive cancer centers who underwent completion ALND after resection of a metastatic SLN from 1995 to 2002. Clinicopathologic features were analyzed by univariate and multivariate logistic regression. Forty-one cases (14%) were found to have at least four positive nodes after ALND. RESULTS: Fisher's exact test revealed the following features to be significantly (P < .05) associated with having four or more nodal metastases: tumor size >2 cm, lymphovascular invasion, an increasing ratio of positive SLNs to the total number of resected SLNs, extranodal extension, and the size of the SLN metastasis. Patients whose largest SLN metastasis was <2 mm had only a 1.4% risk of having four or more metastatic nodes (P < .0001). CONCLUSIONS: We conclude that patients with SLN micrometastases face an extremely low likelihood of having extensive nodal disease on completion ALND. Patients with larger primary tumors, lymphovascular invasion, and extranodal extension are more likely to have ALND findings that will affect their cancer management.