Background In breast cancer patients with nodal metastases at presentation, false-negative rates <10% have been demonstrated for sentinel node biopsy (SLNB) after neoadjuvant chemotherapy (NAC) when ≥3 negative sentinel nodes (SLNs) are retrieved, but the frequency with which axillary dissection (ALND) can be avoided is uncertain. Methods Among 534 prospectively identified consecutive patients with clinical stage II–III cancer receiving NAC from 11/2013–11/2015, all biopsy-proven node-positive (N+) cases were identified. Patients who were clinically node-negative post-NAC were SLNB-eligible. ALND was indicated for failed mapping, <3 SLNs retrieved, or positive SLNs. Results Of 288 N+ patients, 195 completed surgery. 132/195 (68%) were SLNB-eligible. Of these, median age was 50yrs, 73(55%) were ER+, 21(16%) ER−/HER2+, 38(29%) triple negative. SLNB was deferred intraoperatively in 4 cases. Among 128 SLNB attempts, ≥3 SLNs were retrieved in 110 (86%), 1–2 SLNs in 15(12%), 3 (2%) failed mapping. ALND was indicated in 66 cases: 54(82%) for positive SLNs, 9(14%) for <3 negative SLNs, 3(4%) for failed mapping. 17% with <3 negative SLNs retrieved had persistent disease. 62/128 (48%) had SLNB alone with ≥3 SLNs retrieved. Among 195 N+ patients completing surgery, nodal pathologic complete response (pCR) was achieved in 49%, ranging from 21% in ER+/HER2− to 97% in ER−/HER2+ cases, and was significantly more common than breast pCR in ER+/HER2− and triple-negative cases. Conclusions Nearly 70% of N+ patients were SLNB-eligible post-NAC. ALND was avoided in 48%, supporting the role of NAC in reducing the need for ALND among patients presenting with nodal metastases.

Objective To determine rates of axillary dissection (ALND) and nodal recurrence in patients eligible for ACOSOG Z0011. Summary Background Data Z0011 demonstrated that patients with cT1-2N0 breast cancers and 1–2 involved sentinel lymph nodes (SLNs) having breast-conserving therapy (BCT) had no difference in locoregional recurrence or survival after SLN biopsy alone or ALND. The generalizability of the results and importance of nodal radiotherapy (RT) is unclear. Methods Patients eligible for Z0011had SLN biopsy alone. Prospectively defined indications for ALND were metastases in ≥3 SLNs or gross extracapsular extension. Axillary imaging was not routine. SLN and ALND groups and radiation fields were compared with chi-square and t-tests. Cumulative incidence of recurrences was estimated with competing risk analysis. Results From 8/2010–12/2016, 793 patients met Z0011 eligibility criteria and had SLN metastases. 130 (16%) had ALND; ALND did not vary based on age, estrogen receptor, progesterone receptor, or HER2 status. 5-year event-free survival after SLN alone is 93% with no isolated axillary recurrences. Cumulative 5-year rates of breast+nodal and nodal+distant recurrence were each 0.7%. In 484 SLN-only patients with known RT fields (103 prone, 280 supine tangent, 101 breast+nodes) and follow-up≥12 months, the 5-year cumulative nodal recurrence rate was 1% and did not differ significantly by RT fields. Conclusions We confirm that even without preoperative axillary imaging or routine use of nodal RT, ALND can be avoided in a large majority of Z0011-eligible patients with excellent regional control. This approach has the potential to spare substantial numbers of women the morbidity of ALND.

There is an urgent need for reliable markers to identify patients whose prostate cancer (PCa) will recur after initial therapy and progress to lethal disease. Gleason score (GS) is considered the most accurate predictive marker for disease-specific mortality after primary treatment of localized PCa. The majority of PCas cluster into groups of GS 6 and 7 with considerable variation in the disease recurrence and disease-specific death. In preclinical PCa models, Stat5a/b promotes PCa growth and progression. Stat5a/b is critical for PCa cell viability in vitro and for tumor growth in vivo and promotes metastatic dissemination of cancer in nude mice. Here, we analyzed the predictive value of high nuclear Stat5a/b protein levels in two cohorts of PCas: Material I (n=562) PCas treated by radical prostatectomy (RP), and Material II (n=106) PCas treated by deferred palliative therapy. In intermediate GS PCas treated by radical prostatectomy, high levels of nuclear Stat5a/b predicted both early recurrence (univariate analysis; p<0.0001, multivariate analysis; HR=1.82, p=0.017) and early PCa-specific death (univariate analysis; p=0.028). In addition, high nuclear Stat5a/b predicted early disease recurrence in both univariate (p<0.0001) and multivariate (HR=1.61; p=0.012) analysis in the entire cohort of patients treated by RP regardless of the GS. Patients treated by deferred palliative therapy, elevated nuclear Stat5a/b expression was associated with early PCa-specific death by univariate Cox regression analysis (HR=1.59; 95% CI=[1.04, 2.44]; p=0.034). If confirmed in future prospective studies, nuclear Stat5a/b may become a useful independent predictive marker of recurrence of lethal PCa after RP for intermediate GS PCas.

Background Re-excision rates in patients undergoing breast-conserving surgery (BCS) for early-stage invasive breast cancer are highly variable. The Society of Surgical Oncology (SSO) and American Society for Radiation Oncology (ASTRO) published consensus guidelines to help standardize practice. We sought to determine re-excision rates before and after guideline adoption at our institution. Methods We identified patients with stage I or II invasive breast cancer initially treated with BCS between 06/01/2013–10/31/2014. Margins were defined as positive (tumor on ink), close (≤1 mm), or negative (>1 mm), and were recorded for both invasive cancer and ductal carcinoma in situ (DCIS) components. Re-excision rates were quantified, characteristics were compared between groups, and multivariable logistic regression was performed. Results 1205 patients were identified; 504 pre-, and 701 post-guideline adoption (01/01/2014). Clinical and pathologic characteristics were similar between time periods. Re-excision rates significantly declined from 21.4% to 15.1% (p=0.006) after guideline adoption. A multivariable model identified extensive intraductal component (odds ratio (OR)=2.5,95% CI 1.2–5.2), multifocality (OR=2.0, 1.2–3.6), positive (OR=844.4, 226.3–5562.5) and close (OR=38.3, 21.5–71.8) DCIS margin, positive (OR=174.2, 66.2–530.0) and close (OR=6.4, 3.0–13.6) invasive margin, and time period (OR=0.5, 0.3–0.9 for post- versus pre-) as independently associated with re-excision. Conclusion Overall re-excision rates declined significantly after guideline adoption. Close invasive margins were associated with higher rates of re-excision than negative invasive margins in both time periods; however, the effect diminished in the post-guideline adoption period. Thus we expect continued decline in re-excision rates as adherence to guidelines becomes more uniform.

IMPORTANCEProspective trials have demonstrated sentinel lymph node (SLN) false-negative rates of less than 10% when 3 or more SLNs are retrieved in patients with clinically node-positive breast cancer rendered clinically node-negative with neoadjuvant chemotherapy (NAC). However, rates of nodal recurrence in such patients treated with SLN biopsy (SLNB) alone are unknown because axillary lymph node dissection (ALND) was performed in all patients, limiting adoption of this approach. OBJECTIVE To evaluate nodal recurrence rates in a consecutive cohort of patients with clinically node-positive (cN1) breast cancer receiving NAC, followed by a negative SLNB using a standardized technique, and no further axillary surgery. DESIGN, SETTING, AND PARTICIPANTSFrom November 2013 to February 2019, a cohort of consecutively identified patients with cT1 to cT3 biopsy-proven N1 breast cancer rendered cN0 by NAC underwent SLNB with dual tracer mapping and omission of ALND if 3 or more SLNs were identified and all were pathologically negative. Metastatic nodes were not routinely clipped, and localization of clipped nodes was not performed. The study was performed in a single tertiary cancer center.INTERVENTION Omission of ALND in patients with cN1 breast cancer after NAC if 3 or more SLNs were pathologically negative. MAIN OUTCOME AND MEASURESThe primary outcome was the rate of nodal recurrence among patients with cN1 breast cancer treated with SLNB alone after NAC. RESULTSOf 610 patients with cN1 breast cancer treated with NAC, 555 (91%) converted to cN0 and underwent SLNB; 234 (42%) had 3 or more negative SLNs and had SLNB alone. The median (IQR) age of these 234 patients was 49 (40-58) years; median tumor size was 3 cm; 144 (62%) were ERBB2 (formerly HER2)-positive, and 43 (18%) were triple negative. Most (212 [91%]) received doxorubicin-based NAC; 205 (88%) received adjuvant radiotherapy (RT), and 164 (70%) also received nodal RT. At a median follow-up of 40 months, there was 1 axillary nodal recurrence synchronous with local recurrence in a patient who refused RT. Among patients who received RT (n = 205), there were no nodal recurrences.CONCLUSIONS AND RELEVANCE This cohort study found that in patients with cN1 disease rendered cN0 with NAC, with 3 or more negative SLNs with SLNB alone, nodal recurrence rates were low, without routine nodal clipping. These findings potentially support omitting ALND in such patients.

Background.-Axillary lymph node dissection (ALND) can be avoided in node-positive patients who receive neoadjuvant chemotherapy (NAC) if ≥3 negative sentinel lymph nodes (SLNs) are retrieved. We evaluate how often node-positive patients avoid ALND with NAC, and identify predictors of identification of ≥3 SLNs and of nodal pathological complete response (pCR).Methods.-From 11/2013-07/2019, all patients with cT1-3, biopsy-proven N1 tumors who converted to cN0 after NAC received sentinel lymph node biopsy (SLNB) with dual mapping and were identified from a prospectively maintained database.Results.-630 consecutive N1 patients were eligible for axillary downstaging with NAC; 573 (91%) converted to cN0 and had SLNB. 531 patients (93%) had ≥3 SLNs identified. Lymphovascular invasion (OR 0.46, 95% CI 0.24-0.87,p=0.02) and increasing BMI (OR 0.77, 95% CI 0.62-0.96 per 5-unit increase,p=0.02) were significantly associated with failure to identify ≥3 SLNs. 255/573 (46%) patients achieved nodal pCR; 237 (41%) had adequate mapping. Factors associated with ALND avoidance included high grade (OR 2.51,p=0.001) and receptor status (HR+/HER2− [referent]: OR 1.99, 95% CI 1. 15-3.46 [p=0.01] for HR−/HER2−, OR 3.93, 95% CI 2. 40-6.44 [p<0.001] for HR+/HER2+, and OR 8.24, 95% CI 4. 16-16.3 [p<0.001] for HR−/HER2+). LVI was associated with lower likelihood of avoiding ALND (OR 0.28, 95% CI 0.18-0.43,p<0.001).Conclusions.-ALND was avoided in 41% of cN1 patients after NAC. Increased BMI and LVI were associated with lower retrieval rates of ≥3 SLNs. ALND avoidance rates varied with receptor status, grade, and LVI. These factors help select patients most likely to avoid ALND.Terms of use and reuse: academic research for non-commercial purposes, see here for full terms. https://www.springer.com/aamterms-v1

Background False-negative rates (FNR) of sentinel node biopsy (SNB) after neoadjuvant chemotherapy (NAC) in node-positive (N+) breast cancer patients are < 10% when ≥ 3 negative SNs are obtained. Marking positive nodes has been suggested to reduce FNR. Identification of treatment effect in the nodes post-NAC is an alternative to decrease FNR. We evaluated the frequency of treatment effect in N+ patients after a pathologic complete response (pCR) with NAC. Methods Biopsy-proven N+ patients receiving NAC were identified. Patients with nodal pCR after ALND or SNB with dual mapping and ≥ 3 SNs removed were evaluated for treatment effect; ALND and SNB patients were compared. Results From 01/09–12/15, 528 N+ patients received NAC. Of these, 204 had a nodal pCR; 135 had an ALND and 69 had SNB. Median age was 49yrs, 15% were hormone receptor positive (HR+)/HER2-, 27% triple negative, and 58% HER2+. The median number of nodes removed in ALND patients was 17 versus 4 in SNB patients. Treatment effect in nodes was identified in 192 (94%) patients, and was more common in ALND versus SNB patients (97% versus 88%, p=0.02). HR+ patients and patients without a breast pCR were less likely to have treatment effect in the nodes (p=0.05). Other characteristics did not differ. Conclusions Following NAC, SNs with treatment effect were retrieved in 88% of patients without marking nodes, suggesting that nodal clipping may not be necessary to achieve an acceptable FNR. Longer follow-up is needed to determine regional recurrence rates in the SN-only cohort.

Background ACOSOG Z0011 demonstrated the safety of omitting axillary dissection (ALND) in women with <3 positive sentinel lymph nodes (SLNs) undergoing breast-conservation therapy (BCT). Since most were postmenopausal with ER-positive cancers, applicability to younger patients or those with triple-negative (TN) or HER2 overexpressing (HER2+) tumors remains controversial. Methods From 8/2010–12/2015, patients undergoing BCT for cT1-2N0 disease and found to have positive SLNs were prospectively followed. ALND was indicated for >2 positive SLNs or gross extracapsular extension. Clinicopathologic characteristics, axillary surgery, nodal burden, and outcomes were compared between high-risk (TN, HER2+, or age<50 years), and the remaining patients, termed average-risk. Results Among 701 consecutive patients, 242 (35%) were high-risk: 31 (13%) TN, 48 (20%) HER2+, 130 (54%) age<50, and 33 (14%) >1 high-risk feature; 459 (65%) were average-risk. High-risk patients were younger, with higher-grade tumors (p<0.0001), and more often had abnormal nodes imaged (p=0.02). SLNB alone was performed in 85% high-risk vs. 82% average-risk cases (p=0.39): median 4 vs. 3 SLNs excised (p=0.04), and median of 1 positive SLN in both groups. 62% high-risk vs. 65% average-risk (p=0.8) had additional positive nodes at ALND, with a median of 3 positive nodes in both groups. At median follow-up of 31 months, there were no isolated axillary recurrences. Conclusions ALND was no more likely to be indicated in high-risk patients. In patients undergoing ALND, nodal burden was similar. ALND is not indicated based upon age or subtype in patients otherwise meeting Z0011 clinical eligibility criteria.