Sentinel node staging for breast cancer: Intraoperative molecular pathology overcomes conventional histologic sampling errors

BACKGROUND: When sentinel node dissection reveals breast cancer metastasis, completion axillary lymph node dissection is ideally performed during the same operation. Intraoperative histologic techniques have low and variable sensitivity. A new intraoperative molecular assay (GeneSearch BLN Assay; Veridex, LLC, Warren, NJ) was evaluated to determine its efficiency in identifying significant sentinel lymph node metastases (\u3e.2 mm). METHODS: Positive or negative BLN Assay results generated from fresh 2-mm node slabs were compared with results from conventional histologic evaluation of adjacent fixed tissue slabs. RESULTS: In a prospective study of 416 patients at 11 clinical sites, the assay detected 98% of metastases \u3e2 mm and 88% of metastasis greater \u3e.2 mm, results superior to frozen section. Micrometastases were less frequently detected (57%) and assay positive results in nodes found negative by histology were rare (4%). CONCLUSIONS: The BLN Assay is properly calibrated for use as a stand alone intraoperative molecular test

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

The results of the American College of Surgeons Oncology Group Z0011 (ACOSOG Z0011) trial were first reported in 2005 with a median follow-up of 6.3 years. Longer follow-up was necessary because the majority of the patients had estrogen receptor–positive tumors that may recur later in the disease course (the ACOSOG is now part of the Alliance for Clinical Trials in Oncology)

Management of ductal carcinoma in situ with accelerated partial breast irradiation brachytherapy: Implications for guideline expansion.

PURPOSE: Accelerated partial breast irradiation (APBI) for patients with ductal carcinoma in situ (DCIS) is controversial, and the suitability criteria from the American Brachytherapy Society (ABS), American Society of Therapeutic Radiology and Oncology (ASTRO), and the European Society for Radiotherapy and Oncology (GEC-ESTRO) have important differences. METHODS AND MATERIALS: This is a single-institution retrospective review of 169 consecutive patients with DCIS who underwent lumpectomy followed by APBI intracavitary brachytherapy from 2003 to 2018. Outcomes, including overall survival, recurrence-free survival (RFS), ipsilateral breast tumor recurrence, and distant metastasis, were estimated with the Kaplan-Meier method. RESULTS: The median followup time was 62.5 months. Median age was 66 years (47-89 years). The majority of patients had estrogen receptor-positive disease (89%). Fifty patients (30%) had Grade 3 disease. Of the 142 patients with adequate pathology interpretation, 91 and 108 cases had margins ≥ 3 mm and ≥2 mm, respectively. Most patients (72%) were prescribed and started endocrine therapy. Of the patients evaluable for ABS criteria (N = 130), 97 met the suitability criteria. Of the patients evaluable for ASTRO criteria (N = 129), 42 were deemed cautionary and 33 were deemed unsuitable. Of the patients evaluable for GEC-ESTRO criteria (N = 143), 141 cases were at intermediate risk and two were at high risk. Five-year ipsilateral breast tumor recurrence, RFS, and overall survival were 0.6%, 97.7%, and 97.2%, respectively. The ABS, ASTRO, and GEC-ESTRO criteria failed to significantly predict for RFS. CONCLUSIONS: These results, although limited by short-term followup, indicate that expansion of the eligibility criteria of APBI for patients with DCIS should be considered

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

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

Increased Risk for Ipsilateral Breast Tumor Recurrence in Invasive Lobular Carcinoma after Accelerated Partial Breast Irradiation Brachytherapy.

BACKGROUND: The suitability criteria for accelerated partial breast irradiation (APBI) from the American Brachytherapy Society (ABS), American Society for Radiation Oncology (ASTRO), and The Groupe Européende Curiethérapie European SocieTy for Radiotherapy & Oncology (GEC-ESTRO) have significant differences. MATERIALS AND METHODS: This is a single institution retrospective review of 946 consecutive patients with invasive breast cancer who underwent lumpectomy and APBI intracavitary brachytherapy from 2003 to 2018. Overall survival (OS), breast cancer-specific survival (BCSS), relapse-free survival (RFS), and ipsilateral breast tumor recurrence (IBTR) were estimated with Kaplan-Meier method. RESULTS: Median follow-up time was 60.2 months. Median age was 68 years (46-94 years). The majority of patients had estrogen receptor (ER)-positive disease (94%). There were 821 (87%) cases of invasive ductal carcinoma and 68 cases (7%) of invasive lobular carcinoma (ILC). The 5-year OS, BCSS, RFS, and IBTR were 93%, 99%, 90%, and 1.5%, respectively. Upon univariate analysis, ILC (hazard ratio [HR], 4.6; p = .008) and lack of nodal evaluation (HR, 6.9; p = .01) were risk factors for IBTR. The 10-year IBTR was 2.5% for IDC and 14% for ILC. While the ABS and ASTRO criteria could not predict IBTR, the GEC-ESTRO intermediate risk group was associated with inferior IBTR (p = .04) when compared to both low risk and high risk groups. None of the suitability criteria was able to predict RFS. CONCLUSION: These results show that APBI is an effective treatment for patients with invasive breast cancer. Expansion of the current eligibility criteria should be considered, although prospective validation is needed. Caution is required when considering APBI for patients with ILC. IMPLICATIONS FOR PRACTICE: In a large retrospective review of 946 patients with early breast cancer treated with partial mastectomy and accelerated partial breast irradiation (APBI) intracavitary brachytherapy, this study demonstrates durable local control. Patients deemed unsuitable or high risk by the American Brachytherapy Society, American Society for Radiation Oncology, and European Society for Radiotherapy and Oncology guidelines were not at increased risk for ipsilateral breast tumor recurrence (IBTR), suggesting that expansion of the current criteria should be considered. Importantly, however, these results demonstrate that caution should be taken when considering APBI for patients with invasive lobular carcinoma, as these patients had relatively high risk for IBTR (10-year IBTR, 14%)

Association of Occult Metastases in Sentinel Lymph Nodes and Bone Marrow With Survival Among Women With Early-Stage Invasive Breast Cancer

CONTEXT: Immunochemical staining of sentinel lymph nodes (SLNs) and bone marrow identifies breast cancer metastases not seen with routine pathologic or clinical examination. OBJECTIVE: To determine the association between survival and metastases detected by immunochemical staining of SLNs and bone marrow from patients with early-stage breast cancer. DESIGN, SETTING, AND PATIENTS: From May 1999 to May 2003, 126 sites in the American College of Surgeons Oncology Group Z0010 trial enrolled women with clinical T1–T2, N0, M0 invasive breast carcinoma in a prospective observational study. INTERVENTIONS: All patients underwent breast-conserving surgery and SLN dissection; bone marrow aspiration at the time of operation was initially optional and subsequently mandatory (March 2001). SLN specimens (hematoxylin-eosin negative) and bone marrow specimens were sent to a central laboratory for immunochemical staining; treating clinicians were blinded to results. MAIN OUTCOME MEASURES: Overall survival (primary end point) and disease-free survival (a secondary end point). RESULTS: Of 5119 (98.3%) SLN specimens, 3904 (76.3%) were tumor-negative by hematoxylin-eosin staining. Of 3326 SLN specimens examined by immunohistochemistry, 349 (10.5%) were tumor-positive. Of 3413 bone marrow specimens examined by immunocytochemistry, 104 (3.0%) were positive. At a median follow-up of 6.3 years (through April 2010), 435 patients had died and 376 had disease recurrence. Immunohistochemical evidence of SLN metastases was not significantly associated with overall survival (5-year rates: 95.7% (95% CI, 95.0%–96.5%) for immunohistochemical positive and 95.1% (95% CI, 92.7%–97.5% for immunohistochemical negative disease, P=0.64), unadjusted hazard ratio [HR], 0.90; 95% confidence interval [CI], 0.59–1.39; P=.64). Bone marrow metastases were associated with decreased overall survival (5-year rates: 95.0% (95% CI, 94.3%–95.8%) and 90.1% (95% CI, 84.5%–96.1%), respectively (P=.01) (unadjusted HR, 1.94; 95% CI, 1.02–3.67; P=.04), but neither immunohistochemical evidence of tumor in SLNs (adjusted HR, 0.88; 95% CI, 0.45–1.71; P=.70) nor immunocytochemical evidence of tumor in bone marrow (adjusted HR, 1.83; 95% CI, 0.79–4.26; P=.15) was statistically significant on multivariable analysis. CONCLUSION: Among women receiving breast-conserving therapy and SLN dissection, immunochemical evidence of SLN metastasis was not associated with decreased overall survival over a median of 6.3 years whereas, occult bone marrow metastasis, although rare, was associated with decreased survival. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT0000385