David J. Winchester

Factors Predicting the Use of Breast-Conserving Therapy in Stage I and II Breast Carcinoma

PURPOSE To define patterns of care for the local therapy of stage I and II breast cancer and to identify factors used to select patients for breast-conserving therapy (BCT). PATIENTS AND METHODS A convenience sample of 16,643 patients with stage I and II breast cancer treated in 1994 was obtained from hospital-based tumor registries. Histologic variables were determined from original pathology reports. RESULTS BCT was performed in 42.6% of patients. Multivariate analysis demonstrated that living in the Northeast United States (odds ratio [OR], 2.48; 95% confidence interval [CI], 2.16 to 2.84), having a clinical T1 tumor (OR, 2.51; 95% CI, 2.27 to 2.78), and having a tumor without an extensive intraductal component (OR, 2.07; 95% CI, 1.81 to 2.37) were the strongest predictors of breast-conserving surgery. Radiation therapy was given to 86% of patients who had breast-conserving surgery. Age less than 70 years was the most significant predictor of receiving radiation (OR, 2.11; 95% CI, 1.77 to 2.25). Tumor variables did not correlate with the use of radiation, but favorable tumor characteristics were associated with the use of breast-conserving surgery. CONCLUSION Despite strong evidence supporting the use of BCT, the majority of women continue to be treated with mastectomy. Predictors of the use of BCT do not correspond to those suggested in guidelines.

Comparison of Sentinel Lymph Node Biopsy Alone and Completion Axillary Lymph Node Dissection for Node-Positive Breast Cancer

PURPOSE For women with breast cancer, the role of completion axillary lymph node dissection (ALND) after identification of nodal metastases by sentinel lymph node biopsy (SLNB) has been questioned. Our objectives were to assess national nodal evaluation practice patterns and to examine differences in recurrence and survival for SLNB alone versus SLNB with completion ALND. PATIENTS AND METHODS From the National Cancer Data Base (1998 to 2005), women with clinically node-negative breast cancer who underwent SLNB and who had nodal metastases were identified. Practice patterns and outcomes were examined for patients who underwent SLNB alone versus SLNB with completion ALND (median follow-up, 63 months). RESULTS Of 97,314 patients, 20.8% underwent SLNB alone, and 79.2% underwent SLNB with completion ALND. In 2004 to 2005, patients were significantly more likely to undergo SLNB alone if they were older, had smaller tumors, or were treated at non-National Cancer Institute-designated cancer centers. In patients with macroscopic nodal metastases (n = 20,075 during 1998 to 2000), there was a nonsignificant trend toward better outcomes for completion ALND (v SLNB alone) after analysis was adjusted for differences between the two groups: axillary recurrence (hazard ratio [HR], 0.58; 95% CI, 0.32 to 1.06) and overall survival (HR, 0.89; 95% CI, 0.76 to 1.04). In patients with microscopic nodal metastases (n = 2,203 during 1998 to 2000), there were no significant differences in axillary recurrence or survival for patients who underwent SLNB alone versus completion ALND. CONCLUSION Compared with SLNB alone, completion ALND does not appear to improve outcomes for breast cancer patients with microscopic nodal metastases; however, there was a nonsignificant trend toward better outcomes with completion ALND for those with macroscopic disease.

Adult soft tissue sarcomas. A pattern of care survey of the American College of Surgeons.

A nationwide survey of the clinical presentation, pathology, and management of soft tissue sarcomas in adults was carried out under the auspices of the Commission on Cancer of the American College of Surgeons. Two separate 2-year periods were used to allow assessment of changes in patterns of care. Data were obtained from 504 hospitals in 1977–1978 (2355 patients) and 645 institutions in 1983–1984 (3457 patients). Pretreatment findings of interest included some evidence of physician delay in diagnosis, overuse of excisional biopsy as opposed to the generally preferred approach of incisional biopsy, a low rate of usage of the American Joint Committee for Cancer Staging (AJCSS) system, and major reliance on CT for pretreatment patient evaluation. Operation was the primary treatment, with or without adjuvant therapies, in approximately three fourths of the patients. The other one fourth were primarily patients with distant metastasis at the time of diagnosis. Some increase in multimodal therapy did occur in the second period but the rate of amputation was low (approximately 10%) in both periods studied. Survival curves support the prognostic validity of the AJCCS system and the value of complete resection of soft tissue sarcomas. Adverse prognostic factors included positive surgical margins, large tumors, retro- peritoneal or mediastinal primary sites, some histologic types, and the perceived need for adjuvant therapy. Patients receiving adjuvant radiation or chemotherapy had less favorable survival data than those treated by operation alone due to criteria used for selecting patients for these therapies. Approximately one half of the treatment failures in the 1977–1978 series were locoregional, whereas 18% were limited to lung metastasis. Salvage therapy for these two forms of treatment failure yielded 61% and 21% 5-year survival rates.

The National Cancer Data Base 10-year survey of breast carcinoma treatment at hospitals in the United States

The National Cancer Data Base (NCDB), a joint project of the American College of Surgeons Commission on Cancer and the American Cancer Society, is a cancer management and outcome data base for health care organizations. It provides a comparative summary of patient care that is used by participating hospitals and communities for self‐assessment. The most current (1995) data are described herein.

Lymphedema after sentinel lymphadenectomy for breast carcinoma

Initial studies of sentinel lymphadenectomy for patients with breast carcinoma confirmed that the status of the sentinel lymph nodes was an accurate predictor of the presence of metastatic disease in the axillary lymph nodes. Sentinel lymphadenectomy, as an axillary staging procedure, has risks of morbidity that have yet to be defined.

BAG‐1, a negative regulator of Hsp70 chaperone activity, uncouples nucleotide hydrolysis from substrate release

Molecular chaperones influence the process of protein folding and, under conditions of stress, recognize non‐native proteins to ensure that misfolded proteins neither appear nor accumulate. BAG‐1, identified as an Hsp70 associated protein, was shown to have the unique properties of a negative regulator of Hsp70. Here, we demonstrate that BAG‐1 inhibits the in vitro protein refolding activity of Hsp70 by forming stable ternary complexes with non‐native substrates that do not release even in the presence of nucleotide and the co‐chaperone, Hdj‐1. However, the substrate in the BAG‐1‐containing ternary complex does not aggregate and remains in a soluble intermediate folded state, indistinguishable from the refolding‐competent substrate–Hsp70 complex. BAG‐1 neither inhibits the Hsp70 ATPase, nor has the properties of a nucleotide exchange factor; instead, it stimulates ATPase activity, similar to that observed for Hdj‐1, but with opposite consequences. In the presence of BAG‐1, the conformation of Hsp70 is altered such that the substrate binding domain becomes less accessible to protease digestion, even in the presence of nucleotide and Hdj‐1. These results suggest a mechanistic basis for BAG‐1 as a negative regulator of the Hsp70–Hdj‐1 chaperone cycle.

Intraoperative radioisotope sentinel lymph node mapping in non–small cell lung cancer

BACKGROUND Lymph node metastases are the most significant prognostic factor in localized non-small cell lung cancer (NSCLC). Nodal micrometastases may not be detected. Identification of the first nodal drainage site (sentinel node) may improve detection of metastatic nodes. We performed intraoperative Technetium 99m sentinel lymph node (SN) mapping in patients with resectable NSCLC. METHODS Fifty-two patients (31 men, 21 women) with resectable suspected NSCLC were enrolled. At thoracotomy, the primary tumor was injected with 2 mCi Tc-99. After dissection, scintographic readings of both the primary tumor and lymph nodes were obtained with a handheld gamma counter. Resection with mediastinal node dissection was performed and findings were correlated with histologic examination. RESULTS Seven of the 52 patients did not have NSCLC (5 benign lesions, and 2 metastatic tumors) and were excluded. Forty-five patients had NSCLC completely resected. Mean time from injection of the radionucleide to identification of sentinel nodes was 63 minutes (range 23 to 170). Thirty-seven patients (82%) had a SN identified; 12 (32%) had metastatic disease. 35 of the 37 SNs (94%) were classified as true positive with no metastases found in other intrathoracic lymph nodes without concurrent SN involvement. Two inaccurately identified SNs were encountered (5%). SNs were mediastinal (N2) in 8 patients (22%). CONCLUSIONS Intraoperative SN mapping with Tc-99 is an accurate way to identify the first site of potential nodal metastases of NSCLC. This method may improve the precision of pathologic staging and limit the need for mediastinal node dissection in selected patients.

Axillary Recurrence After Sentinel Node Biopsy

BackgroundSentinel node biopsy (SNB) has evolved as the standard of care in the surgical staging of breast cancer. This technique is accurate for surgical staging of axillary nodal disease. We hypothesized that axillary recurrence after SNB is rare and that SNB may provide regional control in patients with microscopic nodal involvement.MethodsWith institutional review board approval, SNB was performed with peritumoral injection of 99mTc-labeled sulfur colloid. From 1996 to 2003, 1167 patients were entered into a prospective cancer database after surgical therapy; 916 patients consented to long-term follow-up. Fifty-two patients (5.7%) did not map successfully and were excluded, leading to a study population of 864 patients. The median follow-up was 27.4 months (range, 1–98 months).ResultsThe median number of sentinel nodes harvested was 2, and 633 (73%) patients had negative sentinel nodes. Thirty (4.7%) of those sentinel node–negative patients underwent completion axillary dissection, whereas 592 (94%) patients were followed up with observation. A total of 231 (27%) had positive sentinel nodes: 158 (68%) of these patients underwent completion axillary dissection, and 73 (32%) were managed with observation alone. Two (.32%) patients who were sentinel node negative had an axillary recurrence; one of these patients had undergone completion axillary dissection. No patient in the observed sentinel node–positive group had an axillary recurrence (odds ratio, .37; P = .725).ConclusionsOn the basis of a median follow-up of 27.4 months, axillary recurrence after SNB is extraordinarily rare regardless of nodal involvement, thus indicating that this technique provides an accurate measure of axillary disease and may impart regional control for patients with node-positive disease.

Prognostic significance of occult lymph node metastases in node-negative breast cancer.

AbstractBackground: Lymph node status, established by a single hematoxylin and eosin (H&E) section from each node, remains an important prognostic indicator in patients with breast cancer, but used alone it is insufficient to identify patients who will develop metastatic disease. This study was conducted to assess the significance of detecting occult metastases in 86 patients with breast cancer originally reported to be histologically node negative. None of the patients received adjuvant systemic therapy. Methods: Five additional levels from formalin-fixed, paraffin-embedded nodes were examined at 150-µm intervals with H&E staining and a cocktail of antikeratin antibodies (AE1/AE3) recognizing low molecular weight acidic keratins. Results: Nodes from 11 (12.8%) of 86 patients contained occult metastases. All metastases identified by cytokeratin antibody were also detected in H&E-stained sections. With median follow-up of 80 months, distant metastases occurred in five of 11 occult node-positive patients (45%) and 13 of 75 patients whose nodes were negative on review (17%). Median time to recurrence was 89 months for occult node-positive patients and not yet reached for node-negative patients (p=0.048). The disease-specific 5-year survival rate was 90% for occult node-positive patients and 95% for node-negative patients. Conclusions: The presence of occult metastases shortened the disease-free interval and suggested that more diligent axillary staging would more accurately identify patients who would benefit from systemic adjuvant treatment.

Sentinel lymphadenectomy for breast cancer: experience with 180 consecutive patients: efficacy of filtered technetium 99m sulphur colloid with overnight migration time.

BACKGROUND Axillary node status remains the most important prognostic indicator of survival in breast cancer patients. Only 25% to 35% of patients having standard level I/II axillary dissection have involved nodes, yet all accept the potential for morbidity after the operation. This study was conducted to assess whether status of the sentinel node(s) was an accurate predictor of the presence of metastatic disease in axillary or internal mammary nodes. STUDY DESIGN In 180 patients, technetium 99m sulphur colloid was injected in a 4-quadrant peritumoral distribution. During the first phase of the study, 72 patients had sentinel node excision followed by a level I/II axillary dissection. During the second phase of the study, 108 patients had sentinel node excision and only those with positive nodes had completion axillary dissection. Nodes were examined after formalin fixation by taking 10 sections at 20-microm intervals and staining with hematoxylin-eosin. RESULTS Sentinel nodes were found in 162 (90%) of 180 patients. The mean number of sentinel nodes examined was 3.1. Of the 162 patients with successful lymphatic mapping, positive sentinel nodes were found in 44 (27%). In 23 (66%) of 35 patients with positive sentinel nodes who had a completion level I/II axillary dissection, the sentinel nodes were the only positive nodes. The concurrent negative predictive value was 4% in the first 72 patients who had completion axillary dissection after sentinel node excision, and 2% for the entire series. With evolution of technique, identification of sentinel nodes with radiolabeled colloid was successful in 97% of the last 100 patients. CONCLUSIONS Because the concurrent negative predictive value was low, sentinel node excision appeared to accurately identify node status, potentially avoiding the need for standard level I/II axillary dissection in sentinel node-negative patients.