Residual metastatic axillary lymph nodes following neoadjuvant chemotherapy predict disease-free survival in patients with locally advanced breast cancer

BACKGROUND: This study was performed to validate the prognostic significance of residual axillary lymph node metastases in patients with locally advanced breast cancer (LABC) treated with neoadjuvant chemotherapy and to analyze other clinicopathologic factors that might be independent predictors of disease-free survival (DFS) in an attempt to identify patients in whom axillary dissection might be omitted. METHODS: One hundred sixty-five assessable patients with LABC were treated in a prospective trial of neoadjuvant chemotherapy utilizing four cycles of 5-fluorouracil, doxorubicin, and cyclophosphamide. Responding patients were treated with segmental mastectomy and axillary dissection or modified radical mastectomy. Patients subsequently received additional chemotherapy followed by irradiation of the breast or chest wall and draining lymphatics. The median follow-up was 35 months. RESULTS: Clinical tumor response to neoadjuvant chemotherapy (P = 0.046) and the number of residual metastatic axillary lymph nodes found at axillary dissection (P = 0.05) were the only independent predictors of DFS. Patients with a complete clinical response had a predictably excellent DFS and those with no change or progressive disease had a poor DFS. In patients with a partial response, the number of residual metastatic lymph nodes further stratified patients with respect to DFS (P = 0.006). CONCLUSIONS: Clinical response and residual metastatic axillary lymph nodes following neoadjuvant chemotherapy are important predictors of DFS. Patients with a clinically positive axilla following neoadjuvant chemotherapy should undergo axillary dissection to ensure local control. However, the benefit of axillary dissection in patients with a clinically negative axilla may be minimal if the axilla will be irradiated, and histologic staging does not affect subsequent systemic treatment. A prospective randomized trial of axillary dissection versus axillary radiotherapy in patients with a clinically negative axilla following neoadjuvant chemotherapy is presently under way to evaluate this hypothesis.     

Role of axillary lymph node dissection after tumor downstaging with induction chemotherapy for locally advanced breast cancer

BACKGROUND: Induction chemotherapy has become the standard of care for patients with locally advanced breast cancer (LABC) and currently is being evaluated in prospective clinical trials in patients with earlier-stage disease. To better gauge the role of axillary lymph node dissection in patients with LABC this study was performed to assess initial axillary status on physical and ultrasound examination, axillary tumor downstaging following induction chemotherapy, and the accuracy of physical examination compared with axillary sonography in predicting which patients will have axillary lymph node metastases found on pathologic examination. METHODS: Between 1992 and 1996, 147 consecutive patients with LABC were registered in a prospective trial of induction chemotherapy using 5-fluorouracil, doxorubicin, and cyclophosphamide. Physical and ultrasound examinations of the axilla were performed at diagnosis and after induction chemotherapy. Segmental resection with axillary lymph node dissection or modified radical mastectomy was performed, followed by postoperative chemotherapy and irradiation of the breast or chest wall and regional lymphatics. RESULTS: Following induction chemotherapy, 43 (32%) of the 133 patients with clinically positive lymph nodes on initial examination had axillary tumor downstaging as assessed by physical and ultrasound examination. The sensitivity of axillary sonography in identifying axillary metastases was significantly higher than that of physical examination (62% vs. 45%, P=.012). The specificity of physical examination (84%) was higher than that of sonography (70%), but the difference did not reach statistical significance. Among the 55 patients in whom the findings of both physical and ultrasound examination of the axilla were negative following induction chemotherapy, 29 patients (53%) were found to have axillary lymph node metastases on pathologic examination of the axillary contents. However, 28 (97%) of these patients had either 1 to 3 positive lymph nodes or only micrometastases 2 to 5 mm in diameter. CONCLUSIONS: Preoperative clinical assessment of the axilla by physical examination combined with ultrasound examination is not completely accurate in predicting metastases in patients with LABC following tumor downstaging. However, patients with negative findings on both physical and ultrasound examinations of the axilla may be potential candidates for omission of axillary dissection if the axilla will be irradiated because minimal axillary disease remains. Patients who have positive findings on preoperative physical or ultrasound examinations should receive axillary dissection to ensure local control. A prospective randomized trial of axillary dissection versus axillary radiotherapy in patients with a clinically negative axilla following induction chemotherapy is currently underway.     

Gamma-probe-guided resection of the sentinel lymph node in breast cancer

Regional lymph node metastases in patients with breast cancer have fundamental staging, prognostic, and treatment implications. Classically, axillary lymph node sampling requires a dissection under general anesthesia. The concept that a primary, or sentinel, lymph node is the first node to receive drainage from a tumor has been established in patients with malignant melanomas using radiolabeled tracers and vital dyes. This study proposed two hypotheses: (1) radiolabeled sentinel lymph nodes can be identified in most patients with breast cancer, and (2) radiolabeled sentinel lymph node biopsy accurately predicts axillary lymph node metastases in those patients. Patients with operable breast cancer had Tc-99 sulphur colloid injected around their breast tumors 1-6 hours preoperatively. Patients underwent gamma probe identification of sentinel lymph nodes that were biopsied. All patients underwent axillary lymphadenectomy in conjunction with lumpectomy or mastectomy. Fifty female patients ages 26 to 90 years underwent lumpectomies with axillary dissections (40 patients) or modified radical mastectomies (10 patients). Sentinel lymph nodes were identified in 42 of 50 patients (84%). Eight patients (16%) had metastases to the axillary lymph nodes. In 7 patients, sentinel lymph nodes correctly predicted the status of the axillary nodes. There was one false negative result. A total of 550 lymph nodes were resected for an average of 11.2 nodes per patient. Sentinel lymph node scintigraphy and biopsy accurately predicted the axillary lymph node status in 41 of 42 patients (98%). Scintigraphy can identify sentinel lymph nodes in a large majority of patients. Sentinel lymph node biopsy is an accurate predictor of axillary lymphatic metastases.     

Assessment of axillary lymph node involvement in breast cancer patients with positron emission tomography using radiolabeled 2-(fluorine-18)-fluoro-2-deoxy-D-glucose

BACKGROUND: The presence of metastatic tumor cells in the axillary lymph nodes is an important factor when deciding whether or not to treat breast cancer patients with adjuvant therapy. Positron emission tomography (PET) imaging with the radiolabeled glucose analogue 2-(fluorine-18)-fluoro-2-deoxy-D-glucose (F-18 FDG) has been used to visualize primary breast tumors as well as bone and soft-tissue metastases. PURPOSE: This study was undertaken to evaluate before surgery the diagnostic accuracy of PET for detection of axillary lymph node metastases in patients suspected of having breast cancer. METHODS: Women who were scheduled to undergo surgery for newly discovered, suspected breast cancers were referred for PET imaging of the axilla region. The women were first clinically examined to determine the status of their axillary lymph nodes (i.e., presence or absence of metastases). Fifty-one women were intravenously administered F-18 FDG and were studied by PET imaging. Attenuation-corrected transaxial and coronal images were visually evaluated by two nuclear medicine physicians (blinded to the patient's medical history) for foci of increased F-18 FDG uptake in the axilla region. All patients underwent surgery for their suspected breast cancers. Axillary lymph node dissection was also performed on all patients with breast cancer, with the exception of four patients who received primary chemotherapy for locally advanced breast cancer. A single pathologist analyzed breast tumor and lymph node tissue specimens. RESULTS: The overall sensitivity (i.e., the ability of the test to detect disease in patients who actually have disease) and specificity (i.e., the ability of the test to rule out disease in patients who do not have disease) of this method for detection of axillary lymph node metastases in these patients were 79% and 96%, respectively. When only patients with primary breast tumors larger than 2 cm in diameter (more advanced than stage pT1; n = 23) were considered, the sensitivity of axillary PET imaging increased to 94%, and the corresponding specificity was 100%. Lymph node metastases could not be identified in four of six patients with small primary breast cancers (stage pT1), resulting in a sensitivity of only 33%. Axillary PET imaging provided additional diagnostic information in 12 (29%) of 41 breast cancer patients with regard to the extension of disease to other sites (i.e., other lymph nodes, skin, bone, and lung). CONCLUSIONS: PET imaging with F-18 FDG allowed accurate and noninvasive detection of axillary lymph node metastases, primarily in patients with breast cancer more advanced than stage pT1. Detection of micrometastases and small tumor-infiltrated lymph nodes is limited by the currently achievable spatial resolution of PET imaging. IMPLICATIONS: In clinical practice, PET imaging cannot substitute for histopathologic analysis in detecting axillary lymph node metastases in breast cancer patients. PET imaging, however, improves the preoperative staging of the disease in breast cancer patients and, therefore, might alter therapeutic regimen options.     

Experience with lymphatic mapping in breast cancer using isosulfan blue dye

Sentinel (first tumor-draining) lymph node (SLN) biopsy directed by the blue dye technique may be as accurate as complete axillary lymph node dissection (ALND) in determining whether breast cancer has metastasized to the lymph nodes and may have fewer surgical complications because it is less invasive. Breast cancer patients scheduled for ALND between February and June 1997 who did not have prior axillary surgery, prior radiation therapy, or preoperative chemotherapy were included. Isosulfan blue dye was injected around the primary tumor or the biopsy cavity just before ALND. Operations were performed in a tertiary breast center by two breast surgeons who did not have experience with the technique before this study. The results of blue stained nodes were compared to those of the ALND. Blue-stained nodes were identified in 35 of 40 patients (88%), and the results were concordant with ALND in 33 of 35 (94%), 7 patients were concordant for positive results and 26 for negative results. We identified SLNs in patients whose cancers were either in the medial or lateral halves of the breast. Average time for SLN dissection was 19 +/- 9 minutes, and there were no complications. The diagnostic accuracy of the isosulfan blue dye technique for SLN biopsy, 94%, is high enough to warrant further research. The lack of complications and the short time needed to perform the technique are attractive features. Broader experience with the technique is required to evaluate the reliability and reproducibility of this method.     

Micrometastatic breast cancer cells in bone marrow at primary surgery: prognostic value in comparison with nodal status

BACKGROUND: Approximately 30% of the patients with primary breast cancer who have no axillary lymph node involvement (i.e., lymph node negative) at the time of surgery will relapse within 10 years; 10%-20% of the patients with distant metastases will be lymph node negative at surgery. Axillary lymph node dissection, as a surgical procedure, is associated with frequent complications. A possible alternative to nodal dissection in terms of prognosis may be the immunocytochemical detection of tumor cells in bone marrow. PURPOSE: In a prospective study, the value of tumor cell detection (TCD) in bone marrow was compared with axillary lymph node dissection in the prognosis of primary breast cancer after surgery. METHODS: Data from 727 patients with primary, operable breast cancer were included in the analysis. All patients had surgery, including axillary lymph node dissection, from May 1985 through July 1994 at the Women's Hospital of the University of Heidelberg (Federal Republic of Germany). Bone marrow aspiration at two sites on each anterior iliac crest was performed immediately after surgery while the patients were under general anesthesia. Most patients received some type of systemic adjuvant therapy. The monoclonal antibody 2E11, directed against the polymorphic epithelial mucin TAG12, was used to detect tumor cells in bone marrow samples. The association of TCD with recognized prognostic indicators was evaluated by means of chi-squared tests. Survival without the development of distant metastases (i.e., distant disease-free survival) and overall survival were estimated by use of the Kaplan-Meier method; the logrank test was used to compare survival curves. A multivariate Cox regression analysis with stratification according to adjuvant treatment type was used to assess the independent prognostic value of TCD in bone marrow in relation to other variables. Reported P values are two-sided. RESULTS: Tumor cells were detected in the bone marrow of 203 (55%) of 367 lymph node-positive patients and in 112 (31%) of 360 lymph node-negative patients. TCD was associated with larger tumors (P < .001), lymph node involvement (P = .001), and higher tumor grade (i.e., more undifferentiated) (P = .002). After a median follow-up of 36 months, patients with tumor cells in their bone marrow experienced reduced distant disease-free survival and overall survival (both P values < .001). TCD was an independent prognostic indicator for both distant disease-free survival and overall survival that was superior to axillary lymph node status, tumor stage, and tumor grade. Among patients with tumors less than 2 cm in diameter, TCD was the most powerful predictor of outcome. CONCLUSIONS AND IMPLICATIONS: TCD in the bone marrow of patients with breast cancer is a valuable prognostic tool associated with negligible morbidity. Prospective randomized studies should be performed to determine whether TCD might replace axillary lymph node dissection in a defined subgroup of patients with small tumors.     

Is axillary dissection always indicated in invasive breast cancer?

In light of the changing trends in the diagnosis and management of invasive breast cancer, the practice of routine axillary dissection should be reevaluated. A growing number of patients with breast cancer are diagnosed as having small tumors with an associated low risk of lymph node metastases. The pathologic features of the primary tumor are increasingly being used as a prognostic guide for recommendations about adjuvant systemic therapy, and there are recent reports suggesting a superior prognostic value for tumor cells detected in bone marrow, as compared to axillary lymph node metastases. Consequently, axillary lymph node status is no longer the single prognostic guide for recommendations about adjuvant systemic therapy. For treatment of the axilla, there is evidence that, in clinical N0 patients, radiation therapy to the axilla is an effective alternative to axillary dissection. Finally, there are cost and morbidity considerations for patients undergoing axillary dissection in whom the indications of the procedure are equivocal. In the management of invasive breast cancer, a selective policy toward axillary lymph node dissection should be considered. This review discusses the nonsurgical management of the axilla; ie, radiation therapy to the axilla and observation of the axilla as an alternative to axillary dissection.     

Inhibitory effect of cycloartenol ferulate, a component of rice bran, on tumor promotion in two-stage carcinogenesis in mouse skin

Sentinel lymph node (SN) biopsy in primary breast cancer seems to be an alternative to complete axillary lymph node dissection for evaluation of the axillary lymph node status in selected patients. Following evaluation of the technique of SN biopsy, we applied SN biopsy clinically to 23 selected patients. A lymphoscintigraphy was performed preoperatively to evaluate lymphatic drainage. The SN was identified in the operating room by use of a hand-held gamma camera and a blue vital dye. The SN was found in all 23 patients. In 17/23 the SN was tumor free and no axillary dissection was performed; 6/23 showed a positive SN and complete axillary dissection was done. Intraoperative lymphatic mapping and SN biopsy may be the treatment of choice for evaluation of axillary node status in selected patients, for it combines accurate nodal staging and low morbidity.     

Identification of sentinel and axillary node involvement in breast cancer

Axillary node dissection for breast cancer is important for staging and prognosis. "Sentinel nodes" are the first nodes into which primary cancer drains. Identification, removal and pathological examination of those nodes indicates whether completion of axillary lymphadenectomy is required. The sentinel nodes are identified using a vital dye injected at the primary tumor site. With this technique we were able to identify sentinel nodes in 46 of 48 (95%) women examined. An average of 2.7 +/- 1.2 nodes were identified as sentinel nodes. In 81% of cases there was a correlation between involvement of sentinel nodes and of other axillary nodes as well. In 10% of patients sentinel nodes were involved with tumor while other axillary nodes were negative. The major problem in routine application of this is relationship in surgical decisions is reliable real time pathological identification of lymph node involvement by tumor.     

Generation of superoxide anion and induction of superoxide dismutase and peroxidase in bean leaves infected with pathogenic fungi

PURPOSE: The purpose of this study was to review management strategies with respect to systemic therapy, radiation therapy treatment techniques, and patient outcome (local regional control, distant metastases, and overall survival) in patients undergoing conservative surgery and radiation therapy (CS + RT) who had four or more lymph nodes involved at the time of original diagnosis. METHODS AND MATERIALS: Of 1040 patients undergoing CS + RT at our institution prior to December 1989, 579 patients underwent axillary lymph node dissection. Of those patients undergoing axillary lymph node dissection, 167 had positive nodes and 51 of these patients had four or more positive lymph nodes involved and serve as the patient population base for this study. All patients received radiation therapy to the intact breast using tangential fields with subsequent electron beam boost to the tumor bed to a total median dose of 64 Gy. The majority of patients received regional nodal irradiation as follows: 40 patients received RT to the supraclavicular region without axilla to a median dose of 46 Gy, 10 patients received radiation to the supraclavicular region and axilla to a median dose of 46 Gy. Thirty of the 51 patients received a separate internal mammary port with a mixed beam of photons and electrons. One patient received radiation to the tangents alone without regional nodal irradiation. Adjuvant systemic therapy was used in 49 of the 51 patients (96%) with 27 patients receiving chemotherapy alone, 14 patients receiving cytotoxic chemotherapy and tamoxifen, and 8 patients receiving tamoxifen alone. RESULTS: As of December 1994, with a minimum evaluable follow-up of 5 years and a median follow-up of 9.29 years, there have been 18 distant relapses, 2 nodal relapses, and 5 breast relapses. Actuarial statistics reveal a 10-year distant metastases-free rate of 65%, 10-year nodal recurrence-free rate of 96%, and a 10-year breast recurrence-free rate of 82%. All five patients who sustained a breast relapse were successfully salvaged with mastectomy. Both patients with nodal relapses (one supraclavicular and one axillary/supraclavicular) failed within the irradiated volume. Of the 40 patients treated to the supraclavicular fossa (omitting complete axillary radiation), none failed in the dissected axilla. With a median follow-up of nearly 10 years, 29 of the 51 patients (57%) remain alive without evidence of disease, 15 (29%) have died with disease, 2 (4%) remain alive with disease, and 5 (10%) have died without evidence of disease. Overall actuarial 10-year survival for these 51 patients is 58%. CONCLUSIONS: We conclude that in patients found to have four or more positive lymph nodes at the time of axillary lymph node dissection, conservative surgery followed by radiation therapy to the intact breast with appropriate adjuvant systemic therapy results in a reasonable long-term survival with a high rate of local regional control. Omission of axillary radiation in this subset of patients appears appropriate because there were no axillary failures among the 41 dissected but unirradiated axillae.     

Sentinel lymphadenectomy: an alternative to axillary lymphadenectomy in breast carcinoma

BACKGROUND: Axillary lymph node status is an important determinant of prognosis in breast cancer. However, lymphadenectomy does not benefit half of the patients in whom axillary nodes are free of disease. Sentinel lymph node biopsy is a new technique which allows accurate staging of breast carcinoma without performing total axillary dissection. We describe our experience with the introduction of sentinel lymphadenectomy. METHODS: Thirty-seven sentinel lymphadenectomies were performed in 35 patients referred to the Department of Obstetrics and Gynaecology of the University of Berne between December 1997 and June 1998. Mapping procedures were performed using a combination of vital blue dye with preoperative lymphscintigraphy with 99mTechnetium-labelled colloidal albumin and intraoperative use of a gamma probe. Complete axillary lymphadenectomy was then performed in 34 patients. RESULTS: One or more lymph nodes were identified in 33 of 37 procedures (89%). With the combination of both localisation techniques the sentinel nodes were identified in all (100%) of the last 19 patients. Sentinel and non-sentinel lymph nodes were always concordant. In this series the negative predictive value is 100% (95% confidence interval: 87.7%-100%). Metastases were found in the sentinel node in 11 of 30 patients (37%). From these 11 patients, 3 (27%) had micrometastases. CONCLUSIONS: Histopathologic examination of the sentinel lymph node accurately predicts the axillary lymph-node status. Patients with sentinel nodes free of metastases could avoid the unnecessary peri- and postoperative complications of complete axillary dissection. Further studies are needed to assess whether the improved diagnosis of micrometastases by sentinel lymphadenectomy influences the long-term prognosis of breast cancer.     

Breast-conserving surgery and radiotherapy for early breast cancer

Breast conservation is not a commonly prescribed treatment option for breast cancer in Taiwan. We report 42 patients with 43 early-stage breast cancers who were treated with breast-conserving surgery and radiotherapy at the Koo Foundation Sun Yat-Sen Cancer Center from April 1990 to December 1994. Included in this study were 33 patients with stage I cancers and 10 with stage II. Breast-conserving surgery consisted of wide local excision and ipsilateral axillary lymph node dissection. Radiotherapy was given 2 to 6 weeks after surgery, with a dose of 46 to 50 Gy, 2 Gy per fraction per day, to the whole breast, and an additional 14 to 18 Gy to the original tumor site. Irradiation to the regional lymph nodes was not performed in patients with negative axillary lymph nodes. Sixteen out of 43 (37%) patients were treated with adjuvant chemotherapy. The local control rate 3 years after treatment was 97% and relapse-free survival was 91%. The cosmetic outcome in 41 treated breasts that were rendered relapse-free by conserving treatment were evaluated and graded by the physicians as excellent, good, fair or poor using a standardized scale. Forty breasts (98%) were scored as excellent or good for their cosmetic results. Breast-conserving surgery and radio-therapy offer Taiwanese women with early breast cancer excellent local control and a highly satisfactory cosmetic outcome.     

Radioimmunoguided surgery after primary treatment of locally advanced breast cancer

PURPOSE: To assess the role of radioimmunoguided surgery (RIGS) using a handheld intraoperative gamma-detecting probe (GDP) to identify neoplastic disease after primary chemotherapy in locally advanced breast cancer (LABC) patients injected with iodine 125-labeled monoclonal antibodies (MAbs). PATIENTS AND METHODS: Twenty-one patients with histologically documented LABC were treated with a combined modality approach. After three courses of primary chemotherapy and before modified radical mastectomy, the 125I-radiolabeled MAbs B72.3 (anti-TAG72) and FO23C5 (anti-carcinoembryonic antigen [CEA]) were administered to 11 patients (group A) and 10 patients (group B), respectively. At surgery, a GDP was used to locate the primary tumor and to assess possible tumor multicentricity and the presence of ipsilateral axillary metastases. Routine pathologic examination was performed in neoplastic and normal tissue specimens of all 21 patients. In addition, immunohistochemical assay for TAG72 and CEA expression was performed. RESULTS: In group A patients, RIGS identified primary tumor in seven of 11 patients (63.3%) and unpalpable multicentric tumor lesions were located in two of four (50%). Positive axillary lymph nodes were histologically documented in eight of 11 patients (72.7%) and RIGS identified three of eight (37.5%). In group B, RIGS located the primary tumor lesion in four of 10 patients (40%); in two cases, the tumor was not clinically evident. Multicentricity was observed in one of two patients and lymph node involvement in three of nine (33.3%). No false-positive results were observed in either group A or B. CONCLUSION: RIGS appears to be a safe and reliable technique. However, the MAbs used in this study are not sufficiently specific. RIGS represents a technique for which the full potential for intraoperative assessment of breast cancer lesions can be reached when more specific antibodies become readily available.     

Sentinel node detection in breast carcinoma

The aim of sentinel node biopsy (SN) in breast cancer patients is to detect the tumor-draining lymph node by means of isosulfan blue or 99mTc-labelled colloids. SN can be detected in 80 to 85% of the patients, depending on the size of the tumor. Preoperative lymphoscintigraphy permits the draining nodes along the internal mammary artery also to be visualized. The predictive value of the histological findings of SN for lymph nodes obtained from axillary dissection is about 95%. Because of different diagnostic procedures using various radiotracers each center has to follow its own learning curve. To be sure that the nodal status derived from a SN procedure is of identical value to axillary dissection about 100 patients have to undergo sentinel node detection, followed by axillary dissection, and concordant results should be obtained in 95% of them at least. The SN, however, offers a chance of assessing the lymph node at risk for metastasis by more detailed histological procedures. Morbidity as a result of treatment for primary breast cancer can be decreased if only patients suffering from metastatic disease are subjected to axillary dissection. Currently, the indication criteria for a SN procedure should be restricted to small tumors (T1) with clinically uninvolved axillary status and patients with ductal carcinoma in situ (DCIS).     

Axillary node metastasis from T1N0M0 breast cancer: possible avoidance of dissection in a subgroup

BACKGROUND: Axillary lymph node dissection is now no longer considered to be the standard treatment in all patients with invasive breast cancer. We have attempted to identify a sub-group of patients with invasive breast carcinoma who may not need to undergo axillary lymph node dissection. METHODS: Patients (n = 823) with T1 N0M0 invasive breast cancer treated at our hospital between 1970 and 1994 were studied. We investigated the relationship between positive axillary lymph nodes and the following clinico-pathological factors: patient age, menopausal status, contralateral breast cancer (synchronous or asynchronous), tumor location, tumor size (T:cm), histopathology, histological grade, presence or absence of malignant microcalcification or spiculation on mammography and estrogen receptor status. RESULTS: The incidence of axillary lymph node metastases in patients with T1N0M0 invasive breast cancer was 25% (208/823). The node-negative group was significantly older than the node-positive group. Premenopausal patients had a higher rate of lymph node metastases although this was not significant. The frequency of nodal metastases when related to the tumor size was as follows: T< or =1.0 cm, 17%; T< or =1.5 cm, 25%; T< or =2.0 cm, 29%. Mammography revealed that patients with malignant calcification or spiculation had a significantly higher rate of nodal metastases than those without these findings. Certain tumor types (medullary, mucinous and tubular carcinomas) had lower positive rates for lymph node involvement. With regard to the histological grade, lymph node positivity increased significantly with high-grade tumors. No correlation was observed between any other factors and the presence or absence of lymph node metastases. CONCLUSIONS: It may be possible to avoid axillary lymph node dissection in postmenopausal patients (50 years or older) where the histological type is favorable when the tumor diameter is < or =1.0 cm and when microcalcification or spiculation is absent on mammography.     

三阴性乳腺癌5年随访

Objective: The aim of the study was to investigate the long-term therapeutic effects of triple negative breast cancers (TNBCs) and find a standardized treatment. Methods: The clinical data and survival status of 69 patients with TNBC were collected, who were treated from 2003 to 2007 at Chongqing Cancer Institute, China. Results: Median observation for 61 months showed the local recurrence rate was 13.0% (9/69), the overall survival (OS) rate was 76.8% (53/69) and the disease free survival (DFS) rate was 59.4% (41/69). Log-rank univariate survival analysis showed the OS and DFS rates of TNBCs with axillary lymph node metastasis were 38.1% and 23.8%, respectively, and the OS and DFS rates of triple negative breast cancer with axillary lymph node non-metastasis were 93.8% and 75.0%, respectively. There were significant differences comparing with two groups. Indictor analysis of age, menstruation status, tumor size, TNM stage, histological type,neoadjuvant chemotherapy and p53 did not show any prognostic influence. Conclusion: The axillary nodes metastasis is associated with DFS and OS in triple negative breast cancers. Cisplatin-based chemotherapy may be good choice for triple negative breast cancers with metastasis or local recurrence, who received Anthracyciine and Taxane-based chemotherapy.Targeted therapies strategies such as EGFR-targeted therapy may be necessary.     

Extracapsular axillary node extension in patients receiving adjuvant systemic therapy: an indication for radiotherapy?

PURPOSE: This is a retrospective review into the patterns of failure of 82 patients with Stage II or III breast cancer who had extracapsular extension (ECE) of axillary nodal metastases and who received systemic chemotherapy or hormonal therapy without loco-regional radiation. METHODS AND MATERIALS: The clinical records of patients with axillary node positive (T1-T3, N1, 2) Stage II or III breast cancer seen at the London Regional Cancer Centre between 1980-1989 were reviewed. Patients were identified who underwent segmental mastectomy with axillary node dissection or modified radical mastectomy and received adjuvant chemotherapy or tamoxifen but did not undergo loco-regional radiation. Eighty-two patients within this group had pathologic evidence of extracapsular axillary node extension (ECE). For 45 of these patients the extension was extensive, and for the remaining 37 it was microscopic. This ECE-positive group was compared to a subgroup of 172 patients who did not have pathologic evidence of extracapsular axillary node extension but had metastatic carcinoma confined within the nodal capsule. RESULTS: Median age of the 82 ECE-positive patients was 56 years. Twenty-five patients had had a segmental mastectomy, the remainder a modified radical mastectomy. Median actuarial survival was 60 months, with a median disease-free and loco-regional failure-free survival of 38 months. Seventy-eight percent of these patients developed a recurrence, which was loco-regional in 60% (21% local, 21% regional, 2% local and regional, and 16% loco-regional and metastatic). There was a 36% recurrence rate in intact breast, 14% the chest wall following modified radical mastectomy, 7% relapsed in the axilla, 12% in supraclavicular nodes, and 1% in the internal mammary nodes. A comparison of the 82 ECE-positive patients with a group of 172 ECE-negative patients determined that there was a statistically significant difference between the two groups in terms of survival (overall and disease-free) and loco-regional recurrence. Univariate analysis of the entire 254 node-positive patient group revealed extracapsular nodal extension (ECE) to be a prognostically significant factor for actuarial and disease-free survival as well as for loco-regional failure, but ECE did not remain an independently prognostic factor after multivariate analysis. Segmental mastectomy, positive resection margins, and ER negative status increased the risk of loco-regional recurrence within the ECE-positive group. CONCLUSIONS: Extracapsular axillary node extension is a prognostically significant factor for actuarial survival, disease-free survival, and loco-regional failure but not independent of other adverse prognostic factors. It is a marker for increased loco-regional recurrence associated with doubling of breast, chest wall, and supraclavicular recurrence rates. The risk of axillary relapse in patients who have had an adequate level I and II axillary dissection but demonstrate extracapsular extension is low (7%). We recommend breast/chest wall and supraclavicular radiation for all patients with pathologic evidence of such extranodal extension who have had a level I and II axillary dissection regardless of the number of positive axillary nodes. Axillary irradiation should be considered for patients who have had only an axillary sampling or level I axillary dissection.     

Pathologic correlates of prognosis in lymph node-positive breast carcinomas

BACKGROUND: Many pathologic features of breast carcinomas have been proposed as prognostic correlates; their interrelationships and their relative value as prognostic indicators were studied. METHODS: A series of 399 axillary lymph node-positive infiltrating ductal breast carcinomas was studied histologically and compared with the patient prognosis. RESULTS: Many pathologic findings fit into two groups of closely related features--those related to the extent of local spread and those related to histologic anaplasia and mitotic count. Both groups correlated with the primary tumor size. The best predictors of long-term survival were measures of the extent of axillary metastasis (the number of axillary metastases, the size of the largest metastasis, and lymph node capsular invasion), which are components of the pathologic node stage. The mitotic count, tumor grade, primary tumor stage, smooth tumor border, tumor necrosis, and multifocal primary tumors were weaker but significant survival correlates. The mitotic count and Bloom-Richardson grade best predicted the survival time of patients with node-positive disease who died. Four years after diagnosis, less than 25% of the patients who would die of breast carcinoma in the low mitotic count and Bloom-Richardson Grade 1 (well differentiated) groups already had died; more than 75% of those in the high mitotic count and Bloom-Richardson Grade 3 (poorly differentiated) groups already had died. Among patients with small tumors (< 1.8 cm in diameter), those with one micrometastasis (1-2 mm) had a worse prognosis than those with uninvolved lymph nodes of similar size. CONCLUSION: The extent of axillary metastasis best predicted the long-term prognosis of patients with infiltrating ductal carcinoma and axillary metastases. The mitotic count and tumor grade best predicted the survival time of those who died.     

Purification of the porcine platelet GP IIb-IIIa complex and the propolypeptide of von Willebrand factor

BACKGROUND: In response to the importance of early stage breast carcinoma as a public health concern and to the complexity of the clinical literature devoted to treatment of the disease, the National Institutes of Health has held a series of Consensus Development Conferences on the treatment of early stage breast carcinoma. The authors assessed compliance with standards of care for women treated in two states. METHODS: The authors identified patients diagnosed at 18 randomly selected hospitals (N = 1514) in Massachusetts and at 30 hospitals (N = 1061) in Minnesota. They collected data from medical records, patients, and their surgeons to assess compliance with four indicators of quality of care: radiation therapy after breast-conserving surgery, axillary lymph node dissection, chemotherapy for premenopausal women with positive lymph nodes, and hormonal therapy for postmenopausal women with positive lymph nodes and positive estrogen receptor status. RESULTS: Rates of compliance for 3 of the 4 standards of care were > 80% in both states. Only the rate for hormonal therapy for postmenopausal women was low (< 64%). However, the proportion of these women who received either chemotherapy or hormonal therapy was > 90% in both states. CONCLUSIONS: In the states studied, practice appears to be consistent with the results of national consensus conferences and clinical trials regarding the treatment of early stage breast carcinoma. For practices demonstrated to be associated definitively with better outcomes (for example, chemotherapy for premenopausal women with positive lymph nodes) or to be important with respect to prognosis (axillary lymph node dissection) high rates of compliance were observed.