Uninvolved Axillary Nodes Research Articles

Retrospective audit of the yield of internal mammary lymph node dissection and literature review in the management of breast cancer.

Treatment of lymph node basins is prognostic and therapeutic for axillary lymph nodes (ALN) as well as internal mammary lymph nodes (IMLNs) in breast cancer. IMLNs can be the first echelon node for the inner/central quadrants of the breast. We evaluated the yield of IMLN dissection (IMLND) mainly in patients with inner and central tumors. IMLND was performed in 199 patients between 2000 and 2018, 127 of whom had tumors in the inner/ central quadrants. Clinico-pathological data were retrieved from Electronic Medical Records (EMR). The median age was 50 (range: 24-81). Primary surgery was performed in 82 (41.2%), while 117 (58.8%) were operated post-chemotherapy. Overall, 124/199 (62.3%) had nodes identified in the specimen, more often in primary (61/82, 74.4%) than post-chemotherapy settings (63/117, 53.8%) (P = 0.003). A median of 1 (average: 1.24, range: 0-7) lymph nodes was dissected, and 1 (average: 1.5, range: 1-4) was involved. IMLN was positive in 46/199 (23.1%) patients, not significantly different in primary (21/82, 25.6%) versus post-chemotherapy (25/117, 21.4%) settings (P = 0.545). IMLN was involved in 44.8% of patients with ≥4 involved ALN and 8.2% with uninvolved ALN (P < 0.001). In the absence of ALN involvement and <2cm pT size, 9% of patients had positive IMLN in inner/central quadrant tumors. In univariate analysis, ALN positivity (P < 0.001), pT size (P = 0.023), and grade (P = 0.041) in primary and ALN involvement (P = 0.011) in post-chemotherapy patients were associated with IMLN involvement. On logistic regression, tumor size (OR: 13.914, P = 0.017) and ALN involvement (OR: 11.400, P = 0.005) in primary surgery and ALN involvement (OR: 7.294, P = 0.003) in post-chemotherapy patients correlated with IMLN involvement. In inner/central quadrant tumors, IMLN is more likely involved with high ALN burden and tumor size >2 cm, whereas those with ≤2cm inner/central quadrant tumors and negative ALN have <10% probability of IMLN involvement.

Concordance between Axillary Ultrasound and Sentinel Biopsy in Clinically Node-Negative Early Breast Cancer

Objective: To determine the sensitivity of axillary ultrasound in detecting axillary nodal metastasis in clinically and radiologically uninvolved axillary nodes in early carcinoma breast by comparing with sentinel node biopsy histopathology on frozen section. Study Design: Comparative cross-sectional study Place and Duration of Study: Breast Clinic, CMH, Rawalpindi Pakistan, from Aug 2020 to May 2021. Methodology: Patients included in the study presented with breast cancer lesions with clinically impalpable axillary lymph nodes aged 18-75. Patients with clinically impalpable nodes underwent an ultrasound of the axilla; if suspicious nodes were found, the patient had subsequent axillary node dissection. Sentinel node biopsy (SLNB) was performed on axillary ultrasound in all patients with no suspicious or benign-looking nodes. Histopathological reporting was taken as standard. Lymph nodal status on axillary ultrasound, SLN biopsy and axillary lymph node clearance were documented and analyzed. Results: Twenty-nine patients were included who had benign-looking lymph nodes on axillary ultrasound and underwent sentinel lymph node biopsy. The mean age of the patients was 54.03 ± 7.94. Out of 29 patients, 24(82.8%) patients had negative Sentinel lymph node biopsy, and 5(17.2%) had positive Sentinel lymph node biopsy, who then underwent axillary lymph node dissection. Conclusion: Sentinel lymph node biopsy is the gold standard to determine axillary lymph nodes involved in early carcinoma breast, which seem benign on pre-operative axillary ultrasound.

Prognostic role of immune environment in luminal B early breast cancer.

The importance of the immune microenvironment in triple negative and HER2-amplified breast cancer (BC) is well-established; less is known about the immune environment in luminal breast cancers. We aimed to assess for the impact of immune biomarkers on BC outcome in a group of luminal B patients with archived tissue and annotated clinical information. Patients with early breast cancer (EBC) treated in a single institution over a 14-year period, with prospectively collected data were included. Luminal B EBC patients were identified and defined into three cohorts: A: grade 2 or 3, ER & PR positive, HER2-negative; B: Any grade, ER positive, PR and HER2-negative (Ki67 ≥ 14% in cohorts A & B); and C: Any grade, ER or PR positive, HER2-positive. Within each cohort, patients with a relapsed BC event (R) were compared on a 1:1 basis with a control patient (C) who remained disease-free, balanced for key characteristics in an effort to balance the contribution of each clinical group to outcome. Archival breast, involved and uninvolved axillary nodes were assessed by immunohistochemistry for biomarkers identifying effector and suppressor immune cells, and compared between R and C. In total, 120 patients were included (80, 22, and 18 patients in cohorts A, B, and C, respectively). R were 1.5 years older (p=0.016), with all other characteristics being balanced. Overall, there were no statistically significant differences in immune biomarkers in breast or nodal tissue of R and C. However, there was a trend toward higher levels of TILs in breast tumors of C, while GAL-9 was consistently expressed on lymphocytes and tumor cells in all breast and nodes of C and was absent from all tissues of R. These trends in checkpoint molecule expression deserve further research.

Abstract 2032: Germline genetic variants in GATA3 and breast cancer treatment outcomes in SWOG 8897 trial

Abstract Purpose: GATA3 is involved in estrogen signaling and mammary cell differentiation, and is frequently mutated in breast cancer. Germline variations of GATA3 are prognostic in childhood acute lymphoblastic leukemia (ALL). Thus, we sought to examine their prognostic and predictive role in breast cancer. Methods: SWOG S8897 comprised two groups of breast cancer patients. In the first high-risk group, women were randomly assigned to CAF vs. CMF, and secondarily randomized to tamoxifen or not. In the second low risk group, women did not receive any adjuvant therapy after surgery. Germline DNA was extracted from uninvolved axillary lymph nodes and 12 candidate GATA3 SNPs were genotyped. Associations of genotypes with treatment outcomes were evaluated in 441 women in the treated and 799 in the untreated groups separately. Hazard ratio (HR) for disease free (DFS) and overall survival (OS) for each SNP was estimated using multivariate Cox hazard regression. Further stratified analyses by tamoxifen were performed in the treated group. Results: After correcting for multiple testing, we identified significant associations of two variants (rs3802604 and rs568727) with DFS and OS for patients who received adjuvant chemotherapy. Women carrying the variant GG genotype at rs3802604 had significantly poorer DFS (HR = 1.95, 95% CI: 1.27-2.99, p = 0.002) and OS (HR = 2.45, 95% CI: 1.48-4.05, p = 0.0005), compared to women carrying the common AA genotype. Associations of similar magnitude were found for rs568727. In contrast, no association with either SNP was found in the untreated group. Subgroup analysis suggested that these two SNPs more strongly influenced treatment outcomes in the patients who also received tamoxifen. Seven additional variants were also associated with OS and DFS in the tamoxifen treated group. Only 3 of the 12 SNPs analyzed in GATA3 were not associated with survival in this subgroup; however, these three SNPs (rs3781093, rs3824662, and rs3802600) associated with OS in the group not treated with tamoxifen. Functional annotation revealed that several GATA3 SNPs, e.g., rs3802604, rs369421, and rs3824662, are likely to function by affecting transcription factor binding and/or altering regulatory chromatin states at this locus. Conclusions: GATA3 harbors common germline genetic variants that are related to survival following adjuvant chemotherapy and endocrine therapy in breast cancer patients. Citation Format: Victoria L. Larsen, William E. Barlow, Jun J. Yang, Qianqian Zhu, Laura F. Hutchins, Susan A. Kadlubar, Kathy S. Albain, Robert B. Livingston, James M. Rae, I-Tien Yeh, Peter M. Ravdin, Silvana Martino, Alan P. Lyss, C. Kent Osborne, Gabriel N. Hortobagyi, Daniel F. Hayes, Christine B. Ambrosone, Song Yao. Germline genetic variants in GATA3 and breast cancer treatment outcomes in SWOG 8897 trial. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2032.

Predicting the status of axillary lymph nodes in breast cancer: A multiparameter approach including axillary ultrasound scanning

In a prospective study, we attempted to predict axillary metastases in 135 breast cancer patients by a preoperative multiparameter evaluation including axillary ultrasound scanning (US). After surgery, factors associated with lymph node metastases by univariate analysis were included in a multivariate model. By multivariate analysis, the stronger independent predictors of lymph node metastases were suspicious axillary US ( p < 0.001), tumor location in the outer quadrants ( p = 0.001) and high Ki-67 index (>10%) ( p = 0.002). A predictive model based on these variables, identified a high-risk group (20.0%) represented by women with suspicious axillary US, tumor in the outer quadrants and high Ki-67 index, with axillary metastases in 100%, whereas all patients with opposite features (8.1%) had uninvolved axillary lymph nodes. This multiparameter evaluation including axillary US may be used to optimize the selection of breast cancer patients candidate to sentinel lymph node biopsy or axillary lymph node dissection. The accuracy of this predictive model still requires prospective validation in a larger sample of women.

Touch Imprint Cytology of the Sentinel Lymph Nodes Might Not Be Indicated in Early Breast Cancer Patients with Ultrasonically Uninvolved Axillary Lymph Nodes

Touch imprint cytology (TIC) is a fast, cheap and specific intraoperative examination of the sentinel lymph nodes (SLNs) in early breast cancer patients. The results of TIC in patients with ultrasonically (US) uninvolved axillary lymph nodes are not known. The objective of our study was to compare the results of TIC in the patients with US uninvolved axillary lymph nodes (US group) and those with only clinically uninvolved axillary lymph nodes (non-US group). A total of 470 patients were included in the study, 257 in the US group and 213 in the non-US group. TIC results were compared to the definite histology, and the sensitivity of TIC was calculated for both groups of patients. A subgroup analysis of TIC findings with regard to the primary tumor size was performed. Overall sensitivity and sensitivity for detecting macrometastases was significantly lower in the US group compared with the non-US group. In the US group, TIC results changed the course of treatment in 9% of patients, while in the non-US group, the course of treatment was changed in 22% of patients. In the non-US group, the proportion of positive TIC results increased with increasing tumor size, whereas in the US group it did not. The sensitivity of TIC is lower in the patients with US uninvolved axillary lymph nodes compared to those with only clinically uninvolved axillary lymph nodes. TIC might not be indicated in patients with US uninvolved axillary lymph nodes as it changes the course of treatment in only 9% of patients.

When Sentinel Lymph Node is Intramammary

Sentinel lymph node biopsy is an accepted standard of care for staging the axilla in patients with early-stage breast cancer. Little attention has been placed to the presence of intramammary sentinel lymph nodes (intraMSLNs) on preoperative lymphoscintigraphy. Between December 2001 and September 2006, in 9632 breast cancer patients with clinically uninvolved axillary nodes, lymphoscintigraphy was performed at the European Institute of Oncology (EIO). An axillary SLN (axSLN) was identified in 99.4% of cases. An intraMSLN was identified in association with the axillary sentinel lymph node in 22 patients (0.2%). In 15 cases both the axSLN and the intraMSLN were excised. The intraMSLN was positive in six patients (micrometastatic in three cases). The axSLNs were negative in all 15 cases. Two patients with positive intraMSLNs and one patient with a negative intraMSLN underwent axillary dissection; all three cases had negative axillary nodes. At a median follow-up of 24 months, no locoregional or systemic recurrences were observed. Positive intraMSLNs can improve disease staging but do not necessarily portend axillary lymph node metastasis. When intraMSLNs and axSLNs are present, we advocate biopsy of both sites and that management of the axilla should rely on axSLN status. In cases with intraMSLNs as the only draining site on lymphoscintigraphy, decisions on axillary management should be made on individualized basis.

Unnecessary axillary node dissections in the sentinel lymph node era

In the sentinel lymph node era, axillary lymph node dissection (ALND) for uninvolved axillary lymph nodes should be considered unnecessary and inappropriate. Between January 2000 and August 2005, 3487 out of 10,031 invasive breast cancer patients consecutively operated at the European Institute of Oncology were considered not suitable for sentinel lymph node biopsy (SNB) and were directly submitted to ALND (‘direct ALND’). In 2875 cases (82%) a variable grade of axillary involvement was shown, while in 612 patients (18%) no evidence of metastatic spreading was documented in the axilla. In particular, the presence of suspicious nodes at pre-operative clinical evaluation of the axilla (191 patients), neoadjuvant treatment (188 patients), large tumour >2 cm (88 patients), multifocality of disease (76 patients), previous excisional biopsy (49 patients), were considered the most frequent contraindications to SNB and led to an ‘unnecessary ALND’. According to the wider extension of the indications for SNB over the time, the number of ‘unnecessary ALNDs’ progressively decreased from 26% (in 2000) to 9% of the ‘direct ALNDs’ (in 2005). As the clinical indications to SNB are progressively extending to encompass most breast cancer patients with non-metastatic disease who were previously excluded, great effort should be made to avoid ‘unnecessary ALNDs’.

Second axillary sentinel node biopsy for ipsilateral breast tumour recurrence

Sentinel lymph node biopsy (SLNB) is the standard procedure for axillary staging in patients with primary operable breast cancer and uninvolved axillary nodes. These patients increasingly have breast-conserving surgery (BCS), and 5 to 10 per cent develop ipsilateral breast tumour recurrence during follow-up. If axillary nodes remain clinically uninvolved after a previous negative SLNB the question remains whether second SLNB is a suitable option. Between January 2000 and October 2006, 202 patients who had previously had BCS and a negative SLNB developed an ipsilateral breast tumour recurrence. Of these, 65 women with clinically negative axillary nodes were offered a second SLNB; 57 had received adjuvant radiotherapy after BCS. In 63 women, preoperative lymphoscintigraphy showed an axillary sentinel node (identification rate 97 per cent). In five, this was associated with extra-axillary migration. Sentinel node metastases were detected in seven women; in two this was the only metastasis. At a median follow-up of 45.9 months, no axillary recurrence had occurred in the women who had not had axillary dissection. Second SLNB after previous BCS and negative SLNB plus adjuvant radiotherapy may be offered to selected women with ipsilateral breast tumour recurrence.

Patients with preoperatively ultrasonically uninvolved axillary lymph nodes: a distinct subgroup of early breast cancer patients

Ultrasound (US) preoperative examination of the axillary lymph nodes combined with the fine needle aspiration biopsy (FNAB) is often used in order to reduce the number of sentinel lymph node (SLN) biopsy procedures in clinically node negative breast cancer patients. The pathohistological characteristics of the ultrasonically negative axillary lymph nodes in clinically negative axillary lymph nodes are not known. The aim of our study was to compare the pathohistological characteristics of ultrasonically uninvolved axillary lymph nodes (US group) versus clinically uninvolved axillary lymph nodes (non-US group) in SLN biopsy candidates. We included 658 patients after SLN biopsy; 286 patients in the US group and 372 in the non-US group. The pathohistological characteristics of axillary lymph nodes were evaluated by univariate analysis and logistic regression. In the univariate analysis, the proportion of macrometastastic SLN, total number of metastatic lymph nodes per patient, proportion of nonsentinel lymph node (NSLN) metastases and proportion of NSLN macrometastases were found to be lower in the US group compared to the non-US group. In the logistic regression model, only US of the axilla (p=0.010; OR: 0.57) and tumor size were significant predictors for the presence of SLN macrometastases or macrometastatic NSLN (p<0.001; OR: 0.23). The patients with US negative axillary lymph nodes form a distinct subgroup of early breast cancer patients having a significantly lower tumor burden in the axillary lymph nodes compared to those with only clinically negative axillary lymph nodes.

Radiation-Induced Heart Disease: Vigilance Is Still Required

Radiation therapy (RT) plays an important role in the multimodality management of patients with breast cancer. Trials conducted in the 1970s established that survival is equivalent after either breast conservation (local excision and RT) or mastectomy. Studies performed in the 1980s showed that the addition of RT to lumpectomy significantly reduces the risk of local recurrence and, in a meta-analysis, enhanced survival as well. Finally, trials conducted in the 1980s also demonstrated that RT after mastectomy dramatically decreases locoregional recurrence and significantly improves overall survival in patients with involved axillary nodes or large primary tumors. This silver cloud unfortunately has a black lining. In the late 1980s, data emerged that older radiotherapy (RT) techniques used in the treatment of breast cancer, particularly after mastectomy, resulted in increased rates of both cardiac morbidity and mortality. In a meta-analysis involving 19,582 women with breast cancer enrolled onto 40 randomized trials begun before 1990, the Early Breast Cancer Trialists Collaborative Group found that RT reduced the annual mortality from breast cancer by 13% but increased the annual mortality rate from other causes by 21% and that this increase was due primarily to an excess number of deaths from vascular causes (death rate ratio, 1.3 [SE 0.09]). In a similar meta-analysis, Cuzick et al reviewed individual patient-level data from 7,941 women enrolled onto 10 randomized trials of mastectomy, with or without RT, initiated before 1975 and found that the standardized mortality ratio was significantly higher for patients treated with RT compared with controls (1.11 v 0.69; P .001). Critical factors in the genesis of radiation-induced heart disease are the volume of heart exposed and the radiation dose deposited in that volume. Older methods of delivering postmastectomy RT resulted in relatively large volumes of heart being incidentally exposed to moderate to high doses of radiation. The main culprit was thought to be the use of anterior photons to treat the ipsilateral internal mammary nodes, often as part of a larger L-shaped socalled hockey-stick field that also covered the supraclavicular and sometimes the axillary nodes. Once the adverse effects of RT on the heart were recognized, techniques evolved to irradiate the chest wall and regional nodes while reducing exposure of the heart. The hockey-stick method was abandoned by most radiation oncologists in favor of methods that included the internal mammary nodes (IMNs) within the same tangential RT fields used to irradiate the chest wall (so-called deep or partially wide tangents) or treated the IMNs mostly or entirely with superficially penetrating electrons, rather than deeply penetrating photons. Given the controversy about the necessity of treating the IMNs and the possible increased cardiac risk that came from electively doing so, other radiation oncologists elected to abandon IMN treatment altogether. The safety of irradiating the chest wall was also improved by the development of treatment planning based on computed tomography that enabled better visualization of the heart, leading to the selection of RT fields that minimized cardiac exposure. These heart-sparing RT methods for irradiating the chest wall (with or without the regional nodes), were also applied to the treatment of patients with an intact breast, which rapidly gained in popularity following the publication of the randomized trials comparing mastectomy with breast conservation. For patients with an intact breast, but uninvolved axillary lymph nodes, tangential fields that minimized cardiac exposure were used to treat only the breast itself. Have these modern methods of delivering adjuvant RT following mastectomy or lumpectomy eliminated the risk of cardiac injury? In this issue of the Journal of Clinical Oncology, Patt et al from the M.D. Anderson Cancer Center (Houston, TX) attempt to answer this question. Using data from the Surveillance, Epidemiology, and End Results JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 23 NUMBER 30 OCTOBER 2

Minimal risk of macrometastases in the non-sentinel axillary lymph nodes in breast cancer patients with micrometastatic sentinel lymph nodes and preoperatively ultrasonically uninvolved axillary lymph nodes

Micrometastases in the sentinel lymph node (SLN) carry a considerable risk of macrometastases in the non-sentinel lymph nodes (NSLN), resulting in axillary lymph node dissection (ALND). Preoperative ultrasound (US) examination of the axillary lymph nodes combined with a fine-needle aspiration biopsy (FNAB) has been proved to discover metastases in the axillary lymph nodes. The aim of our study was to assess the risk of macrometastases in NSLN in patients with micrometastatic SLN after a preoperative US examination of the axillary lymph nodes. The study included 36 patients in whom, after preoperative axillary US, micrometastases in the SLN were revealed and ALND was subsequently performed. At final histopathology, no macrometastases were discovered in the NSLN. In four patients, additional micrometastases were discovered in the NSLN. In conclusion, the risk of macrometastases in the NSLN in patients with preoperatively ultrasonically uninvolved axillary lymph nodes is minimal.

Radiation therapy plus tamoxifen versus tamoxifen alone after breast-conserving surgery in postmenopausal women with stage I breast cancer: a decision analysis.

To compare outcomes for hypothetical cohorts of postmenopausal patients with estrogen receptor-positive tumors that are < or = 2 cm in size, with pathologically uninvolved axillary nodes, treated with radiation therapy plus tamoxifen versus tamoxifen alone after breast-conserving surgery. A Markov model was used to simulate patients' clinical course and estimate overall survival, recurrence-free survival, time with an intact breast, and death from breast cancer. Probabilities were derived from randomized trials and retrospective studies. Analyses were performed separately by age of diagnosis in 5-year increments from 50 to 80 years. Sensitivity analyses tested the stability of radiation benefit. The modeled recurrence-free survival benefit of giving radiation therapy was 3.35 years for women who were 50 years of age at diagnosis, versus 0.61 years for women who were 80 years of age. In the 50-year-old cohort, radiation therapy resulted in additional 0.60 years survival, compared with 0.04 years among 80-year-olds. A 50-year-old woman who received radiation therapy plus tamoxifen was less likely to die from breast cancer than if she received tamoxifen alone (2.43% v 5.29%; relative-risk reduction, 54%). An 80-year-old woman had a 1.17% chance of dying from breast cancer if she received radiation therapy plus tamoxifen, versus 2.02% with tamoxifen alone (relative-risk reduction, 42%). Sensitivity analyses showed that the magnitude of benefit was strongly influenced by including unequal rates of developing distant disease after breast recurrence between the treatment arms and varying rates of local recurrence. The absolute and relative benefits of radiation therapy and individual patient preferences for different health states should be considered when selecting treatment.

Functional form of the effect of the numbers of axillary nodes on survival in early breast cancer.

The change in survival in function of the numbers of involved and uninvolved axillary nodes in early breast cancer - i.e. the functional form - was investigated to search for prognostic cutoffs and to assess if ratio-based characterization of node involvement is a significant prognostic factor or not. Women aged 40-69, diagnosed in 1988-1997 with T1-T2 invasive breast carcinoma, who underwent axillary dissection, are selected from the SEER public database. The method determines the functional form by applying smoothed plots to the martingale residuals obtained from a proportional hazards model. The results on 55,267 selected patients find that the ratio of involved nodes on examined nodes, in a multivariate model that takes into account known prognostic factors (age, race, tumor size, topography, histology, grade, hormone receptors), is associated with a relative mortality hazard of 1.012 (95% confidence interval 1.010-1.014; relative increase of mortality of 1.2% for each 1% increase in the percentage of involved nodes). The functional form for the number of uninvolved nodes shows that the relative mortality hazard initially steeply decreases and then tends to level off beyond 5-10 uninvolved nodes. For the number of involved nodes, the relative mortality hazard continues to increase with each involved node without any obvious cutpoint. Even when the number of involved nodes is already large, each additional involved node increases the relative mortality hazard by at least 1.3%.

Effect of the number of uninvolved nodes on survival in early breast cancer

A high number of uninvolved axillary nodes was found by some authors to be associated with poor survival in node-negative breast cancer. We searched for confirmation and extend the investigation to node-positive cases, using population data from the SEER Program. Patients selected were women aged 40-69 years, diagnosed 1988-1997, T1-T2 breast cancer, undergoing axillary dissection with 4-35 nodes examined. Survivals were estimated by the product-limit method and were computed on pooled data. Results in node-negative patients (n=37,519) showed a 5-year overall survival from 92% (95% confidence interval: 88-95%) with 4 uninvolved nodes, to 93% (87-98%) with 34 uninvolved nodes. In node-positive patients (n=16,978), the 5-year survival increased from 50% (44-56%) with 0 uninvolved nodes, to 91% (82-100%) with 30 uninvolved nodes. Survival graphs indicated an improvement or a plateau with higher number of uninvolved nodes. The graphs also suggested that the ratio of involved and uninvolved nodes might be correlated with survival. We conclude that there was no evidence of poor outcome associated with a high number of uninvolved nodes. The incidental finding that ratio-based characterization of node involvement might be a prognostic factor will be further investigated.

Evaluation of the axilla and current standards of pathological work-up

SUMMARY The axillary sentinel node biopsy has emerged recently as a most useful procedure to stage patients with small primary breast carcinomas and clinically uninvolved axillary nodes, and to guide therapy with minimal morbidity. Indeed, the histological examination of axillary sentinel nodes is highly predictive of the nonsentinel axillary node status and may spare axillary clearing in patients with histologically uninvolved sentinel nodes. To avoid the need for two separate surgical sessions the results of sentinel node examination may be known intraoperatively. Routine frozen section examination of sentinel nodes, however, is liable to yield false-negative results. An extensive intraoperative examination of frozen sentinel nodes, which would attain a sensitivity comparable to that obtained by routine histological analysis, has been therefore devised. To facilitate the detection of micrometastatic disease in the sentinel nodes, immunocytochemical and molecular biology techniques can be adopted. Indeed, the identification of specific epithelial antigens or mRNA markers may be useful adjuncts to the histological examination of the sentinel nodes.

Sentinel lymph node dissection in breast cancer.

During the last years, the efficacy and reliability of the sentinel lymph node biopsy (snb) as a minimal invasive diagnostic procedure for the nodal status has been intensively evaluated. After the widespread clinical use in the staging of melanoma patients the snb is currently introduced in the clinical management of breast cancer patients. We present our experience with this method during 3, 5 years and discuss its potential and pitfalls. From 11/95 to 3/99 we performed sentinel node detection in 146 patients with breast cancer stage I to III, consisting of 127 patients with pT1/2-tumors and 19 patients with pT3/4-tumors. We used the radionuclid method including preoperative lymphoscintigraphy and intraoperative gamma-probe detection. The detection rate varied with the tumor size between 94% for tumors with a diameter < 1 cm, 85% (1-3 cm), 70% (3-5 cm) and 63% (> 5 cm). The accuracy of the snb in the prediction of the nodal status changed also with the tumor diameter between 100% for very small tumors (< 1 cm), 97% (1-3 cm), 88% (3-5 cm) and 67% (> 5 cm). In the subgroup of patients restricted to T1-2-tumors (n = 106). 57 patients (53%) showed true negative snb. 38 patients (36%) revealed tumor cells in the H&E-staining and an additional 7 patients (7%) solely in the immunohistochemical staining. 4 (4%) of these patients, all of them from the first half of the study period, underwent false-negative snb, 3 of them showing lymphangiosis carcinomatosa. The presented results show, that snb using the radionuclid method is a reliable method for the evaluation of the nodal status in early breast cancer patients with a tumor size up to ca. 3 cm. Therefore the sn procedure should be restricted to small tumors with clinically uninvolved axillary nodes or patients with a ductal carcinoma in situ (DCIS) to rule out invasiveness.

Long-term follow-up of elderly patients with operable breast cancer treated with surgery without axillary dissection plus adjuvant tamoxifen.

Between 1982 and 1990, 321 elderly patients (range 70-92 years, median age 77) with operable breast cancer (T1 in 219, T2 in 77, T3 in one and T4b in 24 patients) and clinically uninvolved axillary nodes underwent surgery without axillary dissection and received adjuvant tamoxifen. All patients had surgery performed under local anaesthesia. Tamoxifen was given after surgery at the dose of 20 mg daily, indefinitely. With a median follow-up of 67 months (range 42-141), 17 patients developed local relapse, 14 ipsilateral axillary recurrence, five ipsilateral breast cancer, five contralateral breast cancer, 13 second primary and 23 developed distant metastases. The cumulative probability of developing a local, axillary and distant recurrence at 72 months was estimated to be 5.4%, 4.3% and 6.2%, respectively. Out of 244 patients who did not develop any relapse, 83 (25.8%) died from intercurrent disease. The 72 month relapse-free survival rate was 76%. This experience suggests that elderly patients with small tumours without clinical axillary involvement may be satisfactorily treated with conservative surgery and tamoxifen. The importance of axillary dissection is controversial owing to a high response rate to hormonal therapy and an increased death rate due to concomitant diseases.

Oestrogen receptors, clinical features and prognosis in stage III breast cancer

One hundred and twenty-four patients with stage III breast cancer who had oestrogen receptor analyses (ER) performed on primary tumour were studied. For operable disease (T 3 a ; N 0.1, M 0), patients with ER-negative (ER < 5 fmol/ mg cytosol protein) tumours had a shorter duration of symptoms, but no other differences were observed at presentation. In patients with inoperable (T 3 b,4 , N 0.1, M 0 or any T, N 2,3, M 0) tumours there were no differences in the clinical characteristics that rendered the primary tumour inoperable between those with ER+ or ER− tumours. The median disease-free interval (DFI) in patients with operable tumours and uninvolved axillary nodes was significantly longer in those with ER+ tumours ( P < 0.05). Median survival was significantly longer in patients with ER+ tumours than in those with ER− tumours (50 vs 27.5 months, P <0.05), and when survival was analysed according to various methods of initial treatment, it was significantly prolonged in patients with operable (T 3 a , N 0.1, M 0) ER+ tumours compared to those with operable ER− tumours. In patients with inoperable tumours no effect of ER status on prognosis was demonstrated. These results suggest that oestrogen receptor content may be a prognostic variable in patients with operable stage III breast cancer, but further studies of patients with similar methods of initial treatment are needed to confirm this. Patients with operable stage III tumours should be considered separately from those with locally advanced inoperable tumours in view of the significant differences in their survival prospects.