Axillary lymph node dissection on the run?

The standard approach of performing a completion axillary lymph node dissection (cALND) after a positive sentinel node for breast cancer patients is no longer generally accepted. This study applied the criterion of a 27% risk of having residual positive lymph nodes calculated by the MD Anderson nomogram to perform a cALND. This 27% cut-off is based on the number of positive non-sentinels in the Z0011 trial. A cohort of 166 cN0, sentinel positive breast cancer patients was used to validate the MD Anderson nomogram. ROC (Receiver Operating Characteristic) analysis shows an AUC (Area Under the Curve) of 0.76 and an optimal cut-off at 34% risk of positive non- SLNs (sensitivity 86%, specificity 57%). The 27% cut-off has a sensitivity of 88% and a specificity of 41% to detect positive non-sentinels. In a second cohort (N= 114) the 27% cut-off criterion was prospectively applied and appeared to be practice changing. Although we take minimal risk to leave disease behind (2/166 patients >3 positive nodes), 30.7 % in the first cohort and 54.4 % of the patients in the second cohort could be spared a cALND. The Z0011 criteria would have had more impact, omitting 90% of the cALND, but leaves more disease behind. The impact of leaving disease behind on survival remains unanswered but is awaited by long term follow up of large prospective cohort studies.

Systematic review of breast cancer related lymphoedema: making a balanced decision to perform an axillary clearance.

AIM: Breast cancer-related lymphoedema (BCRL) is a disabling complication developing after breast cancer treatment in a proportion of patients. Its impact on quality of life becomes more substantial as survival after breast cancer diagnosis increases. The incidence of BCRL following breast cancer treatment varies due to a lack of -uniform definition and measurement criteria. This review aims to determine the prevalence of BCRL following axillary lymph node dissection (ALND) as a benchmark to be used in a risk-benefit medical decision whether to proceed with ALND or not. The risk of leaving unresected non-sentinel metastatic lymph nodes with a presumed inherent risk of local recurrence will be balanced against the risk of BCRL following a potentially unnecessary ALND. METHODS: Pubmed and Embase databases were searched for all publications on BCRL in order to estimate its -incidence and to decide on the most appropriate measurement method to use in clinical practice. RESULTS: 51 articles were identified on BCRL incidence and measurement technique. Most studies measured BCRL based on differences in arm circumference (n = 18) or by self-reported symptoms (n = 18). The weighted average of BCRL incidence following ALND measured by self-report and circumference method was 28% and 16%, respectively. CONCLUSION: The importance of ALND and irradiation as part of the treatment of operable breast carcinoma is well established, but its morbidity is less well documented. We argue self-report as the most appropriate method to -establish a diagnosis of BCRL. Therefore a 28% risk of finding non-sentinel lymph node metastases in a completion ALND will be regarded as the cut-off in a medical decision to proceed with ALND.

Outcome of per protocol best-evidence based routine breast cancer care in a large regional hospital in Belgium: the importance of a prospective database in quality assurance.

AIM: Criteria for future accreditation of breast cancer centres in Belgium will be mainly based on the case load per surgeon or per centre. We would like to argue that the prospective collection of relevant data and the analysis of treatment related outcome derived from these data is feasible and should be the ultimate criterion for quality assessment and thus for accreditation since outcome is a more direct measurement of quality. METHODS: Data were prospectively collected on 715 invasive non metastatic breast cancers between 2002 and 2007 treated according to standard, best-evidence protocols in the setting of a large district hospital. Univariate and multivariate survival analysis were performed and compared to national and international databases. RESULTS: 5 year disease-free survival (DFS) and overall survival (OS) in our series were respectively 77 and 84%. In the multivariate analysis of DFS, only her-2-neu status (her-2-neu positivity being associated with a poor prognosis) and age (older age being a worse prognostic factor) were statistically significant prognostic factors. For OS, her-2-neu, age, and positive nodes were statistically significant prognostic factors. The outcome is comparable to other data sets. CONCLUSION: Centres dedicated to the care of women with breast cancer have the moral duty to produce outcome based results of their treatment. This report shows that such a collection of data is feasible and can be imposed as a prerequisite for accreditation. We also argue that outcome based data of treatment are a more solid base for quality assurance than case load.

Evaluation of the histological size of the sentinel lymph node metastases using RT-PCR assay: a rapid tool to estimate the risk of non-sentinel lymph node invasion in patients with breast cancer.

A RT-PCR assay (GeneSearch™, Veridex, LLC), FDA approved and CE marked to detect metastases > 0.2 mm in sentinel lymph nodes (SLNs) is used intra-operatively for the management of patients with breast cancer. The assay provides qualitative results by applying cut-off values to cycle times (Ct) for mammaglobin (MG) and cytokeratin-19 (CK19) genes. Aims of this study were to evaluate the performance of the quantitative Ct values to estimate the size of nodal metastases and the risk of additional disease in non-SLNs. SLNs from 367 patients were clinically processed using both BLN assay and post-operative histology. Complementary axillary lymph node dissection (ALND) was performed concurrently in case of BLN assay positivity or tumour size > 2 cm. BLN positivity was reported in 19.6% of the patients for a sensitivity of 89%. BLN specificity (94.5%) and negative predictive value (97.5%) clearly demonstrated its reliability to guide ALND decision. All, except one, residual axillary metastases were found in BLN-positive patients. Considering the 78 patients with SLN positivity or discordant status according to both criteria, the metastases histological size was significantly correlated to the expression level of MG (ρ = 0.62) and CK19 (ρ = 0.64) genes (P < 10E-6). Moreover, ALND status positivity was significantly associated to Ct value of MG (z = 2.4; P = 0.018) and CK19 (z = 3.2; P = 0.001). The high intra-operative quality performance of the BLN assay minimizes the need for second surgeries for ALND. Results from this investigational study suggest that markers Ct value may provide, intra-operatively, valuable metastases size data and a risk prediction of additional disease in non-SLNs.

Clinical validation of a molecular assay for intra-operative detection of metastases in breast sentinel lymph nodes.

BACKGROUND: In breast cancer patients, the status of the sentinel lymph nodes (SLNs) has been shown to accurately reflect the presence of metastases in the axillary lymph nodes (ALNs). Intra-operative SLN evaluation by frozen section histology may miss positive cases, leading to a second surgery for complete ALN dissection. Permanent section histology itself has tissue sampling limitations and is partially dependent on pathologist expertise. METHODS: A prospective study (N=78) was conducted in our institution to validate a new intra-operative molecular assay, the GeneSearch breast lymph node (BLN) assay. This assay quantifies the expression of mammaglobin and cytokeratin-19 genes using quantitative RT-PCR technology to determine SLN status. Fresh SLN sections (2 mm thick) were analyzed alternatively by BLN assay or post-operative histology (haematoxylin-eosin and immunohistochemistry). The subject was considered positive when histology revealed a focus >0.2 mm. RESULTS: BLN assay results corroborated with histologic results in 75 out of 78 patients for an overall agreement of 96%, a sensitivity of 92%, and a specificity of 97%. The positive and negative predictive values of the BLN assay were of 86% (12/14) and 98% (63/64), respectively. Interestingly, a statistically significant correlation was observed between the metastases' histologic size and both assay markers' expression levels as represented by cycle time to positivity (rho > or = 0.71, all p<0.0001). CONCLUSIONS: The performance of the BLN assay in identifying nodal metastases >0.2 mm was similar to that of permanent section histology, with the added advantages of an objective and rapid output that could be used for intra-operative decision to remove additional ALN.

The construct of breast cancer risk perception: need for a better risk communication?

Breast cancer risk assessment and communication are much neglected aspects of women's health care. Breast cancer is the most prevalent cancer-related disease that touches the deepest of a women's feelings and the subject thus attracts much of the attention of the media. Disease prevalence and media coverage are the roots of inappropriate breast cancer risk perception. Many women overestimate their personal breast cancer risk. Inappropriate risk perception precedes inappropriate health behaviour and it is pivotal to understand the underlying mechanisms in order to plan intervention. Whether interventions such as patient education through counselling and objective risk assessment are effective in restoring inappropriate breast cancer risk perception remains a question unanswered, but the tools to measure breast cancer risk are available and were validated.

Isotope labelling and axillary node harvesting strategies for breast cancer.

AIMS: The objective of this study was to assess the value of superficial (intradermal) and paratumoral (above the tumor) (ID) injection of labeled colloids for imaging sentinel lymph nodes (SLN) as a rescue technique in breast cancer patients for whom deep (intraparenchymatous) and peritumoral (around the tumor) (IP) injections had failed. METHODS: We assessed data from 2 groups of women: 469 women for whom IP injections successfully visualized a SLN (IP-only) and 52 women for whom IP injections were unsuccessful and ID injection was performed (IP0-ID). Patient characteristics and SLN results were compared. RESULTS: Most characteristics of the two patients series were similar. However, IP0-ID patients were on average 10years older than the IP-only patients and had more grade-III tumors. The false negative rate (FNR) for the IP0-ID patients (9/25, 23.8%) was significantly higher than for the IP-only patients (12/240, 5%; p<0.01) and for a subgroup of IP-only patients older than 50 years (8/159, 5%; p=0.009). Four of five false negatives in the IP0-ID group involved a tumor in the outer quadrants. The FNR for cases with external tumors was 33% for the IP0-ID patients, a percentage significantly higher than the corresponding values for the IP-only patients (5.8%) and for the IP-only patients older than 50 years (5.7%). CONCLUSION: In patients with unsuccessful deep IP injections, superficial ID injections lead to a high percentage of false negative SLN conclusions, merely when tumours were located in the outer quadrants. Thus, it is recommended that patients with unsuccessful intra-parenchymatous and peritumoral injections of radiocolloids for tumors in outer quadrants undergo complete axillary dissection.

[Neoadjuvant radiochemotherapy and surgery of locally advanced cervical carcinoma: review of 22 patients treated at the Bordet Institute]. / Traitement par radio-chimiothérapie néoadjuvante et chirurgie du cancer du col utérin localement avancé: revue de 22 patientes à l'Institut Bordet.

OBJECTIVES: Concomitant chemoradiation is the "new gold standard" for dealing with locally advanced cervical carcinoma, but what about surgery? We don't know yet to what extent surgery is necessary and how radical it must be when it is performed. In this study, we present the analysis of the results obtained in patients treated by concomitant chemoradiation followed by radical surgery. MATERIALS AND METHODS: Twenty-two patients, median age 49 years, with I(b) - III(a) cervical tumors were enrolled to be treated by concomitant chemoradiation followed by radical surgery. The chemoradiation protocol included external radiotherapy to the pelvis: 45 Gy; Cisplatin 40 mg/m(2) in continuous intravenous infusion once a week (5 weeks) followed by brachytherapy one week later. Surgery was performed 4 to 6 weeks later and consisted in radical hysterectomy with pelvic lymphadenectomy. RESULTS: 20/22 patients underwent surgery after chemoradiation because of a diagnosis of lung metastases in one and presence of a nonresectable metastasis for the other. A complete pathological response was demonstrated in 12/20 patients (60%), a microscopic residual tumor in 7 patients (35%), and residual disease <1cm in 1 patient (5%). CONCLUSION: This study showed a particularly high rate of pathologic responses (T(0)+T(mic): 95%) and of local control. We don't know yet if surgery is a real necessity or if it could be less extended after concomitant chemoradiation.