E.M. Heuts

Internal mammary lymph drainage and sentinel node biopsy in breast cancer - A study on 1008 patients.

INTRODUCTION Nowadays, axillary sentinel node (SN) biopsy is a standard procedure in the staging of breast cancer. Although the internal mammary (IM) lymph node status is a major independent prognostic factor in breast cancer patients, sampling of IM sentinel nodes (IMSNs) is not performed routinely. The aim of this study was to determine the likelihood of finding IM lymph node metastases in case of IM hotspots on lymphoscintigraphy and evaluate the relevance of IMSN biopsy as a method to improve staging. PATIENTS AND METHODS Between April 1997 and May 2006, a total of 1008 consecutive patients with clinically node-negative operable primary breast cancer were enrolled in a prospective study on SN biopsy. Both axillary and IMSNs were sampled, based on lymphoscintigraphy, intraoperative gamma probe detection and blue dye mapping, using 10 mCi (370 MBq) (99m)Tc-nanocolloid injected peritumorally, and 0.5-1.0 ml Patent Blue V injected intradermally. RESULTS Lymphoscintigraphy showed axillary sentinel nodes in 98% (989/1008) and IMSNs in 20% of the patients (196/1008). Sampling the IM basin, as based on the results of lymphoscintigraphy, was successful in 71% of the patients (139/196) and revealed metastases in 22% (31/139). In 29% of the patients with positive IMSNs (9/31) no axillary metastases were found. CONCLUSION Evaluation of IMSNs improves nodal staging in breast cancer. Patients with IM hotspots on lymphoscintigraphy have a substantial risk (22%) of metastatic involvement of the IM chain. In addition, true IM node-negative patients can be spared the morbidity associated with adjuvant radiotherapy.

‘Reconstruction: Before or after postmastectomy radiotherapy?’ A systematic review of the literature

OBJECTIVE The aim of this review is to investigate the effect of timing of the reconstruction and radiotherapy, with respect to complication rate and cosmetic outcome, with a special focus on the timing of the placement of the definite implant. METHODS PubMed was searched for publications between January 2000 and December 2012. Of 37 eligible studies, timing of reconstruction, type, and incidence of complications were recorded. First, we calculated the weighted mean including confidence intervals for complications and cosmetic outcome overall, and for the following subgroups: (1) Autologous reconstruction after radiotherapy; (2) Definite implant reconstruction after radiotherapy; (3) Autologous reconstruction before radiotherapy; (4) Definite implant reconstruction before radiotherapy. A second analysis was performed using only studies that directly compared group 1 versus 3 and 2 versus 4. RESULTS A large variation in complication rates (8.7-70.0%) and in acceptable cosmetic outcome (41.4-93.3%) was reported. The first analysis showed more complications and a higher revision rate if an implant reconstruction was performed after radiotherapy; for autologous reconstruction fibrosis occurred more often if reconstruction was applied first. The second analysis showed no significant differences in total complication rate. Only implant failure occurred more often if applied after radiotherapy (odds ratio (OR) 3.03 [1.59-5.77]). No differences were found in both patient and physician satisfaction. CONCLUSIONS A definite implant reconstruction placed before radiotherapy limits the rate of complications. For autologous reconstruction, less fibrosis is seen if reconstruction is performed after radiotherapy, but timing had no significant impact on total complication rate.

Microsurgical techniques for the treatment of breast cancer-related lymphedema: a systematic review.

BACKGROUND Upper limb lymphedema is one of the most underestimated and debilitating complications of breast cancer treatment. The aim of this review is to summarize the recent literature for evidence of the effectiveness of lymphatic microsurgery for the treatment of breast cancer-related lymphedema (BCRL). METHODS A search was conducted for articles published from January 2000 until January 2012. Only studies on secondary lymphedema after breast cancer treatment and those examining the effectiveness of microsurgery were included. RESULTS No randomized clinical trials or comparative studies were available. Ten case-series met inclusion criteria: (composite) tissue transfer (n = 4), lymphatic vessel transfer (n = 2), and derivative microlymphatic surgery (n = 4). Limb volume/circumference reduction varied from 2 to 50% over a follow-up time ranging from 1 to 132 months. Postoperative discontinuation rates of conservative therapy were only reported after composite tissue transfer, ranging from 33 to 100% after 3 to 24 months. Clear selection criteria for lymphatic surgery and lymphatic flow assessment were absent in most studies. CONCLUSION We identified important methodological shortcomings of the available literature. Evidence acquired through comparative studies with uniform patient selection is lacking. Consistent positive findings with regards to limb volume reduction and limited complications are reasons to further explore these techniques in methodologically superior studies.

Noninvasive nodal staging in patients with breast cancer using gadofosveset-enhanced magnetic resonance imaging: a feasibility study.

ObjectivesThe objectives of this study were to evaluate whether the axillary lymph nodes show enhancement on magnetic resonance imaging (MRI) after gadofosveset administration, to assess the time to peak enhancement, and to determine the diagnostic performance of gadofosveset-enhanced MRI for axillary nodal staging. Materials and MethodsTen women whose conditions had been diagnosed with invasive breast cancer (>2 cm) underwent both nonenhanced and gadofosveset-enhanced 3-dimensional T1-weighted axillary MRI. Signal intensity of the axillary lymph nodes and different adjacent tissues was measured, and relative signal intensity (rSI) was calculated. A Wilcoxon signed rank test was used to compare results of rSI between different time intervals. A radiologist evaluated all lymph nodes with regard to size, morphologic features, and gadofosveset uptake. All MRI-depicted lymph nodes were matched with the lymph nodes that were removed during surgery. Nodal status was investigated by a pathologist. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of gadofosveset-enhanced MRI for axillary lymph node staging were calculated. ResultsAfter contrast administration, a significant signal increase was observed in the lymph nodes (P < 0.05). When compared with muscle or fat, rSI of the lymph nodes demonstrated a significant postcontrast peak enhancement between 11 minutes and 30 seconds and 20 minutes and 50 seconds (P < 0.05). A total of 152 lymph nodes were harvested during sentinel lymph node biopsy or axillary lymph node dissection, of which 116 were matched with the lymph nodes that were depicted on MRI. Histopathological examination resulted in 21 macrometastases and 8 micrometastases. Using contrast-enhanced MRI, 20 lymph nodes were rated as true positive; 83 as true negative; 4 as false positive; and 9 as false negative. This resulted in an overall node-by-node sensitivity, specificity, PPV, and NPV of 69%, 95%, 83%, and 90%, respectively. If the micrometastases were excluded from the analysis, MRI showed a sensitivity of 86% and a specificity of 94%. Calculated PPV and NPV were 75% and 97%, respectively. ConclusionsThe axillary lymph nodes show enhancement on MRI after gadofosveset administration, with a peak enhancement between 11 minutes and 30 seconds and 20 minutes and 50 seconds. Diagnostic performance of gadofosveset-enhanced axillary lymph node imaging in patients with breast cancer is promising, but further studies need to confirm these results.

Results of tailored treatment for breast cancer patients with internal mammary lymph node metastases

Although the internal mammary (IM) lymph node status is a major prognostic factor in breast cancer, IM nodal staging is not common practice. In order to improve nodal staging, we have routinely performed IM sentinel node (SN) biopsy and have adjusted adjuvant treatment accordingly. We reviewed the outcome of these patients. Data from 764 patients were available for follow-up. A total of 406 patients had no lymph node metastases (group 1), 330 patients had axillary metastases (group 2), 7 patients had IM metastases only (group 3) and 21 patients had both axillary and IM metastases (group 4). Mean follow-up was 46 months. Prognosis did not appear to be worse for patients with IM metastases compared to those with axillary metastases only, which might indicate that they benefit from improved staging and tailored adjuvant treatment algorithms. However, long-term follow-up data, preferably in larger series, are needed to support our findings.

The Quality of Tumor Size Assessment by Contrast-Enhanced Spectral Mammography and the Benefit of Additional Breast MRI

Background - Contrast-enhanced spectral mammography (CESM) is a promising new breast imaging modality that is superior to conventional mammography for breast cancer detection. We aimed to evaluate correlation and agreement of tumor size measurements using CESM. As additional analysis, we evaluated whether measurements using an additional breast MRI exam would yield more accurate results. Methods - Between January 1st 2013 and April 1st 2014, 87 consecutive breast cancer cases that underwent CESM were collected and data on maximum tumor size measurements were gathered. In 57 cases, tumor size measurements were also available for breast MRI. Histopathological results of the surgical specimen served as gold standard in all cases. Results - The Pearsons correlation coefficients (PCC) of CESM versus histopathology and breast MRI versus histopathology were all >0.9, p<0.0001. For the agreement between measurements, the mean difference between CESM and histopathology was 0.03 mm. The mean difference between breast MRI and histopathology was 2.12 mm. Using a 2x2 contingency table to assess the frequency distribution of a relevant size discrepancy of >1 cm between the two imaging modalities and histopathological results, we did not observe any advantage of performing an additional breast MRI after CESM in any of the cases. Conclusion - Quality of tumor size measurement using CESM is good and matches the quality of these measurement assessed by breast MRI. Additional measurements using breast MRI did not improve the quality of tumor size measurements.

Incidence of axillary recurrence in 344 sentinel node negative breast cancer patients after intermediate follow-up. A prospective study into the accuracy of sentinel node biopsy in breast cancer patients.

Abstract Sentinel lymph node biopsy (SLNB) has been validated in the treatment of breast carcinoma and is considered to stage the axilla adequately in this disease. However, long-term follow-up data are scarce. We evaluated the results of SLNB with respect to loco-regional failures in the axilla in SN-negative patients with invasive breast carcinoma and analysed their causal factors. Between 1997 and May 2004, 656 patients without clinically palpable lymph nodes were included in our study. Data with regard to demographics, diagnostics, therapy and follow up were gathered prospectively from all patients. Patients treated after May 2004 were excluded from this study to permit at least one year of follow-up. Out of the 656 patients, 344 patients with a negative sentinel lymph node biopsy did not undergo axillary dissection and were followed up clinically. Median follow up was 43 months. In 3 patients (0.9%) axillary recurrences developed. All three patients subsequently underwent a completion axillary dissection, chemotherapy and radiotherapy. The low rate of clinical axillary recurrence after an intermediate follow up period suggests that a negative SN biopsy accurately reflects the nodal stage in patients with breast cancer.

Diagnostic Performance of Dedicated Axillary T2- and Diffusion-weighted MR Imaging for Nodal Staging in Breast Cancer

PURPOSE To evaluate the diagnostic performance of unenhanced axillary T2-weighted and diffusion-weighted (DW) magnetic resonance (MR) imaging for axillary nodal staging in patients with newly diagnosed breast cancer, with node-by-node and patient-by-patient validation. MATERIALS AND METHODS Institutional review board approval and informed consent were obtained. Fifty women (mean age, 60 years; range, 22-80 years) underwent high-spatial-resolution axillary 3.0-T T2-weighted imaging without fat suppression and DW imaging (b = 0, 500, and 800 sec/mm(2)), followed by either sentinel lymph node biopsy (SLNB) or axillary lymph node dissection. Two radiologists independently scored each lymph node on a confidence level scale from 0 (benign) to 4 (malignant), first on T2-weighted MR images, then on DW MR images. Two researchers independently measured the mean apparent diffusion coefficient (ADC) of each lymph node. Diagnostic performance parameters were calculated on the basis of node-by-node and patient-by-patient validation. RESULTS With respective node-by-node and patient-by-patient validation, T2-weighted MR imaging had a specificity of 93%-97% and 87%-95%, sensitivity of 32%-55% and 50%-67%, negative predictive value (NPV) of 88%-91% and 86%-89%, positive predictive value (PPV) of 60%-70% and 62%-75%, and area under the receiver operating characteristic curve (AUC) of 0.78 and 0.80-0.88, with good interobserver agreement (κ = 0.70). The addition of DW MR imaging resulted in lower specificity (59%-88% and 50%-84%), higher sensitivity (45%-64% and 75%-83%), comparable NPV (89% and 90%-91%), lower PPV (23%-42% and 34%-60%), and lower AUC (0.68-0.73 and 0.70-0.86). ADC measurement resulted in a specificity of 63%-64% and 61%-63%, sensitivity of 41% and 67%, NPV of 85% and 85%-86%, PPV of 18% and 35%-36%, and AUC of 0.54-0.58 and 0.69-0.74, respectively, with excellent interobserver agreement (intraclass correlation coefficient, 0.83). CONCLUSION Dedicated high-spatial-resolution axillary T2-weighted MR imaging showed good specificity on the basis of node-by-node and patient-by-patient validation, with good interobserver agreement. However, its NPV is still insufficient to substitute it for SLNB for exclusion of axillary lymph node metastasis. DW MR imaging and ADC measurement were of no added value.

Quality of Life in Patients with Breast Cancer–Related Lymphedema and Reconstructive Breast Surgery

Background To evaluate the quality of life (QOL) of breast cancer survivors who have undergone breast reconstruction and have breast cancer-related lymphedema (BCRL). Methods Patients with a unilateral mastectomy with or without breast reconstruction were evaluated for BCRL and their QOL. Patients were divided into a non-BCRL and a BCRL group. Patients with subjective complaints of arm swelling and/or an interlimb volume difference of >200 mL, or undergoing treatment for arm lymphedema were defined as having BCRL. QOL was assessed using cancer-specific (EORTC QLQ-C30 and EORTC QLQ-B23) and disease specific (Lymph-ICF) questionnaires. Results In total, 253 patients with a mean follow-up time of 51.7 (standard deviation = 18.5) months since mastectomy completed the QOL questionnaires. Of these patients, 116 (46%) underwent mastectomy alone and 137 (54%) had additional breast reconstruction. A comparison of the QOL scores of 180 patients in the non-BCRL group showed a significantly better physical function (p = 0.004) for patients with reconstructive surgery compared with mastectomy patients. In the 73 patients with BCRL, a comparison of the QOL scores showed no significant differences between patients with mastectomy and reconstructive surgery. After adjusting for potential confounders, multivariate analysis showed a significant impact of BCRL on physical function (β =  - 7.46; p = 0.009), role function (β =  - 15.75; p = 0.003), cognitive function (β =  - 11.56; p = 0.005), body vision (β =  - 11.62; p = 0.007), arm symptoms (β = 20.78; p = 0.000), and all domains of the Lymph-ICF questionnaire. Conclusions This study implies that BCRL has a negative effect on the QOL of breast cancer survivors, potentially negating the positive effects on QOL reconstructive breast surgery has.

No increase of local recurrence rate in breast cancer patients treated with skin-sparing mastectomy followed by immediate breast reconstruction

BACKGROUND The aim of this study was to evaluate the incidence of local recurrence after SSM with IBR and to determine whether complications lead to postponement of adjuvant therapy. METHOD Patients that underwent IBR after SSM between 2004 and 2011 were included. RESULTS A total of 157 reconstruction procedures were performed in 147 patients for invasive breast cancer (n = 117) and ductal carcinoma in situ (n = 40). The median follow-up was 39 months [range 6-97]. Estimated 5-year local recurrence rate was 2.9% (95% CI 0.1-5.7). The median time to start adjuvant therapy was 27.5 days [range 19-92] in 18 patients with complications, and 23.5 days [range 8-54] in 46 patients without complications (p = 0.025). CONCLUSION In our single-institution cohort, IBR after SSM carried an acceptable local recurrence rate. Complications caused a delay of adjuvant treatment but this was within guidelines and therefore not clinically relevant.