Surgical outcomes and prognosis of HER2+ invasive breast cancer patients with a DCIS component treated with breast-conserving surgery after neoadjuvant systemic therapy.

INTRODUCTION: In up to 72 % of HER2+ invasive breast cancer (IBC), a ductal carcinoma in situ (DCIS) component is present. The presence of DCIS is associated with increased positive surgical margins after breast-conserving surgery (BCS). The aim of this study was to assess surgical margins, recurrence and survival in a nationwide cohort of HER2+ IBC with versus without a DCIS component, treated with neoadjuvant systemic therapy (NST) and BCS. MATERIALS AND METHODS: Women diagnosed with HER2+ IBC treated with NST and BCS, between 2010 and 2019, were selected from the Netherlands Cancer Registry and linked to the Dutch Nationwide Pathology Databank. Kaplan-Meier and Cox regression analyses were performed to determine locoregional recurrence rate (LRR) and overall survival (OS) and associated clinicopathological variables. Surgical outcomes and prognosis were compared between IBC only and IBC+DCIS. RESULTS: A total of 3056 patients were included: 1832 with IBC and 1224 with IBC+DCIS. Patients with IBC+DCIS had significantly more often positive surgical margins compared to IBC (12.8 % versus 4.9 %, p < 0.001). Five-year LRR was significantly higher in patients with IBC+DCIS compared to IBC (6.8 % versus 3.6 %, p < 0.001), but the presence of DCIS itself was not significantly associated with LRR after adjusting for confounders in multivariable analysis. Five-year OS did not differ between IBC+DCIS and IBC (94.9 % versus 95.7 %, p = 0.293). CONCLUSION: The presence of DCIS is associated with higher rates of positive surgical margins, but not with LRR and lower OS when adjusted for confounders. Further research is necessary to adequately select IBC+DCIS patients for BCS after NST.

Management of soft tissue sarcomas of the chest wall: a comprehensive overview.

Sarcomas of the chest wall are rare and their current treatment regimen is diverse and complex due to the heterogeneity of these tumors as well as the variations in tumor location and extent. They only account for 0.04% of newly diagnosed cancers of whom about 45% comprise soft tissue sarcomas. Larger cohort studies are scarce and often focus on one specific treatment item. We therefore aim to provide helicopter view for clinicians treating patients with sarcomas of the chest wall, focusing mainly on soft tissue sarcomas. This overview includes the value of neoadjuvant systemic or radiotherapy, surgical resection, approaches for thoracic wall reconstruction, and the need for follow-up. Provided the heterogeneity and relative rarity, we recommend that treatment decisions in soft tissue sarcoma of the chest wall are discussed in a multidisciplinary tumor board at a reference sarcoma center or within sarcoma networks to ensure personalized, rational decision making. A surgical oncologist specialized in sarcoma surgery is crucial, and for extensive resections involving the thoracic cavity we recommend involvement of a thoracic surgeon. In addition, a specialized medical- and radiation oncologist as well as a plastic surgeon is required to ensure the best multimodality treatment plan to optimize patient outcome.

Lipid profiling of electrosurgical vapors for real-time assistance of soft tissue sarcoma resection.

BACKGROUND: Soft tissue sarcomas (STS) constitute a heterogeneous group of rare tumor entities. Treatment relies on challenging patient-tailored surgical resection. Real-time intraoperative lipid profiling of electrosurgical vapors by rapid evaporative ionization mass spectrometry (REIMS) may aid in achieving successful surgical R0 resection (i.e., microscopically negative-tumor margin resection). Here, we evaluate the ex vivo accuracy of REIMS to discriminate and identify various STS from normal surrounding tissue. METHODS: Twenty-seven patients undergoing surgery for STS at Maastricht University Medical Center+ were included in the study. Samples of resected STS specimens were collected and analyzed ex vivo using REIMS. Electrosurgical cauterization of tumor and surrounding was generated successively in both cut and coagulation modes. Resected specimens were subsequently processed for gold standard histopathological review. Multivariate statistical analysis (principal component analysis-linear discriminant analysis) and leave-one patient-out cross-validation were employed to compare the classifications predicted by REIMS lipid profiles to the pathology classifications. Electrosurgical vapors produced during sarcoma resection were analyzed in vivo using REIMS. RESULTS: In total, 1200 histopathologically-validated ex vivo REIMS lipid profiles were generated from 27 patients. Ex vivo REIMS lipid profiles classified STS and normal tissues with 95.5% accuracy. STS, adipose and muscle tissues were classified with 98.3% accuracy. Well-differentiated liposarcomas and adipose tissues could not be discriminated based on their respective lipid profiles. Distinction of leiomyosarcomas from other STS could be achieved with 96.6% accuracy. In vivo REIMS analyses generated intense mass spectrometric signals. CONCLUSION: Lipid profiling by REIMS is able to discriminate and identify STS with high accuracy and therefore constitutes a potential asset to improve surgical resection of STS in the future.

Pathologic complete response of ductal carcinoma in situ to neoadjuvant systemic therapy in HER2-positive invasive breast cancer patients: a nationwide analysis.

PURPOSE: Ductal carcinoma in situ (DCIS) is present in more than half of HER2-positive invasive breast cancer (IBC). Recent studies show that DCIS accompanying HER2-positive IBC can be completely eradicated by neoadjuvant systemic therapy (NST). Our aim was to determine the percentage of pathologic complete response of the DCIS component in a nationwide cohort and to assess associated clinicopathologic variables. Furthermore, the impact on surgical treatment after NST was investigated. METHODS: Women diagnosed with HER2-positive IBC, treated with NST and surgery, between 2010 and 2020, were selected from the Netherlands Cancer Registry. Pre-NST biopsy and postoperative pathology reports were obtained from the Dutch Nationwide Pathology Databank and assessed for the presence of DCIS. Clinicopathologic factors associated with DCIS response were assessed using logistic regression analyses. RESULTS: A DCIS component was present in the pre-NST biopsy in 1403 (25.1%) of 5598 included patients. Pathologic complete response of the DCIS component was achieved in 730 patients (52.0%). Complete response of DCIS occurred more frequently in case of complete response of IBC (63.4% versus 33.8%, p < 0.001). ER-negative IBC (OR 1.79; 95%CI 1.33-2.42) and more recent years of diagnosis (2014-2016 OR 1.60; 95%CI 1.17-2.19, 2017-2019 OR 1.76; 95%CI 1.34-2.34) were associated with DCIS response. Mastectomy rates were higher in IBC+DCIS compared to IBC (53.6% versus 41.0%, p < 0.001). CONCLUSION: Pathologic complete response of DCIS occurred in 52.0% of HER2-positive IBC patients and was associated with ER-negative IBC and more recent years of diagnosis. Future studies should investigate imaging evaluation of DCIS response to improve surgical decision making.

Imaging findings for response evaluation of ductal carcinoma in situ in breast cancer patients treated with neoadjuvant systemic therapy: a systematic review and meta-analysis.

OBJECTIVES: In approximately 45% of invasive breast cancer (IBC) patients treated with neoadjuvant systemic therapy (NST), ductal carcinoma in situ (DCIS) is present. Recent studies suggest response of DCIS to NST. The aim of this systematic review and meta-analysis was to summarise and examine the current literature on imaging findings for different imaging modalities evaluating DCIS response to NST. More specifically, imaging findings of DCIS pre- and post-NST, and the effect of different pathological complete response (pCR) definitions, will be evaluated on mammography, breast MRI, and contrast-enhanced mammography (CEM). METHODS: PubMed and Embase databases were searched for studies investigating NST response of IBC, including information on DCIS. Imaging findings and response evaluation of DCIS were assessed for mammography, breast MRI, and CEM. A meta-analysis was conducted per imaging modality to calculate pooled sensitivity and specificity for detecting residual disease between pCR definition no residual invasive disease (ypT0/is) and no residual invasive or in situ disease (ypT0). RESULTS: Thirty-one studies were included. Calcifications on mammography are related to DCIS, but can persist despite complete response of DCIS. In 20 breast MRI studies, an average of 57% of residual DCIS showed enhancement. A meta-analysis of 17 breast MRI studies confirmed higher pooled sensitivity (0.86 versus 0.82) and lower pooled specificity (0.61 versus 0.68) for detection of residual disease when DCIS is considered pCR (ypT0/is). Three CEM studies suggest the potential benefit of simultaneous evaluation of calcifications and enhancement. CONCLUSIONS AND CLINICAL RELEVANCE: Calcifications on mammography can remain despite complete response of DCIS, and residual DCIS does not always show enhancement on breast MRI and CEM. Moreover, pCR definition effects diagnostic performance of breast MRI. Given the lack of evidence on imaging findings of response of the DCIS component to NST, further research is demanded. KEY POINTS: • Ductal carcinoma in situ has shown to be responsive to neoadjuvant systemic therapy, but imaging studies mainly focus on response of the invasive tumour. • The 31 included studies demonstrate that after neoadjuvant systemic therapy, calcifications on mammography can remain despite complete response of DCIS and residual DCIS does not always show enhancement on MRI and contrast-enhanced mammography. • The definition of pCR has impact on the diagnostic performance of MRI in detecting residual disease, and when DCIS is considered pCR, pooled sensitivity was slightly higher and pooled specificity slightly lower.

Research highlight: surgical outcomes of gluteal VY plasty after extensive abdominoperineal resection or total pelvic exenteration.

OBJECTIVE: To describe a suitable alternative technique for reconstruction of the pelvic floor after extensive resection. To review our outcomes of gluteal VY plasty in the reconstruction of the pelvic floor after extensive abdominoperineal resection (conventional or extralevator abdominoperineal resection, total pelvic exenteration, or salvage surgery). DESIGN: Retrospective cohort study. SETTING: An academic hospital and tertiary referral centre for the treatment of locally advanced or locally recurrent rectal cancer, and salvage surgery in The Netherlands. PATIENTS: Forty-one consecutive patients who underwent a pelvic floor reconstruction with gluteal VY plasty at Maastricht University Medical Centre between January 2017 and February 2021 were included. The minimum duration of follow-up was 2 years. MAIN OUTCOME MEASURES: Perineal herniation is the primary outcome measure. Furthermore, the occurrence of minor and major postoperative complications and long-term outcomes were retrospectively assessed. RESULTS: Thirty-five patients (85.4%) developed one or more complications of whom twenty-one patients experienced minor complications and fourteen patients developed major complications. Fifty-seven percent of complications was not related to the VY reconstruction. Six patients (14.6%) recovered without any postoperative complications during follow-up. Three patients developed a perineal hernia. CONCLUSIONS: A gluteal VY plasty is a suitable technique for reconstruction of the pelvic floor after extensive perineal resections resulting in a low perineal hernia rate, albeit the complication rate remains high in this challenging group of patients.

Prediction of Primary Tumour and Axillary Lymph Node Response to Neoadjuvant Chemo(Targeted) Therapy with Dedicated Breast [18F]FDG PET/MRI in Breast Cancer.

BACKGROUND: The aim of this study was to investigate whether sequential hybrid [18F]FDG PET/MRI can predict the final pathologic response to neoadjuvant chemo(targeted) therapy (NCT) in breast cancer. METHODS: Sequential [18F]FDG PET/MRI was performed before, halfway through and after NCT, followed by surgery. Qualitative response evaluation was assessed after NCT. Quantitatively, the SUVmax obtained by [18F]FDG PET and signal enhancement ratio (SER) obtained by MRI were determined sequentially on the primary tumour. For the response of axillary lymph node metastases (ALNMs), SUVmax was determined sequentially on the most [18F]FDG-avid ALN. ROC curves were generated to determine the optimal cut-off values for the absolute and percentage change in quantitative variables in predicting response. Diagnostic performance in predicting primary tumour response was assessed with AUC. Similar analyses were performed in clinically node-positive (cN+) patients for ALNM response. RESULTS: Forty-one breast cancer patients with forty-two primary tumours and twenty-six cases of pathologically proven cN+ disease were prospectively included. Pathologic complete response (pCR) of the primary tumour occurred in 16 patients and pCR of the ALNMs in 14 cN+ patients. The AUC of the qualitative evaluation after NCT was 0.71 for primary tumours and 0.54 for ALNM responses. For primary tumour response, combining the percentage decrease in SUVmax and SER halfway through NCT achieved an AUC of 0.78. The AUC for ALNM response prediction increased to 0.92 by combining the absolute and the percentage decrease in SUVmax halfway through NCT. CONCLUSIONS: Qualitative PET/MRI after NCT can predict the final pathologic primary tumour response, but not the ALNM response. Combining quantitative variables halfway through NCT can improve the diagnostic accuracy for final pathologic ALNM response prediction.

Fear of Cancer Recurrence in Sarcoma Survivors: Results from the SURVSARC Study.

Fear of cancer recurrence (FCR) is often reported as an unmet concern by cancer patients. The aim of our study was to investigate (1) the prevalence of FCR in sarcoma survivors; (2) the factors associated with a higher level of FCR; the relationship between (3) FCR and global health status and (4) FCR and use of follow-up care. METHODS: A cross-sectional study was conducted among sarcoma survivors 2 to 10 years after diagnosis. Patients completed the Cancer Worry Scale (CWS), the global health status subscale of the EORTC QLQ-C30 and a custom-made questionnaire on follow-up care. RESULTS: In total, 1047 patients were included (response rate 55%). The prevalence of high FCR was 45%. Factors associated with high FCR were female sex with 1.6 higher odds (95% CI 1.22-2.25; p = 0.001); having ≥1 comorbidities and receiving any treatment other than surgery alone with 1.5 (95% CI 1.07-2.05; p = 0.017) and 1.4 (95% CI 1.06-1.98; p = 0.020) higher odds, respectively. Patients on active follow-up had 1.7 higher odds (95% CI 1.20-2.61; p = 0.004) and patients with higher levels of FCR scored lower on the global health status scale (72 vs. 83 p ≤ 0.001). CONCLUSIONS: Severe FCR is common in sarcoma survivors and high levels are related to a decreased global health status. FCR deserves more attention in sarcoma survivorship, and structured support programs should be developed to deliver interventions in a correct and time adequate environment.

Diagnosed with a Rare Cancer: Experiences of Adult Sarcoma Survivors with the Healthcare System-Results from the SURVSARC Study.

The aim of this study was to explore the experience of rare cancer patients with the healthcare system and examine differences between age groups (adolescents and young adults (AYA, 18-39 years), older adults (OA, 40-69 years) and elderly (≥70 years)). Dutch sarcoma patients, 2-10 years after diagnosis, completed a questionnaire on their experience with the healthcare system, satisfaction with care, information needs, patient and diagnostic intervals (first symptom to first doctor's visit and first doctor's visit to diagnosis, respectively) and received supportive care. In total, 1099 patients completed the questionnaire (response rate 58%): 186 AYAs, 748 OAs and 165 elderly. Many survivors experienced insufficient medical and non-medical guidance (32% and 38%), although satisfaction with care was rated good to excellent by 94%. Both patient and diagnostic intervals were >1 month for over half of the participants and information needs were largely met (97%). AYAs had the longest patient and diagnostic intervals, experienced the greatest lack of (non-)medical guidance, had more desire for patient support groups and used supportive care most often. This nationwide study among sarcoma survivors showed that healthcare experiences differ per age group and identified needs related to the rarity of these tumors, such as improvements concerning (non-)medical guidance and diagnostic intervals.

Diagnostic Performance of Noninvasive Imaging for Assessment of Axillary Response After Neoadjuvant Systemic Therapy in Clinically Node-positive Breast Cancer: A Systematic Review and Meta-analysis.

OBJECTIVE: The purpose of this study was to perform a systematic review and meta-analysis to determine the diagnostic performance of current noninvasive imaging modalities for assessment of axillary response after neoadjuvant systemic therapy (NST) in clinically node-positive breast cancer patients. SUMMARY OF BACKGROUND DATA: NST can lead to downstaging of axillary lymph node disease. Imaging can potentially provide information about the axillary response to NST and, consequently, tailor the surgical management. METHODS: PubMed and Embase were searched for studies that compared noninvasive imaging after NST with axillary surgery outcome to identify axillary response in patients with initial pathologically proven axillary lymph node metastasis. Two reviewers independently screened the studies and extracted the data. A meta-analysis was performed by computing the pooled sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). RESULTS: Thirteen studies describing 2380 patients were included for final analysis. Of these patients, 1322 had undergone axillary ultrasound, 849 breast MRI, and 209 whole-body 18F-FDG PET-CT. The overall axillary pathologic complete response rate was 39.5% (941/2380). For axillary ultrasound, the pooled sensitivity, specificity, PPV, and NPV were 65%, 69%, 77%, 50%, respectively. For breast MRI, the pooled sensitivity, specificity, PPV, and NPV were 60%, 76%, 78%, 58%, respectively. For whole-body 18F-FDG PET-CT, the pooled sensitivity, specificity, PPV, and NPV were 38%, 86%, 78%, 49%, respectively. CONCLUSIONS: The diagnostic performance of current noninvasive imaging modalities is limited to accurately assess axillary response after NST in clinically node-positive breast cancer patients.

Avelumab for advanced Merkel cell carcinoma in the Netherlands: a real-world cohort.

BACKGROUND: Merkel cell carcinoma (MCC) is associated with high recurrence rates and poor survival when metastatic disease is present. The immune checkpoint inhibitor avelumab has shown high response rates (RRs) and durable responses in patients with advanced MCC (aMCC) in clinical trials. To date, only results from clinical trials, patients treated in an expanded access program and very small numbers of patients have been reported. In this study, detailed real-world efficacy and toxicity data of avelumab in patients with aMCC are reported. METHODS: Patients with aMCC treated in four dedicated referral centers in the Netherlands were analyzed from February 2017 until December 2019. Patients were included if they had received at least one administration of avelumab, regardless of previous lines of therapy. Patient data were collected retrospectively from patient records. Primary endpoints were response rate (RR) and duration of response (DOR). Secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity. RESULTS: Fifty-four patients received avelumab. Eight (15%) patients had locally advanced disease (laMCC). In 40 (74%) patients, avelumab was first-line treatment, these included all patients with laMCC. The median follow-up was 8.9 (range 0.5-35.9) months. RR was 57% (n=31) with 24% (n=13) of patients achieving a complete response. The median DOR was 8.4 (range 1.3-22.1) months and 23 (43%) patients had an ongoing response at the end of the study. The median PFS was 8.6 (95% CI 1.6-15.5) months, and the median OS was 25.8 (95% CI 9.1-42.4) months. Six (11%) patients experienced grade 3 toxicity. No grade 4-5 toxicity was seen. CONCLUSIONS: In this real-world cohort, clinical efficacy and toxicity outcomes in clinical practice were in line with results from clinical trials and showed relatively high RRs and durable responses in patients with aMCC.

Correlation Between Pathologic Complete Response in the Breast and Absence of Axillary Lymph Node Metastases After Neoadjuvant Systemic Therapy.

OBJECTIVE: The aim was to investigate whether pathologic complete response (pCR) in the breast is correlated with absence of axillary lymph node metastases at final pathology (ypN0) in patients treated with neoadjuvant systemic therapy (NST) for different breast cancer subtypes. BACKGROUND: Pathologic complete response rates have improved on account of more effective systemic treatment regimens. Promising results in feasibility trials with percutaneous image-guided tissue sampling for the identification of breast pCR after NST raise the question whether breast surgery is a redundant procedure. Thereby, the need for axillary surgery should be reconsidered as well. METHODS: Patients diagnosed with cT1-3N0-1 breast cancer and treated with NST, followed by surgery between 2010 and 2016, were selected from the Netherlands Cancer Registry. Patients were compared according to the pathologic response of the primary tumor with associated pathologic axillary outcome. Multivariable analysis was performed to determine clinicopathological variables correlated with ypN0. RESULTS: A total of 4084 patients were included for analyses, of whom 986 (24.1%) achieved breast pCR. In clinically node negative patients (cN0), 97.7% (432/442) with breast pCR had ypN0 compared with 71.6% (882/1232) without breast pCR (P < 0.001). In clinically node positive patients (cN1), 45.0% (245/544) with breast pCR had ypN0 compared with 9.4% (176/1866) without breast pCR (P < 0.001). The odds of ypN0 was decreased in case of clinical T3 stage (OR 0.59, 95% CI 0.40-0.87), cN1 (OR 0.03, 95% CI 0.02-0.04) and ER+HER2- subtype (OR 0.30, 95% CI 0.20-0.44), and increased in case of breast pCR (OR 4.53, 95% CI 3.27-6.28). CONCLUSIONS: Breast pCR achieved after NST is strongly correlated with ypN0 in cN0 patients, especially in ER+HER2+, ER-HER2+, and triple negative subtypes. These results provide data to proceed with future clinical trials to investigate if axillary surgery can be safely omitted in these selected patients when image-guided tissue sampling identifies a breast pCR.

Hybrid 18F-FDG PET/MRI might improve locoregional staging of breast cancer patients prior to neoadjuvant chemotherapy.

PURPOSE: Our purpose in this study was to assess the added clinical value of hybrid 18F-FDG-PET/MRI compared to conventional imaging for locoregional staging in breast cancer patients undergoing neoadjuvant chemotherapy (NAC). METHODS: In this prospective study, primary invasive cT2-4 N0 or cT1-4 N+ breast cancer patients undergoing NAC were included. A PET/MRI breast protocol was performed before treatment. MR images were evaluated by a breast radiologist, blinded for PET images. PET images were evaluated by a nuclear physician. Afterwards, a combined PET/MRI report was written. PET/MRI staging was compared to conventional imaging, i.e., mammography, ultrasound and MRI. The proportion of patients with a modified treatment plan based on PET/MRI findings was analyzed. RESULTS: A total of 40 patients was included. PET/MRI was of added clinical value in 20.0% (8/40) of patients, changing the treatment plan in 10% and confirming the malignancy of suspicious lesions on MRI in another 10%. In seven (17.5%) patients radiotherapy fields were extended because of additional or affirmative PET/MRI findings being lymph node metastases (n = 5) and sternal bone metastases (n = 2). In one (2.5%) patient radiotherapy fields were reduced because of fewer lymph node metastases on PET/MRI compared to conventional imaging. Interestingly, all treatment changes were based on differences in number of lymph nodes suspicious for metastasis or number of distant metastasis, whereas differences in intramammary tumor extent were not observed. CONCLUSION: Prior to NAC, PET/MRI shows promising results for locoregional staging compared to conventional imaging, changing the treatment plan in 10% of patients and potentially replacing PET/CT or tissue sampling in another 10% of patients.

Axillary staging in breast cancer patients treated with neoadjuvant chemotherapy in two Dutch phase III studies.

BACKGROUND: Primary aim of our study was to assess the impact of timing of sentinel node procedure, pre- versus post-neoadjuvant chemotherapy, on final pathologic node-negative rate (pN0) in patients with clinically node-negative (cN0) breast cancer. Secondary endpoint was the usability of the sentinel node procedure in patients with clinically node-positive disease that converted to cN0 after neoadjuvant chemotherapy. PATIENTS AND METHODS: Patients were enrolled in two sequentially conducted Dutch phase III trials, studying the impact of two neoadjuvant chemotherapy schedules and use of zoledronic acid on complete pathologic response rate. For the present analyses, patients were excluded if they had not undergone surgical axillary staging. RESULTS: In total 439 patients were included, of whom 230 (52%) had pre-treatment cN0. In this group, pN0 status was seen in 58% (N = 23) of patients with a sentinel node biopsy post-neoadjuvant chemotherapy compared to 51% (N = 83) pre-neoadjuvant chemotherapy, including the axillary lymph node dissection whenever performed. In multivariable analysis, timing of sentinel node procedure (pre- versus post- neoadjuvant chemotherapy) was, however, not significantly associated with final pN0/pN0(i+) status, with an odds ratio of 1.18 (95% CI 0.64 - 2.18) after correction for age, clinical tumor status, histology, grade, hormone- and HER2 receptor. Of patients with clinically node-positive disease only 15% had a final pN0 status, with a false-negative rate of the sentinel node of 30%. CONCLUSION: In breast cancer patients with cN0 disease, sentinel node procedure performed post-neoadjuvant chemotherapy led to nodal down staging, although not statistically significant after multivariate correction for patient and tumor characteristics.

[A woman with lumps in her breast]. / Een vrouw met knobbeltjes in de borst.

A 61-year-old woman was examined for multiple lumps and an ulcer in her breast, 23 years after breast-conserving therapy for breast cancer, including surgery, chemotherapy and radiation therapy. Clinical examination and imaging showed extensive calcifications as a late effect of irradiation, which was confirmed by the pathologist after surgery.

Improved overall survival after contralateral risk-reducing mastectomy in BRCA1/2 mutation carriers with a history of unilateral breast cancer: a prospective analysis.

Data on survival of BRCA1/2-associated primary breast cancer (PBC) patients who opt for subsequent contralateral risk-reducing mastectomy (CRRM) are scarce and inconsistent. We examined the efficacy of CRRM on overall survival in mutation carriers with a history of PBC. From a Dutch multicentre cohort, we selected 583 BRCA-associated PBC patients, being diagnosed between 1980 and 2011. Over time, 242 patients (42%) underwent CRRM and 341 patients (58%) remained under surveillance. Survival analyses were performed using Cox models, with CRRM as a time-dependent covariate. The median follow-up after PBC diagnosis was 11.4 years. In the CRRM group, four patients developed contralateral breast cancer (2%), against 64 patients (19%) in the surveillance group (p < 0.001). The mortality was lower in the CRRM group than in the surveillance group (9.6 and 21.6 per 1000 person-years of observation, respectively; adjusted hazard ratio 0.49, 95% confidence interval 0.29-0.82). Survival benefit was especially seen in young PBC patients (<40 years), in patients having a PBC with differentiation grade 1/2 and/or no triple-negative phenotype, and in patients not treated with adjuvant chemotherapy. We conclude that CRRM is associated with improved overall survival in BRCA1/2 mutation carriers with a history of PBC. Further research is warranted to develop a model based on age at diagnosis and tumour and treatment characteristics that can predict survival benefit for specific subgroups of patients, aiming at further personalized counselling and improved decision making.

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

OBJECTIVES: The 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 METHODS: Ten 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. RESULTS: After 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. CONCLUSIONS: The 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.

Breast density as indicator for the use of mammography or MRI to screen women with familial risk for breast cancer (FaMRIsc): a multicentre randomized controlled trial.

BACKGROUND: To reduce mortality, women with a family history of breast cancer often start mammography screening at a younger age than the general population. Breast density is high in over 50% of women younger than 50 years. With high breast density, breast cancer incidence increases, but sensitivity of mammography decreases. Therefore, mammography might not be the optimal method for breast cancer screening in young women. Adding MRI increases sensitivity, but also the risk of false-positive results. The limitation of all previous MRI screening studies is that they do not contain a comparison group; all participants received both MRI and mammography. Therefore, we cannot empirically assess in which stage tumours would have been detected by either test.The aim of the Familial MRI Screening Study (FaMRIsc) is to compare the efficacy of MRI screening to mammography for women with a familial risk. Furthermore, we will assess the influence of breast density. METHODS/DESIGN: This Dutch multicentre, randomized controlled trial, with balanced randomisation (1:1) has a parallel grouped design. Women with a cumulative lifetime risk for breast cancer due to their family history of ≥20%, aged 30-55 years are eligible. Identified BRCA1/2 mutation carriers or women with 50% risk of carrying a mutation are excluded. Group 1 receives yearly mammography and clinical breast examination (n = 1000), and group 2 yearly MRI and clinical breast examination, and mammography biennially (n = 1000).Primary endpoints are the number and stage of the detected breast cancers in each arm. Secondary endpoints are the number of false-positive results in both screening arms. Furthermore, sensitivity and positive predictive value of both screening strategies will be assessed. Cost-effectiveness of both strategies will be assessed. Analyses will also be performed with mammographic density as stratification factor. DISCUSSION: Personalized breast cancer screening might optimize mortality reduction with less over diagnosis. Breast density may be a key discriminator for selecting the optimal screening strategy for women < 55 years with familial breast cancer risk; mammography or MRI. These issues are addressed in the FaMRIsc study including high risk women due to a familial predisposition. TRIAL REGISTRATION: Netherland Trial Register NTR2789.