Impact of Second Opinions in Breast Cancer Diagnostics and Treatment: A Retrospective Analysis.

BACKGROUND: Breast cancer care is becoming increasingly complex, and patients with breast cancer are increasingly aware of the different treatment options, resulting in requests for second opinions (SOs). The current study investigates the impact of breast cancer SOs on final diagnosis and treatment in the Netherlands Cancer Institute (NCI) using a newly designed Breast Cancer Second Opinion (BCSO) classification system. METHODS: Patients who visited the NCI for an SO between October 2015 and September 2016 were included. Demographics, diagnostics, and treatment proposals were compared between first and SO. Discrepancy was categorized using our BCSO classification system, categorizing SOs into (1) noncomparable, (2) identical, and (3) minor or (4) major discrepancy. RESULTS: The majority of SOs (n = 591) were patient initiated (90.7%). A total of 121 patients underwent treatment prior to their SO, leaving 470 patients for assessment of discrepancies according to our BCSO classification system. More than 45% of these SOs resulted in at least one discrepancy, with comparable rates for physician- and patient-initiated SOs (42.5% vs. 45.6%, p = 0.708). Significantly more discrepancies were observed in patients with additional imaging (51.3% vs. 37.2%, p = 0.002) and biopsies (53.7% vs. 40.3%, p = 0.005). Almost 60% of all discrepancies were categorized as major (neoadjuvant systemic treatment instead of primary surgery, breast-conserving surgery instead of mastectomy, and proposing postmastectomy immediate breast reconstruction). CONCLUSIONS: Our findings show substantial differences in diagnostic and treatment options in breast cancer patients visiting the Netherlands Cancer Institute for an SO, thereby emphasizing more consensus for the indications of these treatment modalities.

[A woman with a painful swelling in the breast]. / Een vrouw met een pijnlijke zwelling in de borst.

BACKGROUND: A hibernoma is a rare benign lipomatous tumour, consisting of brown and white fat cells. In general, a hibernoma is an asymptomatic swelling that increases slowly in size, but it can sometimes cause pain. CASE DESPRIPTION: A 62-year-old woman presented at the breast clinic with a painful swelling in the right breast that was increasing in size. Radiological examination initially suggested a hamartoma. However, on the basis of histological examination of a biopsy, the diagnosis of hibernoma was made. The hibernoma was removed surgically. CONCLUSION: A hibernoma of the breast can grow to such a size that pain can arise due to compression of the mammary parenchyma. Surgical resection is only indicated if the hibernoma causes symptoms or for cosmetic reasons.

Identifying pathologic complete response of the breast after neoadjuvant systemic therapy with ultrasound guided biopsy to eventually omit surgery: Study design and feasibility of the MICRA trial (Minimally Invasive Complete Response Assessment).

PURPOSE: Improvements in neoadjuvant systemic therapy (NST) for breast cancer patients have led to increasing rates of pathologic complete response (pCR). The MICRA trial (NTR6120) aims at identifying pCR with post-NST biopsies. Here, we report the study design and feasibility. METHODS: The MICRA-trial is a multi-center prospective cohort study. Patients with a pre-NST placed marker and radiologic complete (rCR) or partial response on MRI after NST are eligible for inclusion. Ultrasound guided biopsy of the original tumor area is performed. Pathology results of the biopsies and surgery specimens are compared. The primary endpoint is false-negative rate of biopsies in identifying pCR. RESULTS: During the first year of the trial 58 patients with rCR were included. One patient was a screening failure and excluded for analysis. Twenty-one percent had hormone receptor (HR)+/HER2- tumors, 21% HR+/HER2+ tumors, 18% HR-/HER2+ tumors and 40% TN tumors. Overall pCR was 68%. In seven patients biopsies could not be obtained: in 6 patients, the marker could not be identified on ultrasound in the OR and in 1 patient there were technical difficulties. A median of eight biopsies was obtained (range 4-9). The median of histopathological representative biopsies was 4 (range 1-8). CONCLUSION: Ultrasound guided biopsy of the breast in patients with excellent response on MRI after NST is feasible. Accuracy results of the MICRA trial will be presented after inclusion of 525 patients to determine if ultrasound guided biopsy is an accurate alternative to surgical resection for assessment of pCR after NST.

Feasibility of magnetic marker localisation for non-palpable breast cancer.

OBJECTIVES: Accurate tumour localisation is essential for breast-conserving surgery of non-palpable tumours. Current localisation technologies are associated with disadvantages such as logistical challenges and migration issues (wire guided localisation) or legislative complexities and high administrative burden (radioactive localisation). We present MAgnetic MArker LOCalisation (MaMaLoc), a novel technology that aims to overcome these disadvantages using a magnetic marker and a magnetic detection probe. This feasibility study reports on the first experience with this new technology for breast cancer localisation. MATERIALS AND METHODS: Fifteen patients with unifocal, non-palpable breast cancer were recruited. They received concurrent placement of the magnetic marker in addition to a radioactive iodine seed, which is standard of care in our clinic. In a subset of five patients, migration of the magnetic marker was studied. During surgery, a magnetic probe and gammaprobe were alternately used to localise the markers and guide surgery. The primary outcome parameter was successful transcutaneous identification of the magnetic marker. Additionally, data on radiologist and surgeon satisfaction were collected. RESULTS: Magnetic marker placement was successful in all cases. Radiologists could easily adapt to the technology in the clinical workflow. Migration of the magnetic marker was negligible. The primary endpoint of the study was met with an identification rate of 100%. Both radiologists and surgeons reflected that the technology was intuitive to use and that it was comparable to radioactive iodine seed localisation. CONCLUSION: Magnetic marker localisation for non-palpable breast cancer is feasible and safe, and may be a viable non-radioactive alternative to current localisation technologies.

Neoadjuvant chemotherapy adaptation and serial MRI response monitoring in ER-positive HER2-negative breast cancer.

BACKGROUND: Changing the neoadjuvant chemotherapy regimen in insufficiently responding breast cancer is not a standard policy. We analysed a series of patients with 'luminal'-type breast cancer in whom the second half of neoadjuvant chemotherapy was selected based on the response to the first half. METHODS: Patients with oestrogen receptor-positive (ER+) human epidermal growth factor receptor 2-negative (HER2-) breast cancer received three courses of neoadjuvant dose-dense doxorubicin and cyclophosphamide (ddAC). Three further courses of ddAC were administered in case of a 'favourable response' on the interim magnetic resonance imaging (MRI) and a switch to docetaxel and capecitabine (DC) was made in case of an 'unfavourable response', using previously published response criteria. The efficacy of this approach was evaluated by tumour size reductions on serial contrast-enhanced MRI, pathologic response and relapse-free survival. RESULTS: Two hundred and forty-six patients received three courses of ddAC. One hundred and sixty-four patients (67%) had a favourable response at the interim MRI, with a mean tumour size reduction of 31% after the first three courses and 34% after the second three courses. Patients with unfavourable responsive tumours had a mean tumour size reduction of 12% after three courses and received three courses of DC rather than ddAC. This led to a mean shrinkage of 27%. CONCLUSION: The tumour size reduction of initially less responsive tumours after treatment adaptation adds further evidence that a response-adapted strategy may enhance the efficacy of neoadjuvant chemotherapy.

Ankle-arm index, angiography, and duplex ultrasonography after recanalization of occlusions in femoropopliteal arteries: comparison of long-term results.

PURPOSE: Comparison of the relative values of the ankle-arm index (AAI) at rest and after exercise, angiography, and duplex ultrasonography for the follow-up of percutaneous transluminal angioplasty (PTA) in patients with peripheral vascular disease. METHODS: Thirty-two patients were prospectively followed after technically and clinically successful PTA of a femoropopliteal occlusion. The patency of the femoropopliteal artery was assessed for 1 year using AAI measurements at rest and after exercise; duplex ultrasonography at 4, 12, 24, 36, and 52 weeks; and angiography at 3 and 12 months after PTA. RESULTS: Patency was highly dependent on the measurement technique. The cumulative patency after 1 year determined with the AAI at rest and during exercise, by angiography, and by duplex ultrasonography was 74%, 19%, 31%, and 32%, respectively. Seventy-five percent of the restenoses occurred at the site of the treated occlusion. CONCLUSION: Duplex ultrasonography is most suitable for this assessment, as it causes no patient discomfort and the specificity is better than AAI after exercise because vascular disease in other, proximal segments does not interfere with the results.

Interobserver variation in duplex sonographic scanning in the femoropopliteal tract.

The diagnostic value of duplex sonographic scanning was demonstrated in a number of studies, but there is lack of consensus on which characteristic of the Doppler spectrum correlates best with the severity of peripheral vascular disease. In a prospective study we quantified the interobserver variation in duplex scanning for the diagnosis of peripheral vascular disease. Forty-one patients with intermittent claudication were independently examined by two observers. The observers were unaware of the angiographic findings. Reproducibility of classification and separate characteristics of the Doppler spectrum were expressed as kappa coefficients, Pearson correlation coefficients, and repeatability coefficients. PSV was the most reproducible characteristic of the Doppler spectrum. The classification of peripheral disease in 0 to 19%, 20 to 49%, 50 to 99%, and 100% diameter reduction was highly reproducible (kappa 0.68). The other characteristics of the Doppler spectrum were moderately to poorly reproducible; wave form contour, spectral broadening, and end diastolic velocity had kappa values of 0.56, 0.20, and 0.56, respectively. Our findings justify a simplification of the criteria for duplex sonographic scanning for diagnosis of peripheral vascular disease.

A four-generation Dutch family with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), linked to chromosome 19p13.

We describe a four-generation Dutch family suffering from cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Of twenty affected family members, ten are still alive. Age at onset of the strokes was between 29 and 52 years, with a mean of 41.8 years. This family has the typical clinical and radiological features of CADASIL (except for the occurrence of ischemic heart disease at a relatively young age in some subjects), and is linked to chromosome 19p13. This disease has so far been described in families from Finland, France, Germany, Italy, Japan, Spain and the United Kingdom, and there is a remarkable clinical and genetical homogeneity among all families reported, including this Dutch family.

[Diagnosis and treatment of renal artery stenosis in patients with a transplanted kidney]. / Diagnostiek en behandeling van nierarteriestenose bij patiënten met een transplantatienier.

Among the complications of kidney transplantation renal artery stenosis occurs in approximately 10% of patients. It may lead to progressive hypertension and loss of graft function. In this article possibilities and restrictions of new diagnostic and therapeutic methods are described on the basis of three case histories. Duplex Doppler ultrasonography is a useful diagnostic instrument for detection of renal artery stenosis in patients with kidney transplants. Because of its non-invasive character it is an attractive alternative to angiography. Treatment of these patients by percutaneous transluminal angioplasty (PTA) appears to give satisfying results than surgery more frequently. Although it is not always successful, PTA may be regarded as the treatment of choice since it also causes less stress than surgical management.