M.T.F.D. Vrancken Peeters

The role of FDG PET/CT in patients with locoregional breast cancer recurrence: a comparison to conventional imaging techniques.

PURPOSE The aim of this study was to evaluate the impact of (18)F-fluorodeoxyglucose positron-emission tomography/computed tomography (FDG PET/CT) on clinical management in patients with locoregional breast cancer recurrence amenable for locoregional treatment and to compare the PET/CT results with the conventional imaging data. PATIENTS AND METHODS From January 2006 to August 2008, all patients with locoregional breast cancer recurrence underwent whole-body PET/CT. PET/CT findings were compared with results of the conventional imaging techniques and final pathology. The impact of PET/CT results on clinical management was evaluated based on clinical decisions obtained from patient files. RESULTS 56 patients were included. In 32 patients (57%) PET/CT revealed additional tumour localisations. Distant metastases were detected in 11 patients on conventional imaging and in 23 patients on PET/CT images (p < 0.01). In 25 patients (45%), PET/CT detected additional lesions not visible on conventional imaging. PET/CT had an impact on clinical management in 27 patients (48%) by detecting more extensive locoregional disease or distant metastases. In 20 patients (36%) extensive surgery was prevented and treatment was changed to palliative treatment. The sensitivity, specificity, accuracy, positive and negative predictive values of FDG PET/CT were respectively 97%, 92%, 95%, 94% and 96%. CONCLUSIONS PET/CT, in addition to conventional imaging techniques, plays an important role in staging patients with locoregional breast cancer recurrence since its result changed the clinical management in almost half of the patients. PET/CT could potentially replace conventional staging imaging in patients with a locoregional breast cancer recurrence.

Indicators of homologous recombination deficiency in breast cancer and association with response to neoadjuvant chemotherapy

BACKGROUND Tumors with homologous recombination deficiency (HRD), such as BRCA1-associated breast cancers, are not able to reliably repair DNA double-strand breaks (DSBs) and are therefore highly sensitive to both DSB-inducing chemotherapy and poly (ADP-ribose) polymerase inhibitors. We have studied markers that may indicate the presence of HRD in HER2-negative breast cancers and related them to neoadjuvant chemotherapy response. PATIENTS AND METHODS Array comparative genomic hybridization (aCGH), BRCA1 promoter methylation, BRCA1 messenger RNA (mRNA) expression and EMSY amplification were assessed in 163 HER2-negative pretreatment biopsies from patients scheduled for neoadjuvant chemotherapy. RESULTS Features of BRCA1 dysfunction were frequent in triple-negative (TN) tumors: a BRCA1-like aCGH pattern, promoter methylation and reduced mRNA expression were observed in, respectively, 57%, 25% and 36% of the TN tumors. In ER+ tumors, a BRCA2-like aCGH pattern and the amplification of the BRCA2 inhibiting gene EMSY were frequently observed (43% and 13%, respectively) and this BRCA2-like profile was associated with a better response to neoadjuvant chemotherapy. CONCLUSIONS Abnormalities associated with BRCA1 inactivation are present in about half of the TN breast cancers but were not predictive of chemotherapy response. In ER+/HER2- tumors, a BRCA2-like aCGH pattern was predictive of chemotherapy response. These findings should be confirmed in independent series.

Marking the axilla with radioactive iodine seeds (MARI procedure) may reduce the need for axillary dissection after neoadjuvant chemotherapy for breast cancer

An important benefit of neoadjuvant chemotherapy is the increased potential for breast‐conserving surgery. At present the response of axillary lymph node metastases to chemotherapy is not easily assessed, rendering axilla‐conserving treatment difficult. The aim was to assess a new surgical method for evaluating the axillary response to chemotherapy.

Molecular Imaging in Breast Cancer: From Whole-Body PET/CT to Dedicated Breast PET

Positron emission tomography (PET), with or without integrated computed tomography (CT), using 18F-fluorodeoxyglucose (FDG) is based on the principle of elevated glucose metabolism in malignant tumors, and its use in breast cancer patients is frequently being investigated. It has been shown useful for classification, staging, and response monitoring, both in primary and recurrent disease. However, because of the partial volume effect and limited resolution of most whole-body PET scanners, sensitivity for the visualization of small tumors is generally low. To improve the detection and quantification of primary breast tumors with FDG PET, several dedicated breast PET devices have been developed. In this nonsystematic review, we shortly summarize the value of whole-body PET/CT in breast cancer and provide an overview of currently available dedicated breast PETs.

The use of radioactive iodine-125 seed localization in patients with non-palpable breast cancer: A comparison with the radioguided occult lesion localization with 99m technetium

BACKGROUND Radioactive Seed Localization with a radioactive iodine-125 seed (RSL) and Radioguided Occult Lesion Localization with 99mTechnetium colloid (ROLL) are both attractive alternatives to wire localization for guiding breast conserving surgery (BCS) of non-palpable breast cancer. The aim of this study was to evaluate and compare the efficacy of RSL and ROLL. METHODS We retrospectively analyzed 387 patients with unifocal non-palpable ductal carcinoma in situ (DCIS) or invasive carcinoma treated with BCS at the Netherlands Cancer Institute. In total 403 non-palpable lesions were localized either by RSL (N = 128) or by ROLL (N = 275). Primary outcome measures were positive margins and re-excision rates; the secondary outcome measure was weight of the specimen. RESULTS Pre-operative mammography or ultrasound showed similar sizes of DCIS and invasive tumours in both RSL and ROLL groups. In the RSL group, more lesions were DCIS (58%) than in the ROLL group, where 32% of the lesions were pure DCIS. The proportions of focally positive margins (11% vs. 10%) and more than focally positive margins (9% vs. 9%) were comparable between the RSL and the ROLL group, resulting in the same re-excision rate in both RSL and ROLL groups (9% vs. 10%). For DCIS lesions, the specimen weight was significantly lower in the RSL group than in the ROLL group after adjusting for tumour size on mammography (12 g; 95% CI 2.6-21). CONCLUSION Margin status and re-excision rates were comparable for RSL and ROLL in patients with non-palpable breast lesions. Because of the significant lower weight of the resected specimen in DCIS, the feasibility of position verification of the I-125 seed and more convenient logistics, we favour RSL over ROLL to guide breast-conserving therapy.

Radioactive seed localization in breast cancer treatment.

Breast cancer screening, improved imaging and neoadjuvant systemic therapy (NST) have led to increased numbers of non‐palpable tumours suitable for breast‐conserving surgery (BCS). Accurate tumour localization is essential to achieve a complete resection in these patients. This study evaluated the role of radioactive seed localization (RSL) in improving breast‐ and axilla‐conserving surgery in patients with breast cancer with or without NST.

Radioguided occult lesion localisation (ROLL) in breast-conserving surgery after neoadjuvant chemotherapy

BACKGROUND An important benefit of neoadjuvant chemotherapy, as compared to adjuvant chemotherapy, in breast cancer patients is down staging of the primary tumour, which allows for more breast-conserving surgery. When a tumour becomes non-palpable after this down staging, precise localisation of the original tumour bed is crucial to be able to perform breast-conserving surgery. Radioguided Occult Lesion Localisation with (99m)Technetium (ROLL-(99m)Tc) is commonly used to perform breast-conserving surgery in patients with non-palpable breast tumours. We modified this technique to use it in the neoadjuvant setting. The present analysis was performed to assess its feasibility and analyse the number of patients in which a mastectomy was correctly withheld using this technique. METHODS A retrospective analysis was performed for all patients who were treated with neoadjuvant chemotherapy between 2007 and 2010 in our institute and underwent breast-conserving surgery with the ROLL-(99m)Tc technique afterwards. The status of the margins and the weight of the resected specimen were assessed. RESULTS The median weight of the resected specimen in these 83 patients was 53 g (range: 11-204 g). Eleven of the 58 patients with residual disease revealed positive margins at pathological examination. However, in only 5 of those 11 patients a secondary mastectomy was indicated. This means that in 94% of all included patients a mastectomy was correctly withheld. CONCLUSION The ROLL-(99m)Tc technique is a feasible technique that can be used to perform breast-conserving surgery after neoadjuvant chemotherapy in a carefully selected group of patients.

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.

Large variation between hospitals in immediate breast reconstruction rates after mastectomy for breast cancer in the Netherlands

BACKGROUND The present study aimed to describe the use of immediate breast reconstruction (IBR) after mastectomy for invasive breast cancer and ductal carcinoma in situ (DCIS) in hospitals in the Netherlands and determine whether patient and tumor factors account for the variation. METHODS Patients undergoing mastectomy for primary invasive breast cancer or DCIS diagnosed between January 1, 2011 and December 31, 2013 were selected from the NABON Breast Cancer Audit. All the 92 hospitals in the Netherlands were included. The use of IBR in all hospitals was compared using unadjusted and adjusted analyses. Patient and tumor factors were evaluated by univariate and multivariate analyses. RESULTS In total, 16,953 patients underwent mastectomy: 15,072 for invasive breast cancer and 1881 for DCIS. Unadjusted analyses revealed considerable variation between hospitals in postmastectomy IBR rates for invasive breast cancer (mean 17%; range 0-64%) and DCIS (mean 42%; range 0-83%). For DCIS, younger age and multifocal disease were factors that significantly increased IBR rates. For patients diagnosed with invasive breast cancer, IBR was more often used in younger patients, multifocal tumors, smaller tumors, tumors with a lower grade, absence of lymph node involvement, ductal carcinomas, or hormone-receptor positive/HER2-positive tumors. After case-mix adjustments for these factors, the variation in the use of IBR between hospitals remained large (0-43% for invasive breast cancer and 0-74% for DCIS). CONCLUSIONS A large variation between hospitals was found in postmastectomy IBR rates in the Netherlands for both invasive breast cancer and DCIS even after adjustment for patient and tumor factors.

Combined PET–CT and axillary lymph node marking with radioactive iodine seeds (MARI procedure) for tailored axillary treatment in node‐positive breast cancer after neoadjuvant therapy

The treatment of axillary lymph node metastases after neoadjuvant systemic therapy (NST) remains debatable and axillary lymph node dissection (ALND) is still the standard of care. Marking axillary lymph nodes with radioactive iodine seeds (MARI procedure) is accurate in restaging the axilla after NST (false‐negative rate 7 per cent). Here, the potential of tailored axillary treatment, determined by combining the results of PET–CT before NST with those of the MARI procedure after NST, was analysed.