Recurrence in lobular carcinoma of the breast: A 14-year review.

INTRODUCTION: The two most common types of breast cancer are invasive or infiltrating ductal carcinoma (IDC) and invasive or infiltrating lobular carcinoma (ILC) (Pestalozzi et al., J. Clin. Oncol., 26, 2008, 3006). Between 5% and 15% of invasive breast carcinomas are lobular carcinomas (Pestalozzi et al., J. Clin. Oncol., 26, 2008, 3006; Dossus and Benusiglio, Breast Cancer Res., 17, 2015, 37; Braunstein et al., Breast Cancer Res. Treat., 149, 2015, 555). The paucity of data relating to recurrence rates of lobular cancers prompted this study. METHODS: A retrospective cohort study of all cases of lobular breast carcinoma reported to the Western Australia Cancer Registry with the clinical and pathological details between 2000 and 2014. RESULTS: Overall, 2463 subjects with a total of 2526 events of invasive lobular carcinoma of the breast. 11/2463 (0.45%) subjects met criteria for local recurrence of invasive lobular breast cancer, with an incidence of 1 in 224. CONCLUSION: There are clinical implications for the management and follow-up for patients with a diagnosis of lobular cancer of the breast. Due to the low recurrence rate, now, the standard practice in our institution does not offer magnetic resonance imaging (MRI) as part of the follow-up for ILC patients. Other centres should establish local recurrence rates to aid development of appropriate management protocols.

Localisation accuracy with iodine-125 seed versus wire guidance for breast cancer surgery.

INTRODUCTION: Impalpable breast lesions generally require image-guided localisation for breast-conserving surgery. A standard technique is to place a hook wire (HW) within the lesion. Radioguided occult lesion localisation using iodine seeds (ROLLIS) involves inserting a 4.5 mm iodine-125 seed (seed) into the lesion. We hypothesised that a seed could be more precisely positioned in relation to the lesion than a HW and that this may be associated with a lower re-excision rate. METHODS: Retrospective review of consecutive participant data from three ROLLIS RCT (ACTRN12613000655741) sites. Participants underwent preoperative lesion localisation (PLL) with seed or HW between September 2013 and December 2017. Lesion and procedural characteristics were recorded. Distances between (1) any part of the seed or thickened segment of the HW ('TSHW') and the lesion/clip ('distance to device' DTD) and (2) centre of the TSHW/seed and centre of the lesion/clip (device centre to target centre 'DCTC') were measured on immediate postinsertion mammograms. Pathological margin involvement and re-excision rates were compared. RESULTS: A total of 390 lesions (190 ROLLIS and 200 HWL) were analysed. Lesion characteristics and guidance modality used were similar between groups. Ultrasound-guided DTD and DCTC for seed were smaller than for HW (77.1% and 60.6%, respectively, P-value < 0.001). Stereotactic-guided DCTC for seeds was 41.6% smaller than for HW (P-value = 0.001). No statistically significant difference in the re-excision rates was found. CONCLUSION: Iodine-125 seeds can be more precisely positioned for preoperative lesion localisation than HW, however, no statistically significant difference in re-excision rates was detected.

Breast incidentalomas on 18-Fluorodeoxyglucose positron emission tomography-computed tomography performed for a non-mammary cause: Significance and outcomes.

INTRODUCTION: The aim of the study was to determine the rate of malignancy in breast incidentalomas found on 18-Fluorodeoxyglucose Positron Emission Tomography-Computed tomography (18 FDG PET-CT) performed for non-mammary causes and evaluate outcomes. METHODS: A single-centre, retrospective review of 5728 18-FDG PET-CT scans performed between January 1, 2017 and April 30, 2019 was undertaken. Cases with known primary breast cancer or metastases to the breast in the previous ten years were excluded. Diagnosis was confirmed with breast imaging, histology and 2-year follow-up. Data analysed included age, the pattern of uptake on 18-FDG PET-CT, lesion size and BIRADS score. RESULTS: Thirty-two Breast incidentalomas were identified in 27/5728 scans (0.47%). 18 lesions (56.3%) were malignant. Five underwent curative surgery. Nine lesions (28.1%) were benign and five (15.6%) were false positive. CONCLUSION: Breast incidentalomas are uncommon on 18-FDG PET-CT but require work-up for malignancy. BIRADS score has a high sensitivity and specificity for malignancy in18-FDG PET-CT incidentalomas but age, size of the lesion and the pattern of uptake on 18-FDG PET-CT were not useful in differentiating benign from malignant incidentalomas.

ROLLIS roll-out: Pitfalls, errors, lessons learned and recommendations from Australian and New Zealand experience during the randomised controlled trial, implementing a novel localisation method for impalpable malignant breast lesions, radio-guided occult lesion localisation with iodine-125 (125 I) seed (ROLLIS).

INTRODUCTION: Breast cancer surgery aims to excise lesions with clear margins and provide optimal cosmesis with a low re-excision rates. These aims are aided by accurate lesion localisation and a surgical choice of incision site with minimal removal of healthy tissue. Problems associated with hookwires have led to adoption of non-wire methods including radioguided occult lesion localisation using iodine-125 (ROLLIS). This paper outlines the problems encountered and lessons learnt during the largest RCT involving 659 participants, conducted at eight sites (seven Australian, one New Zealand centres) between September 2013 and April 2018.* METHODS: Data, along with substantive comments, regarding each ROLLIS procedure, documenting each step from the seed insertion, ease of operative retrieval, to return of the seed to medical physics, from a shared on-line secure database and a separate site email survey, were synthesised and categorised. RESULTS: The Australian and New Zealand ROLLIS RCT experience highlights several important issues. Lessons learned were related to licencing the seed and tracking protocols. A Designated Team Lead, who is a good communicator, ensuring the Tracking Protocols were accurately followed and updated, subspecialty leads and a Co-ordinator, responsible for training, logbook maintenance and seed ordering, enhanced the success and acceptance of the programme. Addressing radiation issues, fears, education of staff and seed loss was imperative. CONCLUSION: The Australian and New Zealand ROLLIS RCT experience highlights the need for adherence to local licencing laws and protocols, appointing a dedicated ROLLIS Designated Team Lead with good communication and a ROLLIS Co-ordinator. These facilitate the adoption of a successful ROLLIS programme.

Is staging breast magnetic resonance imaging prompted upgrade to mastectomy appropriate?

BACKGROUND: Breast magnetic resonance imaging (MRI) use for surgical staging is increasing, though remains controversial. We aimed to evaluate the accuracy of MRI in surgical decision-making to determine if mastectomy prompted by MRI was appropriate. METHODS: A single-centre observational study in Perth, Western Australia, with the inclusion of all preoperative and postoperative studies (e.g. involved margins after breast-conserving surgery) undergoing staging breast MRI from 1 January 2015 to 26 August 2019. A standard protocol using gadolinium contrast was used. The reference standard was postoperative histopathology or, for studies without additional surgery after MRI following breast-conserving surgery, the next and subsequent annual screening episodes. By reviewing the final histopathology, the medical case notes and multidisciplinary team decision process, we evaluated whether the reported MRI disease extent was accurate in prompting an appropriate upgrade to mastectomy. Outcomes are reported with descriptive statistics. RESULTS: Of 130 cancers staged with MRI; seven were excluded as information was incomplete, 104 were performed preoperatively and 19 postoperatively. The majority (60%) staged lobular carcinoma (invasive 59%, in situ 1%) compared to ductal carcinoma (invasive 31%, in situ 8%). For preoperative MRI, half (54% - 56/104) underwent subsequent mastectomy. Of these, MRI prompted mastectomy in 45% (25/56), all appropriate for disease extent. In the postoperative staging group, two mastectomies were performed, one planned before imaging, the other prompted when MRI diagnosed residual disease and confirmed on histopathology. No false-negative staging MRI was identified. CONCLUSIONS: In our cohort, MRI prompted an upgrade to mastectomy in 21% (26/123), appropriate for cancer extent.

Can micro-computed tomography imaging improve interpretation of macroscopic margin assessment of specimen radiography in excised breast specimens?

INTRODUCTION: Peri-operative macroscopic margin assessment with standard intraoperative specimen radiography (IOSR) results in improved re-excision rates in excised breast tissue specimens but is limited. This study sought to improve the intraoperative margin assessment on standard IOSR techniques by utilizing noninvasive X-ray micro-computed tomography (micro-CT) imaging of breast tissue specimens to compare margins in three-dimensional with two-dimensional IOSR. METHODS: Patients with impalpable breast carcinoma, or suspected breast carcinoma, who were eligible for breast-conserving surgery were recruited. Margins were assessed within each specimen using standard IOSR, micro-CT, and histology techniques. RESULTS: Six malignant and three benign lesions were included for the analysis in this study. Micro-CT identified the same positive margin as IOSR in 3 out of 6 malignancies. However, margin status identified by micro-CT was concordant with pathological assessment in only one specimen. In comparison, margin assessment by IOSR correctly correlated with pathological margin status in three malignant specimens. CONCLUSION: The use of micro-CT imaging in this study did not improve margin assessment in impalpable breast specimens when compared to standard specimen radiography (SR) assessment. However, future improvements in sample preparation and CT image acquisition processes may enhance the potential of micro-CT as a valuable imaging tool for improving margin assessment.

The technique and accuracy of breast specimen ultrasound in achieving clear margins in breast conserving surgery.

INTRODUCTION: The aim of this prospective study was to determine whether breast specimen ultrasound (SUS) can reliably be used to confirm whether ultrasound (US) visible breast malignancies are excised with clear margins during breast-conserving surgery (BCS), in order to avoid a second operation and recurrence. METHODS: A total of 95 consecutive participants with US visible malignancies, undergoing BCS, had the excised breast specimen transported to the radiology department intraoperatively. Breast SUS was used to confirm the presence of the lesion and measure the medial, lateral, superior and inferior margins. Margins < 10mm prompted a call to theatre to recommend an immediate cavity shave. The accuracy of the SUS technique in confirming the lesion is contained within the specimen, and the correlation of radial margins on US and histology was assessed retrospectively. RESULTS: Breast SUS had 100% accuracy in confirming the presence of 99 lesions. 384 corresponding US and invasive carcinoma histological margins were compared. A 10mm or greater margin on US has a sensitivity of 56% (95% CI 21-86), specificity of 93% (95% CI 90-95) and accuracy of 92% (95% CI 89-95) in predicting no ink on tumour histologically, with a positive predictive value of 16% (95% CI 5-34) and negative predictive value of 99% (95% CI 97-99%). The area under the curve was 0.746 (95% CI 0.572-0.921). CONCLUSIONS: Breast SUS is a fast and reliable technique. Mammographically occult breast malignancies that are sonographically evident should undergo SUS to confirm the presence of the lesion and assess its macroscopic margins to avoid a re-excision.

Does Medicare-eligible high-risk breast cancer screening MRI target the right women?

INTRODUCTION: MRI is the most sensitive modality to screen for breast cancer, but it is expensive with somewhat limited access. Audit of screening performance should reflect appropriate population targeting. METHODS: An observational study on consecutively screened high-risk women, assessment of the contralateral breast staging a new cancer, or surveillance in women with prior breast cancer or high-risk lesion in Perth, Western Australia. All breast MRI studies from 1 January 2015 to 7 September 2018 were included. Studies were 3T comprising T2, DWI, ADC and T1-weighted +/- fat saturation +/- IV gadolinium, +/- subtraction. DCE was read on the dynamics or DynaCAD (Invivo, Gainesville, FL, USA). Fellowship-trained breast radiologists blindly double-read by consensus; additional reader/s arbitrated. The reference standard was the histopathology result or cancer registry notification for cancer diagnoses and benign biopsies, benign follow-up imaging or subsequent screening MRI. RESULTS: Of 993 MRI studies in 554 women, 870 eligible MRI were performed in 471 women, and 706 had a reference standard. Median age was 44 years (range 18-80). The majority of studies (65% 457/706) were screening Medicare rebate-eligible high familial risk; 26% for surveillance after a breast cancer or contralateral staging; 6% screened BRCA carriers. Eleven cancers were diagnosed, eight were MRI-detected. Only two of these were at high-risk screening MRI. Five were detected at staging contralateral ILC, after negative 2D mammography and ultrasound. Cancer prevalence was highest for staging contralateral ILC, at 600/10,000 MRI, for high-risk screening 77/10,000 MRI and surveillance 116/10,000 MRI. CONCLUSIONS: Cancers were predominantly detected in women undergoing preoperative staging of new invasive lobular carcinoma in the contralateral breast, rather than the Medicare rebate-eligible high-risk screening group.

Recurrent complications of PAAG implants during lactation.

A 35-year-old lactating woman with pre-existing polyacrylamide gel (PAAG) implants for 10 years presented on numerous occasions following both her pregnancies with bilateral recurrent breast infection, pain and finally massive breast enlargement with a ruptured galactocoele necessitating surgical intervention. As the safety of PAAG for the breastfeeding baby is not known, breastfeeding with PAAG implants is not recommended.

Comparison of the time taken for localised breast surgery pre- and post-introduction of intra-operative digital specimen mammography.

INTRODUCTION: More than half of the patients with an impalpable malignant breast lesion have a mammographically detected and imaged-guided localisation, which can be technically challenging for the breast surgeon. Specimen imaging is used to confirm successful excision of the localised index lesion and has improved the operating list efficiency resulting in a higher number of excisions per surgical list. The aim of this study was to evaluate whether introducing IDSM (intra-operative digital specimen mammography) saved operation time for localised breast surgery. METHODS: A single-centre retrospective review was undertaken to compare the operation time (from incision to wound closure) taken for excision of 114 consecutive image-guided localised impalpable breast lesions, performed using departmental specimen radiography (DSR), 6 months prior to the introduction of IDSM (Hologic, Trident® ) in March 2013, with the theatre time taken for excision of 121 consecutive image-guided localised impalpable breast lesions in the 6 months following introduction of IDSM. RESULTS: There was no significant difference in mean surgical time, which were 47.8 (±27.3) minutes in the CSR group and 48.8 (±25.7) minutes in the IDSM group. CONCLUSION: We were expecting to confirm a reduction in theatre time with the introduction of IDSM. Surprisingly, no difference in operating times was demonstrated. Factors that influenced the impact of IDSM included the proximity of the imaging department to the operating theatre.

Patient satisfaction with Radioguided Occult Lesion Localisation using iodine-125 seeds ('ROLLIS') versus conventional hookwire localisation.

BACKGROUND: Women with impalpable or poorly palpable breast cancer require radiologically guided localisation prior to breast conserving surgery. Radioguided Occult Lesion Localisation using Iodine-125 Seed (ROLLIS) is an emerging alternative to conventional Hookwire Localisation (HWL). We compared ROLLIS with conventional HWL with respect to patient reported stress and discomfort related to the localisation procedure. PATIENTS AND METHODS: From September 2013 to January 2016, women who were eligible for breast conserving surgery with impalpable or poorly palpable histologically confirmed invasive or in-situ carcinoma were recruited to the multi-centre ROLLIS randomised controlled trial and underwent either ROLLIS or HWL. Following surgery, a questionnaire was administered to each participant regarding the stress and discomfort related to the localisation procedure. Multivariate analysis was performed to compare the primary outcome of patient-reported stress and discomfort between localisation groups. RESULTS: 218 participants with 220 lesions were randomised and underwent breast conserving surgery following localisation. 201 (92.2%) and 202 (92.7%) of participants provided responses to the stress and discomfort components of the questionnaire respectively. HWL was associated with a statistically significant increased odds of greater stress and discomfort when compared to ROLLIS (OR = 2.07, p = 0.01 and OR = 1.94, p = 0.01 respectively). Insertion of multiple localisation devices was also associated with increased stress (OR = 5.68, p < 0.01) and discomfort (OR = 2.96, p < 0.01). CONCLUSION: When compared with conventional HWL, ROLLIS is associated with significantly less stress and discomfort for patients prior to breast conserving surgery.

Intraoperative Localisation of Impalpable Breast Lesions Utilising the ROLLIS Technique Following Peritumoral 99mTc-colloid Sentinel Node Lymphoscintigraphy.

BACKGROUND: Ultrasound or stereotactic guided hook-wire localisation has been the standard-of-care for the pre-surgical localisation of impalpable breast lesions, which account for approximately a third of all breast cancer. Radioguided occult lesion localisation using I-125 seeds (ROLLIS) is a relatively new technique for guiding surgical excision of impalpable breast lesions, and is a promising alternative to the traditional hook-wire method. When combined with Tc-99m labelled colloid for sentinel node mapping in clinically indicated cases, there has been uncertainty regarding whether the downscatter of Tc-99m into the I-125 energy spectrum could adversely affect the intra-operative detection of the I-125 seed, especially pertaining to a peritumoral injection. OBJECTIVE: To evaluate the percentage contribution of downscattered activity from Tc-99m into the I-125 energy spectrum in simulated intra-operative resections of an I-125 seed following different sentinel node injection techniques. METHOD: Two scenarios were simulated using breast phantoms with lean chicken breast. The first scenario, with a 2cm distance between the Tc-99m injection site and the I-125 seed, simulated a periareolar ipsiquadrant injection with the subdermal or intradermal technique. The second scenario simulated a peritumoral injection technique with the Tc-99m bolus and an I-125 seed at the same site. Count rates were acquired with a hand-held gamma probe, and the percentage contribution of downscattered Tc-99m gamma photons to the I-125 energy window was calculated. RESULTS: In scenarios one and two, downscattered Tc-99m activity contributed 0.5% and 33% respectively to the detected count rate in the I-125 energy window. In both scenarios, the I-125 seed was successfully localised and removed using the gamma probe. CONCLUSION: There is no significant contribution of downscattered activity associated with a peritumoral injection of Tc-99m to adversely affect the accurate intra-operative localisation of an I- 125 seed.

Iodine-125 seeds to guide removal of impalpable breast lesions: radio-guided occult lesion localization - a pilot study.

BACKGROUND: The aim of this study was to confirm that radio-guided occult lesion localization using low activity iodine 125 (I-125) seeds (ROLLIS) could be safely and accurately used for localization and guided excision of impalpable breast lesions in different multidisciplinary settings and to prepare staff for a randomized controlled trial. METHOD: Preoperative image-guided localization of 102 lesions using one or two I-125 seeds with hook-wire back-up was performed in 99 participants at two tertiary hospitals. Preoperative core biopsy in 24 lesions was benign or indeterminate (Group A) and malignant in 78 lesions (Group B). Imaging and histopathology findings and re-excision rates were recorded. Training requirements for new staff and seed handling protocols were refined. RESULTS: All seeds and lesions were successfully removed. In five of 23 Group A participants, malignancy on final pathology required definitive surgery for positive margins. The re-excision rate in Group B was 17%. Overall re-excision rate was 18%. Thirty-seven clinical staff members were trained. Sentinel node localization was successful in all 76 cases. Seeds of low activity were successfully used. CONCLUSION: The ROLLIS technique using a lower dose (∼2 MBq) seed is safe, effective and can easily be adopted in a large multi-disciplinary setting.

A spontaneously resolving breast lesion: imaging and cytological findings of nodular fasciitis of the breast with FISH showing USP6 gene rearrangement.

We report a case of nodular fasciitis of the breast in a 48-year-old woman who presented with a tender rapidly growing right breast lump. Ultrasound guided fine needle aspiration (FNA) of the solid mass was performed. Cytology was reported as atypical spindle cell neoplasm and the patient was referred to a breast surgeon at a tertiary institution for a definitive diagnosis and further management. Follow-up ultrasound showed partial regression and MRI, mammogram after 2-3 weeks confirmed spontaneous and total resolution of the lesion. Nodular fasciitis of the breast is rarely diagnosed on cytology alone and a histological diagnosis is usually required for a definitive diagnosis. However, in this case, the lesion spontaneously resolved prior to core biopsy or diagnostic open biopsy. The cytological features in conjunction with immunohistochemistry and the clinical history strongly suggest nodular fasciitis, which is further supported by a USP6 FISH positive result.

Pseudoangiomatous stromal hyperplasia causing massive breast enlargement.

Pseudoangiomatous stromal hyperplasia (PASH) of the breast is a benign mesenchymal proliferative process, initially described by Vuitch et al. We report an unusual case of a 46-year-old woman who presented with a 6-week history of bilateral massive, asymmetrical, painful enlargement of her breasts, without a history of trauma. On clinical examination, both breasts were markedly enlarged and oedematous, but there were no discrete palpable masses. Preoperative image-guided core biopsies and surgery showed PASH. PASH is increasingly recognised as an incidental finding on image-guided core biopsy performed for screen detected lesions. There are a few reported cases of PASH presenting as rapid breast enlargement. In our case, the patient presented with painful, asymmetrical, massive breast enlargement. Awareness needs to be raised of this entity as a differential diagnosis in massive, painful breast enlargement.

Predictors of re-excision in wire-guided wide local excision for early breast cancer: a Western Australian multi-centre experience.

BACKGROUND: A significant proportion of breast cancers present as impalpable lesions requiring radiological guidance prior to surgical excision, commonly by hook-wire placement. Complete lesion excision is an essential part of treatment, and re-excision may be needed to ensure this and minimize local recurrence. We explore a 1-year audit of re-excision of hook-wire-guided excisions in two large public breast units in Western Australia and define factors associated with the requirement for re-excision. METHODS: A retrospective review of wire-localized wide local excisions for early breast cancer in 2009 at two tertiary breast centres in Western Australia. RESULTS: Of 148 localized lesions, 44 (30%) underwent re-excision. The only significant preoperative finding was the location of tumour in the breast. The intra-operative specimen radiograph provided useful information that influenced re-excision. Smaller (≤5 mm) and larger (>20 mm) tumours on final pathological size were more likely to undergo re-excision as well as a larger difference in actual size to predicted size. The presence of ductal carcinoma in situ (DCIS) increased re-operation, as did multifocality. CONCLUSION: This study highlights factors that should make the surgeon more cautious for re-excision. Suspicion of DCIS, especially at the periphery of tumours, and a central tumour location increase risk. Lesion localization techniques play an important role in minimizing risk while maintaining cosmesis.

Radioguided occult lesion localisation using iodine-125 seeds ('ROLLIS') for removal of impalpable breast lesions: First Australian experience.

INTRODUCTION: Approximately one-third of breast cancers are impalpable and require pre-operative image-guided localisation. Hook-wire localisation (HWL) is commonly used but has several disadvantages. Use of a low-activity radioactive iodine-125 seed is a promising alternative technique used in the USA and the Netherlands. This pilot study describes the first use of this in Australia. METHODS: In this prospective pilot study, 21 participants with biopsy-proven breast cancer underwent radioguided occult lesion localisation using iodine-125 seed(s) (ROLLIS) with insertion of a hook-wire for back up. Sentinel node biopsy was performed where indicated. Ease of hook-wire and seed insertion, duration of the procedure, dependence on the seed versus hook-wire during surgery, lesion location within the specimen, histopathology including size of radial margins, the ease of seed retrieval in pathology, and safe return of seeds for disposal were documented. Radiation dosimetry of staff was performed. RESULTS: All seeds were placed within 3.5 mm of the lesion. All lesions and seeds were removed. One participant needed re-excision for involved margins. Radiologists and surgeons both preferred ROLLIS. Surgeons were able to depend on the seed for localisation in all but one case. Sentinel node biopsy was successfully performed when required. Pathologists found seed retrieval quick and easy, with no detrimental effect on tissue processing. No radiation doses measurably above background were received by staff. CONCLUSION: ROLLIS is an easily learnt, safe and effective alternative technique to standard HWL.

Malignant phyllodes tumour presenting as a massive fungating breast mass and silent thrombo-embolism.

INTRODUCTION: We report an unusual case of a massive malignant phyllodes tumour that had almost replaced the entire breast presenting with severe chronic blood loss, extensive deep venous thrombosis (DVT) and a silent pulmonary embolus. PRESENTATION: Long-standing neglected massive fungating ulcerative mass larger than the left haemothorax. DISCUSSION: Phyllodes tumours are rare fibro-epithelial breast lesions that have the propensity to grow rapidly to a large size if neglected. Larger tumours are more likely to be malignant with an overall metastatic rate around 10%. An incidental pulmonary embolus arising from extensive silent lower limb deep vein thrombosis requiring an IVC filter complicated the surgical management. CONCLUSION: Phyllodes tumours are rare and account for approximately 0.3-0.5% of all breast tumours [1]. They have the propensity to be fast growing. However, tumours reaching a massive size (>10cm) are rare with few reports in the literature.

The disappearing clip: an unusual complication in MRI biopsy.

MRI-guided biopsies are being increasingly used for otherwise occult breast lesions. Clip migration has been reported however, to the best of our knowledge, there have been no documented cases of entire disappearance of a marker clip. Absence of the postbiopsy marker clip was noted when our patient returned for preoperative hook-wire localisation even though accurate clip placement had been confirmed on the post-MRI biopsy mammogram.