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1.
World J Surg ; 44(5): 1547-1551, 2020 05.
Article in English | MEDLINE | ID: mdl-32002582

ABSTRACT

BACKGROUND: Neoadjuvant chemotherapy (NAC) can improve cosmesis by reducing resection volume. Breast-conserving surgery (BCS) aims to achieve clear excision margins while optimizing cosmesis. However, the influence of NAC on margin re-excision after BCS is unclear. This study examines the rate and determinants of margin re-excision in patients undergoing BCS following NAC in our institution. METHODS: From 2011-2015, all patients treated with NAC prior to BCS were identified from a prospectively maintained database. Mann-Whitney and Fisher's exact test tests were used to compare variables in patients who did and did not require re-excision. Patients undergoing primary surgical treatment in 2015 comprised an unmatched comparison group. RESULTS: Of 211 patients treated with NAC, 69 initially underwent BCS. The re-excision rate was 32% (n = 22) compared to 17% in the primary operable group (38 of 221, p = 0.02). Re-excision rates were lowest in triple-negative and HER2+ tumors (0% and 10%, respectively). Lobular carcinoma and ER+ tumors had a significantly higher rate of re-excision (100% and 42%, respectively). Of 22 patients undergoing re-excision, 9 had further BCS and 13 had a mastectomy. CONCLUSION: The re-excision rate following NAC is almost twice that of patients who underwent primary operative management. Her2+ and triple-negative tumors have lower re-excision rates and may represent a selected cohort most suitable for BCS. Patients with invasive lobular carcinoma or ER+ disease have significantly higher rates of margin positivity, and these patients should be considered for a cavity shave during primary surgery to reduce the rates of re-excision.


Subject(s)
Breast Neoplasms/surgery , Carcinoma, Ductal, Breast/surgery , Carcinoma, Lobular/surgery , Neoadjuvant Therapy , Reoperation , Triple Negative Breast Neoplasms/surgery , Antineoplastic Agents/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , Carcinoma, Ductal, Breast/drug therapy , Carcinoma, Ductal, Breast/metabolism , Carcinoma, Lobular/drug therapy , Carcinoma, Lobular/metabolism , Female , Humans , Margins of Excision , Mastectomy, Segmental , Middle Aged , Receptor, ErbB-2/metabolism , Receptors, Estrogen/metabolism , Retrospective Studies , Triple Negative Breast Neoplasms/drug therapy
2.
Br J Cancer ; 119(3): 374-380, 2018 08.
Article in English | MEDLINE | ID: mdl-29773838

ABSTRACT

BACKGROUND: The optimal timing of (neo)adjuvant trastuzumab initiation with respect to chemotherapy and surgery remains undefined. METHODS: Retrospective analysis of a large institutional database of HER2-positive patients who received anti-HER2 therapy. We included all Stage I to III patients treated with trastuzumab with a minimum follow up of 3 years. The date of first breast biopsy was recorded as initial diagnosis. RESULTS: A total of 506 patients [adjuvant: 386 (76%)-neo-adjuvant: 120 (24%)] were included. The median time-to-first-trastuzumab (TFT) from diagnosis was 12 weeks (range 1.9-122.3). Median follow-up is 73.3 months (range 1.4-176.3). TFT was significantly shorter in the neo-adjuvant than in the adjuvant cohort (median: 4.4 vs. 14 weeks, p < 0.00001). Despite the neo-adjuvant cohort having significantly more node-positive patients (75 vs. 53%, p < 0.0001), DFS rate (neo-adjuvant: 12.5 vs. adjuvant: 18%, p = 0.094) was numerically superior in neo-adjuvant patients. A TFT ≤ 12 weeks was associated with significantly superior DFS and OS over TFT > 12 weeks. Early concomitant regimens were associated with superior DFS over delayed-concomitant and sequential regimens. CONCLUSIONS: Initiating trastuzumab more than 12 weeks from diagnosis has a negative impact on clinical outcome. Neo-adjuvant anti-HER2 therapy could be the optimal strategy to treat early stage HER2-positive breast cancer.


Subject(s)
Breast Neoplasms/drug therapy , Chemotherapy, Adjuvant/methods , Neoplasm Recurrence, Local/drug therapy , Trastuzumab/administration & dosage , Adult , Aged , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Chemotherapy, Adjuvant/adverse effects , Disease-Free Survival , Drug Administration Schedule , Female , Humans , Middle Aged , Neoplasm Recurrence, Local/genetics , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Receptor, ErbB-2/genetics , Retrospective Studies , Trastuzumab/adverse effects , Treatment Outcome
3.
Tumour Biol ; 40(5): 1010428318776169, 2018 May.
Article in English | MEDLINE | ID: mdl-29775157

ABSTRACT

Biomarkers are the key to personalized treatment in patients with breast cancer. While tissue biomarkers are most useful in determining prognosis and upfront predicting response to therapy, circulating protein biomarkers such as CA 15-3 and carcinoembryonic antigen are mainly used in monitoring response to endocrine or chemotherapy in patients with advanced disease. Although several centers measure biomarkers in asymptomatic patients following curative surgery for primary breast cancer, the clinical utility of this practice is unclear. Promising new biomarkers for breast cancer include circulating tumor DNA and circulating tumor cells. In contrast to circulating protein biomarkers, measurement of circulating tumor DNA-based biomarkers is potentially useful in identifying mechanisms of resistance to ongoing therapies as well as identifying new targets for further treatment. To increase clinical utility, both the established and emerging circulating biomarkers should where possible be incorporated into randomized trials evaluating new therapies in patients with breast cancer.


Subject(s)
Biomarkers, Tumor/blood , Breast Neoplasms/blood , Circulating Tumor DNA/blood , Carcinoembryonic Antigen/blood , Female , Humans , Mucin-1/blood , Neoplastic Cells, Circulating , Peptides/blood , Randomized Controlled Trials as Topic/methods , Receptor, ErbB-2/blood
4.
BMC Med ; 15(1): 101, 2017 06 05.
Article in English | MEDLINE | ID: mdl-28578692

ABSTRACT

BACKGROUND: Cutaneous melanoma is the deadliest skin cancer, with an increasing incidence and mortality rate. Currently, staging of patients with primary melanoma is performed using histological biomarkers such as tumor thickness and ulceration. As disruption of the epigenomic landscape is recognized as a widespread feature inherent in tumor development and progression, we aimed to identify novel biomarkers providing additional clinical information over current factors using unbiased genome-wide DNA methylation analyses. METHODS: We performed a comprehensive DNA methylation analysis during all progression stages of melanoma using Infinium HumanMethylation450 BeadChips on a discovery cohort of benign nevi (n = 14) and malignant melanoma from both primary (n = 33) and metastatic (n = 28) sites, integrating the DNA methylome with gene expression data. We validated the discovered biomarkers in three independent validation cohorts by pyrosequencing and immunohistochemistry. RESULTS: We identified and validated biomarkers for, and pathways involved in, melanoma development (e.g., HOXA9 DNA methylation) and tumor progression (e.g., TBC1D16 DNA methylation). In addition, we determined a prognostic signature with potential clinical applicability and validated PON3 DNA methylation and OVOL1 protein expression as biomarkers with prognostic information independent of tumor thickness and ulceration. CONCLUSIONS: Our data underscores the importance of epigenomic regulation in triggering metastatic dissemination through the inactivation of central cancer-related pathways. Inactivation of cell-adhesion and differentiation unleashes dissemination, and subsequent activation of inflammatory and immune system programs impairs anti-tumoral defense pathways. Moreover, we identify several markers of tumor development and progression previously unrelated to melanoma, and determined a prognostic signature with potential clinical utility.


Subject(s)
DNA Methylation , DNA, Neoplasm/metabolism , Melanoma/genetics , Melanoma/physiopathology , Skin Neoplasms/genetics , Skin Neoplasms/physiopathology , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/genetics , Disease Progression , Female , Humans , Male , Middle Aged , Prognosis , Melanoma, Cutaneous Malignant
5.
Ann Surg ; 262(2): 243-8, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25822674

ABSTRACT

BACKGROUND: Sentinel lymph node biopsy (SLNB) has become the gold standard for axillary staging. Debate remains as to the optimal method of SLN detection. OBJECTIVES: Determine whether patients undergoing an SLNB required the addition of isosulfan blue dye to radioisotope when an SLN was identified on a preoperative lymphoscintigram. METHODS: A prospective randomized controlled trial comparing the combination of radioisotope and blue dye versus radioisotope alone was performed between March 2010 and September 2012. The trial protocol was registered with Current Controlled Trials. Women with clinically and radiologically node-negative breast cancer with a positive preoperative lymphoscintigram were eligible for inclusion. RESULTS: A total of 667 patients were included in the analysis with 342 patients receiving the combination (blue dye and radioisotope) and 325 patients receiving radioisotope alone. The groups were evenly matched both demographically and pathologically. The mean age was 48 years (48.3 vs 47.7 years; P = 0.47), the mean tumour size was 24.2 mm (24.3 mm vs 24.1 mm; P = 0.7) and there was no statistically significant difference in the grade of the tumors between the 2 groups (P = 0.58). There was no difference in the identification rate, nor was that in the number of nodes retrieved between the 2 groups (P = 0.30). There was no difference in the number of positive lymph nodes that were identified between the 2 groups (23.8% vs 22.1%; P = 0.64). CONCLUSIONS: This study failed to demonstrate an advantage with the addition of isosulfan blue dye to radioisotope in the identification of the SLN in the presence of a positive preoperative lymphoscintigram.


Subject(s)
Breast Neoplasms/pathology , Coloring Agents , Lymphoscintigraphy , Radiopharmaceuticals , Rosaniline Dyes , Sentinel Lymph Node Biopsy/methods , Adult , Aged , Aged, 80 and over , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/therapy , Female , Humans , Mastectomy , Middle Aged , Predictive Value of Tests , Prospective Studies , Sodium Pertechnetate Tc 99m
7.
Oncologist ; 18(4): 391-407, 2013.
Article in English | MEDLINE | ID: mdl-23576482

ABSTRACT

Pheochromocytomas (PCCs) and paragangliomas (PGLs) are rare catecholamine-secreting tumors derived from chromaffin cells originating in the neural crest. These tumors represent a significant diagnostic and therapeutic challenge because the diagnosis of malignancy is frequently made in retrospect by the development of metastatic or recurrent disease. Complete surgical resection offers the only potential for cure; however, recurrence can occur even after apparently successful resection of the primary tumor. The prognosis for malignant disease is poor because traditional treatment modalities have been limited. The last decade has witnessed exciting discoveries in the study of PCCs and PGLs; advances in molecular genetics have uncovered hereditary and germline mutations of at least 10 genes that contribute to the development of these tumors, and increasing knowledge of genotype-phenotype interactions has facilitated more accurate determination of malignant potential. Elucidating the molecular mechanisms responsible for malignant transformation in these tumors has opened avenues of investigation into targeted therapeutics that show promising results. There have also been significant advances in functional and radiological imaging and in the surgical approach to adrenalectomy, which remains the mainstay of treatment for PCC. In this review, we discuss the currently available diagnostic and therapeutic options for patients with malignant PCCs and PGLs and detail the molecular rationale and clinical evidence for novel and emerging diagnostic and therapeutic strategies.


Subject(s)
Adrenal Gland Neoplasms/genetics , MicroRNAs/genetics , Paraganglioma/genetics , Pheochromocytoma/genetics , Adrenal Gland Neoplasms/diagnosis , Adrenal Gland Neoplasms/drug therapy , Adrenal Gland Neoplasms/surgery , Adrenalectomy , Diagnostic Imaging , Humans , Mutation , Neoplasm Recurrence, Local/genetics , Neoplasm Recurrence, Local/pathology , Paraganglioma/diagnosis , Paraganglioma/drug therapy , Paraganglioma/surgery , Pheochromocytoma/diagnosis , Pheochromocytoma/drug therapy , Pheochromocytoma/surgery , Prognosis
8.
Oncologist ; 18(9): 994-1003, 2013.
Article in English | MEDLINE | ID: mdl-23881987

ABSTRACT

Primary thyroid lymphoma is rare, composing approximately 5% of all thyroid malignancies and less than 3% of all extranodal lymphomas. It typically presents as a rapidly enlarging goiter with associated compressive symptoms. Thyroid ultrasound and fine needle aspiration cytology, using flow cytometry and immunohistochemistry, remain the main modalities used to confirm the presence of lymphoma. The increasing use of an ultrasound-guided core biopsy to achieve an accurate diagnosis has further limited the role of surgery. An open surgical biopsy may still be required not only for definitive diagnosis but also to confirm the subtype of lymphoma. There are limited numbers of randomized or prospective trials to guide management, and controversy remains over optimal treatment. Treatment and prognosis of this disease can be dichotomized into two separate groups: pure mucosa-associated lymphoid tissue (MALT) lymphoma and diffuse large B-cell lymphoma (DLBCL) or mixed subtypes. Early stage (stage IE) intrathyroidal MALT lymphomas typically have an indolent course and may be treated with single-modality surgery, radiotherapy, or a combination of both. DLBCLs are more aggressive, and survival outcomes are highest with multimodal therapy incorporating monoclonal antibodies, chemotherapy, and radiotherapy. The prognosis is generally excellent but can be varied because of the heterogeneous nature of thyroid lymphomas. The aim of this paper is to discuss the changes in diagnostic modalities and to focus on the recent alterations in the management of this rare disease, including targeted therapies as well as the more limited role of the endocrine surgeon.


Subject(s)
Lymphoma/diagnosis , Lymphoma/therapy , Thyroid Neoplasms/diagnosis , Thyroid Neoplasms/therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Humans , Lymphoma/pathology , Prognosis , Thyroid Neoplasms/pathology
9.
Expert Rev Proteomics ; 9(4): 415-23, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22967078

ABSTRACT

Despite advances in our knowledge of the disease, malignant melanoma remains an unpredictable entity. The revolution in molecular biological techniques, such as DNA sequencing and gene-expression profiling, has uncovered many potential protein targets and biomarkers relevant to melanoma progression. Successful clinical application would be aided significantly by downstream proteomic validation of those candidate markers using a combination of immunohistochemistry and tissue microarrays. Yet, research in this context seems to lag behind the output of genomic data relating to melanoma. In this article, we look at the strengths and pitfalls of tissue microarrays in malignant melanoma. We will show how tissue microarrays have become a vital step in the transition from molecular techniques to useful clinical assays and interventions and look at likely future developments for advances in this field.


Subject(s)
Melanoma/diagnosis , Neoplasm Proteins/chemistry , Tissue Array Analysis/methods , Biomarkers, Tumor/chemistry , Clinical Trials as Topic , Disease Progression , Gene Expression Profiling/methods , Genetic Testing/methods , Humans , Immunohistochemistry , Melanoma/chemistry , Melanoma/genetics , Neoplasm Staging/methods , Prognosis , Sensitivity and Specificity
11.
World J Surg ; 36(5): 1175-81, 2012 May.
Article in English | MEDLINE | ID: mdl-22170475

ABSTRACT

BACKGROUND: Improved preoperative localizing studies have facilitated minimally invasive approaches in the treatment of primary hyperparathyroidism (PHPT). Success depends on the ability to reliably select patients who have PHPT due to single-gland disease. We propose a model encompassing preoperative clinical, biochemical, and imaging studies to predict a patient's suitability for minimally invasive surgery. METHODS: For the purposes of the present study, 180 consecutive patients were included for analysis. A 5-variable model based on preoperative ionized serum calcium (>1.4 mmol/l), intact parathyroid hormone level (≥ 2 times the upper limit of normal), positive sestamibi scan for a single affected gland, positive ultrasound scan for a single gland, and concordance between the two imaging modalities for single-gland disease at a similar location was employed, where a score of 1 was allocated for each variable present. RESULTS: Of the 180 patients, 62 (34%) underwent bilateral exploration, 63 (36%) underwent unilateral exploration, and 55 (30%) underwent minimally invasive parathyroidectomy. The results showed that 92% had single-gland disease, 3% had double adenomas, and 5% had hyperplasia. Biochemical cure was achieved in 98.9%. Mean follow-up was 153 days (range: 80-342 days). With the predictive scoring model, a score of ≥ 3 had a positive predictive value of 100% for single-gland disease. CONCLUSIONS: A scoring model encompassing preoperative biochemical and imaging data can be successfully employed to predict suitability for minimally invasive surgery in the majority of patients with single-gland disease.


Subject(s)
Decision Support Techniques , Hyperparathyroidism, Primary/surgery , Minimally Invasive Surgical Procedures , Parathyroidectomy/methods , Adolescent , Adult , Aged , Aged, 80 and over , Biomarkers/blood , Calcium/blood , Female , Follow-Up Studies , Humans , Hyperparathyroidism, Primary/blood , Hyperparathyroidism, Primary/diagnosis , Hyperparathyroidism, Primary/etiology , Male , Middle Aged , Models, Theoretical , Parathyroid Hormone/blood , Preoperative Care/methods , Treatment Outcome , Young Adult
12.
BJS Open ; 6(1)2022 01 06.
Article in English | MEDLINE | ID: mdl-35143625

ABSTRACT

BACKGROUND: The significance of exogenous hormone manipulation as part of fertility treatment and its relationship to the development of breast cancer remains uncertain. Several historical reviews have been performed with conflicting results. This study is an updated meta-analysis to determine whether there is a causal relationship between different fertility treatments and breast cancer. METHODS: The study report is based on the guidelines of PRISMA and Meta-Analysis of Observational Studies in Epidemiology. Studies published within the last 20 years were included to reflect up to date in vitro fertilization (IVF) practice. This study was prospectively registered on PROSPERO on 07/04/2021, registration identification CRD42021247706. The primary outcome of the study was to determine whether there is an increased incidence of breast cancer in women treated with hormonal fertility treatment. The secondary outcomes were to determine whether fertility treatments were individually associated with excess breast-cancer risk. RESULTS: Overall, 25 studies, including 617 479 participants, were eligible for inclusion. There was no significant breast-cancer risk association with fertility treatment (compared with general and subfertility reference groups). Summary odds ratio of all included studies was 0.97 (95 per cent c.i. 0.90 to 1.04). Women who received six or more IVF cycles did not have an increased risk of breast cancer. Similarly, there was no excess breast-cancer risk associated with clomiphene, human chorionic gonadotropin, gonadotropin analogues and progesterone when examined individually. Comparably, there was no significant association between fertility treatment and excess breast-cancer risk in patients with more than 10 years' follow-up. Summary odds ratio was 0.97 (95 per cent c.i. 0.85 to 1.12). CONCLUSION: This meta-analysis did not find a significant association between fertility treatments and excess breast-cancer risk. Women considering IVF should be informed that it does not appear to increase breast-cancer risk.


Subject(s)
Breast Neoplasms , Ovulation Induction , Breast Neoplasms/epidemiology , Female , Fertilization in Vitro/adverse effects , Fertilization in Vitro/methods , Humans , Ovulation Induction/adverse effects , Ovulation Induction/methods
13.
Tumour Biol ; 32(3): 441-50, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21153724

ABSTRACT

The S100 gene family encode low molecular weight proteins implicated in cancer progression. In this study, we analyzed the expression of four S100 genes in one cohort of patients with breast cancer and 16 S100 genes in a second cohort. In both cohorts, the expression of S100A8 and S1009 mRNA level was elevated in high-grade compared to low-grade tumors and in estrogen receptor-negative compared to estrogen receptor-positive tumors. None of the S100 transcripts investigated were significantly associated with the presence of lymph node metastasis. Notably, multiple S100 genes, including S100A1, S100A2, S100A4, S100A6, S100A8, S100A9, S100A10, S100A11, and S100A14 were upregulated in basal-type breast cancers compared to non-basal types. Using Spearman's correlation analysis, several S100 transcripts correlated significantly with each other, the strongest correlation has been found between S100A8 and S100A9 (r = 0.889, P < 0.001, n = 295). Of the 16 S100 transcripts investigated, only S100A11 and S100A14 were significantly associated with patient outcome. Indeed, these two transcripts predicted outcome in the cohort of patients that did not receive systemic adjuvant therapy. Based on our findings, we conclude that the different S100 genes play varying roles in breast cancer progression. Specific S100 genes are potential targets for the treatment of basal-type breast cancers.


Subject(s)
Breast Neoplasms/etiology , S100 Proteins/genetics , Adult , Aged , Cohort Studies , Disease Progression , Female , Humans , Middle Aged , RNA, Messenger/analysis , S100 Proteins/physiology
14.
Eur J Surg Oncol ; 47(7): 1507-1513, 2021 Jul.
Article in English | MEDLINE | ID: mdl-33589241

ABSTRACT

BACKGROUND: Administration of chemotherapy before breast surgery has the potential to reduce the risk of distant recurrence by targeting micrometastasis as well as allowing a more minimalistic approach to surgical intervention. We performed a systematic review to determine the optimum timing of surgery post breast cancer neoadjuvant chemotherapy (NACT). METHODS: The primary outcome was to determine whether the timing of surgery post NACT impacted overall survival (OS) and disease-free survival (DFS). We compared patient outcomes between those who had surgery within 8 weeks of completion of NACT to those that had surgery after 8 weeks. An outcome comparison between <4 weeks and 4-8 weeks was also performed. Secondary outcome included complete pathological response (pCR) post NACT. A meta-analysis was performed using the Mantel-Haenszel method. RESULTS: Five studies, including 8794 patients were eligible for inclusion. Patients that had surgery within 8 weeks of completion of NACT had a statistically significant improved OS(OR 0.47, 95% c. i 0.34-0.65) and DFS(OR 0.71 (95% c. i 0.52-0.98, P = 0.04). There were no survival advantages associated with having surgery less than 4 weeks post completion of NACT (OR 0.78, 95% c. i 0.46-1.33, P = 0.37). There was no difference in pCR rate between those that had surgery <4 weeks and 4-8 weeks (OR 1.01, 95% c. i 0.80-1.28, P = 0.93). CONCLUSION: This meta-analysis shows that the optimum timing of surgery post completion of NACT is 4-8 weeks as it is associated with increased OS and DFS.


Subject(s)
Breast Neoplasms/surgery , Time-to-Treatment , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Chemotherapy, Adjuvant , Female , Humans , Neoadjuvant Therapy
15.
Clin Breast Cancer ; 21(4): e377-e387, 2021 08.
Article in English | MEDLINE | ID: mdl-33451964

ABSTRACT

The association between immediate breast reconstruction (IBR)-related wound complications and breast cancer recurrence (BCR) remains uncertain. This study aimed to investigate the oncological outcomes in patients with wound complications following mastectomy and IBR. A comprehensive search was undertaken for all studies describing complications in patients with breast cancer following IBR. Studies were included if they reported on complications and investigated their relationship with BCR. A meta-analysis was performed using a random-effects model, with data presented as odds ratios and 95% confidence intervals. A total of 1418 patients from five studies were included in the final analysis. The mean age of patients included was 47.2 years. A total of 382 (26.9%) patients had postoperative complications following a majority of implant-based IBR (929/1418). A total of 158 (11.1%) recurrences, which included 63 locoregional and 106 distant recurrences, was noted at a mean follow-up of 66 months. Although there was an increase in recurrence rates in the complication group (n = 66/382; 17.3% vs. n = 92/1036; 8.9%), there was no significant association between complications and BCR (17.3% vs. 8.9%; P = .18) or mortality (3.6% vs. 2.3%; P = .15). Time to adjuvant therapy was significantly increased in patients with complications (mean difference, 8.69 days; range, 1.18-16.21 days; P = .02; I2 = 0.02). This meta-analysis demonstrated a higher incidence of wound complications following IBR and a statistically significant increased time to adjuvant therapy. However, this did not translate into adverse oncological outcomes in patients with breast cancer undergoing IBR.


Subject(s)
Breast Neoplasms/mortality , Breast Neoplasms/surgery , Mammaplasty/adverse effects , Mastectomy/adverse effects , Postoperative Complications/epidemiology , Adult , Breast Neoplasms/pathology , Female , Humans , Middle Aged
16.
Breast Cancer ; 28(1): 168-174, 2021 Jan.
Article in English | MEDLINE | ID: mdl-32780320

ABSTRACT

BACKGROUND: Breast fibromatosis is a rare clinical entity, but poses significant diagnostic and therapeutic challenges. In light of recent changes in management practices, the aim was to review our institutional experience of breast fibromatosis and provide a review of current available literature on such management. METHODS: A search of pathological databases within two tertiary institutions for all patients diagnosed with fibromatosis of the breast over a 10-year period (2007-2016) was performed. Clinicopathological characteristics and modes of treatment were recorded for each patient. Concurrently a comprehensive literature search was performed and studies relating to breast fibromatosis and its management were identified and reviewed. RESULTS: Sixteen patients were identified. Median age at diagnosis was 42 (range 21-70) and all patients were diagnosed with core biopsy. The most useful imaging modality in diagnosis was ultrasonography and magnetic resonance imaging. 13/16 were treated surgically whilst 3/16 were treated using a watch-and-wait approach. 6/13 (46%) required re-excision of margins and 2/13 (15%) had recurrence after surgery. On review of the literature, there is no dedicated guideline in place for the management of breast fibromatosis. Currently a 'watch and wait' approach is favoured over surgical intervention due to high levels of recurrence and associated surgical morbidity. All cases should be discussed at a sarcoma multidisciplinary team meeting and tyrosine kinase inhibitors should be considered in advanced cases. CONCLUSIONS: Breast fibromatosis is rare but affects young patients. Active surveillance is now favoured over surgical resection due to high recurrence rates and extensive morbidity. Dedicated guidelines are required to ensure best outcomes.


Subject(s)
Breast Neoplasms/therapy , Fibroma/therapy , Mastectomy/statistics & numerical data , Neoplasm Recurrence, Local/epidemiology , Watchful Waiting/statistics & numerical data , Adult , Aged , Biopsy, Large-Core Needle , Breast/diagnostic imaging , Breast/pathology , Breast/surgery , Breast Neoplasms/diagnosis , Breast Neoplasms/epidemiology , Breast Neoplasms/pathology , Female , Fibroma/diagnosis , Fibroma/epidemiology , Fibroma/pathology , Humans , Magnetic Resonance Imaging , Mastectomy/adverse effects , Mastectomy/standards , Middle Aged , Neoplasm Recurrence, Local/prevention & control , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Postoperative Complications/prevention & control , Practice Guidelines as Topic , Reoperation/statistics & numerical data , Ultrasonography, Mammary , Watchful Waiting/standards , Young Adult
17.
Glycobiology ; 20(10): 1283-8, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20581008

ABSTRACT

One of the most urgent requirements in breast cancer is the development of a blood-based test for early detection and prognosis. Previously published results found a significant difference between specific glycan levels in patients with advanced breast cancer and healthy controls. The aim of this investigation was to address a more clinically relevant problem, i.e., whether the measurement of specific glycans could identify women with aggressive disease at an early stage. In order to reduce potential bias in this study, blood samples from patients were collected, stored and analyzed in a similar manner. Agalactosyl biantennary glycans (FA2) and glycans containing the sialyl Lewis x epitope (A3F1G1 and A2F1G1) were measured using high throughput normal-phase high-performance liquid chromatography in combination with exoglycosidase digestions in sera from 52 patients with early breast cancer (21 with lymph node-negative and 20 with lymph node-positive disease) and 134 women with benign breast disease. The combined levels of the glycans were significantly higher in patients with lymph node metastases compared to women without these metastases. Lymph node status is the single most important determinant of survival in early stage breast cancer. As high levels of these glycans were associated with nodal metastases, their measurement may provide a new non-invasive approach to determining prognosis in women with newly diagnosed breast cancer.


Subject(s)
Adenocarcinoma, Mucinous/blood , Breast Neoplasms/blood , Carcinoma, Ductal, Breast/blood , Carcinoma, Lobular/blood , Lymph Nodes/metabolism , Polysaccharides/blood , Adenocarcinoma, Mucinous/secondary , Axilla , Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/secondary , Carcinoma, Lobular/secondary , Chromatography, High Pressure Liquid , Female , Humans , Lewis X Antigen/blood , Lymph Nodes/pathology , Lymphatic Metastasis , Middle Aged , Neoplasm Staging , Prognosis , Sialyl Lewis X Antigen
18.
Breast J ; 16(5): 533-6, 2010.
Article in English | MEDLINE | ID: mdl-20626393

ABSTRACT

Sentinel node (SN) micrometastases are an indication to proceed to axillary clearance. The aim of this study is to determine the extent and level of axillary clearance required for patients with SN micrometastases. All patients with SN micrometastases which were followed by axillary clearances from 1999 to 2007 were identified. Slides were reviewed by a histopathologist to detail characteristics of SN micrometastases including size and site. The SN micrometastases and primary tumor characteristics were correlated with the presence and level of non-SN micrometastases. Fifty patients who had micrometastases followed by axillary clearances were identified. Of those 18% (n = 9) had non-SN metastases.Seven patients had metastases to level I, one patient had metastases to level I and III and one patient had non-SN metastases to level III only. No patient had metastases to level II. Patients with non-SN metastases had very limited number of non-SNs involved (maximum 2 non-SNs). No variable, including site of the micrometastasis, was predictive of non-SN metastases. In patients with SN micrometastases, a limited level I axillary clearance can be justified in view of the low number of additional nodes involved and in particular, the low (4%) rate of spread to level II / III nodes.


Subject(s)
Axilla/pathology , Breast Neoplasms/pathology , Lymph Nodes/pathology , Neoplasm Micrometastasis/pathology , Female , Humans , Lymph Node Excision , Middle Aged , Neoplasm Micrometastasis/diagnosis , Sentinel Lymph Node Biopsy
19.
Ann Surg ; 249(5): 834-9, 2009 May.
Article in English | MEDLINE | ID: mdl-19387317

ABSTRACT

BACKGROUND: The value of level III axillary clearance is contentious, with great variance worldwide in the extent and levels of clearance performed. OBJECTIVE: To determine rates of level III positivity in patients undergoing level I-III axillary clearance, and identify which patients are at highest risk of involved level III nodes. METHODS: From a database of 2850 patients derived from symptomatic and population-based screening service, 1179 patients who underwent level I-III clearance between the years 1999-2007 were identified. The pathology, surgical details, and prior sentinel nodes biopsies of patients were recorded. RESULTS: Eleven hundred seventy nine patients had level I-III axillary clearance. Of the patients, 63% (n = 747) were node positive. Of patients with node positive disease, 23% (n = 168) were level II positive and 19% (n = 141) were level III positive. Two hundred fifty patients had positive sentinel node biopsies prior to axillary clearance. Of these, 12% (n = 30) and 9% (n = 22) were level II and level III positive, respectively. On multivariate analysis, factors predictive of level III involvement in patients with node positive disease were tumor size (P < 0.001, OR = 1.36; 95% CI: 1.2-1.5), invasive lobular disease (P < 0.001, OR = 3.6; 95% CI: 1.9-6.95), extranodal extension (P < 0.001, OR = 0.27; 95% CI: 0.18-0.4), and lymphovascular invasion (P = 0.04, OR = 0.58; 95% CI: 0.35-1). Lobular invasive disease (P = 0.049, OR = 4.1; 95% CI: 1-16.8), extranodal spread (P = 0.003, OR = 0.18; 95% CI: 0.06-0.57), and having more than one positive sentinel node (P = 0.009, OR = 4.9; 95% CI: 1.5-16.1) were predictive of level III involvement in patients with sentinel node positive disease. CONCLUSION: Level III clearance has a selective but definite role to play in patients who have node positive breast carcinoma. Pathological characteristics of the primary tumor are of particular use in identifying those who are at various risk of level III nodal involvement.


Subject(s)
Axilla/surgery , Breast Neoplasms/pathology , Lymph Node Excision , Lymph Nodes/surgery , Sentinel Lymph Node Biopsy , Axilla/pathology , Female , Humans , Lymph Nodes/pathology , Lymphatic Metastasis , Middle Aged , Neoplasm Staging
20.
Can J Surg ; 52(3): 201-6, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19503664

ABSTRACT

BACKGROUND: Predicting the clinical course in adhesional small bowel obstruction is difficult. There are no validated clinical or radiologic features that allow early identification of patients likely to require surgical intervention. METHODS: We conducted a retrospective review of 100 patients consecutively admitted to a tertiary level teaching hospital over a 3-year period (2002-2004) who had acute adhesional small bowel obstruction and underwent computed tomography (CT). The primary outcomes that we assessed were conservative management or the need for surgical intervention. We investigated time to physiologic gastrointestinal function recovery as a secondary outcome. We examined independent predictors of surgical intervention in a bivariate analysis using a stepwise logistic regression analysis. RESULTS: Of the 100 patients investigated, we excluded 12. Of the 88 remaining patients, 58 (66%) were managed conservatively and 30 (34%) underwent surgery. Peritoneal fluid detected on a CT scan (n = 37) was associated more frequently with surgery than conservative management (46% v. 29%, p = 0.046, chi(2)). Logistical regression identified peritoneal fluid detected on a CT scan as an independent predictor of surgical intervention (odds ratio 3.0, 95% confidence interval 1.15-7.84). CONCLUSION: The presence of peritoneal fluid on a CT scan in patients with adhesional small bowel obstruction is an independent predictor of surgical intervention and should alert the clinician that the patient is 3 times more likely to require surgery.


Subject(s)
Ascitic Fluid/diagnostic imaging , Intestinal Obstruction/diagnostic imaging , Intestinal Obstruction/surgery , Intestine, Small , Aged , Aged, 80 and over , Cohort Studies , Female , Gastrointestinal Transit , Humans , Intestinal Obstruction/complications , Male , Middle Aged , Predictive Value of Tests , Recovery of Function , Retrospective Studies , Tomography, X-Ray Computed , Treatment Outcome
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