| 1. |
- Jazrawi, Allan
(författare)
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Optimizing the magnetic tracer technique for sentinel lymph node detection and tumour localization in breast cancer surgery
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Breast cancer is the most common form of cancer in women, and the primary treatment modalities are still breast-conserving surgery (BCS) and sentinel lymph node dissection (SLND) in most cases. Superparamagnetic iron oxide nanoparticles (SPIO) are gaining momentum as a tracer for sentinel lymph node detection. The aim of this thesis is to further refine the magnetic method and investigate its postoperative effects.Paper I: This feasibility study, involving 79 patients, explored the use of SPIO-guided Magnetic resonance imaging (MRI)-lymphography and magnetic-guided axillary ultrasound (MagUS) with core biopsy for sentinel lymph node (SLN) localization and SLN status. MagUS, outperformed baseline axillary ultrasound and successfully traced SLNs in all cases, detecting macro-metastases accurately and missed only one micro-metastasis. The findings suggest that the MagUS technique enables minimally invasive approach in axillary mapping that can meet tailored patient needs and reduce the need for diagnostic surgery. Paper II: This study aimed to compare skin staining incidence and size between different doses of SPIO and blue dye (BD), evaluating their persistence over time. Among 270 women receiving SPIO, 204 also received BD. At six months, 21.5% had SPIO stains and 25% had BD stains Incidence and size decreased reciprocally, with no significant difference between the tracers regarding skin staining after 24 months. Paper III: This study compared the magnetic technique using Magseed® for non-palpable breast tumor localization with guidewire localization and SPIO for sentinel lymph node detection. In a prospective analysis of 426 women, reoperation rates, resection ratios, and SLN detection were assessed. No significant differences were found between the techniques in terms of re-excisions, resection ratios, or SLN detection. However, the magnetic technique showed more successful localizations, shorter operation time, and better overall experience among surgeons, radiologists, and theater coordinators, making it a good alternative for BCS.Paper IV: In this prospective observational study, the impact of postoperative MRI outcome was explored in patients undergoing BCS with a peritumoral SPIO injection for SLN detection. The study affirms SPIO as a safe tracer for SLN detection without compromising MRI interpretation after BCS, ensuring reliable breast cancer recurrence assessment.
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| 2. |
- Hersi, Abdi-Fatah, 1989-
(författare)
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Superparamagnetic iron oxide nanoparticles, a novel tracer in breast cancer surgery
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The most common surgical choice of treatment in breast cancer is breast-conserving surgery (BCS) together with sentinel lymph node biopsy (SNB). Around 10% of breast cancer diagnosis are ductal carcinoma in situ (DCIS). Superparamagnetic iron oxide nanoparticles (SPIO) are a novel tracer for sentinel lymph node (SN) detection. The aim of this thesis was to investigate the unique applications and functionality of a magnetic approach in breast cancer surgery.Paper I was a two-centre pilot study of 32 patients with non-palpable breast cancer who were scheduled for BCS together with SNB. They received SPIO for SNB and a magnetic seed (Magseed®) for localization of the breast tumour. All 32 patients underwent microscopically radical resection and SNB was successfully performed in all included patients.Paper II was a multicentre prospective single-cohort study. It was a pre-planned interim analysis of 189 patients with “high-risk” DCIS who received SPIO at primary surgery but without performing SNB. If an invasive breast cancer was shown by the final histopathology report, the patient was scheduled for second surgery to undergo SNB. Because SPIO has a much longer half-life than the radioisotope, the magnetic signal at the second surgery was sufficient for detecting SNs; in fact, in patients with DCIS, it reduced from around 50% to 22%. Paper III was a multicentre prospective trial. Two consecutive cohorts of patients with breast cancer scheduled for SNB (n = 328) were included. Lower doses of a refined SPIO suspension were tested in different time frames and injection sites. Analyses were performed as a one-step individual patient-level meta-analysis using patient-level data from a similar previous cohort (n = 206) as a third reference group. In 534 patients, the SPIO SN detection rates were comparable (97.5% vs. 100% vs. 97.6%, p = 0.11) and were noninferior to the dual technique. Paper IV was a multicentre randomized pilot trial aimed to compare tumour localization in nonpalpable breast cancers using either Magseed® or guidewire in patients scheduled for BCS + SNB. All patients received SPIO for the SNB preoperatively. Patients who were randomized to the magnetic seed cohort received their Magseed® at the same time as the SPIO injection preoperatively while the guidewire placement was performed on the same day as surgery. In 207 patients, there were no significant differences in reoperation rate (3% in the magnetic seed cohort vs 7% in the guidewire cohort, p = 0.35).
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| 3. |
- Karakatsanis, Andreas, 1980-
(författare)
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Sentinel Node Biopsy for Breast Cancer : Aspects and evolution
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Sentinel Node Biopsy (SNB) in clinical practice was pivotal to the shaping of modern diagnosis, staging and treatment of patients with breast cancer. The use of radioisotope (RI) and blue dye (BD) has led to high detection rates with low false negatives, but delivery-of-care limitations connected to these tracers as well as the need for methods addressing new clinical conundrums delineates the urge for new tracers with comparable performance, easier logistics and, ideally expanded implementations. Aim of the present thesis is to examine the outcomes of Superparamagnetic Iron Oxide (SPIO) nanoparticles, a new tracer based on magnetism for the detection of the sentinel nodes.Paper I is a prospective multicentre trial comparing SPIO to RI+BD, with all tracers injected at the same patient. In 206 patients, SPIO had a similar detection rate (97.6 vs 97.1%, p=0.76) whereas concordance between methods was 98%. The study was completed by a meta-analysis of similar trials published until that point. The detection rates were comparable (fixed OR:1.10; 0.67,1.79, p=0.71), and so was concordance between tracers (fixed RD: 0.00; -0.01, 0.01, p=0.82). Discoloration was present after periareolar SPIO injection in 39% of patients, almost exclusively treated with breast conservation, which reduced to 8.6% after 15 months of follow-up.Paper II was a pilot study of twelve patients with breast cancer and SNB performed where SPIO and the combination of RI+BD were injected, but SPIO was injected up to 15 days preoperatively, with total success in detection and complete concordance.Paper III tested the performance of SPIO as a sole tracer in a pragmatic double-arm non-randomised trial comparing it to the combination of RI+BD. Detection was 95.7% for SPIO and 96.8% for RI (p = 0.59). The preoperative injection of SPIO (1-27 d) enhanced SPIO specific detection (95.7 vs 86%, p=0.002).Paper IV is an interim analysis of a multicentre cohort study including patients with high-risk DCIS planned for breast conservation or any DCIS planned for mastectomy. SPIO was injected to “mark” the sentinel node but SNB was performed in a second operation only if invasive cancer was found at the first operation. In 151 included patients, this technique led to avoidance of 81.5% SNB, with a cost reduction of 14.1% for the entire cohort and 25.8% for the patients that did not have invasive cancer. The detection rate at reoperation was superior for SPIO and comparable with SNB detection at primary operation.In conclusion, SPIO is a novel tracer for SNB in breast cancer with comparable performance, fit for performance in a global setting and with wider clinical implementations compared to RI+BD.
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| 4. |
- Wadsten, Charlotta, 1964-
(författare)
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DCIS of the breast : aspects on treatment and prognosis
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Breast cancer is the most common cancer form and a leading cause of death in women worldwide. Ductal breast carcinoma in situ (DCIS) is characterized by a proliferation of malignant cells confined within the mammary ducts and is a potential precursor of invasive breast cancer. The risk estimations of a DCIS to develop into invasive cancer over a 10 year period range from 30-50%. In the past 25 years, concomitant with the implementation of screening mammography, the incidence of DCIS has increased dramatically and presently almost 1 000 women are diagnosed with DCIS each year in Sweden. The increased incidence poses concerns of overtreatment and current research aim at identifying clinical or pathological markers that can reliably distinguish hazardous from harmless DCIS. The overall aim of this thesis was to explore the prognostic significance of clinical and tumourbiological characteristics of DCIS and to assess the benefits and harms of adjuvant treatment.In a population-based cohort of 2 952 women with primary DCIS, we analysed trends in incidence, treatment and outcome over a 20-year period (paper I). Information was obtained from the regional breast cancer register in Uppsala-Örebro healthcare region between 1992 and 2012. A validation of 300 randomly selected women revealed high overall completeness and reliability of most key variables, whereas follow-up data were of moderate quality with only 65% of the recurrences reported to the register.The major finding of the study was a trend towards more intensified treatment over time. The frequency of mastectomy increased from 23.0% to 39.0% and the proportion of patients receiving adjuvant radiotherapy after breast-conserving surgery increased from 30.1% to 67.6%. This did not, however, translate into any noteable improvements in outcome. Relative survival was >97% after 10 years with no significant variation over time. In conclusion, these results may reflect adequate treatment selection, but may also indicate a significant overtreatment.In paper II and III, a nested case-control study was conducted from a cohort of 6 964 women with primary DCIS to identify clinical characteristics in DCIS associated with subsequent breast cancer death. Ninety-six women who later died from breast cancer were compared to 318 controls selected by incidence density sampling. Information was obtained from medial records and histopathology reports.Tumour size over 25 mm or multifocal DCIS (OR 2⋅55; 95%CI 1⋅53 to 4⋅25), a positive or uncertain margin status (OR 3⋅91; 95%CI 1⋅59 to 9⋅61) and detection outside the screening programme (OR 2⋅12; 95%CI 1⋅16 to 3⋅86) increased the risk of death from breast cancer. In the multivariable analysis, tumour size (OR 1⋅95; 95%CI 1⋅06 to 3⋅67) and margin status (OR 2⋅69; 95%CI 1⋅15 to 7⋅11) remained significant. More extensive treatment was not associated with lower risk, which may be due to confounding by indication, or indicate that some DCIS have an inherent potential for metastatic spread. In paper III, to further explore the association of tumour biology and risk of breast cancer death, archival tumour blocks were collected. Freshly cut hematoxylin and eosin (H&E) stained sections of the primary DCIS were histopathologically evaluated for nuclear grade, presence of comedonecrosis and lymphocytic infiltration (LI). Tissue microarrays were constructed for immunohistochemical analysis (IHC) of oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and Ki67. Using the results of the IHC analyses, tumours were classified into surrogate molecular subtypes.Presence of intense periductal LI was associated with an increased risk of subsequent breast cancer death (OR 2.25; 95%CI 1.02 to 4.99). None of the other biomarkers were individually related to breast cancer death, nor were there any statistically significant differences in risk between the molecular subtypes. In multivariable analysis, stepwise adjusting for age, tumour size and treatment, PR negativity in combination with LI; PR negativity, LI and presence of comedonecrosis and the combination of PR negativity, LI, comedonecrosis and HER2 positivity were all independently associated with increased risk of breast cancer death. The significance of features in the peritumoral stroma need further investigation and may have implications for targeted treatments.In paper IV, we studied the risk of ischemic heart disease (IHD) after treatment for DCIS. Postoperative radiotherapy (RT) in DCIS reduces recurrence rates by half but confers no benefits in terms of survival. It is thus of major importance to consider long-term adverse effects. Left-sided breast irradiation may involve exposure of the heart to ionising radiation with an associated risk of subsequent cardiovascular disease. The cumulative incidence of IHD was analysed in a population-based cohort of 6270 women with DCIS compared 31 257 women without a history of breast cancer. Of the women with DCIS, 38.9% had received adjuvant RT.After a median follow-up of 8 years, there was no increased risk of IHD for women with DCIS versus the comparison cohort. The risk was lower for women with DCIS allocated to RT compared to non-irradiated women and to the comparison cohort, probably due to patient selection. Comparison of RT by laterality did not show any over-risk for irradiation of the left breast. These results are reassuring, but longer follow-up may be warranted considering the continuously increasing use of RT in DCIS management.
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| 5. |
- Zhou, Wenjing, 1979-
(författare)
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Aspects of Progression in Breast Carcinoma : from ductal carcinoma in situ to invasive cancer
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In the past decades our knowledge concerning breast cancer progression from ductal carcinoma in situ (DCIS) to invasive cancer has grown rapidly. However, molecular factors driving the progression are still largely unknown.In the first study, we investigated tumor evolution in breast cancer by analyzing TP53 mutation status in tumors from various stages of the disease. Presence of the same TP53 mutations in both DCIS and invasive components from the same tumor indicates same cellular origin. The role of mutant TP53 in the progression of breast cancer is less clear and may vary between subtypes.In the second study, we studied the prognosis of basal-like DCIS in a large population-based cohort. Basal-like DCIS was associated with about doubled but not statistically significant risk for local recurrence compared with the other molecular subtypes. Molecular subtype was a better prognostic parameter than histopathological grade.In the third study, we studied markers in primary DCIS in relation to type of recurrence. Interestingly, recurrences after an ER-/HER2+, ER negative or EGFR positive primary DCIS were more often of the in situ type. The molecular subtype ER+/HER2+, FOXA1 positivity and FOXC1 positivity were risk factors for any recurrence.In the fourth study, we proposed a histological classification system for a new entity: neoductgenesis. We also evaluated histologic criteria for neoductgenesis. According to our criteria, good agreements among pathologists were achieved. Neoductgenesis was related to more aggressive tumor biology and to mammographic features. The result indicates potential benefits for women earlier considered having pure DCIS but later diagnosed as breast carcinoma with neoductgenesis, suggesting a need to develop appropriate treatment regiments. Our findings have to be repeated and the relation to prognosis warrants further studies.
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