| 1. |
|
|
| 2. |
- Adra, Jamila, et al.
(författare)
-
Distribution of locoregional breast cancer recurrence in relation to postoperative radiation fields and biological subtypes.
- 2019
-
Ingår i: International journal of radiation oncology, biology, physics. - : Elsevier BV. - 1879-355X .- 0360-3016. ; 105:2, s. 285-295
-
Tidskriftsartikel (refereegranskat)abstract
- and purpose: To investigate incidence and location of locoregional recurrence (LRR) in patients who have received postoperative locoregional radiotherapy (LRRT) for primary breast cancer. LRR-position in relation to applied radiotherapy and the primary tumours biological subtype were analysed with the aim to evaluate current target guidelines and RT techniques in relation to tumour biology.Medical records were reviewed for all patients who received postoperative LRRT for primary BC in southwestern Sweden from 2004-2008 (N=923). Patients with LRR as a first event were identified (N=57, distant failure and death were considered competing risks). CT images identifying LRR were used to compare LRR locations to postoperative LRRT fields. LRR risk and distribution were then related to the primary BC biological subtype and to current target guidelines.Cumulative LRR incidence after 10 years was 7.1% (95%CI 5.5-9.1). Fifty-seven of the 923 patients in the cohort developed LRR (30 local recurrences (LR), 30 regional recurrences (RR), of which 3 cases of simultaneous LR/RR). Most cases of LRR developed fully (56%) or partially (26%) within postoperatively irradiated areas. The most common location for out-of-field RR was cranial to RT fields in the supraclavicular fossa. Patients with an ER- (HR 4.6, p<0.001, 95%CI 2.5-8.4) or HER2+ (HR 2.4, p=0.007, 95%CI 1.3-4.7) primary BC presented higher risks of LRR compared to those with ER+ tumours. ER-/HER2+ tumours more frequently recurred in-field (68%) rather than marginal/out-of-field (32%). In addition, 75% of in-field recurrences derived from an ER-/HER+ tumour, compared to 45% of marginal/out-of-field recurrences. A complete pathological response in the axilla after neoadjuvant treatment was associated with a lower degree of LRR risk (p=0.022).Incidence and locations of LRR seems to be related to the primary BC biological subtype. Individualized LRRT according to tumour biology may be applied to improve outcomes.
|
|
| 3. |
- Alkner, Sara, et al.
(författare)
-
AIB1 is a predictive factor for tamoxifen response in premenopausal women
- 2010
-
Ingår i: ANNALS OF ONCOLOGY. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 21:2, s. 238-244
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Clinical trials implicate the estrogen receptor ( ER) coactivator amplified in breast cancer 1 (AIB1) to be a prognostic and a treatment-predictive factor, although results are not unanimous. We have further investigated this using a controlled randomised trial of tamoxifen versus control. Materials and methods: A total of 564 premenopausal women were entered into a randomised study independent of ER status. Using a tissue microarray, AIB1 and ER were analysed by immunohistochemistry. Results: AIB1 scores were obtained from 349 women. High AIB1 correlated to factors of worse prognosis (human epidermal growth factor receptor 2, Nottingham histological grade 3, and lymph node metastases) and to ER negativity. In the control arm, high AIB1 was a negative prognostic factor for recurrence- free survival (RFS) (P = 0.02). However, ER-positive patients with high AIB1 responded significantly to tamoxifen treatment (P = 0.002), increasing RFS to the same level as for systemically untreated patients with low AIB1. Although ER-positive patients with low AIB1 had a better RFS from the beginning, this was not further improved by tamoxifen (P = 0.8). Conclusions: In the control group, high AIB1 was a negative prognostic factor. However, ER-positive patients with high AIB1 responded significantly to tamoxifen. This implicates high AIB1 to be an independent predictive factor of improved response to tamoxifen and not, as has previously been discussed, a factor predicting tamoxifen resistance.
|
|
| 4. |
- Alkner, Sara
(författare)
-
Predicting Prognosis and Tamoxifen Response in Breast Cancer. With a special focus on contralateral breast cancer.
- 2012
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- One of the great challenges in breast cancer treatment today is to customize adjuvant treatment to each patient’s individual needs. To do this it is necessary to learn more about the prognostic and treatment predictive factors that determine the risk of relapse and response to a certain mode of treatment. This thesis describes studies on the effect of amplified in breast cancer 1 (AIB1), a coactivator of the oestrogen receptor, on prognosis and tamoxifen response through a controlled trial on premenopausal patients randomized to tamoxifen or a control group. AIB1 was found to be a negative prognostic factor, although patients with high AIB1 responded very well to tamoxifen. The findings were validated in two independent cohorts, one consisting of premenopausal patients not receiving tamoxifen, and the other of pre- and postmenopausal patients receiving tamoxifen. It has recently been suggested that the effect of AIB1 is modified by paired box 2 gene product (PAX2). PAX2 is a transcription factor important during embryogenesis, and may also play a role in carcinogenesis. This is the first time PAX2 has been investigated in well-defined cohorts of patients receiving or not receiving tamoxifen. PAX2 was not found to affect prognosis on its own, or to modify the effect of AIB1. The second part of this thesis focuses on contralateral breast cancer (CBC). Within their lifetime, previous breast cancer patients have a 2-20% risk of developing a second tumour in the contralateral breast. From the trial on premenopausal patients randomized to tamoxifen or control, it was found that without tamoxifen 12% developed CBC within a median follow-up period of 14 years. This risk was even higher in the youngest women (<40 years), in which 20% developed CBC. Treatment with tamoxifen reduced the risk by 50% in all patients, and by 90% in the youngest women. Since CBC is still a rather rare event, previous studies are often small or based only on register data. Detailed patient, tumour and treatment information has been collected for a large cohort (>700) of patients with CBC in the Southern Healthcare Region of Sweden. From these data it was found that a short time interval between tumours was associated with a poorer prognosis, especially in young patients. This could indicate that some of these CBCs are in fact metastases of the first tumour, and would thus require different treatment. It could also be that tumours that develop soon after previous treatment have developed resistance to treatment and are of a more aggressive phenotype. Finally, it was found that patients who first noticed symptoms of their CBC themselves had a higher risk of developing metastases than patients diagnosed by mammography or clinical examination in a follow-up programme. The difference in prognosis in relation to mode of detection remained even when the time interval between tumours was ≥10 years, indicating that a long follow-up period is valuable.
|
|
| 5. |
- Alkner, Sara, et al.
(författare)
-
Prediction of outcome after diagnosis of metachronous contralateral breast cancer.
- 2011
-
Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 11
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Although 2-20% of breast cancer patients develop a contralateral breast cancer (CBC), prognosis after CBC is still debated. Using a unique patient cohort, we have investigated whether time interval to second breast cancer (BC2) and mode of detection are associated to prognosis. METHODS: Information on patient-, tumour-, treatment-characteristics, and outcome was abstracted from patients' individual charts for all patients diagnosed with metachronous CBC in the Southern Healthcare Region of Sweden from 1977-2007. Distant disease-free survival (DDFS) and risk of distant metastases were primary endpoints. RESULTS: The cohort included 723 patients with metachronous contralateral breast cancer as primary breast cancer event. Patients with less than three years to BC2 had a significantly impaired DDFS (p = 0.01), and in sub-group analysis, this effect was seen primarily in patients aged <50. By logistic regression analysis, patients diagnosed with BC2 within routine follow-up examinations had a significantly lower risk of developing metastases compared to those who were symptomatic at diagnosis (p < 0.0001). Chemotherapy given after breast BC1 was a negative prognostic factor for DDFS, whereas endocrine treatment and radiotherapy given after BC2 improved DDFS. CONCLUSIONS: In a large cohort of patients with CBC, we found the time interval to BC2 to be a strong prognostic factor for DDFS in young women and mode of detection to be related to risk of distant metastases. Future studies of tumour biology of BC2 in relation to prognostic factors found in the present study can hopefully provide biological explanations to these findings.
|
|
| 6. |
|
|
| 7. |
- Alkner, Sara, et al.
(författare)
-
Prior Adjuvant Tamoxifen Treatment in Breast Cancer Is Linked to Increased AIB1 and HER2 Expression in Metachronous Contralateral Breast Cancer.
- 2016
-
Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:3
-
Tidskriftsartikel (refereegranskat)abstract
- The estrogen receptor coactivator Amplified in Breast Cancer 1 (AIB1) has been associated with an improved response to adjuvant tamoxifen in breast cancer, but also with endocrine treatment resistance. We hereby use metachronous contralateral breast cancer (CBC) developed despite prior adjuvant tamoxifen for the first tumor as an "in vivo"-model for tamoxifen resistance. AIB1-expression in the presumable resistant (CBC after prior tamoxifen) and naïve setting (CBC without prior tamoxifen) is compared and correlated to prognosis after CBC.
|
|
| 8. |
|
|
| 9. |
- Alkner, Sara, et al.
(författare)
-
Protocol for the T-REX-trial: tailored regional external beam radiotherapy in clinically node-negative breast cancer patients with 1-2 sentinel node macrometastases - an open, multicentre, randomised non-inferiority phase 3 trial.
- 2023
-
Ingår i: BMJ open. - 2044-6055. ; 13:9
-
Tidskriftsartikel (refereegranskat)abstract
- Modern systemic treatment has reduced incidence of regional recurrences and improved survival in breast cancer (BC). It is thus questionable whether regional radiotherapy (RT) is still beneficial in patients with sentinel lymph node (SLN) macrometastasis. Postoperative regional RT is associated with an increased risk of arm morbidity, pneumonitis, cardiac disease and secondary cancer. Therefore, there is a need to individualise regional RT in relation to the risk of recurrence.In this multicentre, prospective randomised trial, clinically node-negative patients with oestrogen receptor-positive, HER2-negative BC and 1-2 SLN macrometastases are eligible. Participants are randomly assigned to receive regional RT (standard arm) or not (intervention arm). Regional RT includes the axilla level I-III, the supraclavicular fossa and in selected patients the internal mammary nodes. Both groups receive RT to the remaining breast. Chest-wall RT after mastectomy is given in the standard arm, but in the intervention arm only in cases of widespread multifocality according to national guidelines. RT quality assurance is an integral part of the trial.The trial aims to include 1350 patients between March 2023 and December 2028 in Sweden and Norway. Primary outcome is recurrence-free survival (RFS) at 5years. Non-inferiority will be declared if outcome in the de-escalation arm is not >4.5percentage units below that with regional RT, corresponding to an HR of 1.41 assuming 88% 5-year RFS with standard treatment. Secondary outcomes include locoregional recurrence, overall survival, patient-reported arm morbidity and health-related quality of life. Gene expression analysis and tumour tissue-based studies to identify prognostic and predictive markers for benefit of regional RT are included.The trial protocol is approved by the Swedish Ethics Authority (Dnr-2022-02178-01, 2022-05093-02, 2023-00826-02, 2023-03035-02). Results will be presented at scientific conferences and in peer-reviewed journals.NCT05634889.
|
|
| 10. |
|
|
| 11. |
- Alkner, Sara, et al.
(författare)
-
Quality assessment of radiotherapy in the prospective randomized SENOMAC trial
- 2024
-
Ingår i: Radiotherapy and Oncology. - : Elsevier. - 0167-8140 .- 1879-0887. ; 197
-
Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Recommendations for regional radiotherapy (RT) of sentinel lymph node (SLN)-positive breast cancer are debated. We here report a RT quality assessment of the SENOMAC trial. Materials and Methods: The SENOMAC trial randomized clinically node-negative breast cancer patients with 1-2 SLN macrometastases to completion axillary lymph node dissection (cALND) or SLN biopsy only between 2015-2021. Adjuvant RT followed national guidelines. RT plans for patients included in Sweden and Denmark until June 2019 were collected (N = 1176) and compared to case report forms (CRF). Dose to level I (N = 270) and the humeral head (N = 321) was analyzed in detail.
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
- Alkner, Sara, et al.
(författare)
-
Tamoxifen reduces the risk of contralateral breast cancer in premenopausal women : Results from a controlled randomised trial
- 2009
-
Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 45:14, s. 2496-2502
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Adjuvant treatment with tamoxifen reduces the risk of contralateral breast cancer in hormone-responsive postmenopausal patients, whereas the effect in premenopausal women has not been fully elucidated. We have therefore studied the effect of tamoxifen on contralateral breast cancer in premenopausal women in a controlled randomised trial. Patients and methods: Premenopausal women (564) with stage II breast cancers were randomised to 2 years of tamoxifen versus control irrespective of oestrogen receptor (ER) and progesterone receptor (PgR) status. The median follow-up for patients not developing a contralateral cancer was 14 years. Results: In the control group 35 women, and in the tamoxifen group 17 women, developed a contralateral breast cancer as a primary event. Tamoxifen significantly reduced the risk of contralateral breast cancer in all women regardless of age (hazard ratio (HR) 0.5, p = 0.02). In subgroup analysis the risk reduction was most pronounced in patients less than40 years of age (HR 0.09, p = 0.02). A risk reduction was also seen in women 40-49 years of age or ≥50 years of age, although in these subgroups this did not reach statistical significance. The reduced risk of contralateral breast cancer was persistent during the whole follow-up time. Conclusion: In this randomised trial, adjuvant treatment using tamoxifen for 2 years reduced the incidence of contralateral breast cancer by 50% in all premenopausal women, and by 90% in women less than40 years of age. The effect of tamoxifen was not significantly dependent on time.
|
|
| 15. |
- Alkner, Sara, et al.
(författare)
-
The role of AIB1 and PAX2 in primary breast cancer: validation of AIB1 as a negative prognostic factor.
- 2013
-
Ingår i: Annals of Oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 24:5, s. 1244-1252
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe steroid-receptor coactivator amplified in breast cancer one (AIB1) is implicated to be a prognostic factor, although the results are not unanimous. Recently its effect was suggested to be modified by paired box 2 gene product (PAX2).Patients and methodsUsing immunohistochemistry (IHC) AIB1 and PAX2 were investigated in two cohorts of early breast cancer, including systemically untreated premenopausal lymph-node-negative women and pre- and postmenopausal women receiving tamoxifen.ResultsAIB1 scores were available for 490 patients and PAX2 scores were available for 463 patients. High AIB1 was a negative prognostic factor for distant disease-free survival (DDFS, P = 0.02) and overall survival (OS, P < 0.001) in systemically untreated women, while no prognostic effect was seen in the tamoxifen-treated cohort, indicating AIB1 to be a predictor of tamoxifen response. In systemically untreated patients, PAX2 was not a prognostic factor, nor did it modify the effect of AIB1. However, in ER-positive patients receiving tamoxifen, PAX2 appeared to be a positive prognostic factor in premenopausal patients, while a negative factor in postmenopausal. The interaction between the menopausal status and PAX2 was significant (P = 0.01).ConclusionsIn an independent cohort of low-risk premenopausal patients, we validate AIB1 as a negative prognostic factor, indicating AIB1 to be an interesting target for new anti-cancer therapies. The effect of PAX2 warrants further studies.
|
|
| 16. |
- Appelgren, M., et al.
(författare)
-
Patient-reported outcomes one year after positive sentinel lymph node biopsy with or without axillary lymph node dissection in the randomized SENOMAC trial
- 2022
-
Ingår i: Breast. - : Elsevier BV. - 0960-9776 .- 1532-3080. ; 63, s. 16-23
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: This report evaluates whether health related quality of life (HRQoL) and patient-reported arm morbidity one year after axillary surgery are affected by the omission of axillary lymph node dissection (ALND). Methods: The ongoing international non-inferiority SENOMAC trial randomizes clinically node-negative breast cancer patients (T1-T3) with 1-2 sentinel lymph node (SLN) macrometastases to completion ALND or no further axillary surgery. For this analysis, the first 1181 patients enrolled in Sweden and Denmark between March 2015, and June 2019, were eligible. Data extraction from the trial database was on November 2020. This report covers the secondary outcomes of the SENOMAC trial: HRQoL and patient-reported arm morbidity. The EORTC QLQC30, EORTC QLQ-BR23 and Lymph-ICF questionnaires were completed in the early postoperative phase and at one-year follow-up. Adjusted one-year mean scores and mean differences between the groups are presented corrected for multiple testing.
|
|
| 17. |
- Ceberg, Sofie, et al.
(författare)
-
Surface guided radiotherapy decreases the uncertainty in breast cancer patient setup
- 2018
-
Konferensbidrag (refereegranskat)abstract
- (Sunday, 7/29/2018) 3:00 PM - 6:00 PMRoom: Exhibit HallPurpose: The aim was to investigate if the setup of breast cancer patients could be improved using surface guided radiotherapy, compared to the conventional method using lasers and skin markings.Methods: Forty-seven patients, who received tangential or locoregional adjuvant radiotherapy, were positioned using a surface-based setup (SBS). Thirty-eight patients were positioned using the conventional laser-based setup (LBS). For the patient group positioned using a SBS, correction for posture was performed under guidance of a color map projected onto the patients' skin in real time. The surface tolerance for the color map was 5 mm. For both setup techniques the deviation of the breast position was measured using verification images. In total, 897 images were analysed. The frequency distributions of the deviations were analysed.Results: The result showed a significant improvement in the interfractional variation of the setup deviation for SBS compared to the LBS (pConclusion: Conventional laser-based setup can be replaced by surface-based setup, both for tangential and locoregional breast cancer treatments.
|
|
| 18. |
- de Boniface, Jana, et al.
(författare)
-
Completion axillary lymph node dissection for the identification of pN2–3 status as an indication for adjuvant CDK4/6 inhibitor treatment : a post-hoc analysis of the randomised, phase 3 SENOMAC trial
- 2024
-
Ingår i: The Lancet Oncology. - : Elsevier. - 1470-2045 .- 1474-5488. ; 25:9, s. 1222-1230
-
Tidskriftsartikel (refereegranskat)abstract
- Background: In luminal breast cancer, adjuvant CDK4/6 inhibitors (eg, abemaciclib) improve invasive disease-free survival. In patients with T1–2, grade 1–2 tumours, and one or two sentinel lymph node metastases, completion axillary lymph node dissection (cALND) is the only prognostic tool available that can reveal four or more nodal metastases (pN2–3), which is the only indication for adjuvant abemaciclib in this setting. However, this technique can lead to substantial arm morbidity in patients. We aimed to pragmatically describe the potential benefit and harm of this strategy on the individual patient level in patients from the ongoing SENOMAC trial.Methods: In the randomised, phase 3, SENOMAC trial, patients aged 18 years or older, of any performance status, with clinically node-negative T1–T3 breast cancer and one or two sentinel node macrometastases from 67 sites in five European countries (Denmark, Germany, Greece, Italy, and Sweden) were randomly assigned (1:1), via permutated block randomisation (random block size of 2 and 4) stratified by country, to either cALND or its omission (ie, they had a sentinel lymph node biopsy only). The primary outcome is overall survival, which is yet to be reported. In this post-hoc analysis, patients from the SENOMAC per-protocol population, with luminal oestrogen-receptor positive, HER2-negative, T1–2, histological grade 1–2 breast cancer, with tumour size of 5 cm or smaller were selected to match the characteristics of cohort 1 of the monarchE trial who would only have an indication for adjuvant abemaciclib if found to have 4 or more nodal metastases. The primary study objective was to determine the number of patients who developed patient-reported severe or very severe impairment of physical arm function after cALND (as measured by the Lymphedema Functioning, Disability, and Health [Lymph-ICF] Questionnaire) 1 year after surgery to avoid one invasive disease-free survival event at 5 years with 2 years of adjuvant abemaciclib, using invasive disease-free survival event data from cohort 1 of the monarchE trial. The SENOMAC trial is registered with ClincialTrials.gov, NCT02240472, and is closed to accrual and ongoing.Findings: Between Jan 31, 2015, and Dec 31, 2021, 2766 patients were enrolled in SENOMAC and randomly assigned to cALND (n=1384) or sentinel node biopsy only (n=1382), of whom 2540 were included in the per-protocol population. 1705 (67%) of 2540 patients met this post-hoc study's eligibility criteria, of whom 802 (47%) had a cALND and 903 (53%) had a sentinel lymph node biopsy only. Median age at randomisation was 62 years (IQR 52–71), 1699 (>99%) of 1705 patients were female, and six (<1%) were male. Among 1342 patients who responded to questionnaires, after a median follow-up of 45·2 months (IQR 25·6–59·8; data cutoff Nov 17, 2023), patient-reported severe or very severe impairment of physical arm function was reported in 84 (13%) of 634 patients who had cALND versus 30 (4%) of 708 who had sentinel lymph node biopsy only (χ2 test p<0·0001). To avoid one invasive disease-free survival event at 5 years with adjuvant abemaciclib, cALND would need to be performed in 104 patients, and would result in nine patients having severe or very severe impairment of physical arm function 1 year after surgery.Interpretation: As a method to potentially identify an indication for abemaciclib, and subsequently avoid invasive disease-free survival events at 5 years with 2 years of adjuvant abemaciclib, cALND carries a substantial risk of severe or very severe arm morbidity and so cALND should be discouraged for this purpose. Funding: Swedish Research Council, the Swedish Cancer Society, the Nordic Cancer Union, and the Swedish Breast Cancer Association.
|
|
| 19. |
- Edvardsson, Anneli, et al.
(författare)
-
Comparative treatment planning study for mediastinal Hodgkin’s lymphoma : impact on normal tissue dose using deep inspiration breath hold proton and photon therapy
- 2019
-
Ingår i: Acta Oncologica. - 0284-186X. ; 58:1, s. 95-104
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Late effects induced by radiotherapy (RT) are of great concern for mediastinal Hodgkin’s lymphoma (HL) patients and it is therefore important to reduce normal tissue dose. The aim of this study was to investigate the impact on the normal tissue dose and target coverage, using various combinations of intensity modulated proton therapy (IMPT), volumetric modulated arc therapy (VMAT) and 3-dimensional conformal RT (3D-CRT), planned in both deep inspiration breath hold (DIBH) and free breathing (FB). Material and methods: Eighteen patients were enrolled in this study and planned with involved site RT. Two computed tomography images were acquired for each patient, one during DIBH and one during FB. Six treatment plans were created for each patient; 3D-CRT in FB, 3D-CRT in DIBH, VMAT in FB, VMAT in DIBH, IMPT in FB and IMPT in DIBH. Dosimetric impact on the heart, left anterior descending (LAD) coronary artery, lungs, female breasts, target coverage, and also conformity index and integral dose (ID), was compared between the different treatment techniques. Results: The use of DIBH significantly reduced the lung dose for all three treatment techniques, however, no significant difference in the dose to the female breasts was observed. Regarding the heart and LAD doses, large individual variations were observed. For VMAT, the mean heart and LAD doses were significantly reduced using DIBH, but no significant difference was observed for 3D-CRT and IMPT. Both IMPT and VMAT resulted in improved target coverage and more conform dose distributions compared to 3D-CRT. IMPT generally showed the lowest organs at risk (OAR) doses and significantly reduced the ID compared to both 3D-CRT and VMAT. Conclusions: The majority of patients benefited from treatment in DIBH, however, the impact on the normal tissue dose was highly individual and therefore comparative treatment planning is encouraged. The lowest OAR doses were generally observed for IMPT in combination with DIBH.
|
|
| 20. |
- Ehinger, Anna, et al.
(författare)
-
Quality of up to 35 years old archival breast cancer tissue in paraffinblocks for estrogen receptor evaluation
- 2017
-
Ingår i: Virchows Archiv. - : Springer Science and Business Media LLC. - 1432-2307 .- 0945-6317. ; 471:Suppl. 1, s. 54-54
-
Konferensbidrag (refereegranskat)abstract
- Objective: Estrogen receptor (ER) positive breast cancer (BC) can havean insidious course with disease-relapse decades after primary surgery.New analysis performed on archived formalin-fixed paraffin-embedded(FFPE) tissue are important for disease-management in late BC-relapseand an important tool in BC-research. However, although loss of immunoreactivityin tissue slides after sectioning has been shown, little isknown of the preservation of biomarker-expression in FFPE tumourblocks.We aim to investigate the quality of immunohistochemical(IHC) ER-evaluation in FFPE-tissue over time (1978–2000).Method: Tissue-microarrays from a Swedish multicenter cohort of 728patients with contralateral BC was used for ER IHC-evaluation. BC wasstudied in three periods (1958–1985, 1986–1993, 1994–2000), and retrospectiveER IHC-data was correlated to corresponding prospective ERcytosol-analysis performed on fresh BC-tissue.Results: The concordance between the original ER cytosol-analysis andthe new IHC was substantial (1978–1985: 82 %, (117/142), Kappa 0.52.1986–1993: 91 %, (194/213), Kappa 0.72. 1994–2000: 86 %, (187/218),Kappa 0.61). Discrepancies were mostly found for tumours with ERvaluesclose to cutoff for one or both of the methods.Conclusion: FFPE BC-tissue from the late 70s to millennium showspreserved ER-antigenicity up to 35 years later.
|
|
| 21. |
|
|
| 22. |
- Gorgisyan, Jenny, et al.
(författare)
-
Evalutation of two commercial deep learning OAR segmentation models for prostate cancer treatment
- 2022
-
Konferensbidrag (refereegranskat)abstract
- Purpose or ObjectiveTo evaluate two commercial, CE labeled deep learning-based models for automatic organs at risk segmentation on planning CT images for prostate cancer radiotherapy. Model evaluation was focused on assessing both geometrical metrics and evaluating a potential time saving.Material and MethodsThe evaluated models consisted of RayStation 10B Deep Learning Segmentation (RaySearch Laboratories AB, Stockholm, Sweden) and MVision AI Segmentation Service (MVision, Helsinki, Finland) and were applied to CT images for a dataset of 54 male pelvis patients. The RaySearch model was re-trained with 44 clinic specific patients (Skåne University Hospital, Lund, Sweden) for the femoral head structures to adjust the model to our specific delineation guidelines. The model was evaluated on 10 patients from the same clinic. Dice similarity coefficient (DSC) and Hausdorff distance (95th percentile) was computed for model evaluation, using an in-house developed Python script. The average time for manual and AI model delineations was recorded.ResultsAverage DSC scores and Hausdorff distances for all patients and both models are presented in Figure 1 and Table 1, respectively. The femoral head segmentations in the re-trained RaySearch model had increased overlap with our clinical data, with a DSC (mean±1 STD) for the right femoral head of 0.55±0.06 (n=53) increasing to 0.91±0.02 (n=10) and mean Hausdorff (mm) decreasing from 55±7 (n=53) to 4±1 (n=10) (similar results for the left femoral head). The deviation in femoral head compared to the RaySearch and MVision original models occurred due to a difference in the femoral head segmentation guideline in the clinic specific data, see Figure 2. Time recording of manual delineation was 13 minutes compared to 0.5 minutes (RaySearch) and 1.4 minutes (MVision) for the AI models, manual correction not included.ConclusionBoth AI models demonstrate good segmentation performance for bladder and rectum. Clinic specific training data (or data that complies to the clinic specific delineation guideline) might be necessary to achieve segmentation results in accordance to the clinical specific standard for some anatomical structures, such as the femoral heads in our case. The time saving was around 90%, not including manual correction.
|
|
| 23. |
- Jögi, Annika, et al.
(författare)
-
Expression of HIF-1α is related to a poor prognosis and tamoxifen resistance in contralateral breast cancer
- 2019
-
Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 14:12
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Adjuvant endocrine treatment improves survival after estrogen receptor (ER) positive breast cancer. Recurrences occur, and most patients with metastatic breast cancer develop treatment resistance and incurable disease. An influential factor in relation to endocrine treatment resistance is tumor hypoxia and the hypoxia inducible transcription factors (HIFs). Poor perfusion makes tumors hypoxic and induces the HIFs, which promote cell survival. We previously showed that hypoxic breast cancer cells are tamoxifen-resistant, and that HIF-inhibition restored tamoxifen-sensitivity. We found that HIF-induced tamoxifen-resistance involve cross-talk with epithelial growth factor receptor (EGFR), which itself is linked to tamoxifen resistance. Contralateral breast cancer (CBC), i.e. development of a second breast cancer in the contralateral breast despite adjuvant tamoxifen treatment is in essence a human in vivo-model for tamoxifen-resistance that we explore here to find molecular pathways of tamoxifen-resistance.Methods: We constructed a tissue-microarray including tumor-tissue from a large well-defined cohort of CBC-patients, a proportion of which got their second breast cancer despite ongoing adjuvant therapy. Using immunohistochemistry >500 patients were evaluable for HIF-1α and EGFR in both tumors, and correlations to treatment, patient outcome, prognostic and predictive factors were analyzed.Results: We found an increased proportion of HIF-1α-positive tumors in tamoxifen-resistant (CBC during adjuvant tamoxifen) compared to naïve tumors (CBC without prior tamoxifen). Tumor HIF-1α-positivity correlated to increased breast cancer mortality, and negative prognostic factors including low age at diagnosis and ER-negativity. There was a covariance of HIF-1α- and EGFR-expression and also EGFR-expression correlated to poor prognosis.Conclusions: The increased percentage of HIF-1α-positive tumors formed during adjuvant tamoxifen suggests a role for HIF-1α in escaping tamoxifen’s restraining effects on breast cancer. Implicating a potential benefit of HIF-inhibitors in targeting breast cancers resistant to endocrine therapy.
|
|
| 24. |
|
|
| 25. |
|
|
| 26. |
- Kügele, Malin, et al.
(författare)
-
Dosimetric effects of intrafractional isocenter variation during deep inspiration breath-hold for breast cancer patients using surface-guided radiotherapy
- 2018
-
Ingår i: Journal of Applied Clinical Medical Physics. - : Wiley. - 1526-9914. ; 19:1, s. 25-38
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate potential dose reductions to the heart, left anterior descending coronary artery (LAD), and ipsilateral lung for left-sided breast cancer using visually guided deep inspiration breath-hold (DIBH) with the optical surface scanning system Catalyst™, and how these potential dosimetric benefits are affected by intrafractional motion in between breath holds. For both DIBH and free breathing (FB), treatment plans were created for 20 tangential and 20 locoregional left-sided breast cancer patients. During DIBH treatment, beam-on was triggered by a region of interest on the xiphoid process using a 3 mm gating window. Using a novel nonrigid algorithm, the Catalyst™ system allows for simultaneous real-time tracking of the isocenter position, which was used to calculate the intrafractional DIBH isocenter reproducibility. The 50% and 90% cumulative probabilities and maximum values of the intrafractional DIBH isocenter reproducibility were calculated and to obtain the dosimetric effect isocenter shifts corresponding to these values were performed in the treatment planning system. For both tangential and locoregional treatment, the dose to the heart, LAD and ipsilateral lung was significantly reduced for DIBH compared to FB. The intrafractional DIBH isocenter reproducibility was very good for the majority of the treatment sessions, with median values of approximately 1 mm in all three translational directions. However, for a few treatment sessions, intrafractional DIBH isocenter reproducibility of up to 5 mm was observed, which resulted in large dosimetric effects on the target volume and organs at risk. Hence, it is of importance to set tolerance levels on the intrafractional isocenter motion and not only perform DIBH based on the xiphoid process.
|
|
| 27. |
- Kügele, Malin, et al.
(författare)
-
Surface guided radiotherapy (SGRT) improves breast cancer patient setup accuracy
- 2019
-
Ingår i: Journal of Applied Clinical Medical Physics. - : Wiley. - 1526-9914. ; , s. 61-68
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: The purpose of the study was to investigate if surface guided radiotherapy (SGRT) can decrease setup deviations for tangential and locoregional breast cancer patients compared to conventional laser-based setup (LBS). Materials and Methods: Both tangential (63 patients) and locoregional (76 patients) breast cancer patients were enrolled in this study. For LBS, the patients were positioned by aligning skin markers to the room lasers. For the surface based setup (SBS), an optical surface scanning system was used for daily setup using both single and three camera systems. To compare the two setup methods, the patient position was evaluated using verification imaging (field images or orthogonal images). Results: For both tangential and locoregional treatments, SBS decreased the setup deviation significantly compared to LBS (P < 0.01). For patients receiving tangential treatment, 95% of the treatment sessions were within the clinical tolerance of ≤ 4 mm in any direction (lateral, longitudinal or vertical) using SBS, compared to 84% for LBS. Corresponding values for patients receiving locoregional treatment were 70% and 54% for SBS and LBS, respectively. No significant difference was observed comparing the setup result using a single camera system or a three camera system. Conclusions: Conventional laser-based setup can with advantage be replaced by surface based setup. Daily SGRT improves patient setup without additional imaging dose to breast cancer patients regardless if a single or three camera system was used.
|
|
| 28. |
- Lempart, Michael, et al.
(författare)
-
Pelvic U-Net : multi-label semantic segmentation of pelvic organs at risk for radiation therapy anal cancer patients using a deeply supervised shuffle attention convolutional neural network
- 2022
-
Ingår i: Radiation Oncology. - : Springer Science and Business Media LLC. - 1748-717X. ; 17:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Delineation of organs at risk (OAR) for anal cancer radiation therapy treatment planning is a manual and time-consuming process. Deep learning-based methods can accelerate and partially automate this task. The aim of this study was to develop and evaluate a deep learning model for automated and improved segmentations of OAR in the pelvic region. Methods: A 3D, deeply supervised U-Net architecture with shuffle attention, referred to as Pelvic U-Net, was trained on 143 computed tomography (CT) volumes, to segment OAR in the pelvic region, such as total bone marrow, rectum, bladder, and bowel structures. Model predictions were evaluated on an independent test dataset (n = 15) using the Dice similarity coefficient (DSC), the 95th percentile of the Hausdorff distance (HD95), and the mean surface distance (MSD). In addition, three experienced radiation oncologists rated model predictions on a scale between 1–4 (excellent, good, acceptable, not acceptable). Model performance was also evaluated with respect to segmentation time, by comparing complete manual delineation time against model prediction time without and with manual correction of the predictions. Furthermore, dosimetric implications to treatment plans were evaluated using different dose-volume histogram (DVH) indices. Results: Without any manual corrections, mean DSC values of 97%, 87% and 94% were found for total bone marrow, rectum, and bladder. Mean DSC values for bowel cavity, all bowel, small bowel, and large bowel were 95%, 91%, 87% and 81%, respectively. Total bone marrow, bladder, and bowel cavity segmentations derived from our model were rated excellent (89%, 93%, 42%), good (9%, 5%, 42%), or acceptable (2%, 2%, 16%) on average. For almost all the evaluated DVH indices, no significant difference between model predictions and manual delineations was found. Delineation time per patient could be reduced from 40 to 12 min, including manual corrections of model predictions, and to 4 min without corrections. Conclusions: Our Pelvic U-Net led to credible and clinically applicable OAR segmentations and showed improved performance compared to previous studies. Even though manual adjustments were needed for some predicted structures, segmentation time could be reduced by 70% on average. This allows for an accelerated radiation therapy treatment planning workflow for anal cancer patients.
|
|
| 29. |
- Lerner, Minna, et al.
(författare)
-
Clinical validation of a commercially available deep learning software for synthetic CT generation for brain
- 2021
-
Ingår i: Radiation Oncology. - : Springer Science and Business Media LLC. - 1748-717X. ; 16:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Most studies on synthetic computed tomography (sCT) generation for brain rely on in-house developed methods. They often focus on performance rather than clinical feasibility. Therefore, the aim of this work was to validate sCT images generated using a commercially available software, based on a convolutional neural network (CNN) algorithm, to enable MRI-only treatment planning for the brain in a clinical setting. Methods: This prospective study included 20 patients with brain malignancies of which 14 had areas of resected skull bone due to surgery. A Dixon magnetic resonance (MR) acquisition sequence for sCT generation was added to the clinical brain MR-protocol. The corresponding sCT images were provided by the software MRI Planner (Spectronic Medical AB, Sweden). sCT images were rigidly registered and resampled to CT for each patient. Treatment plans were optimized on CT and recalculated on sCT images for evaluation of dosimetric and geometric endpoints. Further analysis was also performed for the post-surgical cases. Clinical robustness in patient setup verification was assessed by rigidly registering cone beam CT (CBCT) to sCT and CT images, respectively. Results: All sCT images were successfully generated. Areas of bone resection due to surgery were accurately depicted. Mean absolute error of the sCT images within the body contour for all patients was 62.2 ± 4.1 HU. Average absorbed dose differences were below 0.2% for parameters evaluated for both targets and organs at risk. Mean pass rate of global gamma (1%/1 mm) for all patients was 100.0 ± 0.0% within PTV and 99.1 ± 0.6% for the full dose distribution. No clinically relevant deviations were found in the CBCT-sCT vs CBCT-CT image registrations. In addition, mean values of voxel-wise patient specific geometric distortion in the Dixon images for sCT generation were below 0.1 mm for soft tissue, and below 0.2 mm for air and bone. Conclusions: This work successfully validated a commercially available CNN-based software for sCT generation. Results were comparable for sCT and CT images in both dosimetric and geometric evaluation, for both patients with and without anatomical anomalies. Thus, MRI Planner is feasible to use for radiotherapy treatment planning of brain tumours.
|
|
| 30. |
- Lerner, Minna, et al.
(författare)
-
MRI-only based treatment with a commercial deep-learning generation method for synthetic CT of brain
- 2020
-
Ingår i: ; , s. 47-47
-
Konferensbidrag (refereegranskat)abstract
- ObjectivesTo show feasibility of synthetic computed tomography (sCT) images generated using a commerciallyavailable software, enabling MRI-only treatment planning for the brain in a clinical setting.Patients and Methods20 and 16 patients with brain malignancies, including post-surgical cases, were included for validationand treatment, respectively. Dixon MR images of the skull were exported to the MRI Planner software(Spectronic Medical AB), which utilizes convolutional neural network algorithms for sCT generation.In the validation study, sCT images were rigidly registered and resampled to CT geometry for eachpatient. Treatment plans were optimized on CT and retrospectively recalculated on sCT images forevaluation of dosimetric and geometric endpoints. Clinical robustness in patient setup verification wasassessed by rigidly registering cone beam CT (CBCT) to sCT and CT images, respectively.The treatment study was performed on sCT images, using CT solely for QA purposes.ResultsAll sCT images were successfully generated in the validation study. Mean absolute error of the sCTimages within the body contour for all patients was 62.2 ± 4.1 HU. Average absorbed dose differenceswere below 0.2%. Mean pass rate of global gamma (1%/1mm) for all patients was 100.0 ± 0.0 % withinPTV and 99.1 ± 0.6 % for the full dose distribution. No clinically relevant deviations were found in theCBCT-sCT vs CBCT-CT image registrations. Areas of bone resection due to surgery were accuratelydepicted in the sCT images. Finally, treatment success rate was 15/16. One patient was excluded due tosCT artifacts from a haemostatic substance injected during surgery.Conclusion15 patients have successfully received MRI-only RT for brain tumours using the validated commerciallyavailable sCT software. Validation showed comparable results between sCT and CT images for bothdosimetric and geometric endpoints
|
|
| 31. |
|
|
| 32. |
- Lerner, Minna, et al.
(författare)
-
Prospective Clinical Feasibility Study for MRI-Only Brain Radiotherapy
- 2022
-
Ingår i: Frontiers in Oncology. - : Frontiers Media SA. - 2234-943X. ; 11
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: MRI-only radiotherapy (RT) provides a workflow to decrease the geometric uncertainty introduced by the image registration process between MRI and CT data and to streamline the RT planning. Despite the recent availability of validated synthetic CT (sCT) methods for the head region, there are no clinical implementations reported for brain tumors. Based on a preceding validation study of sCT, this study aims to investigate MRI-only brain RT through a prospective clinical feasibility study with endpoints for dosimetry and patient setup. Material and Methods: Twenty-one glioma patients were included. MRI Dixon images were used to generate sCT images using a CE-marked deep learning-based software. RT treatment plans were generated based on MRI delineated anatomical structures and sCT for absorbed dose calculations. CT scans were acquired but strictly used for sCT quality assurance (QA). Prospective QA was performed prior to MRI-only treatment approval, comparing sCT and CT image characteristics and calculated dose distributions. Additional retrospective analysis of patient positioning and dose distribution gamma evaluation was performed. Results: Twenty out of 21 patients were treated using the MRI-only workflow. A single patient was excluded due to an MRI artifact caused by a hemostatic substance injected near the target during surgery preceding radiotherapy. All other patients fulfilled the acceptance criteria. Dose deviations in target were within ±1% for all patients in the prospective analysis. Retrospective analysis yielded gamma pass rates (2%, 2 mm) above 99%. Patient positioning using CBCT images was within ± 1 mm for registrations with sCT compared to CT. Conclusion: We report a successful clinical study of MRI-only brain radiotherapy, conducted using both prospective and retrospective analysis. Synthetic CT images generated using the CE-marked deep learning-based software were clinically robust based on endpoints for dosimetry and patient positioning.
|
|
| 33. |
|
|
| 34. |
- Narbe, Ulrik, et al.
(författare)
-
AIB1 is a new putative prognostic biomarker in the luminal A and B-like (HER2-negative) classification of invasive lobular carcinoma
- 2017
-
Ingår i: ; , s. 1-07
-
Konferensbidrag (refereegranskat)abstract
- Body: Background: Estrogen receptor (ER) positive HER2-negative breast cancer comprises 75–80% of all breast cancer. Thisfraction is even higher (>90%) in invasive lobular carcinoma (ILC). According to the St Gallen surrogate definitions of the intrinsicsubtypes, Ki67 and progesterone receptor (PgR) are used to classify these tumors as luminal A- and luminal B-like(HER2-negative). These guidelines are based on information derived from patient materials with mixed histological types, wherethe vast majority of the patients have invasive ductal carcinoma. The `luminal-like classification´ together with histological grade,tumor size and lymph node status is widely used in the clinic for prognostication. The aim of the present study was to investigateif the same markers are applicable for ILC, and furthermore, if additional biomarkers involved in the endocrine signaling system,e.g. Amplified in breast cancer 1 (AIB1) and the putative G protein-coupled estrogen receptor (GPER), might providecomplementary prognostic information.Patients: Two hundred and thirty-three (N = 233) well-characterized patients with primary ILC, diagnosed between 1980 and1991 were included. Forty-two percent of the patients received adjuvant endocrine treatment and 2 % received adjuvantchemotherapy. All biomarkers were analyzed immunohistochemically on tissue microarray, whereas histological grade wasevaluated on whole sections according to Elston and Ellis (NHG). The primary endpoint was breast cancer mortality (BCM).Results: In univariable analyses with 10-year follow-up, Ki67 (high vs. low), NHG (3 vs. 1+2) and AIB1 (high vs. low) weresignificantly associated to BCM (Hazard Ratio: 4.7, 95% CI: 2.1–10.4, p 95% CI: 1.4–7.2, p = 0.005 respectively), whereas PgR (respectively). Essentially the same effect was seen after multivariable adjustment for lymph node status (+ vs. -), tumor size (>20mm vs. according to St Gallen surrogate definitions did not show significant prognostic differences between the two groups (p = 0.12).Patients with AIB1) had a 10-year BCM of 4.2% (95% CI: 1.4–12%). This group constituted 34% of the patients included in the present study.Conclusions: In contrast to other previous studies, where breast cancers of mixed histological types were included, PgR was notsignificantly associated to prognosis in the ER-positive HER2-negative subgroup in the present study, consisting only of ILC. Theprognostic role of PgR and the clinical usefulness of the luminal A and B-like (HER2-negative) classification (using only Ki67 andPgR) in ILC is still to be further investigated. The prognostic importance of Ki67 and NHG in this subgroup was, however,confirmed also in ILC, and AIB1 might be a new putative prognostic factor. By combining Ki67, NHG, and AIB1, together withlymph node status and tumor size, a group of patients with an excellent prognosis could be identified.
|
|
| 35. |
- Narbe, Ulrik, et al.
(författare)
-
The estrogen receptor coactivator AIB1 is a new putative prognostic biomarker in ER-positive/HER2-negative invasive lobular carcinoma of the breast
- 2019
-
Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 175:2, s. 305-316
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: According to the 2017 St Gallen surrogate definitions of the intrinsic subtypes, Ki67, progesterone receptor (PR) and Nottingham histological grade (NHG) are used for prognostic classification of estrogen receptor (ER) positive/HER2-negative breast cancer into luminal A- or luminal B-like. The aim of the present study was to investigate if additional biomarkers, related to endocrine signaling pathways, e.g., amplified in breast cancer 1 (AIB1), androgen receptor (AR), and G protein-coupled estrogen receptor (GPER), can provide complementary prognostic information in a subset of ER-positive/HER-negative invasive lobular carcinoma (ILC). Methods: Biomarkers from 224 patients were analyzed immunohistochemically on tissue microarray. The primary endpoint was breast cancer mortality (BCM), analyzed with 10- and 25-year follow-up (FU). In addition, the prognostic value of gene expression data for these biomarkers was analyzed in three publicly available ILC datasets. Results: AIB1 (high vs. low) was associated to BCM in multivariable analysis (adjusted for age, tumor size, nodal status, NHG, Ki67, luminal-like classification, and adjuvant systemic therapy) with 10-year FU (HR 6.8, 95% CI 2.3–20, P = 0.001) and 25-year FU (HR 3.0, 95% CI 1.1–7.8, P = 0.03). The evidence of a prognostic effect of AIB1 could be confirmed by linking gene expression data to outcome in independent publicly available ILC datasets. AR and GPER were neither associated to BCM with 10-year nor with 25-year FU (P > 0.33). Furthermore, Ki67 and NHG were prognostic for BCM at both 10-year and 25-year FU, whereas PR was not. Conclusions: AIB1 is a new putative prognostic biomarker in ER-positive/HER2-negative ILC.
|
|
| 36. |
- Salvestrini, Viola, et al.
(författare)
-
Safety profile of trastuzumab-emtansine (T-DM1) with concurrent radiation therapy : A systematic review and meta-analysis
- 2023
-
Ingår i: Radiotherapy and Oncology. - : ELSEVIER IRELAND LTD. - 0167-8140 .- 1879-0887. ; 186
-
Forskningsöversikt (refereegranskat)abstract
- Background and Purpose: In recent years, the treatment landscape for breast cancer has undergone significant advancements, with the introduction of several new anticancer agents. One such agent is trastuzumab emtansine (T-DM1), an antibody drug conjugate that has shown improved outcomes in both early and advanced breast cancer. However, there is currently a lack of comprehensive evidence regarding the safety profile of combining T-DM1 with radiation therapy (RT). In this study, we aim to provide a summary of the available data on the safety of combining RT with T-DM1 in both early and metastatic breast cancer settings. Materials and Methods: This systematic review and meta-analysis project is part of the consensus recommendations by the European Society for Radiotherapy and Oncology (ESTRO) Guidelines Committee on integrating RT with targeted treatments for breast cancer. A thorough literature search was conducted using the PUBMED/MedLine, Embase, and Cochrane databases to identify original studies focusing on the safety profile of combining T-DM1 with RT. Results: After applying eligibility criteria, nine articles were included in the meta-analysis. Pooled data from these studies revealed a high incidence of grade 3 + radionecrosis (17%), while the rates of grade 3 + radiation-related pneumonitis (<1%) and skin toxicity (1%) were found to be very low. Conclusion: Although there is some concern regarding a slight increase in pneumonitis when combining T-DM1 with postoperative RT, the safety profile of this combination was deemed acceptable for locoregional treatment in non-metastatic breast cancer. However, caution is advised when irradiating intracranial sites concurrently with T-DM1. There is a pressing need for international consensus guidelines regarding the safety considerations of combining T-DM1 and RT for breast cancer.
|
|
| 37. |
- Sandberg, Maria E. C., et al.
(författare)
-
Influence of radiotherapy for the first tumor on aggressiveness of contralateral breast cancer
- 2013
-
Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 132:10, s. 2388-2394
-
Tidskriftsartikel (refereegranskat)abstract
- We aimed to investigate if characteristics of contralateral breast cancer (CBC) are influenced by adjuvant radiotherapy for the first breast cancer. Using information from population-based registers and medical records, we analyzed two cohorts comprising all women with CBC diagnosed >3 months after their first cancer (809 patients in Stockholm 19762005 and 750 patients in South Sweden 19772005). We used Poisson regression to calculate risk of distant metastasis after CBC, comparing patients treated and not treated with radiotherapy for the first cancer. Logistic regression was used to estimate odds ratio (OR) of more aggressive tumor characteristics in the second cancer, compared to the first. For patients with CBC in Stockholm with <5 years between the cancers radiotherapy for the first cancer conferred a nearly doubled risk of distant metastasis [incidence rate ratio (IRR) = 1.91; 95% confidence interval (CI): 1.272.88], compared to those not treated with radiotherapy. This was replicated in the South Swedish cohort [IRR = 2.12 (95% CI: 1.403.23)]. In Stockholm, we found an increased odds that, following radiotherapy, a second cancer was of more advanced TNM-stage [OR 2.16 (95% CI 1.134.11)] and higher histological grade [OR = 2.00 (95% CI 1.083.72)] compared to the first, for patients with CBC with <5 years between the cancers. No effect on any of the investigated outcomes was seen for patients diagnosed with CBC >5 years from the first cancer. In conclusion, patients diagnosed with CBC within 5 years had worse prognosis and more aggressive tumor characteristics of the second cancer, if they had received radiotherapy for their first cancer, compared to no radiotherapy.
|
|
| 38. |
- Tutzauer, Julia, et al.
(författare)
-
Plasma membrane expression of G protein-coupled estrogen receptor (GPER)/G protein-coupled receptor 30 (GPR30) is associated with worse outcome in metachronous contralateral breast cancer
- 2020
-
Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:4
-
Tidskriftsartikel (refereegranskat)abstract
- Background G protein-coupled estrogen receptor (GPER), or G protein-coupled receptor 30 (GPR30), is reported to mediate non-genomic estrogen signaling. GPR30 associates with breast cancer (BC) outcome and may contribute to tamoxifen resistance. We investigated the expression and prognostic significance of GPR30 in metachronous contralateral breast cancer (CBC) as a model of tamoxifen resistance. Methods Total GPR30 expression (GPR30TOT) and plasma membrane-localized GPR30 expression (GPR30PM) were analyzed by immunohistochemistry in primary (BC1; nBC1 = 559) and contralateral BC (BC2; nBC2 = 595), and in lymph node metastases (LGL; nLGL1 = 213; nLGL2 = 196). Death from BC (BCD), including BC death or death after documented distant metastasis, was used as primary end-point. Results GPR30PM in BC2 and LGL2 were associated with increased risk of BCD (HRBC2 = 1.7, p = 0.03; HRLGL2 = 2.0; p = 0.02). In BC1 and BC2, GPR30PM associated with estrogen receptor (ER)-negativity (pBC1<0.0001; pBC2<0.0001) and progesterone receptor (PR)-negativity (pBC1 = 0.0007; pBC2<0.0001). The highest GPR30TOT and GPR30PM were observed in triple-negative BC. GPR30PM associated with high Ki67 staining in BC1 (p<0.0001) and BC2 (p<0.0001). GPR30TOT in BC2 did not associate with tamoxifen treatment for BC1. However, BC2 that were diagnosed during tamoxifen treatment were more likely to express GPR30PM than BC2 diagnosed after treatment completion (p = 0.01). Furthermore, a trend was observed that patients with GPR30PM in an ER-positive BC2 had greater benefit from tamoxifen treatment. Conclusion PM-localized GPR30 staining is associated with increased risk of BC death when expressed in BC2 and LGL2. Additionally, PM-localized GPR30 correlates with prognostic markers of worse outcome, such as high Ki67 and a triple-negative subtype. Therefore, PM-localized GPR30 may be an interesting new target for therapeutic exploitation. We found no clear evidence that total GPR30 expression is affected by tamoxifen exposure during development of metachronous CBC, or that GPR30 contributes to tamoxifen resistance.
|
|
