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- Klevebring, Daniel, et al.
(författare)
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Exome sequencing of contralateral breast cancer identifies metastatic disease
- 2015
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Ingår i: Breast Cancer Research and Treatment. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 0167-6806 .- 1573-7217.
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Tidskriftsartikel (refereegranskat)abstract
- Women with contralateral breast cancer (CBC) have significantly worse prognosis compared to women with unilateral cancer. A possible explanation of the poor prognosis of patients with CBC is that in a subset of patients, the second cancer is not a new primary tumor but a metastasis of the first cancer that has potentially obtained aggressive characteristics through selection of treatment. Exome and whole-genome sequencing of solid tumors has previously been used to investigate the clonal relationship between primary tumors and metastases in several diseases. In order to assess the relationship between the first and the second cancer, we performed exome sequencing to identify somatic mutations in both first and second cancers, and compared paired normal tissue of 25 patients with metachronous CBC. For three patients, we identified shared somatic mutations indicating a common clonal origin thereby demonstrating that the second tumor is a metastasis of the first cancer, rather than a new primary cancer. Accordingly, these patients all developed distant metastasis within 3 years of the second diagnosis, compared with 7 out of 22 patients with non-shared somatic profiles. Genomic profiling of both tumors help the clinicians distinguish between true CBCs and subsequent metastases.
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| 4. |
- Ahlin, Cecilia, et al.
(författare)
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High expression of cyclin D1 is associated to high proliferation rate and increased risk of mortality in women with ER-positive but not in ER-negative breast cancers
- 2017
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Ingår i: Breast Cancer Research and Treatment. - : SPRINGER. - 0167-6806 .- 1573-7217. ; 164:3, s. 667-678
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Tidskriftsartikel (refereegranskat)abstract
- Cyclin D1 has a central role in cell cycle control and is an important component of estrogen regulation of cell cycle progression. We have previously shown that high cyclin D expression is related to aggressive features of ER-positive but not ER-negative breast cancer. The aims of the present study were to validate this differential ER-related effect and furthermore explore the relationship between cyclin D overexpression and CCND1 gene amplification status in a node-negative breast cancer case-control study. Immunohistochemical nuclear expression of cyclin D1 (n = 364) and amplification of the gene CCND1 by fluorescent in situ hybridization (n = 255) was performed on tissue microarray sections from patients with T1-2N0M0 breast cancer. Patients given adjuvant chemotherapy were excluded. The primary event was defined as breast cancer death. Breast cancer-specific survival was analyzed in univariate and multivariable models using conditional logistic regression. Expression of cyclin D1 above the median (61.7%) in ER breast cancer was associated with an increased risk for breast cancer death (OR 3.2 95% CI 1.5-6.8) also when adjusted for tumor size and grade (OR 3.1). No significant prognostic impact of cyclin D1 expression was found among ER-negative cases. Cyclin D1 overexpression was significantly associated to high expression of the proliferation markers cyclins A (rho 0.19, p = 0.006) and B (rho 0.18, p = 0.003) in ER-positive tumors, but not in ER-negative cases. There was a significant association between CCND1 amplification and cyclin D1 expression (p = 0.003), but CCND1 amplification was not statistically significantly prognostic (HR 1.4, 95% CI 0.4-4.4). We confirmed our previous observation that high cyclin D1 expression is associated to high proliferation and a threefold higher risk of death from breast cancer in ER-positive breast cancer.
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| 5. |
- Alkner, S., et al.
(författare)
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Prognostic and predictive importance of the estrogen receptor coactivator AIB1 in a randomized trial comparing adjuvant letrozole and tamoxifen therapy in postmenopausal breast cancer : the Danish cohort of BIG 1-98
- 2017
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Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 166, s. 481-490
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To evaluate the estrogen receptor coactivator amplified in breast cancer 1 (AIB1) as a prognostic marker, as well as a predictive marker for response to adjuvant tamoxifen and/or aromatase inhibitors, in early estrogen receptor-positive breast cancer. Method: AIB1 was analyzed with immunohistochemistry in tissue microarrays of the Danish subcohort (N = 1396) of the International Breast Cancer Study Group’s trial BIG 1-98 (randomization between adjuvant tamoxifen versus letrozole versus the sequence of the two drugs). Results: Forty-six percent of the tumors had a high AIB1 expression. In line with previous studies, AIB1 correlated to a more aggressive tumor-phenotype (HER2 amplification and a high malignancy grade). High AIB1 also correlated to higher estrogen receptor expression (80–100 vs. 1–79%), and ductal histological type. High AIB1 expression was associated with a poor disease-free survival (univariable: hazard ratio 1.35, 95% confidence interval 1.12–1.63. Multivariable: hazard ratio 1.29, 95% confidence interval 1.06–1.58) and overall survival (univariable: hazard ratio 1.34, 95% confidence interval 1.07–1.68. Multivariable: hazard ratio 1.25, 95% confidence interval 0.99–1.60). HER2 did not seem to modify the prognostic effect of AIB1. No difference in treatment effect between tamoxifen and letrozole in relation to AIB1 was found. Conclusions: In a subset of the large international randomized trial BIG 1-98, we confirm AIB1 to be a strong prognostic factor in early breast cancer. Hence, although tumor AIB1 expression does not seem to be useful for the choice of tamoxifen versus an aromatase inhibitor in postmenopausal endocrine-responsive breast cancer, AIB1 is an interesting target for new anti-cancer therapies and further investigations of this biomarker is warranted.
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| 6. |
- Andersson, Yvette, et al.
(författare)
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Do clinical trials truly mirror their target population? : An external validity analysis of national register versus trial data from the Swedish prospective SENOMIC trial on sentinel node micrometastases in breast cancer
- 2019
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Ingår i: Breast Cancer Research and Treatment. - : SPRINGER. - 0167-6806 .- 1573-7217. ; 177:2, s. 469-475
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Increasing evidence suggests that completion axillary lymph node dissection (ALND) may be omitted in breast cancer patients with limited axillary nodal metastases. However, the representativeness of trial participants for the original clinical practice population, and thus, the generalizability of published trials have been questioned. We propose the use of background data from national registers as a means to assess whether trial participants mirror their target population and to strengthen the generalizability and implementation of trial outcomes.Methods: The Swedish prospective SENOMIC trial, omitting a completion ALND in breast cancer patients with sentinel lymph node micrometastases, reached full target accrual in 2017. To assess the generalizability of trial results for the target population, a comparative analysis of trial participants versus cases reported to the Swedish National Breast Cancer Register (NKBC) was performed.Results: Comparing 548 trial participants and 1070 NKBC cases, there were no significant differences in age, tumor characteristics, breast surgery, or adjuvant treatment. Only the mean number of sentinel lymph nodes with micrometastasis per individual was lower in trial participants than in register cases (1.06 vs. 1.09, p=0.037).Conclusions: Patients included in the SENOMIC trial are acceptably representative of the Swedish breast cancer target population. There were some minor divergences between trial participants and the NKBC population, but taking these into consideration, upcoming trial outcomes should be generalizable to breast cancer patients with micrometastases in their sentinel lymph node biopsy.
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| 7. |
- Andersson, Yvette, et al.
(författare)
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Long-term breast cancer survival in relation to the metastatic tumor burden in axillary lymph nodes
- 2018
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Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 171:2, s. 359-369
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The clinical significance of lymph node micrometastases and isolated tumor cells (ITCs) in breast cancer is still controversial. After a median follow-up of 52 months, a report from the Swedish Multicenter Cohort Study presented a worse cancer-specific and event-free survival for patients with micrometastases than node-negative individuals, but could not demonstrate a significant difference in overall survival (OS). Due to the tendency of breast cancer to relapse after more than 5-10 years, we now report the long-term survival of the cohort.Methods: Between September 2000 and January 2004, 3355 breast cancer patients were included in a prospective cohort. Sentinel lymph node biopsy was always performed. Patients were classified in four groups according to their overall nodal stage: node negative (N0, 2372), ITCs (113), micrometastases (123), and macrometastases (747). Kaplan-Meier survival estimates and Cox proportional hazard regression models were applied.Results: Median follow-up was 156 months. Ten-year cancer-specific survival and OS were significantly lower in case of micrometastases than in N0 (84.7 vs. 93.5%, p = 0.001, and 75.5 vs. 84.2%, p = 0.046, respectively). In case of macrometastases, corresponding survival rates were 82.8 and 74.3%. Only for those aged less than 50 years, cancer-specific survival and OS were significantly worse in case of ITCs than N0. Patients with micrometastases received less often chemotherapy than those with macrometastases (24.4 vs. 53.9%).Conclusions: Lymph node micrometastases in breast cancer have a prognostic significance. This study demonstrates a similar survival for patients with micrometastases and those with macrometastases, possibly due to systemic undertreatment.
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| 10. |
- Bens, Annet, et al.
(författare)
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Worse survival after breast cancer in women with anorexia nervosa
- 2018
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Ingår i: Breast Cancer Research and Treatment. - : SPRINGER. - 0167-6806 .- 1573-7217. ; 168:2, s. 495-500
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Tidskriftsartikel (refereegranskat)abstract
- A history of anorexia nervosa has been associated with a reduced risk of developing breast cancer. We investigated survival after breast cancer among women with a prior anorexia nervosa diagnosis compared with women in a population comparison group. This register-based study included combined data from Sweden, Denmark and Finland. A total of 76 and 1462 breast cancer cases identified among 22,654 women with anorexia nervosa and 224,619 women in a population comparison group, respectively, were included in the study. Hazard ratios (HR) for overall and breast cancer-specific mortality after breast cancer diagnosis were estimated using Cox regression. Cause of death was available only for Swedish and Danish women; therefore, the analysis on breast cancer-specific mortality was restricted to these women. We observed 23 deaths after breast cancer among anorexia nervosa patients and 247 among population comparisons. The overall mortality after the breast cancer diagnosis was increased in women with a history of anorexia nervosa compared with population comparisons (HR 2.5, 95% CI 1.6-3.9) after adjustment for age, period and extent of disease. Results were similar for overall (HR 2.3, 95% CI 1.4-3.6) and breast cancer-specific mortality (HR 2.1, 95% CI 1.3-3.6) among Swedish and Danish women. We found that female breast cancer patients with a prior diagnosis of anorexia nervosa have a worse survival compared with other breast cancer patients.
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