| 1. |
- Ahlgren, Johan, 1960-
(författare)
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Studies on Prediction of Axillary Lymph Node Status in Invasive Breast Cancer
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Breast cancer is the most common malignancy among females in Sweden. Axillary lymph-node dissection is a standard procedure in the management of breast cancer, aiming at obtaining prognostic information for adjuvant therapy decisions. Axillary dissection entails considerable morbidity. The aims of this study were to establish more selective surgical approaches and to investigate angiogenesis, a potential predictor for lymph-node metastases and prognosis.Clinical nodal status, tumour size and S-phase were associated with nodal metastases in cohort of 1145 women. The proportion of nodal metastases was 13% in the subgroup with the lowest risk.In a study from two registries, 675 and 1035 breast cancers ≤10 mm diagnosed by screening mammography had nodal metastases in 6,5% and 7%, respectively. Clinically detected cancers had a risk of 16% and 14%, respectively.In a study on 415 women, a 5-node biopsy of the axilla had a sensitivity of 97,3% and a false negative rate of 2,7% in comparison with axillary dissection.Six sections from 21 breast cancers were analysed for microvessel density (MVD). The inter-section variation contributed more to the total variance than inter-tumour variation, 45,0% and 37,3%, respectively.In a cohort of 315 women, breast cancers with high MVD more frequently had p53 mutations (27,1%) compared with cases with low MVD (18,4%). This difference was not statistically significant (p=0,075). p53 mutations were associated with a worse outcome, whereas MVD was not.In conclusion, women with screening detected ≤10 mm breast cancers have a low risk of lymph node metastases and some may not need axillary dissection in the future. The 5-node biopsy could be an alternative to axillary dissection. MVD is associated with methodological weaknesses and routine use is not recommended.
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| 2. |
- Arnesson, Lars-Gunnar, 1947-
(författare)
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Small breast cancers : Diagnosis, prognostic factors and clinical outcome in a screening population
- 1994
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Breast cancer ≤ 10 mm together with ductal in situ cancer of the breast (DCIS) today constitute more than 40% of screening detected breast malignancies. Prognostic factors, diagnosis and clinical outcome for invasive breast cancers ≤ 10 mm and local recurrence in DCIS were evaluated.Histopathological grading was done in 248 ductal breast cancers and grade III was correlated to aneuploidy, increased S-phase fraction and receptor negative tumours. Life table analysis showed a significant increase in breast cancer mortality in grade III tumours (p < 0.001).Hormone receptors and cytometric variables were studied in ≤ 10 mm breast cancers. Around 60% of these small cancers were evaluable. Aneuploidy was found in 52% and SPF ≥ 10 in 20%. Mean SPF was 4.8 in diploid and 7.6 in aneuploid tumours. A potentially high risk group with high SPF figures and receptor negative tumours comprise 7% of the patients.Diagnostic surgery was performed in 314 non-palpable breast lesions. Insufficient excisions were observed in 16 cases (5%), mostly in lesions with microcalcifications and in situ cancers ≥ 30 mm in extent. Underestimation of in situ cancers is the main reason for inadequate surgery.DCIS comprises approx 10% of breast malignancies. In 38 cases operated with breast preserving surgery 13% got local recurrence in median 60 months follow-up.Recurrence free survival in patients with ≤ 10 mm breast cancers were evaluated for 324 cases. Only 8% of these patients had adjuvant treatment. Lymph node involvement was found in 9% of screening detected and 20% in clinically detected cancers (p < 0.03). Median prospective follow-up time was 7 years and distant metastases appeared in 8 patients, local recurrence in 3. Life table analysis showed 97% overall distant recurrence free survival, 99% in node negative and 79% in node positive patients (p < 0.001).We can today, by grading and cytometric variables, find subgroups with high risk of recurrence after breast cancer surgery in small breast cancers. These are probably the only patients that benefit from adjuvant treatment and need follow-up outside mammography screening. Breast conserving surgery can be performed in the majority of DCIS patients.
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| 3. |
- Fagerholm, Rainer, et al.
(författare)
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NAD(P)H:quinone oxidoreductase 1 NQO1*2 genotype (P187S) is a strong prognostic and predictive factor in breast cancer
- 2008
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 40:7, s. 844-53
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Tidskriftsartikel (refereegranskat)abstract
- NQO1 guards against oxidative stress and carcinogenesis and stabilizes p53. We find that a homozygous common missense variant (NQO1(*)2, rs1800566(T), NM_000903.2:c.558C>T) that disables NQO1 strongly predicts poor survival among two independent series of women with breast cancer (P = 0.002, N = 1,005; P = 0.005, N = 1,162), an effect particularly evident after anthracycline-based adjuvant chemotherapy with epirubicin (P = 7.52 x 10(-6)) and in p53-aberrant tumors (P = 6.15 x 10(-5)). Survival after metastasis was reduced among NQO1(*)2 homozygotes, further implicating NQO1 deficiency in cancer progression and treatment resistance. Consistently, response to epirubicin was impaired in NQO1(*)2-homozygous breast carcinoma cells in vitro, reflecting both p53-linked and p53-independent roles of NQO1. We propose a model of defective anthracycline response in NQO1-deficient breast tumors, along with increased genomic instability promoted by elevated reactive oxygen species (ROS), and suggest that the NQO1 genotype is a prognostic and predictive marker for breast cancer.
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| 4. |
- Garcia-Closas, Montserrat, et al.
(författare)
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Heterogeneity of breast cancer associations with five susceptibility loci by clinical and pathological characteristics
- 2008
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 4:4, s. e1000054-
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Tidskriftsartikel (refereegranskat)abstract
- A three-stage genome-wide association study recently identified single nucleotide polymorphisms (SNPs) in five loci (fibroblast growth receptor 2 (FGFR2), trinucleotide repeat containing 9 (TNRC9), mitogen-activated protein kinase 3 K1 (MAP3K1), 8q24, and lymphocyte-specific protein 1 (LSP1)) associated with breast cancer risk. We investigated whether the associations between these SNPs and breast cancer risk varied by clinically important tumor characteristics in up to 23,039 invasive breast cancer cases and 26,273 controls from 20 studies. We also evaluated their influence on overall survival in 13,527 cases from 13 studies. All participants were of European or Asian origin. rs2981582 in FGFR2 was more strongly related to ER-positive (per-allele OR (95%CI) = 1.31 (1.27-1.36)) than ER-negative (1.08 (1.03-1.14)) disease (P for heterogeneity = 10(-13)). This SNP was also more strongly related to PR-positive, low grade and node positive tumors (P = 10(-5), 10(-8), 0.013, respectively). The association for rs13281615 in 8q24 was stronger for ER-positive, PR-positive, and low grade tumors (P = 0.001, 0.011 and 10(-4), respectively). The differences in the associations between SNPs in FGFR2 and 8q24 and risk by ER and grade remained significant after permutation adjustment for multiple comparisons and after adjustment for other tumor characteristics. Three SNPs (rs2981582, rs3803662, and rs889312) showed weak but significant associations with ER-negative disease, the strongest association being for rs3803662 in TNRC9 (1.14 (1.09-1.21)). rs13281615 in 8q24 was associated with an improvement in survival after diagnosis (per-allele HR = 0.90 (0.83-0.97). The association was attenuated and non-significant after adjusting for known prognostic factors. Our findings show that common genetic variants influence the pathological subtype of breast cancer and provide further support for the hypothesis that ER-positive and ER-negative disease are biologically distinct. Understanding the etiologic heterogeneity of breast cancer may ultimately result in improvements in prevention, early detection, and treatment.
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| 5. |
- Turkki, Riku, et al.
(författare)
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Breast cancer outcome prediction with tumour tissue images and machine learning
- 2019
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Ingår i: Breast Cancer Research and Treatment. - : SPRINGER. - 0167-6806 .- 1573-7217. ; 177:1, s. 41-52
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Recent advances in machine learning have enabled better understanding of large and complex visual data. Here, we aim to investigate patient outcome prediction with a machine learning method using only an image of tumour sample as an input.Methods: Utilising tissue microarray (TMA) samples obtained from the primary tumour of patients (N=1299) within a nationwide breast cancer series with long-term-follow-up, we train and validate a machine learning method for patient outcome prediction. The prediction is performed by classifying samples into low or high digital risk score (DRS) groups. The outcome classifier is trained using sample images of 868 patients and evaluated and compared with human expert classification in a test set of 431 patients.Results: In univariate survival analysis, the DRS classification resulted in a hazard ratio of 2.10 (95% CI 1.33-3.32, p=0.001) for breast cancer-specific survival. The DRS classification remained as an independent predictor of breast cancer-specific survival in a multivariate Cox model with a hazard ratio of 2.04 (95% CI 1.20-3.44, p=0.007). The accuracy (C-index) of the DRS grouping was 0.60 (95% CI 0.55-0.65), as compared to 0.58 (95% CI 0.53-0.63) for human expert predictions based on the same TMA samples.Conclusions: Our findings demonstrate the feasibility of learning prognostic signals in tumour tissue images without domain knowledge. Although further validation is needed, our study suggests that machine learning algorithms can extract prognostically relevant information from tumour histology complementing the currently used prognostic factors in breast cancer.
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