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  • 1.
    Razavi, Amir Reza
    et al.
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology.
    Gill, Hans
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology.
    Stål, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences.
    Sundquist, Marie
    Department of Surgery, County Hospital, Kalmar, Sweden.
    Thorstenson, Sten
    Department of Pathology, County Hospital, Kalmar, Sweden.
    Åhlfeldt, Hans
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology.
    Shahsavar, Nosrat
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology.
    The South-East Swedish Breast Cancer Study Group,
    Exploring cancer register data to find risk factors for recurrence of breast cancer: Application of Canonical Correlation Analysis2005In: BMC Medical Informatics and Decision Making, ISSN 1472-6947, Vol. 5, no 29, p. 29-35Article in journal (Refereed)
    Abstract [en]

    Background

    A common approach in exploring register data is to find relationships between outcomes and predictors by using multiple regression analysis (MRA). If there is more than one outcome variable, the analysis must then be repeated, and the results combined in some arbitrary fashion. In contrast, Canonical Correlation Analysis (CCA) has the ability to analyze multiple outcomes at the same time.

    One essential outcome after breast cancer treatment is recurrence of the disease. It is important to understand the relationship between different predictors and recurrence, including the time interval until recurrence. This study describes the application of CCA to find important predictors for two different outcomes for breast cancer patients, loco-regional recurrence and occurrence of distant metastasis and to decrease the number of variables in the sets of predictors and outcomes without decreasing the predictive strength of the model.

    Methods

    Data for 637 malignant breast cancer patients admitted in the south-east region of Sweden were analyzed. By using CCA and looking at the structure coefficients (loadings), relationships between tumor specifications and the two outcomes during different time intervals were analyzed and a correlation model was built.

    Results

    The analysis successfully detected known predictors for breast cancer recurrence during the first two years and distant metastasis 2–4 years after diagnosis. Nottingham Histologic Grading (NHG) was the most important predictor, while age of the patient at the time of diagnosis was not an important predictor.

    Conclusion

    In cancer registers with high dimensionality, CCA can be used for identifying the importance of risk factors for breast cancer recurrence. This technique can result in a model ready for further processing by data mining methods through reducing the number of variables to important ones.

  • 2.
    Sundquist, Marie
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Prognostic Factors in Breast Cancer2000Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Breast cancer is increasing in the industrialised countries. Due to early detection and adjuvaut treatment with radiotherapy, hormones and chemotherapy, mortality has decreased. The different adjuvant treatments have adverse effects. It is an important task is to estimate the risk of recurrence for the individual patient in order to tailor her individual treatment. This thesis aims at identifying predictors for disease development in primary and disseminated breast cancer.

    Histologic grade was strongly correlated to breast cancer mortality in 630 patients with primary breast cancer. The combination of grade, tumour size and lymph node status in the Nottingham Prognostic Index provides a powerful instrument separating patients in groups with excellent, good, intermediate and poor prognosis.

    Grade was more sensitive than S-phase fraction in identifying high risk patients and patients with very good prognosis.

    Presence of cancer cells in blood- and lymph vessels close to the tumour in patients with grade 3 tumours increased the risk oflocoregional recurrence 6-fold as compared to patients with grade 1 or 2 tumours without such vascular invasion.

    The mortality of young women with breast cancer has decreased very little since 1960. Women under 37 years of age had increased tumour size, more metastatic lymph nodes and doubled rate of high grade tumours as compared to older women.

    Disease-free interval and survival in patients with distant recurrence were strongly associated to histologic grade and hormone receptor content. Patients with grade 3, hormone receptor negative tumours had a median survival of 10 months after recurrence while only 15 % of women with receptor positive, grade 1 tumours have so far died after a median follow-up time of 5 years after recurrence.

    The Nottingham Prognostic Index and assessments of presence of tmnour cells in vessels provide important information about the risk oflocoregional and distant recurrence in breast cancer. Treatment decisions, counselling and follow-up programmes should be based on such assessments. For patients with metastatic breast cancer, tumour grade, estrogen receptor status and serum-c-erbB-2 predict the course of the disease.

    List of papers
    1. Applying the Nottingham Prognostic Index to a Swedish breast cancer population
    Open this publication in new window or tab >>Applying the Nottingham Prognostic Index to a Swedish breast cancer population
    1999 (English)In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 53, no 1, p. 1-8Article in journal (Refereed) Published
    Abstract [en]

    The aim of this study was to assess the applicability of histopathological grading according to the protocol of Elston/Ellis and the Nottingham Prognostic Index (NPI) to a defined breast cancer population. The NPI is the sum of the individual scores concerning grade, tumour size, and lymph node status, each weighted according to regression coefficients of a Cox proportional hazard analysis and calculated for each individual breast cancer patient. 630 consecutive patients with invasive breast cancer diagnosed 1988–91 were retrospectively followed up and their tumours reviewed and graded. A Cox proportional hazard analysis was performed. Grade, lymph node status, and tumour size were statistically significant predictors of survival within the follow up period (median 7.2 years). Similar to NPI, a temporary index (Kalmar Prognostic Index, KPI) was derived and normalised to NPI for comparison (KPI(norm)). NPI and KPI(norm) gave similar prognostic power in spite of the differences of the patient populations from which the 2 indices were derived. Patients with NPI 4 or less had 0.66% breast cancer specific mortality during the follow up time. 14% of the patients with NPI 4.1–5 and 32% of those with an index sum 5.1–6 died from breast cancer during this time. Younger patients tended to have higher grade tumours. We advocate the common use of grade and the NPI in order to increase the comparability of groups of patients receiving different therapies.

    Keywords
    breast cancer, histopathological grade, Nottingham Prognostic Index, prognosis
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-25294 (URN)10.1023/A:1006052115874 (DOI)9734 (Local ID)9734 (Archive number)9734 (OAI)
    Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
    2. A comparison between flow cytometric assessment of S-phase fraction and Nottingham histologic grade as prognostic instruments in breast cancer
    Open this publication in new window or tab >>A comparison between flow cytometric assessment of S-phase fraction and Nottingham histologic grade as prognostic instruments in breast cancer
    Show others...
    2000 (English)In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 63, no 1, p. 11-15Article in journal (Refereed) Published
    Abstract [en]

    Flow cytometric DNA analysis with assessment of S-phase fraction and DNA ploidy was compared to Nottingham histologic grade. The study population consisted of 654 patients who presented between 1987 and 1996 with primary operable breast cancer and whose tumours had been analysed for S-phase fraction and DNA ploidy at the time of surgery. Grade, tumour size, node status, steroid receptor status, age, S-phase fraction and DNA ploidy were analysed univariately and multi-variately in a Cox proportional hazard analysis. In the univariate analyses all parameters were statistically significantly associated with breast cancer mortality during the follow-up period of 2–11 years. The most powerful predictor of death from breast cancer in the multiple regression analysis was grade. Patients with grade 1 tumours have excellent prognosis. We conclude that tumour grade is a strong prognostic indicator applicable to all breast cancer patients, regardless of size and nodal status, and advocate its general use.

    Keywords
    breast cancer, prognosis, Nottingham histologic grade, S-phase fraction
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-25288 (URN)10.1023/A:1006494625644 (DOI)9728 (Local ID)9728 (Archive number)9728 (OAI)
    Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
    3. Indicators of loco-regional recurrence in breast cancer
    Open this publication in new window or tab >>Indicators of loco-regional recurrence in breast cancer
    Show others...
    2000 (English)In: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 26, no 4, p. 357-362Article in journal (Refereed) Published
    Abstract [en]

    Aim: The aim of the investigation was to contribute to the identification of patients who have increased or decreased risk of loco-regional recurrence.

    Methods: Six hundred and twenty-nine consecutive patients with primary breast cancer diagnosed between 1988 and 1990 were studied. Two-thirds of the patients underwent mastectomy. Radiotherapy was administered if patients were node positive or breast conserved. The Nottingham histological grading protocol was used and presence of lymphovascular invasion was assessed. Investigated parameters were: age, size, grade, steroid receptor content, surgical radicality, vascular invasion and nodal status. Statistically significant risk factors for loco-regional recurrence using univariate or Cox proportional hazard analysis were grade and lymphovascular invasion.

    Results: Women with grade 1-2, node-negative tumours without vascular invasion had a very low loco-regional recurrence rate - 3.1%. Seventeen percent of patients with grade 3 tumours and vessel invasion had loco-regional recurrence.

    Conclusions: Our findings, and those of others, indicate that the use of adjuvant radiotherapy should be influenced to a greater extent by grade and lymphovascular invasion.

    Keywords
    breast cancer, recurrence, lymphovascular invasion, Nottingham histological grade
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-25179 (URN)10.1053/ejso.1999.0898 (DOI)9616 (Local ID)9616 (Archive number)9616 (OAI)
    Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
    4. Incidence and prognosis in early onset breast cancer
    Open this publication in new window or tab >>Incidence and prognosis in early onset breast cancer
    Show others...
    2002 (English)In: Breast, ISSN 0960-9776, E-ISSN 1532-3080, Vol. 11, no 1, p. 30-35Article in journal (Refereed) Published
    Abstract [en]

    The aim of this study was to assess the incidence and prognosis in early onset breast cancer. Age-adjusted incidence and death rate for the 5394 Swedish women diagnosed with breast cancer under the age of 40 between 1960 and 1996 was studied using data from the Swedish Cancer Registry and Swedish Death Cause Registry. A total of 107 consecutive young patients with invasive breast cancer undergoing surgery during 1980–1993 in the Southeast Swedish health care region were retrospectively followed up and their cancers reviewed and graded blindly. The median follow-up time was 11.2 years. The applicability of the Nottingham Prognostic Index (NPI) as a prognostic tool was investigated. Grade, age, node status, tumour size, S-phase fraction and steroid receptor content were related to survival univariately and multivariately in a Cox proportional hazard analysis.

    The incidence of early onset breast cancer has increased moderately and the survival rate has not improved during the last 35 years. When young women are diagnosed with breast cancer their tumours are larger, their lymph nodes more often involved, and the median grade higher than in older with 64% having grade 3 tumours. Lymph node status was the strongest sole prognostic indicator but the use of NPI gave more accurate prognostic information than node status alone.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-28170 (URN)10.1054/brst.2001.0358 (DOI)12986 (Local ID)12986 (Archive number)12986 (OAI)
    Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
    5. Disease free interval and survival after dissemination of breast cancer
    Open this publication in new window or tab >>Disease free interval and survival after dissemination of breast cancer
    Show others...
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Tumour and patients characteristics were analysed and correlated to disease development in 184 women who were consecutively diagnosed with systemic breast cancer. Nottingham histologic grade (NHG) and steroid receptor content were significantly associated with disease-free interval and survival after dissemination. In the multiple regression analysis, NHG was the strongest predictor. Patients with tumours of grade 1 had median disease-free interval of 8,9 years; tumours of grade 2 4,4 years and patients with grade 3 tumours 1,8 years. Grade 2 patients had a median survival after dissemination of 2,6 years and patients with grade 3 tumours 1,2 years. Only 1 of the 12 grade 1 patients are so far diseased. 85 patients participated in a prospective trial assessing the value of serum cerbb-2 as prognostic indicator. Patients with high serum-cerbb-2 levels when distant disease was diagnosed had a more rapid disease development.

    Tumour grade was associated with disease-free interval and post-recurrence survival. Follow up progranunes could be differentiated according to tumour grade.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-79570 (URN)
    Available from: 2012-08-09 Created: 2012-08-09 Last updated: 2012-08-09Bibliographically approved
  • 3.
    Sundquist, Marie
    et al.
    Department of Surgery, County Hospital, Kalmar, Sweden.
    Nilsson, I.
    Department of Clinical Chemistry, County Hospital, Kalmar, Sweden.
    Thorstenson, Sten
    Department of Cytology and Pathology, County Hospital, Kalmar, Sweden.
    Brudin, Lars
    Department of Physiology, County Hospital, Kalmar, Sweden.
    Nordenskjöld, Bo
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Disease free interval and survival after dissemination of breast cancerManuscript (preprint) (Other academic)
    Abstract [en]

    Tumour and patients characteristics were analysed and correlated to disease development in 184 women who were consecutively diagnosed with systemic breast cancer. Nottingham histologic grade (NHG) and steroid receptor content were significantly associated with disease-free interval and survival after dissemination. In the multiple regression analysis, NHG was the strongest predictor. Patients with tumours of grade 1 had median disease-free interval of 8,9 years; tumours of grade 2 4,4 years and patients with grade 3 tumours 1,8 years. Grade 2 patients had a median survival after dissemination of 2,6 years and patients with grade 3 tumours 1,2 years. Only 1 of the 12 grade 1 patients are so far diseased. 85 patients participated in a prospective trial assessing the value of serum cerbb-2 as prognostic indicator. Patients with high serum-cerbb-2 levels when distant disease was diagnosed had a more rapid disease development.

    Tumour grade was associated with disease-free interval and post-recurrence survival. Follow up progranunes could be differentiated according to tumour grade.

  • 4.
    Sundquist, Marie
    et al.
    Department of Surgery, County Hospital, Kalmar, Sweden.
    Thorstenson, Sten
    Department of Cytology and Pathology, County Hospital, Kalmar, Sweden.
    Brudin, Lars
    Department of Physiology, County Hospital, Kalmar, Sweden.
    Nordenskjöld, Bo
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Applying the Nottingham Prognostic Index to a Swedish breast cancer population1999In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 53, no 1, p. 1-8Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to assess the applicability of histopathological grading according to the protocol of Elston/Ellis and the Nottingham Prognostic Index (NPI) to a defined breast cancer population. The NPI is the sum of the individual scores concerning grade, tumour size, and lymph node status, each weighted according to regression coefficients of a Cox proportional hazard analysis and calculated for each individual breast cancer patient. 630 consecutive patients with invasive breast cancer diagnosed 1988–91 were retrospectively followed up and their tumours reviewed and graded. A Cox proportional hazard analysis was performed. Grade, lymph node status, and tumour size were statistically significant predictors of survival within the follow up period (median 7.2 years). Similar to NPI, a temporary index (Kalmar Prognostic Index, KPI) was derived and normalised to NPI for comparison (KPI(norm)). NPI and KPI(norm) gave similar prognostic power in spite of the differences of the patient populations from which the 2 indices were derived. Patients with NPI 4 or less had 0.66% breast cancer specific mortality during the follow up time. 14% of the patients with NPI 4.1–5 and 32% of those with an index sum 5.1–6 died from breast cancer during this time. Younger patients tended to have higher grade tumours. We advocate the common use of grade and the NPI in order to increase the comparability of groups of patients receiving different therapies.

  • 5.
    Sundquist, Marie
    et al.
    Department of Surgery, County Hospital, Kalmar, Sweden.
    Thorstenson, Sten
    Department of Cytology and Pathology, County Hospital, Kalmar, Sweden.
    Brudin, Lars
    Department of Physiology, County Hospital, Kalmar, Sweden.
    Stål, Olle
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Nordenskjöld, Bo
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    A comparison between flow cytometric assessment of S-phase fraction and Nottingham histologic grade as prognostic instruments in breast cancer2000In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 63, no 1, p. 11-15Article in journal (Refereed)
    Abstract [en]

    Flow cytometric DNA analysis with assessment of S-phase fraction and DNA ploidy was compared to Nottingham histologic grade. The study population consisted of 654 patients who presented between 1987 and 1996 with primary operable breast cancer and whose tumours had been analysed for S-phase fraction and DNA ploidy at the time of surgery. Grade, tumour size, node status, steroid receptor status, age, S-phase fraction and DNA ploidy were analysed univariately and multi-variately in a Cox proportional hazard analysis. In the univariate analyses all parameters were statistically significantly associated with breast cancer mortality during the follow-up period of 2–11 years. The most powerful predictor of death from breast cancer in the multiple regression analysis was grade. Patients with grade 1 tumours have excellent prognosis. We conclude that tumour grade is a strong prognostic indicator applicable to all breast cancer patients, regardless of size and nodal status, and advocate its general use.

  • 6.
    Sundquist, Marie
    et al.
    Department of Surgery, County Hospital, Kalmar, Sweden.
    Thorstenson, Sten
    Department of Cytology and Pathology, County Hospital, Kalmar, Sweden.
    Brudin, Lars
    Department of Cytology and Pathology, County Hospital, Kalmar, Sweden.
    Wingren, Sten
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Nordenskjöld, Bo
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Incidence and prognosis in early onset breast cancer2002In: Breast, ISSN 0960-9776, E-ISSN 1532-3080, Vol. 11, no 1, p. 30-35Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to assess the incidence and prognosis in early onset breast cancer. Age-adjusted incidence and death rate for the 5394 Swedish women diagnosed with breast cancer under the age of 40 between 1960 and 1996 was studied using data from the Swedish Cancer Registry and Swedish Death Cause Registry. A total of 107 consecutive young patients with invasive breast cancer undergoing surgery during 1980–1993 in the Southeast Swedish health care region were retrospectively followed up and their cancers reviewed and graded blindly. The median follow-up time was 11.2 years. The applicability of the Nottingham Prognostic Index (NPI) as a prognostic tool was investigated. Grade, age, node status, tumour size, S-phase fraction and steroid receptor content were related to survival univariately and multivariately in a Cox proportional hazard analysis.

    The incidence of early onset breast cancer has increased moderately and the survival rate has not improved during the last 35 years. When young women are diagnosed with breast cancer their tumours are larger, their lymph nodes more often involved, and the median grade higher than in older with 64% having grade 3 tumours. Lymph node status was the strongest sole prognostic indicator but the use of NPI gave more accurate prognostic information than node status alone.

  • 7.
    Sundquist, Marie
    et al.
    Department of Surgery, County Hospital, Kalmar, Sweden.
    Thorstenson, Sten
    Department of Cytology and Pathology, County Hospital, Kalmar, Sweden.
    Klintenberg, Claes
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Brudin, Lars
    Department of Physiology, County Hospital, Kalmar, Sweden.
    Nordenskjöld, Bo
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Indicators of loco-regional recurrence in breast cancer2000In: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 26, no 4, p. 357-362Article in journal (Refereed)
    Abstract [en]

    Aim: The aim of the investigation was to contribute to the identification of patients who have increased or decreased risk of loco-regional recurrence.

    Methods: Six hundred and twenty-nine consecutive patients with primary breast cancer diagnosed between 1988 and 1990 were studied. Two-thirds of the patients underwent mastectomy. Radiotherapy was administered if patients were node positive or breast conserved. The Nottingham histological grading protocol was used and presence of lymphovascular invasion was assessed. Investigated parameters were: age, size, grade, steroid receptor content, surgical radicality, vascular invasion and nodal status. Statistically significant risk factors for loco-regional recurrence using univariate or Cox proportional hazard analysis were grade and lymphovascular invasion.

    Results: Women with grade 1-2, node-negative tumours without vascular invasion had a very low loco-regional recurrence rate - 3.1%. Seventeen percent of patients with grade 3 tumours and vessel invasion had loco-regional recurrence.

    Conclusions: Our findings, and those of others, indicate that the use of adjuvant radiotherapy should be influenced to a greater extent by grade and lymphovascular invasion.

1 - 7 of 7
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