Predicting Prognosis and Tamoxifen Response in Breast Cancer. With a special focus on contralateral breast cancer.

Research output: ThesisDoctoral Thesis (compilation)

Standard

Predicting Prognosis and Tamoxifen Response in Breast Cancer. With a special focus on contralateral breast cancer. / Alkner, Sara.

Department of Oncology, Clinical Sciences, Lund University, 2012. 105 p.

Research output: ThesisDoctoral Thesis (compilation)

Harvard

APA

Alkner, S. (2012). Predicting Prognosis and Tamoxifen Response in Breast Cancer. With a special focus on contralateral breast cancer. Department of Oncology, Clinical Sciences, Lund University.

CBE

Alkner S. 2012. Predicting Prognosis and Tamoxifen Response in Breast Cancer. With a special focus on contralateral breast cancer. Department of Oncology, Clinical Sciences, Lund University. 105 p.

MLA

Alkner, Sara Predicting Prognosis and Tamoxifen Response in Breast Cancer. With a special focus on contralateral breast cancer. Department of Oncology, Clinical Sciences, Lund University. 2012.

Vancouver

Alkner S. Predicting Prognosis and Tamoxifen Response in Breast Cancer. With a special focus on contralateral breast cancer.. Department of Oncology, Clinical Sciences, Lund University, 2012. 105 p. (Lund University Faculty of Medicine Doctoral Dissertation Series ).

Author

Alkner, Sara. / Predicting Prognosis and Tamoxifen Response in Breast Cancer. With a special focus on contralateral breast cancer.. Department of Oncology, Clinical Sciences, Lund University, 2012. 105 p.

RIS

TY - THES

T1 - Predicting Prognosis and Tamoxifen Response in Breast Cancer. With a special focus on contralateral breast cancer.

AU - Alkner, Sara

N1 - Defence details Date: 2012-09-28 Time: 09:00 Place: The Alwall Lecture Hall, Barngatan 2, Lund External reviewer(s) Name: Lönning, Per Eystein Title: Professor Affiliation: Section for Oncology, Institute of Medicine, University of Bergen, Norway ---

PY - 2012

Y1 - 2012

N2 - 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.

AB - 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.

KW - Breast cancer

KW - prognosis

KW - treatment prediction

KW - endocrine treatment

KW - tamoxifen

KW - coactivator

KW - AIB1

KW - PAX2

KW - SRC

KW - contralateral breast cancer

KW - premenopausal

KW - randomized trial

KW - mode of detection

KW - mammography.

M3 - Doctoral Thesis (compilation)

SN - 978-91-87189-15-9

T3 - Lund University Faculty of Medicine Doctoral Dissertation Series

PB - Department of Oncology, Clinical Sciences, Lund University

ER -