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To predict results of breast cancer therapy

Doktorsavhandling
Författare Anna Nordenskjöld
Datum för examination 2019-03-28
ISBN 978-91-7833-317-2
Förlag Göteborgs universitet
Publiceringsår 2019
Publicerad vid Institutionen för kliniska vetenskaper, Avdelningen för onkologi
Språk en
Länkar hdl.handle.net/2077/58241
Ämnesord breast cancer, endocrine therapy, survival
Ämneskategorier Cancer och onkologi

Sammanfattning

We have used the almost complete national Swedish Cancer register, regional quality management register and one randomized adjuvant endocrine trial to study, the effect of radiotherapy in breast cancer with 1-3 positive nodes (study 1), the effect of tamoxifen in estrogen receptor (ER)-positive tumors depending on expression of the progesterone receptor (PR) (studies 2 and 4) and the development of the survival rates of breast cancer in Sweden 1989-2013 (study 3) Study 1. We compared relative breast cancer survival in two Swedish health care regions that between 1989 and 2006 had different guidelines for postoperative radiotherapy. Patients with 1–3 positive lymph nodes in the western region received radiotherapy of the remaining parts of the breast only, while patients in the south eastern region also received therapy of regional lymph nodes. Other aspects of the guidelines were very similar including those for screening mammography, surgery and adjuvant medical treatment. Results: The 10-year relative survival for patients with 1–3 positive lymph nodes was 78% in the western region and 77% in the southeastern region (p=0.12). Conclusions: There was little or no influence of addition of lymph node radiotherapy on survival in patients with 1–3 positive lymph nodes in a population with screening mammography and modern systemic treatment. Studies 2 and 4 We investigated the independent predictive value of progesterone receptor (PR) determined with immunohistochemistry (IHC) in estrogen receptor (ER) positive tumors from patients participating in the Stockholm trial of adjuvant tamoxifen. Methods We evaluated patients without lymph node metastasis for whom PR in study 2 was determined by IHC in tissue micro arrays (thin cores of tumor tissue). In study 4, PR was scored by gene expression and by IHC of entire tumor sections and separate analyses of patients with luminal A tumors were performed. Conclusions PR positivity determined by IHC or gene expression is a marker indicating long-term benefit from adjuvant tamoxifen. We observed a very marked benefit for patients with PR positive luminal A tumors. Study 3 During the recent decades, breast cancer survival has gradually improved but there is limited knowledge on the improvement in population-based studies of patients diagnosed with different stages of disease and in different age groups. Patients and methods. In two Swedish health care regions a total of 42 220 female breast cancer patients below 90 years of age were diagnosed between 1989 and 2013. Results. Using patients diagnosed 1989-1993 as a reference the relative risk of 5 year mortality decreased with 49% (ci95% 45 – 58) for patients diagnosed in the end of the observation period. Conclusions. Improvements were seen in all age groups but was unevenly distributed between stages and age groups pointing to the need for further improvements for younger and elderly patients. Conclusions in summary: In a population invited to mammography, regional radiotherapy in patients with breast cancer and 1-3 positive nodes seems to result in little or no influence in survival. Expression of PR seems to indicate better long-term effect of tamoxifen in ER-positive tumors. The 5-year mortality in breast cancer has been halved in southeast and western Sweden between 1989-2013.

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