Prognostic factors in breast-conserving therapy: a prospective population-based cohort study

A large cohort study on breast cancer was started that included patients treated with breastconserving therapy, from the early start of this treatment in the Twente – Achterhoek region, till today, with more than 3.800 breast-conserving treatments. Recruitment is still continuing. In chapter 2, on family history, we were able to show that a positive family history with regard to first degree relatives does not result in a worse outcome; on the contrary we demonstrated a trend to a better outcome. In chapter 3 we could establish a young age as a risk factor for local control in breast cancer in accordance with the literature. We also looked at the incidence and outcome for patients with bilateral synchronous breast cancer. We demonstrated that bilateral breast cancer has a poor outcome compared with unilateral breast cancer, in particular in relation to distant metastasis (chapter 4). Boost irradiation in breast-conserving therapy has been an important issue since many years. Not only with regard to the question of the necessity of the boost, but also with regard to the accuracy of delivering the boost to the tumour area. The latest has become more interesting after the introduction of the CT-localisation. We published one of the few papers on external boost volume in breast-conserving therapy (chapter 5) from before the era of the CT-localisation. Most studies describe the impact of boost volume in brachytherapy. We showed no relation of the boost volume to local control despite the fact that probably the accuracy of the boost area was questionable. Timing in breast cancer has become an important item due to the extended treatment with surgery, radiotherapy and systemic therapy. Most studies published focus on local control. We demonstrated in chapter 6 no effect on local control with the start of radiotherapy till twelve weeks after surgery. Surprisingly we also found that a longer time interval leads to favourable results with respect to distant metastasis and survival. One of the items what intrigued us was margin status. We published three papers on this item (chapters 7, 8, and 9). The main contribution to the already existing literature was that we could show a statistical interaction between age and margin status. In our first paper in 2003 (chapter 7) we demonstrated that the value of positive margins for invasive carcinoma was limited to young women. Our second paper in 2007 (chapter 8) on a larger cohort and with long-term follow-up did not only confirm the findings in the first paper, but also showed that the effect of a positive margin was not limited to local control only, but also to distant metastasis and survival. We also demonstrated that a positive margin for ductal carcinoma in situ was a risk factor for local control in women over 40-years. In our last paper (chapter 9) on margin status we restricted ourselves to lobular carcinoma, and demonstrated the same effect of positive margins for invasive carcinoma as with ductal carcinoma, only this time the turning point was not 40-years but 50-years. This means that in clinical practice analysis of the importance of margin status should always be done according to age category. This thesis is not the end of all publications concerning breast cancer from this cohort. In the near future we will publish more data on timing, family history in relation to BRCA-1/2, and prognostic factors as the mitotic activity index.