The background of this study is that in randomised clinical trials we found that breast conserving therapy, which is breast conserving surgery combined with radiotherapy or radiation therapy, and mastectomy had the same survival. Therefore in the guidelines in the Netherlands it is stated that patients with early stage breast cancer, which means breast cancer smaller than 5cm with or without limited lymph node invasion, have indication for either breast conserving therapy or mastectomy. Recent observational studies imply that there was better survival in patients with breast conserving therapy. These observational studies were limited to five years of follow-up and we all know that survival is quite long in breast cancer patients, five years is quite short. So therefore our research question was can we find differences in overall survival in distant metastasis free survival in patients who were treated with breast conserving therapy or with mastectomy in early stage breast cancer.
We conducted this study on observational data from the Netherlands Cancer Registry which is a cancer registry covering all of the Netherlands. We have 17 million inhabitants and our data managers are in all 90 hospitals gathering the data on tumour, patient and treatment.
We selected all women with early stage breast cancer diagnosed between 2000 and 2004. For the first cohort we had the research question on the ten year overall survival and we had more than 37,000 patients included. For the second outcome, which was distant metastasis free survival, we had data from the cohort of 2003. For that the data managers went back to the hospital and looked in their patient file whether there was diagnosis of distant metastasis during follow-up. These were more than 7,500 patients. We performed a Cox regression analysis and we stratified for tumour stage and TNn stage.
The results first of the overall survival was that more than 58% of the patients received breast conserving therapy. These patients were more younger and had more favourable tumour characteristics than the patients in the group who had mastectomy. When we looked at overall survival the left graph is the survival of the different subgroups of tumour stage and we see that if the tumour is larger than 2cm, which is the two dotted lines below, survival is worse. On the left you see the figure of the survival of the whole group and you see that the breast conserving therapy group has better survival than the patients who are treated with mastectomy.
These results were comparable in the different staging subgroups, so T and N0, so tumours that were smaller than 2cm without lymph node invasions, and the other subgroups had the same results – breast conserving therapy is better than having a mastectomy.
When we conducted the Cox regression analysis we could adjust for confounding factors like the difference in age and the difference in hormonal therapy and other differences between the two groups. We saw that there was a hazard ratio of 0.81 which means that the breast conserving therapy had better survival. In the subgroups we saw actually the same results.
Looking at the distant metastasis free survival in the sub-cohort of 2003 we saw that 61% had breast conserving therapy in which 11% developed a distant metastasis in the meantime of ten years of follow-up. 38% had mastectomy and they developed in about 15% distant metastasis. The distribution of the characteristics were almost the same as in the total cohort so we can distribute or extrapolate the findings to the total cohort.
What we saw is actually the same, that in the larger tumours we saw worse survival and we saw better survival in patients who were treated with breast conserving therapy, which is the left figure and the dotted upper line. If we looked into the subgroups we found this result mainly in the T1N0 subgroup, so patients who did not have any lymph node invasion or lymph node involvement and had smaller tumours, smaller than 2cm. We could not find this in the other, larger tumour groups. So corrected for confounding we found that there was a better survival in patients who had breast conserving therapy which was mainly due to the fact that the whole group was dominated by the very small tumour groups.
The limitation of this observational study, of course observational study can be limited by confounding by indication, we corrected this for as much information as we had on age or other adjuvant therapy. Still there could be some residual confounding. We did not have any information on, for instance, comorbidity and we did not have information on the HER2 status because that was not determined at that time so no patient had received trastuzumab, for instance.
To come to my conclusion, the overall survival for breast conserving therapy compared to mastectomy is better in every T and N stage, so in all tumour sizes. The distant metastasis free survival is mainly better in the patients who have tumours smaller than 2cm without lymph node involvement. The main take home message: breast conserving therapy should be the treatment of choice, especially in smaller tumours, when it’s medically feasible and according to the patient’s wish.