Session Item

To investigate the association between irradiated breast volume and breast induration grade 2-3 at 3 years after radiation therapy (RT) in the phase III randomized Danish Breast Cancer Group (DBCG) HYPO trial (NCT00892814) [1] and the importance of patient age and smoking.

In the international DBCG HYPO trial, patients (pts) >40 years being candidates for whole breast irradiation (WBI) were randomized to either 50Gy in 25 fractions or 40Gy in 15 fractions. For this analysis, pts receiving boost were omitted (incl. all pts <50 years). Thus, the study included the 1,305 Danish pts treated without boost. During the accrual 2009-2014, RT plans for the Danish pts were stored in the Danish national RT data bank and the volume of the breast covered with various dose levels was determined. Irradiated breast volume was defined as the volume with D≥50Gy or D≥40Gy in the 50Gy and 40Gy arm, respectively. Model of breast induration according to breast volume irradiated was developed based on individual pt data using logistic regression and stratified by treatment arm, age groups (50-64 vs 65+), and smoking status (never/prior vs current).

RT plans from 1,297 pts (50Gy: 655; 40Gy: 642) from four Danish RT centers were analyzed, and of these 1,131 pts (50Gy: 560; 40Gy: 571) had an induration score at 3 years. A volume effect for risk of induration has previously been described in the DBCG Partial Breast Irradiation (PBI) trial including pts age ≥60 years and not receiving boost [2]. Due to the variation in age distribution in the two trials, age-stratified models were applied to the 40Gy pts in the HYPO trial and the WBI arm of the PBI trial (Figure 1). Both trials show that the previously described volume effect is restricted to pts ≥65 years, whereas there is no association between irradiated volume and risk of induration in pts aged 50-64 years. In the HYPO trial, models stratified on treatment arm show a similar volume effect in the two arms in pts ≥65 years and a lack of volume effect in pts aged 50-64 years but with a slightly lower risk overall in the 40Gy arm (Figure 2). When stratifying models on smoking, the frequency of induration was a factor of two higher for current smokers than for never/prior smokers independent of the irradiated breast volume and age (Figure 2).

The recently published close correlation between irradiated breast volume and 3-year risk of breast induration from the DBCG PBI trial [2] was validated in the DBCG HYPO trial. However, it was demonstrated in both trials that this correlation was only present in older pts, whilst pts <65 years with large irradiated breast volume have no increased risk of breast induration. In the HYPO trial, similar volume effects were observed with the two fractionation schemes whereas smoking was associated with a doubled risk of induration irrespective of irradiated volume and age.

[1] doi: https://doi.org/10.1200/jco.20.01363
[2] doi: https://doi.org/10.1016/radonc.22.09.024