Breast shrinkage can be a devastating toxicity for large-breasted women who undergo breast conservation surgery and radiation therapy. However, surgery rather than radiation therapy appears to be the cause, according to a study published online February 23 in the International Journal of Radiation Oncology, Biology, Physics.
The finding was surprising to the researchers from Cambridge University Hospitals and Addenbrooke's Hospital. The primary objective of the randomized Cambridge Breast Intensity-Modulated Radiotherapy (IMRT) trial was to determine if IMRT could reduce late toxicity compared to conventional 2D radiotherapy, especially if the latter's breast treatment plans produced substantial dose inhomogeneities.
The group hoped to determine whether correcting such dose inhomogeneities could decrease late normal tissue toxicity in patients with early-stage breast cancer.
A total of 1,145 women of all breast sizes who had been diagnosed with invasive breast cancer or ductal carcinoma in situ were enrolled in the clinical trial between April 2003 and June 2007, according to the authors.
Patients with significant dose inhomogeneities, defined by a ≥ 2 cm3 volume that was greater than 107% of the prescribed dose, were randomized to receive either IMRT or standard breast radiation therapy. The IMRT group underwent repeat treatment planning with a manual, forward-planned IMRT technique to reduce the volumes receiving more than 107% and less than 95% of the prescribed dose. Patients with acceptable dose homogeneity were not randomized but received the standard radiotherapy treatment.
All of the patients received a dose of 40 Gy in 15 fractions over a three-week course of treatment. A portion of the patients received nodal radiotherapy treatment and/or a tumor bed boost according to local protocol.
The patients' chests were photographed following surgery prior to radiotherapy treatment, and they were photographed again two years following treatment completion. The research team assessed and scored surgical cosmesis, overall cosmesis, and surgical deficit on a three-point scale. The group also assessed breast shrinkage, breast edema, pigmentation changes, palpable induration (hardening), and telangiectasia (permanent dilation of pre-existing blood vessels).
A total of 130 patients withdrew from the study; 15 had died. Thirty women became ineligible because they developed new or recurring breast cancer.
Ultimately, breast shrinkage at two-year follow-up could be assessed for 852 patients, 71% of whom had been randomized. The researchers found no significant difference in breast shrinkage between patients randomized to IRMT or standard RT, according to co-author Charlotte Coles, PhD, a clinical consultant with the Cambridge Cancer Center of the University of Cambridge, and colleagues.
What the research team did discover was that patients with moderate or poor surgical cosmesis had a nearly five times greater risk of developing breast shrinkage and a nearly three times greater risk of developing breast induration. Surgical cosmesis was adversely affected by a large body mass index. Poor surgical cosmesis was significantly associated with older age, larger breast size and weight, and increased pathological tumor size.
The researchers were unable to determine if induration was caused by radiation therapy or if it was a side effect of surgery.
Coles and colleagues also found that of the women with good baseline surgical cosmesis, those randomized to IMRT were less likely to deteriorate to moderate or poor overall cosmesis. Patients in the IMRT group were also less likely to develop telangiectasia.
So is IMRT a less toxic therapy than conventional radiotherapy? The five-year outcome analysis, the results of which will be reported and published, is needed to address this question, according to the authors.
