Can we predict response to hypofractionated radiotherapy?

The authors aimed to identify predictors of response to hypofractionated radiation therapy in early-stage breast cancer.

Tumor biomarkers are indicators of the state or condition of a tumor, and can predict the response of a tumor to certain treatments. While biomarkers of tumor response to hormonal therapy and chemotherapy have been well defined, those indicating response to radiotherapy are less well studied.

Hypofractionated radiotherapy (HR) is a therapy in which the total dose of radiation is divided into large doses and administered over a shorter period of time (fewer days or weeks) than standard radiation therapy. This can take place after breast-conserving surgery (removes the breast cancer but not the breast itself). It is unclear if biomarkers such as tumor grade (how abnormal the cells look under a microscope), cancer subtype (based on the presence or absence of the female sex hormone estrogen or progesterone receptors, or the HER2 protein receptor) or the presence of oxygen deficiency can indicate response to HR.

The authors evaluated tissue samples from 989 breast cancer patients who were lymph-node negative (did not have cancer in the lymph nodes) and who underwent hypofractionated radiotherapy following breast-conserving surgery. Cancer subtypes were defined as luminal A (estrogen and/or progesterone receptor positive, HER2 negative), luminal B (estrogen and/or progestrogen positive, HER2 positive), HER2-enriched (estrogen and progesterone negative, HER2 positive) or triple-negative (estrogen and progesterone receptor and HER2 negative). The average follow-up was 12 years.

10-year survival without local recurrence (return of the disease near the original site of the cancer) occurred in 93.9% of patients. 10-year survival without disease occurred in 76.6% of patients. 10-year overall survival occurred in 84.2% of patients.

Tumor grade, cancer subtype and hypoxia did not predict response to HR.

Cancer subtype was determined to be the only factor that predicted local recurrence. The 10-year incidence of local recurrence was 4.5% for luminal A and basal-like, 9% for luminal B and 16.9% for HER2-enriched tumors.

The authors concluded that cancer subtype is an independent predictor of local cancer return in early stage breast cancers treated with breast-conserving therapy and HR, and that all subtypes of breast cancer may safely be treated with HR.

Patients were treated before the availability of trastuzumab (Herceptin) which has been shown to reduce the incidence of both local and distant cancer recurrence in HER2 positive breast cancer.