Pre-surgery radiation cuts risk of secondary tumours in breast cancer

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BreastCancerNeoadjuvant radiation therapy may significantly improve disease-free survival, especially for oestrogen receptor-positive patients with early-stage breast cancer.

Women patients who have neoadjuvant radiation therapy have a significantly lower risk of developing a second primary tumour at any site, found a first of its kind study comparing the long-term benefits of radiation therapy in women with breast cancer either before surgery (neoadjuvant) or after surgery (adjuvant).

The majority of patients who have early stage breast cancer have surgery to remove their tumor or a complete mastectomy. Surgery is commonly followed by radiation therapy, which has been shown to increase relapse-free survival. However, in some cases, patients may require neoadjuvant radiation therapy to decrease the size of the tumor before surgery. Currently, there are no studies that have analysed the long-term effects of neoadjuvant radiation therapy on breast cancer patients.

Moffitt Cancer Centre researchers  compared the overall survival and the time to diagnosis of a second tumor, if any, of 250,195 breast cancer patients who received either neoadjuvant or adjuvant radiation therapy. They analysed patient outcomes from a National Cancer Institute (NCI) registry database of cancer incidence and survival rates in the US. They included female patients in the analysis who were diagnosed between 1973 and 2011 with early-stage breast cancer. The analysis included 2,554 women who received localised neoadjuvant breast radiation therapy before surgery and 247,641 women who received localised adjuvant breast radiation therapy after surgery.

The researchers discovered that among the breast cancer patients who tested positive for the oestrogen receptor (ER) biomarker, patients who had neoadjuvant radiation therapy had a significantly lower risk of developing a second primary tumour than patients who had adjuvant radiation therapy. This was true for patients who underwent both partial and complete mastectomies. The researchers found that delaying surgery due to neoadjuvant radiation therapy was not a detriment to survival.

A number of recent studies have suggested that radiation therapy may re-educate and stimulate the immune system to target cancer cells. “The observed benefit of neoadjuvant radiation therapy aligns with the growing body of literature of the immune activation effects of radiation, including shrinking of untreated metastases outside the radiation field,” explained Dr Heiko Enderling, associate member of Moffitt’s integrated mathematical oncology department.

These data are promising, but randomized clinical trials are needed to confirm the benefit of neoadjuvant radiation therapy. “Historic data indicate that disease-free survival is significantly increased when radiation therapy is applied before surgery rather than after surgery, especially for ER-positive patients. These findings are worthy of a prospective clinical trial to confirm potential benefits of neoadjuvant vs adjuvant radiation, and to identify the potential contribution of radiation-induced immunity to vaccinate against future disease,” said Enderling.

Abstract
Background: Compared with surgery alone, postoperative adjuvant radiotherapy (RT) improves relapse-free survival of patients with early-stage breast cancer. We evaluated the long-term overall and disease-free survival rates of neoadjuvant (presurgical) versus adjuvant RT in early-stage breast cancer patients.
Methods: We used the Surveillance, Epidemiology, and End Results (SEER) database provided by the National Institutes of Health to derive an analytic dataset of 250,195 female patients with early-stage breast cancer who received RT before (n = 2554; 1.02%) or after (n = 247,641; 98.98%) surgery. Disease-free survival, defined as time to diagnosis of a second primary tumor at any location, was calculated from automated patient identification matching of all SEER records.
Results: Partial and complete mastectomies were performed in 94.4% and 5.6% of patients, respectively. In the largest cohort of estrogen receptor-positive women who underwent partial mastectomy, the HR of developing a second primary tumor after neoadjuvant compared with adjuvant RT was 0.64 (95% CI 0.55–0.75; P < 0.0001). Overall survival was independent of radiation sequence (HR 1; P = 0.95). Neoadjuvant RT also resulted in a lower HR for second primary cancer among estrogen receptor-positive patients who underwent mastectomy compared with those who received adjuvant RT (HR 0.48, 95% CI 0.26–0.87; P = 0.0162).
Conclusions: Neoadjuvant RT may significantly improve disease-free survival without reducing overall survival, especially for estrogen receptor-positive patients with early-stage breast cancer. This finding warrants further exploration of potential long-term benefits of neoadjuvant radiotherapy for early-stage breast cancer in a controlled, prospective clinical trial setting, with correlative studies done to identify potential mechanisms of superiority.

Authors
Jan Poleszczuk, Kimberly Luddy, Lu Chen, Jae K Lee, Louis B Harrison, Brian J Czerniecki, Hatem Soliman, Heiko Enderling

H Lee Moffat Cancer Centre and Research material
Breast Cancer Research abstract


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