Breast conserving treatment with radiotherapy reduces risk of local recurrence

Sep. 18, 2013 — Results of EORTC trial 10853 appearing in the Journal of Clinical Oncology show that breast conserving treatment combined with radiotherapy reduces the risk of local recurrence in women with ductal carcinoma in situ (DCIS). The incidence of DCIS has been increasing in the past decades, and this has been attributed to increased detection through breast cancer screening using mammograms. In the EORTC study, adjuvant radiotherapy after local excision reduced the incidence of both in situ and invasive local recurrences by a factor of two and resulted in an overall lower risk of mastectomy.

Following the introduction of radiotherapy combined with breast-conserving surgery for operable invasive breast cancer in the 1980's, several trials were launched to investigate the addition of radiotherapy to local excision of DCIS. These trials showed that radiotherapy reduced both the risk of DCIS and invasive local recurrences. Now the long-term outcomes of local recurrences and survival in women receiving radiotherapy in combination with breast conserving surgery for DCIS have been investigated at a median follow-up of 15.8 years.

Dr. Mila Donker of The Netherlands Cancer Institute, Amsterdam, and lead author of this paper says, "Survival after treatment for DCIS is excellent. Therefore, the question rises whether the current treatment for DCIS (local excision and adjuvant radiotherapy of the breast) is overtreatment. To answer this question, not only long-term data about local disease recurrences and prognosis are important, but also information about the prognosis and treatment in case of recurrence."

Between 1986 and 1996, the phase III EORTC trial 10853 randomized 1010 women with complete local excision of DCIS to no further treatment (503 patients) or radiotherapy (507 patients). The risk of any local recurrence was found to be reduced by 48% (HR: 0.52, 95%CI 0.40-0.68, P<0.001) in the patients who also received radiotherapy. The 15-year local recurrence-free rate was 69% for the group of patients receiving breast conserving surgery alone, but this increased to 82% for the group of patients who also received radiotherapy, and the 15-year invasive local recurrence-free rate was 84% versus 90%, respectively (HR: 0.61, 95%CI 0.42-0.87).

The differences observed in local recurrence did not lead to differences in breast cancer specific survival or overall survival, but patients with invasive local recurrence did have a significantly worse breast cancer specific survival (HR: 17.66, 95%CI 8.86-35.18) as well as overall survival (HR: 5.17, 95%CI 3.09-8.66) than those who did not recur. Thus, an invasive recurrence resulted in a worse prognosis.

A lower overall salvage mastectomy rate after a local recurrence was also observed in the group of patients who also received radiotherapy, 13%, than in those patients who just received breast conserving surgery, 19%. Thus, radiotherapy after breast-conserving surgery for DCIS resulted in an overall lower percentage of patients who were treated with a mastectomy after a local recurrence.

This study highlights the importance of conducting long term follow-up.

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Biomarker predicts long-term risk of breast cancer recurrence

Sep. 11, 2013 — A comparison of three methods of predicting the risk of recurrence in women treated for estrogen-receptor (ER)-positive breast cancer finds that only the breast cancer index (BCI) -- a biomarker based on the expression levels of seven tumor-specific genes -- accurately identifies patients who continue to be at risk after five years of treatment with either tamoxifen or the aromatase inhibitor anastrozole. The study comparing the BCI with two other prognostic tests has been published online in Lancet Oncology.

"We have validated a unique 'fingerprint' in the primary tumor of breast cancer patients that can help identify a high or low risk of cancer recurrence," says study co-author Paul Goss, MD, PhD, director of the Breast Cancer Research Program at Massachusetts General Hospital (MGH) Cancer Center. "This should enable us to offer prolonged treatment to patients who remain at risk and, importantly, to avoid the costs and side effects of treatment in those at low risk."

Standard treatment for early-stage, ER-positive breast cancer includes five years of treatment with either tamoxifen or an aromatase inhibitor, drugs that block the action of estrogen. While that approach is sufficient for most patients, some continue to experience recurrence during subsequent years. The study authors note that knowing whether or not a patient continues to be at risk is essential to determining whether prolonged treatment is necessary.

MGH researchers previously developed, in collaboration with investigators from bioTheranostics, Inc., two biomarkers for recurrence risk assessment -- the molecular grade index, which measures expression levels of five genes related to tumor proliferation; and the H/I ratio, which compares expression levels of two other genes. BCI is a combination of both biomarkers and has been shown to identify patients who are at risk of early recurrence despite receiving hormonal treatment.

The current study, led by Dennis Sgroi, MD, of the MGH Cancer Center and Department of Pathology, was designed to compare the ability of the BCI to predict long-term recurrence risk with that of two other gene-expression signatures that can predict risk in the first five years -- the Oncotype Dx Recurrence Score, the current gold standard for guiding clinical decision making, and the less frequently used ICH4 gene signature. All three methods were used to analyze primary tumor samples from more than 650 participants in a clinical trial comparing tamoxifen with anastrozole. Assay results were compared with patient records to determine individual rates of recurrence up to 10 years after initial surgical treatment.

While all three methods were able to predict recurrence risk in the first five years, only the BCI was able to accurately assess long-term recurrence risk. In fact, the BCI was able to clearly distinguish 60 percent of patients whose risk was quite low from 40 percent who continued to be at significant long-term risk. "We know that more than half the instances of recurrence in ER-positive breast cancer occur after five years of therapy with tamoxifen or anastrozole, so these findings are highly relevant to clinical management," says Sgroi. "Since the BCI identifies two distinct risk groups, it may provide a much-needed tool in determining those patients who need extended hormonal therapy and those who may be spared its well-known adverse side effects."

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