RT After Breast-Conserving Surgery Shows No Survival Advantage Decades Later

Radiotherapy after breast-conserving surgery for early breast cancer substantially reduced the risk of disease recurrence, yet the benefit did not translate to an improvement in overall survival (OS) at 30 years, a long-term analysis of the Scottish breast conservation trial showed.

Compared with no radiotherapy, adjuvant locoregional radiotherapy reduced the risk of ipsilateral breast tumor recurrence (IBTR) by 61% (HR 0.39, 95% CI 0.27-0.55, P<0.0001), reported Ian Kunkler, FRCR, of the University of Edinburgh.

“But, what we observed is a differential effect over time,” Kunkler said during a press briefing at the European Breast Cancer Conference. “Most of the reduction in the risk of local recurrence occurs in the first decade. In the second decade, there is no significant difference in the risk of recurrence with or without irradiation.”

At 10 years, local recurrence rates were 8.8% with radiotherapy versus 31% with no radiotherapy; at 20 years, rates were 15.2% and 37.6%, and at 30 years, rates were 27.8% and 42.7%.

Notably, there was no significant difference in OS between patients who received radiotherapy and those who did not (HR 1.08, 95% CI 0.89-1.30, P=0.43). OS rates were 72.5% and 70.8%, respectively, at 10 years; 48.6% and 48.4% at 20 years; and 23.7% and 27.5% at 30 years.

“This is an important study that corroborates previous information that shows that radiation therapy after breast-conserving surgery does not improve survival,” said Stephen Edge, MD, of Roswell Park Comprehensive Cancer Center in Buffalo, New York, who was not involved with the study. “And that’s not the intent of radiation therapy — the intent is to reduce the risk of local recurrence, and it remains a very important component of breast-conserving therapy.”

Edge noted that the NSABP B-06 trial, which was initiated in 1976 and was the first to compare total mastectomy, lumpectomy, and lumpectomy plus irradiation in women with invasive breast cancer, “clearly showed with a 20-year follow up that the addition of radiation therapy to lumpectomy does not improve survival, but that it does have a major impact on the chance of having the cancer recur in the breast.”

In NSABP B-06, the major impact of radiation therapy on local recurrence was seen in the first 10 years, Edge told MedPage Today. “That’s actually almost exactly what the Scottish group showed — that there was a dramatic reduction [in local recurrence] in the first 10 years, and that it rose at about the same rate in both groups over the ensuing 20 years.”

“The difference here is that these women also received stage- and biomarker-appropriate systemic therapy, whereas in NSABP a majority of women did not get it because the studies showing that systemic therapy was effective weren’t completed until the late 1980s, 13 years after the study started,” he continued.

In explaining the rationale behind this study, Kunkler pointed out that while breast-conserving surgery, systemic therapy, and postoperative radiotherapy remain the gold standard for most patients with early breast cancer, with trials confirming that radiotherapy reduces local recurrence, “we have relatively little information on clinical outcomes beyond 10 years of follow-up.”

“I think [this analysis] emphasizes the importance of funding long-term follow-up of adjuvant radiotherapy to assess the benefits and risks of treatment over time, where differential effects may occur,” Kunkler said.

In a press release, Kunkler suggested that the lack of long-term improvement in OS among patients undergoing radiotherapy “may be because, although radiotherapy may help to prevent some breast cancer deaths, it may also cause a few more deaths, particularly a long time after the radiotherapy, from other causes, such as heart and blood vessel diseases.”

“It’s important to note that every woman with breast cancer is different and will have different forms of the disease,” he added. “Decisions about whether or not to have radiotherapy after surgery should be taken by patients and their doctors after careful discussion, taking into account the individual characteristics of their breast cancer and the likely risks of recurrence over the long term, both within and outside the breast, and of treatment-related toxicity.”

The Scottish breast conservation trial enrolled 585 patients ages 70 and younger with primary breast tumors of ≤4 cm in size from 1985 to 1991. After local excision of the tumor (with a safety margin of 1 cm) and an axillary lymph node clearance or sample, all patients received systemic therapy with oral tamoxifen 20 mg daily or six 3-weekly intravenous bolus injections of cyclophosphamide 600 mg, methotrexate 50 mg, and fluorouracil 600 mg/m2, depending on estrogen receptor (ER) status.

Patients were stratified by menopausal and ER status (≥20,<20, unknown) and randomized to either adjuvant radiotherapy (50 Gy to breast with boost to the tumor bed) or to no further local treatment.

In the initial analysis of the trial at 6 years, the IBTR rate was 5.8% in the radiotherapy arm and 24.5% in the no-radiotherapy arm, with no difference in OS.

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    Mike Bassett is a staff writer focusing on oncology and hematology. He is based in Massachusetts.

Disclosures

Kunkler reported no disclosures.