Three Critical Decisions in Breast Cancer Radiotherapy

Roxanne Nelson, BSN, RN

Disclosures

January 22, 2016

Three Critical Decisions

Do All Patients Receiving Breast-Conserving Surgery Need Radiation Therapy?

"We know that radiation reduces first recurrence and mortality, but the absolute benefit is small in some subgroups," he said. "It is now time, or past time, to find ways in which we can safely omit radiation in some patients."

The proof of principle comes from the CALGB 9343 trial, which demonstrated that the omission of radiation therapy after breast-conserving surgery was reasonable in patients who had favorable ER-positive breast cancer, were aged 70 years or older, and were treated with tamoxifen.[8]

"In this trial the distant metastasis rate was 5%, so it's very likely that these patients were all luminal A patients, and some have wondered whether these results are generalizable to all older patients with less favorable breast cancer," he said.

There may be other patient populations that can be spared from radiation therapy, but for right now, the focus is on this particular subset. "Multiple groups, including our own, are looking at older patients with small ER+/ HER2- luminal A cancers," he said.

 
We will be comfortable omitting radiation in a significant portion of patients.
 

In one study conducted in women aged 50-75 years who were T1, N0, ER+/PR+/HER 2-, with grade 1 or 2 tumors, the local recurrence at 5 years was less than 1% and any first recurrence was less than 2%. [Personal communication; Lior Zvi Braunstein; June 6, 2015]

Dr Harris noted that a trial will soon be opening at Dana-Farber that will offer hormone therapy alone to women age 50-75 with small, low-grade, node-negative luminal A breast cancers. "They will be offered and encouraged to choose the option of hormonal therapy alone," he said. "I think that we will be comfortable omitting radiation in a significant portion of patients."

Which Patients Can Be Treated With Hypofractionation?

Hypofractionation has many benefits for the patient. It reduces treatment time from 6 weeks to between 3 and 4 weeks, making it more convenient and more cost-effective than standard radiotherapy regimen. But it is also related to major improvements in the delivery of radiation therapy, such as greater 3-D dose homogeneity and more refined radiobiologic estimates of dose equivalence.

The two Standardisation of Breast Radiotherapy (START-A and START-B) trials [9] provide justification for increased use of hypofractionation. "The results are statistically better with hypofractionation than with conventional fractionation, and although not statistically significant, the rate of local tumor relapse was also better," said Dr Harris.

Hypofractionation resulted in fewer distant metastases, fewer common effects to normal tissue (breast shrinkage, telangiectasia, and breast edema), and improved overall survival (HR 1.00 vs 0.80; P = .04).

However, Dr Harris cautioned that it's not clear whether "these results are real or spurious," and a team in the United Kingdom is working on a model to determine whether these results are related to declines in local recurrence. More important, the same model was replicated in Denmark, so those results should become available in a few years.

"If this survival difference had gone the other way, I'm sure it would have killed hypofractionation for radiation oncologists, but instead, it provides more comfort," Dr Harris said.

In 2011, the American Society for Radiation Oncology amended their guidelines regarding hypofractionation for certain patients.[10] Dr Harris explained that at his institution, the use of hypofractionation has been greatly expanded on the basis of START-B results. "We restrict it to patients getting tangents only because we still have concerns about nodal radiation with these larger fraction sizes and the possible effects on the brachial plexus," he said. "We have also used it with patients who are getting chemotherapy and haven't seen any deleterious effects." But he concluded that the evidence is strong for the use of hypofractionation.

Who Should Get Nodal Radiation Therapy?

"This is a controversial issue, and I don't think there is a clear consensus among experts," Dr. Harris emphasized. "What it boils down to is: How does one reconcile the results from the MA20 trial, which showed a benefit, and the Z11 trials, which did not use nodal radiation?"

The American College of Surgery Oncology Group Z0011 trial (ACOSOG Z11)[11] was a prospective, randomized trial of axillary node dissection (ALND) vs sentinel lymph node dissection (SLND) and no further axillary surgery in women undergoing breast-conserving surgery and whole-breast radiation who were found to have three or fewer positive sentinel nodes. Nearly all patients also had received adjuvant systemic therapy of choice (97%). The standard tangents treat a substantial portion of level I/II of the axilla, but the superior border of the tangents was raised (high tangents) to treat even more axilla, explained Dr Harris.

The 5-year survival results were similar between the two study arms (92% for the ALND vs 95% for SLND alone), as were the results for disease-free survival (82% vs 84%).

Almost half (46%) of the positive sentinel nodes were micrometastases, and importantly, only 27.4% of patients who underwent axillary node dissection had additional positive nodes removed beyond the sentinel node, he explained. "And that's a low percentage compared with unselected patients. These were a highly selected group, and surgeons were very careful to enter only low-risk patients."

The MA20[4] and EORTC[12] trials addressed the value of ipsilateral internal mammary/supraclavicular and axillary lymph node radiation therapy in women who received axillary node dissection. These patients all had macrometastases and showed a small improvement (5%) in disease-free survival at 10 years.

"But as radiation oncologists, we have to recognize that radiation has its complications," he said. "In MA20, grade 2-3 lymphedema increased from 4.5% to 8.4%. It increased the dose to the lung and heart, and there will likely be more second cancers." The issue is whether nodal radiation is optimal for a patient with one to two positive sentinel nodes. "If the patient looks like a Z11, then no," he said.

Jay R. Harris, MD, has disclosed no relevant financial relationships.

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