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SAN ANTONIO -- Postmastectomy chest-wall irradiation (CWI) for intermediate-risk breast cancer had no impact on long-term survival, results of a large British study showed.

After a median follow-up of 9.6 years, irradiated patients had a 10-year overall survival (OS) of 81.4% versus 82% for those who had no CWI. CWI led to a "clinically insignificant" reduction in chest-wall recurrence from 2.5% to 1.1%, representing a total of 29 recurrences among more than 1,600 women.

The results indicate that most women with intermediate-risk breast cancer can safely avoid CWI following mastectomy, said Ian Kunkler, MB BChir, of the University of Edinburgh in Scotland, at the San Antonio Breast Cancer Symposium (SABCS).

"Chest-wall irradiation did not improve 10-year overall survival, and it results in a clinically insignificant reduction in chest-wall recurrence of less than 2%," Kunkler said during a press briefing. "It has no impact on disease-free or metastasis-free survival [DFS/MFS], and we believe these findings are consistent with incremental changes and improvements in multidisciplinary care [for breast cancer] over the period of the trial."

"Adjuvant, chest-wall irradiation should be omitted in most patients meeting the eligibility of the trial," he stated.

Door Not Closed -- Yet

Kunkler left the door open for use of CWI in selected patients, after press briefing moderator Virginia Kaklamani, MD, of UT Health San Antonio Mays Cancer Center, asked, "Come Monday morning, would you change practice based on these results?"

"There is, firstly, a caveat in that there is a preplanned subgroup analysis by age and by nodal status and by molecular subtype," said Kunkler. "If we found patients with any tumor which had a survival of less than 80%, then I think we would be concerned about [omission of CWI] -- particularly, for example, in the triple-negative patients. We have to wait for the preplanned subgroup analysis."

"But overall, with the exception of those tumors or maybe those patients who are very young, I think we should be avoiding chest-wall irradiation," he added.

Recommendations might also be influenced by the ongoing study evaluating radiation therapy in patients with estrogen receptor (ER)-positive, HER2-negative breast cancer and one to three positive lymph nodes, said Kaklamani. Additionally, the trial includes patients who undergo lumpectomy or mastectomy.

"I think what we need to do is really drill down more on these individual subsets," she continued. "I have the same concern about patients with triple-negative breast cancer. More and more patients with triple-negative or HER2-positive disease will be receiving preoperative systemic therapy. In the end, I think this question largely applies to patients with ER-positive disease. Then the importance of biomarkers, I think, will be the next step to really help us understand what to do."

Kunkler fielded numerous questions from the audience following his presentation during a general session at SABCS. Perhaps most thought-provoking, Youssef Zeidan, MD, of Baptist Health in Delray Beach, Florida, asked about the clinical practice implications of SUPREMO in light of recent trials evaluating omission of axillary lymph node dissection, including the COMET trial reported at SABCS.

"Clearly, the practice of axillary management has changed," said Kunkler. "In the context of this trial, all of the patients had an axillary-node dissection, but there's obviously data from the AMAROS trial that in patients with one to two positive nodes, radiotherapy may provide an alternative [to dissection]. I think it is possible that with targeted radiotherapy ... that it's possible that for some of these patients, they might eventually receive axillary irradiation with no chest-wall irradiation. I think the jury probably is still out on patients who have three positive nodes."

"We have to be careful about generalizing the results of this trial to practice, but I suspect that's going to be the direction of travel," Kunkler added.

Session moderator Michael Gnant, MD, of the University of Vienna in Austria, ended the discussion because of time considerations but noted a queue of more than 20 questions submitted online by virtual participants.

History, Key Results

CWI has attracted growing attention since trials from and , published more than 25 years ago, showed significant reductions in recurrence and improved survival with postmastectomy radiation therapy. Postmastectomy radiation became standard of care on the basis of those trials.

However, recurrence rates in the earlier trials were substantially higher as compared with contemporary cohorts, said Kunkler. Moreover, the chemotherapy regimens used at the time were likely suboptimal as compared with modern systemic therapy. Against that historical background, investigators designed the SUPREMO trial to determine the value of postmastectomy CWI in the setting of modern clinical management.

Eligible patients had pT1-2N1M0 or pT3N0M0 disease or pT2N0M0 disease if grade 3 or associated with lymphovascular invasion (LVI). All patients underwent simple mastectomy and axillary staging surgery. Patients with one to three positive nodes had a minimum of eight nodes removed. Eligible patients met fitness criteria for adjuvant chemotherapy and adjuvant endocrine therapy (if indicated), and postoperative irradiation.

Beginning in 2006, SUPREMO investigators randomized 1,679 patients to postmastectomy CWI or none. CWI consisted of a total dose of 40-50 Gy in 15-25 fractions. The primary endpoint was 10-year OS. Secondary endpoints included local and regional recurrence, DFS, and MFS.

The patient population had a median age of 55 years, 92% had stage II or III disease, 25% had node-negative disease, 21% had HER2-positive disease, 11% had triple-negative breast cancer, and 38.5% had LVI.

The primary analysis yielded a hazard ratio (HR) of 1.04 for CWI versus none (95% CI 0.81-1.30). Analysis of OS by nodal status showed no significant impact of CWI in patients with N0 disease (HR 1.21) or those with node-positive disease (HR 0.97).

Patients with CWI did have a lower incidence of chest-wall recurrence (1.1% vs 2.5%, P=0.04). Though statistically significant, the difference was not clinically meaningful, said Kunkler. The overall difference was driven by patients with node-positive disease (HR 0.30, P=0.01). Regional recurrence also favored CWI (2.7% vs 4.5%) but the difference did not achieve statistical significance (P=0.06).

Analyses of MFS and DFS also showed no significant impact of CWI (HR 1.06, HR 0.97, respectively).

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