Patient age, DCIS status predict ipsilateral breast tumor recurrence

Younger patients and patients with ductal carcinoma in situ adjacent to their invasive breast tumor had the highest risk for ipsilateral recurrence of early-stage breast cancer after breast-conserving surgery, according to long-term follow-up a randomized trial.

Although women with high-grade invasive tumors experienced frequent relapse during the first 5 years following surgery, relapse rates stabilized over time for this subgroup, results showed.

“The question we asked ourselves with this study was, if you follow-up patients for a longer period of time and you reanalyze the impact of the pathological factors, do you find the same factors or is there a change?” Conny Vrieling, MD, PhD, radiation oncologist at Clinique des Grangettes in Geneva, Switzerland, said in an interview posted on the JAMA Oncology website. “If you find a change, you need to be aware that you need to follow-up patients for a longer period of time, in order to pick up all the relevant factors.”

Researchers of the EORTC conducted the “boost vs. no boost” trial between 1989 and 1996. The analysis included 5,569 women with early-stage breast cancer treated with breast-conserving surgery and 50 Gy whole-breast irradiation who were randomly assigned to receive a 16-Gy boost to the tumor bed or no boost.

Follow-up analysis conducted at 10 years identified younger patient age, as well high-grade invasive carcinoma, as factors associated with ipsilateral breast tumor recurrence.

Vrieling and colleagues reanalyzed data from 1,616 patients (median age, 54 years) with microscopically complete resection samples available. In this cohort, 815 women had received a tumor bed boost and 801 did not.

Median follow-up was 18.2 years.

One hundred sixty recurrence events occurred (boost, n = 61; no boost, n = 99), which corresponded with a 20-year cumulative incidence of ipsilateral breast tumor recurrence of 15% (95% CI, 12-17). Patients assigned no boost had a higher overall cumulative incidence of recurrence (17% vs. 12%; P < .001).

Young age remained a significant predictor for ipsilateral breast tumor recurrence (P < .001).

Patients aged 27 years to 40 years had the highest cumulative incidence of local recurrence (34%; 95% CI, 25-41), followed by women aged 41 years to 50 years (14%; 95% CI, 10-18) and women aged 50 years or older (11%; 95% CI, 8-15).

Further, the researchers identified the presence of ductal carcinoma in situ (DCIS) adjacent to the invasive tumor as a significant predictor of recurrence (HR = 2.15; 95% CI, 1.36-3.38).

The incidence of recurrence was 18% (95% CI, 14-22) in women with adjacent DCIS and 9% (95% CI, 6-12) among women without DCIS (P < .001).

Although high-grade tumors predicted relapse in the earlier analysis, histologic tumor grade did not significantly influence long-term tumor control. Women with high-grade tumors had a 16% (95% CI, 8-23)15-year cumulative incidence of relapse, with the highest incidence seen in women aged 27 to 40 years (34%) compared with women aged 41 to 50 years (19%) and older than 50 years (6%; P = .04).

Receipt of a tumor bed boost conferred a significant reduction in the 20-year cumulative incidence of recurrence. Among women aged younger than 50 years, incidence of relapse decreased from 24% among women who did not receive a boost to 15% among women who did (HR = 0.51; 95% CI, 0.33-0.77).

Among women with additional DCIS, additional tumor boost reduced the relapse incidence from 22% to 14% (HR = 0.47; 95% CI, 0.31-0.69). Tumor boost also significantly reduced risk for relapse among women who both were younger and had additional DCIS (HR = 0.37; 95% CI, 0.22-0.62).

Further, receipt of a tumor boost reduced the 15-year cumulative incidence among the subgroup of women with high-grade disease (31% vs. 5%; HR = 0.23; 95% CI, 0.07-0.7).

The researchers acknowledged study limitations, including the use of samples from less than one-third of the trial’s population in this analysis.

Further, the risk for ipsilateral breast tumor recurrence has fallen considerably in recent years, suggesting that risk reductions caused by tumor bed boosts may be small.

The researchers also noted that because the initial trial lacked a comparative arm without radiotherapy, they were unable to study the effects of forgoing radiation in favorable subgroups.

“These findings help to personalize follow-up and to realize which patients are at risk for local recurrence at a specific time,” Vrieling said. “Young patients have a high risk for local recurrence, so we need to maximize treatment with good follow-up. Patients with high-grade invasive tumors have higher risk for local recurrence in the first 5 years, whereas patients with DCIS ... have an ongoing risk for local recurrence. The combination of these factors lead to a very high local recurrence rate. The good news is that the boosts we can add significantly decrease the risk in these patients, so these patients specifically need that boost.”

Certain aspects of the initial boost vs. no boost trial may appear antiquated compared with current breast cancer treatment practices, Laurie W. Cuttino, MD, associate professor of radiation oncology at Virginia Commonwealth University, and Charlotte Dai Kubicky, MD, PhD, director of stereotactic body radiation therapy at Oregon Health & Science University, wrote in an accompanying editorial.

“Improvements in breast imaging, surgical techniques, pathologic evaluation, and systemic treatments have significantly reduced the number of local recurrences expected after breast-conserving therapy,” Cuttino and Kubicky wrote. “Only one-third of the patients in the EORTC study received either tamoxifen or chemotherapy, whereas the majority of the patients now receive systemic therapy. Modern trials have demonstrated that the incidence of ipsilateral breast tumor recurrence after breast-conserving surgery and whole-breast radiotherapy plus boost is less than 2% at 5 years. Hypofractionated radiotherapy regimens have become the norm, with the whole-breast component of treatment accomplished in just 15 to 16 fractions.”

New scientific advancements can likely identify which patients will benefit from a boost to the tumor bed after breast-conserving surgery and whole-breast irradiation.

“In the future, the use of molecular subtyping, radiosensitivity signatures and other advances will likely provide more insight into which patients require radiotherapy after breast-conserving surgery, and who will benefit from higher doses to the tumor bed,” Cuttino and Kubicky wrote. –by Cameron Kelsall

Disclosures: The researchers, Cuttino and Kubicky report no relevant financial disclosures.