Risk of Recurrence Low in Small, HER2-Positive Breast Tumors

Lou Fehrenbacher, MD

Patients with small, node-negative, HER2-positive breast cancer tumors had a low risk of invasive recurrence after 5 years, according to an article published in the Journal of Clinical Oncology.¹

Among 171 patients with HER2-positive T1a/T1b N0M0 (≤1 cm) tumors, who did not receive treatment with adjuvant trastuzumab or chemotherapy, the distant recurrence-free interval (DRFI) was 98.2% (95% CI, 94.5-99.4%).

“This is the first large study to demonstrate that the smallest lymph node-negative HER2-positive breast cancers have a very low chance of returning,” lead author Lou Fehrenbacher, MD, medical director of Kaiser Permanente Oncology Clinical Trials, said in a statement.

In the analysis, 234 patients with HER2-positive T1a/T1b N0M0 tumors were identified in a database of 16,975 patient cases from between the years 2000 and 2006. The most commonly used treatments in this population include surgery, radiation therapy, trastuzumab, and chemotherapy.

Of the 234 patients with HER2-positive T1a/T1b N0M0 tumors, 171 were not treated with adjuvant trastuzumab or chemotherapy. The DRFI of patients with T1a tumors was 99.0% (95% CI, 93.0-99.9%), while the DRFI was slightly lower among patients with T1b tumors, at 97.0% (95% CI, 88.6-99.2%).

Locoregional plus distant 5-year invasive recurrence-free interval (IRFI) was 97.0% (95% CI, 90.9-99.0%) for patients with T1a tumors and 91.9% (95% CI, 81.5-96.6%) for T1b tumors. T1b tumors measuring 1.0 cm accounted for 24% of the entire T1a/T1b population and 75% of distant recurrences. For these tumors, the 5-year IRFI was 89.4% compared with 97.4% in T1a tumors.

“These data are of great interest to clinicians in the context of an ongoing struggle to define a threshold, if any exists, below which early-stage HER2-positive breast cancers have a sufficiently favorable prognosis to enable the withholding of trastuzumab-based cytotoxic combination therapy,” Katherine E. Reeder-Hayes, MD, and Lisa A. Carey, MD, from University of North Carolina-Chapel Hill, wrote in an accompanying editorial, also published in the Journal of Clinical Oncology.² “Previous prognostic data in this subgroup have been scant and difficult to interpret.”

A prospective cohort study that was conducted using the NCCN database between the years 2000 and 2009, also published in the Journal of Clinical Oncology, demonstrated similar results.³

In this analysis, 4,113 patients with T1a/T1b N0M0 (≤1 cm) tumors were analyzed. In total, 8% of patients with HR-positive/HER2-negative tumors were treated with chemotherapy while 52% of patients with HER2-positive or HR-negative/HER2-negative tumors received chemotherapy.

The 5-year distant relapse-free survival for chemotherapy-naïve patients with T1a tumors was 93-98% and 90-96% for patients with T1b tumors. The 5-year distant relapse-free survival rate for patients treated with chemotherapy with T1a tumors was 100% and 94-96% for patients with T1b tumors.

Reeder-Hayes and Carey wrote that though the results from these trials “offer hope for improved decision making” in this population of patients, some questions remain. “The favorable prognosis of small HER2-positive tumors means that the choice to receive systemic therapy in this setting is more clearly a preference-sensitive clinical decision, requiring the timeless clinical skills of communicating clearly with patients regarding small and sometimes uncertain risks and benefits, understanding patients' unique values and preferences, and facilitating shared decisions.”

While illuminating, in regard to chemotherapy, both database analyses were conducted prior to the approval of pertuzumab (Perjeta) and ado-trastuzumab emtansine (T-DM1; Kadcyla). The impact and use of these agents for patients with small tumors remains an intriguing question.

In a presentation at the 2014 Miami Breast Cancer Conference, Debu Tripathy, MD, from the USC Norris Comprehensive Cancer Center, said there is a need for molecular and protein assays to help discern which patients with HER2-positive T1a/T1b N0M0 tumors will benefit from treatment with trastuzumab.

“I suspect what’s going to happen in the HER2 field is that we’re going to be developing more and more drugs for patients and we’ll probably be overtreating some patients with multiple drugs that they may not need,” said Tripathy during the meeting. “We’re going to need better risk stratification as we go forward.”

References

1. Fehrenbacher L, Capra AM, Quesenberry Jr CP, et al. Distant Invasive Breast Cancer Recurrence Risk in Human Epidermal Growth Factor Receptor 2—Positive T1a and T1b Node-Negative Localized Breast Cancer Diagnosed From 2000 to 2006: A Cohort From an Integrated Health Care Delivery System [published online June 2, 2014]. J Clin Oncol. 2014;32(20):2151-2158.
2. Reeder-Hayes KE, Carey LA. How Low Should We Go? The Search for Balance in Management of Small Human Epidermal Growth Factor Receptor 2—Positive Breast Cancers [published online June 2, 2014]. J Clin Oncol. 2014;32(20):2122-2124.
3. Vaz-Luis I, Ottesen RA, Hughes ME, et al. Outcomes by Tumor Subtype and Treatment Pattern in Women With Small, Node-Negative Breast Cancer: A Multi-Institutional Study [published online June 2, 2014]. J Clin Oncol. 2014;32(20):2142-2150.