Trastuzumab Reduces Recurrence in Low-Risk HER2 Breast Cancer

HER2-positive breast cancer has long been recognized as an aggressive disease, but women with small node-negative tumors are considered low risk for recurrence and do not always receive adjuvant therapy. Data presented by Heather L. McArthur, MD, MPH, Memorial Sloan-Kettering Cancer Center in New York, and colleagues in a poster session at this week’s Breast Cancer Symposium in San Francisco suggests perhaps they should. In comparing outcomes between women who received adjuvant trastuzumab for low-risk HER2-positive tumors and those treated before trastuzumab was available, they concluded adjuvant trastuzumab (Herceptin) reduces recurrence rates and mortality.

The retrospective study examined records for 495 women who received a diagnosis of a node-negative HER2-positive breast tumor ≤2 cm in 2002—2008. They identified 146 women who received chemotherapy after excision or no adjuvant treatment; 148 women received adjuvant trastuzumab (Herceptin) with or without chemotherapy. The median age of patients in both groups was 53 years, and tumor characteristics were similar. Women in the trastuzumab arm, however, were more likely to have received chemotherapy.

After 2 years of follow up, rates of local and distant recurrence-free survival trended toward the trastuzumab group, but results were not significant. After 4 years, the locoregional recurrence rate in the trastuzumab group was 1.3% versus 9.3% for the pre-trastuzumab group. The distant recurrent rate was 0.0% in the trastuzumab group and 5.6% in the pre-trastuzumab group. Although 2-year survival rates were similar, at 4 years, they significantly favored the trastuzumab arm, with a mortality rate of 0.7% versus 5.6% for the pre-trastuzumab arm. According to Dr McArthur, only 1 patient in the trastuzumab group died, and none experienced recurrence. In comparison, 6 women in the pre-trastuzumab group died, and 19 had recurrences (9 distant).

Dr McArthur noted trastuzumab is approved in the United States in combination with chemotherapy only for “high risk” breast cancers that overexpress HER2, yet women in the “low risk” group clearly derived benefit. Abstract No. 228.

Trastuzumab Arm

(n = 148)

Pre-Trastuzumab Arm

(n = 146)

2-Year Outcomes, %

OS

99

100

Locoregional survival

99

91

Distant RFS

100

98

4-Year Outcomes, %

Mortality rate

0.7

2.8

Locoregional recurrence

1.3

9.3

Distant recurrence

0.0

5.6

OS indicates overall survival; RFS, recurrence-free survival.

These findings support studies presented at the San Antonio Breast Cancer Symposium (SABCS) in December 2008. Ana M. Gonzalez-Angula MD, University of Texas MD Anderson Cancer Center, reported that women with node-negative HER2-positive tumors ≤1 cm had a recurrence rate 2.68 times greater than women with HER2-negative tumors. Their risk of distant recurrence was also 5.3 times higher. She said these women “should be considered for clinical trials if systemic anti-HER2 adjuvant therapy or, if a clinical trial is not available, adjuvant therapy should be discussed with them.”

A second study at SABCS found that women with early stage, low-grade node-negative HER2-positive tumors had a 5-year survival rate of 68% compared with 96% for women with HER2-negative patients. Only half the HER2-positive patients had received trastuzumab. Sian Tovey, MD, Glasgow Royal Infirmary, who presented the data, said, “No HER2-positive patient should be considered low risk...any patient who is HER2-positive should be categorized as high risk and should receive adjuvant trastuzumab therapy.”