SABCS 2008: All HER2-Positive Tumors Need Adjuvant Treatment

Nick Mulcahy

December 15, 2008

December 15, 2008 (San Antonio, Texas) — Currently, small and low-grade HER2-positive tumors do not typically receive adjuvant systemic therapy. However, 2 new studies presented here at the 31st Annual San Antonio Breast Cancer Symposium suggest that they should.

"The biology of the tumor, and not the size or grade, matters most in these patients," said Sian Tovey, MD, from the Glasgow Royal Infirmary, in Scotland, about the 2 studies. "No HER2-positive patient should be considered low risk," she added.

No HER2-positive patient should be considered low risk.

Dr. Tovey presented a study on low-grade HER2-positive tumors at the meeting, which shows that patients with the low-grade tumors have a poor prognosis. The results of this study, and another study that shows that small HER2-positive tumors have an increased risk for recurrence, are both practice changing, said Dr. Tovey. "Practice is already changing in Glasgow [because of] both of these results," she said.

The needed change is simple, she suggested. "Any patient who is HER2 positive should be categorized as high-risk and should receive adjuvant trastuzumab therapy."

In the second study, Ana M. Gonzalez-Angulo, MD from the University of Texas MD Anderson Cancer Center, in Houston, said that their new data also challenge the current approach to HER2-positive patients. In that study, patients with tumors 1 cm or smaller had a significant risk for relapse, compared with other tumor types. "The current guidelines call for no further therapy if the tumors are less than 5 mm or [to] consider therapy if the tumors are from 6 to 10 mm, but these data challenge that thinking and show that this group of women may benefit from additional therapy," said Dr. Gonzalez-Angulo.

Drs. Tovey and Gonzalez-Angulo and their respective colleagues called for clinical trials to assess adjuvant therapy in these patients.

Small Tumors But Increased Risk for Recurrence

The study presented by Dr. Gonzalez-Angulo was a retrospective analysis of 965 patients from the MD Anderson Cancer Center diagnosed with breast cancer between 1990 and 2003. The median age of the patients at diagnosis was 57 years. All tumors were 1 cm or smaller, and the cancers were node-negative. Most of the tumors (68%) were hormone-receptor positive, but 10% were HER2 positive and 23% were triple-receptor negative.

The 5-year recurrence-free survival was 77.1% and 93.7% in patients with HER2-positive and HER2-negative tumors, respectively. The 5-year distant recurrence-free survival was 86.4% and 97.2% in the 2 patient groups. Thus, patients with HER2-positive tumors had a 2.68 times greater risk for recurrence and a 5.3 times higher risk for distant recurrence than those with HER2-negative tumors. HER2 positivity is a powerful negative prognostic factor for patients with tumors 1 cm or less, noted Dr. Gonzalez-Angulo.

"This paper shows that patients with HER2-positive tumors 1 cm or less have a significant risk of relapse and should be considered for clinical trials of systemic anti-HER2 adjuvant therapy or, if a clinical trial is not available, adjuvant therapy should be discussed with them," summarized Dr. Gonzalez-Angulo.

Low-Grade Tumors But Poor Prognosis

In the other study, Dr. Tovey and her Scottish colleagues retrospectively analyzed women with low-grade node-negative HER2-positive tumors. These tumors are typically not treated with adjuvant therapy and are seen as low risk, she noted.

The cohort of 367 early breast cancer patients with grade 1 or 2 cancers were diagnosed between 1980 and 2002 and had a median follow-up6.2 years. The cohort was analyzed to assess the impact of HER2 status on survival. A total of 123 patients in the cohort (12.9%) were HER2 positive.

The overall hazard ratio for HER2 positivity was 6.78, with 5-year breast-cancer-specific survival rates for HER2-negative patients of 96%, compared with only 68% for the HER2-positive patients. The reduction in survival in HER2-positive cases persisted when patients were split into subgroups by estrogen-receptor status, tumor size, and age.

The Scottish study also reviewed all early cases of HER2-positive early breast cancer to determine what percentage of patients received adjuvant therapy. Only 50% of the HER2-positive early breast cancer patients received trastuzumab therapy in 2006. The most common reason for not receiving trastuzumab was low-risk status precluding chemotherapy.

"The substantial reduction in survival shown in our retrospective cohort provides support for the use of trastuzumab in these 'low-risk' HER2-positive patients who typically are classified as [having a] very good prognosis, are not routinely offered standard chemotherapy and, as such, do not fit current prescribing guidelines for trastuzumab," noted Dr. Tovey and colleagues from the Royal Glasgow Infirmary in their poster presentation.

The researchers have disclosed no relevant financial relationships.

31st Annual San Antonio Breast Cancer Symposium (SABCS): Abstracts 701 and 702. Presented December 12, 2008.


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