New Options for Low-Risk, HER2-Positive Tumors Featured in Research Overview

Anita Shaffer
Published: Wednesday, May 07, 2014
Debu Tripathy, MD

Debu Tripathy, MD

Fresh insights into outcomes for patients with low-risk, HER2-positive breast cancer suggest that adjuvant chemotherapy regimens with or without trastuzumab (Herceptin) should be considered as options for managing this growing population, according to Debu Tripathy, MD.

Two abstracts1,2 involving patients whose tumors were categorized as node-negative and T1a or T1b are among the highlights of 2013 that Tripathy reviewed during the 31st Annual Miami Breast Cancer Conference in a presentation entitled “ASCO/ San Antonio Update: Medical Oncology.” His reviews have become an annual feature of the conference. Tripathy has identified noteworthy research in several categories from among abstracts presented last year during the 2013 American Association of Clinical Oncology (ASCO) in June and the 2013 San Antonio Breast Cancer Symposium in December. In an interview, Tripathy said research findings on low-risk, HER2-positive disease are significant enough to change practice.

“This is an area that was a blind spot for us,” said Tripathy, who serves as co-leader of the Women’s Cancer Program at the USC Norris Comprehensive Cancer Center and is one of the MBCC directors. “We obviously know that trastuzumab can improve outcomes when added to chemotherapy for HER2-positive breast cancer, but the dilemma has always been about lowrisk tumors that are T1a or T1b, and node negative.”

Tripathy, whose research has contributed to the development of trastuzumab, said one of the challenges facing clinicians treating patients with low-risk, HER2-positive breast cancer is balancing the potential for adverse events (AEs) with the benefits of adjuvant therapy that may only lower their risk of recurrence by 1% to 2%. “There are obviously side effects from both chemotherapy and trastuzumab, including a small chance of cardiomyopathy,” he said.

Patients deemed low risk receive a wide range of treatments—either no adjuvant therapy, a more intensive chemotherapy/trastuzumab regimen, or perhaps hormone therapy with or without trastuzumab if their tumors are hormone receptor (HR)-positive, said Tripathy. He said a recently presented phase II trial suggests that low-risk patients might benefit from a less intensive chemotherapy regimen of trastuzumab plus weekly paclitaxel for 12 cycles. “Now we have this middle road that seems to be effective,” he said.

Treatment Trends Examined

There is much uncertainty about optimal treatments for patients with T1a/T1b N0M0 (≤1 cm) breast cancer even as mammogram screenings contribute to a rise in the incidence of such early-stage cancers, said Ines Maria Vaz Duarte Luis, MD, MSc, of the Dana-Farber Cancer Institute, in a presentation at ASCO.1 In fact, she said patients with T1a/T1b N0 breast cancer make up approximately 20% of stage I-III disease in the developed world.

Traditionally, such patients have been excluded from clinical trials, resulting in limited data on chemotherapy outcomes for subsets of patients, said Vaz Duarte Luis. In order to gather data on this patient population, researchers analyzed therapy trends and outcomes for women treated for newly diagnosed stage I-III unilateral breast cancer treated from 2000-2009 at eight centers in the National Comprehensive Cancer Network. Survival outcomes at 5 years were analyzed for four subgroups: HR+/ HER2–; HR–/HER2–; HR+/HER2+; and HR–/HER2–. At ASCO, Vaz Duarte Luis and colleagues focused on their findings concerning 4113 patients with T1a/ T1b N0M0 tumors.

Overall, they found that that the use of adjuvant chemotherapy with or without trastuzumab varied widely among subgroups; a high proportion of patients with HER2-positive and HR–/HER2– T1N0 disease received therapy and the percentage of patients with HER2-positive disease receiving therapy increased dramatically over the years (Table 1). The 5-year distant relapse-free survival (DRFS) rates showed most subgroups experienced an improved prognosis with adjuvant therapy compared with those who had not been treated, although there were variations. In the HER2-positive groups, patients who received adjuvant therapy experienced better outcomes.

In the HR+/HER2+ group, the proportion of patients with T1b tumors (N = 199) who received adjuvant chemotherapy with or without trastuzumab rose from 36% in 2003 to 100% in 2009. The 5-year DRFS rate was 91% among those who were not treated as opposed to 95% for those who received adjuvant therapy. Of the patients in this group, 54% received chemotherapy and 36% received trastuzumab.

Table 1. Trends and Outcomes for Patients With T1b Tumors

Subgroups Patients (N) Treatment Trends Chemotherapy ± trastuzumb
(% treated)
DRFS Without chemotherapy or trastuzumab
(5-y median rate)
DRFS With chemotherapy and/or trastuzumab
(5-y median rate)
    2003 2009    
HR+/HER2+ 199 36% 100% 91% (n = 89) 95% (n = 110)
HR–/HER2+ 105 76% 100% 81% (n = 17) 94% (n = 88)
HR+/HER2– 2246 10% 13% 96% (n = 2005) 95% (n = 241)
HR–/HER2– 264 70% 69% 90% (n = 94) 93% (n = 170)

DRFS indicates distant relapse-free survival.
Vaz Duarte Luis et al. 2013 San Antonio Breast Cancer Symposium. Abstract 1006.

In the HR–/HER2+ group, the proportion of patients with T1b tumors (N = 105) who received adjuvant therapy rose from 76% in 2003 to 100% in 2009. The 5-year DRFS rate was 81% among those who were not treated as opposed to 94% for those who received adjuvant therapy. Of the patients in this group, 84% received chemotherapy and 46% received trastuzumab.

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