Study confirms long-lasting benefit of trastuzumab (herceptin) for women with early-stage breast cancer

February 24, 2011

Women with an aggressive type of early-stage breast cancer (HER2-positive disease) given trastuzumab (Herceptin) for one year following standard chemotherapy are at significantly less risk of the cancer returning, and the effect is long lasting, according to the long-term results of the landmark HERA trial published Online First in The Lancet Oncology.

Around 20󈞊% of women with breast cancer have HER2-positive cancer and are at high risk of cancer recurrence and of dying from the disease. Trastuzumab is a monoclonal antibody developed to block the cancer-causing activity of the HER2 protein and has been shown to prolong survival in patients with advanced breast cancer.

The HERA trial was designed to establish whether trastuzumab could increase disease-free survival (DFS) and overall survival (OS) in women with early HER2-positive breast cancer when given after standard chemotherapy. Between December 2001 and June 2005, over 5000 women from 39 countries were enrolled and randomly assigned to observation only, trastuzumab for 1 year, or trastuzumab for 2 years.

In 2005, initial results (median follow-up 1 year) showed that 1 year of adjuvant trastuzumab significantly reduced the risk of disease recurrence by 46%. On the basis of these results, a protocol amendment allowed patients in the observation group who were disease free and had normal heart function to receive trastuzumab. A second analysis published in 2007 (median follow-up 2 years) confirmed the significant improvement in DFS after 1 year of trastuzumab and also showed a significant improvement in OS.

In this study, Luca Gianni from Fondazione San Raffaele, Milan, Italy and international colleagues report the long-term outcomes (median 4 years) of women from the HERA trial treated with trastuzumab for 1 year and examine the outcome of patients who crossed over to trastuzumab treatment.

After 4 years, trastuzumab was associated with significantly better DFS compared with chemotherapy alone (78.6% vs 72.2%), reducing the likelihood of cancer coming back by 24%. However, there was no significant difference in risk of death between the trastuzumab and observation groups (89.3% vs 87.7%), which was most likely the result of the cross-over impact.

Over half (52%) of patients from the observation group crossed over to receive trastuzumab treatment a median of 23 months after randomisation. These patients had fewer recurrences than patients remaining on observation.

Trastuzumab was generally well tolerated, although more serious side-effects were recorded in the trastuzumab group than in the observation group. However, the rate of congestive heart failure remained low during the longer follow-up.

The authors say: "These findings confirm that adjuvant trastuzumab [Herceptin] given sequentially to chemotherapy is associated with significant and persisting benefits, and remains an appropriate treatment modality in patients with HER-2 positive early breast cancer...The optimal duration of trastuzumab therapy is the subject of ongoing studies."

In an accompanying Comment, Heikki Joensuu from Helsinki University Central Hospital, Helsinki, Finland points out that: "When the HERA trial was designed, the preference was to give trastuzumab [Herceptin] in the same manner as endocrine therapy--ie, as a single drug after chemotherapy and for a long period. Yet, mounting evidence suggests that the optimum way to give trastuzumab differs from that of endocrine therapy, and that concomitant administration of trastuzumab with chemotherapy might be more effective compared with trastuzumab given after chemotherapy."

In a second Comment, Evandro de Azambuja from the Institut Jules Bordet and Universite Libre de Bruxelles, Brussels, Belgium and colleagues discuss the best way to combine trastuzumab and chemotherapy and argue that there is insufficient evidence to safely promote the concurrent [at the same time] use of trastuzumab and anthracyclines in patients with primary HER2-positive breast cancer.

Indeed, their combined analysis of the cardiac events observed in published neoadjuvant studies finds that: "The concurrent use of trastuzumab and anthracycline-based chemotherapy significantly increases the risk of cardiac toxicity, even if administered for brief periods in the neoadjuvant setting."

They conclude: "We strongly discourage the concurrent use of trastuzumab and anthracycline-based regimens in clinical practice outside the context of a clinical trial...To validate this treatment approach in the clinical setting, a properly powered, randomised phase 3 clinical trial...[of] sequential versus concomitant administration of trastuzumab and anthracycline-based chemotherapy...is needed."
-end-
Professor Luca Gianni, Fondazione San Raffaele, Milan, Italy. T) +39 02 2643 6529 E) gianni.luca@hsr.it

Professor Heikki Joensuu, Helsinki University Central Hospital, Helsinki, Finland. T) +358 (0)9 471 3200 or +358 (0)40 72 10 438 (mobile) E) heikki.joensuu@hus.fi

Dr Evandro de Azambuja, Institut Jules Bordet and Universite Libre de Bruxelles, Brussels, Belgium. T) + 32 2 541 72 44 E) evandro.azambuja@bordet.be

For full Article and both Comments, see: http://press.thelancet.com/tlohercep.pdf

NOTE: THE ABOVE LINK IS FOR JOURNALISTS ONLY; IF YOU WISH TO PROVIDE A LINK TO THE FREE ABSTRACT OF THIS PAPER FOR YOUR READERS, PLEASE USE THE FOLLOWING, WHICH WILL GO LIVE AT THE TIME THE EMBARGO LIFTS: http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(11)70033-X/abstract

Lancet

Related Breast Cancer Articles from Brightsurf:

Oncotarget: IGF2 expression in breast cancer tumors and in breast cancer cells
The Oncotarget authors propose that methylation of DVDMR represents a novel epigenetic biomarker that determines the levels of IGF2 protein expression in breast cancer.

Breast cancer: AI predicts which pre-malignant breast lesions will progress to advanced cancer
New research at Case Western Reserve University in Cleveland, Ohio, could help better determine which patients diagnosed with the pre-malignant breast cancer commonly as stage 0 are likely to progress to invasive breast cancer and therefore might benefit from additional therapy over and above surgery alone.

Partial breast irradiation effective treatment option for low-risk breast cancer
Partial breast irradiation produces similar long-term survival rates and risk for recurrence compared with whole breast irradiation for many women with low-risk, early stage breast cancer, according to new clinical data from a national clinical trial involving researchers from The Ohio State University Comprehensive Cancer Center - Arthur G.

Breast screening linked to 60 per cent lower risk of breast cancer death in first 10 years
Women who take part in breast screening have a significantly greater benefit from treatments than those who are not screened, according to a study of more than 50,000 women.

More clues revealed in link between normal breast changes and invasive breast cancer
A research team, led by investigators from Georgetown Lombardi Comprehensive Cancer Center, details how a natural and dramatic process -- changes in mammary glands to accommodate breastfeeding -- uses a molecular process believed to contribute to survival of pre-malignant breast cells.

Breast tissue tumor suppressor PTEN: A potential Achilles heel for breast cancer cells
A highly collaborative team of researchers at the Medical University of South Carolina and Ohio State University report in Nature Communications that they have identified a novel pathway for connective tissue PTEN in breast cancer cell response to radiotherapy.

Computers equal radiologists in assessing breast density and associated breast cancer risk
Automated breast-density evaluation was just as accurate in predicting women's risk of breast cancer, found and not found by mammography, as subjective evaluation done by radiologists, in a study led by researchers at UC San Francisco and Mayo Clinic.

Blood test can effectively rule out breast cancer, regardless of breast density
A new study published in PLOS ONE demonstrates that Videssa® Breast, a multi-protein biomarker blood test for breast cancer, is unaffected by breast density and can reliably rule out breast cancer in women with both dense and non-dense breast tissue.

Study shows influence of surgeons on likelihood of removal of healthy breast after breast cancer dia
Attending surgeons can have a strong influence on whether a patient undergoes contralateral prophylactic mastectomy after a diagnosis of breast cancer, according to a study published by JAMA Surgery.

Young breast cancer patients undergoing breast conserving surgery see improved prognosis
A new analysis indicates that breast cancer prognoses have improved over time in young women treated with breast conserving surgery.

Read More: Breast Cancer News and Breast Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.