Adjuvant Trastuzumab did not improve outcomes for patients with HER2-low breast cancer

December 6, 2017

Adding trastuzumab (Herceptin) to standard adjuvant chemotherapy did not improve invasive disease–free survival for patients with early-stage breast cancer found to have low levels of HER2, as defined as immunohistochemistry (IHC) 1+ or 2+ and/or in situ hybridization (ISH) negative, according to data from the randomized, phase III NSABP-B-47 clinical trial presented at the 2017 San Antonio Breast Cancer Symposium, held Dec. 5–9.

"Current guidelines classify a as HER2 positive if immunohistochemistry testing shows it has high levels of HER2 protein, defined as IHC 3+, or in situ hybridization shows it has increased numbers of copies of the HER2 gene, defined as ISH positive" said Louis Fehrenbacher, MD, medical director of Kaiser Permanente Oncology Clinical Trials and an oncologist with the Kaiser Permanente Vallejo Medical Center, California. "Adding one year of treatment with to standard adjuvant chemotherapy significantly reduces cancer recurrence and improves survival for with early-stage HER2-positive breast cancer.

"About 15 percent of breast cancers are HER2 positive, but another 45 percent have low levels of HER2, and these patients are not currently treated with adjuvant trastuzumab," continued Fehrenbacher. "In some of the early trastuzumab clinical , there was a signal that patients with HER2-low breast cancer may benefit from the HER2-targeted therapeutic. We designed and conducted NSABP-B-47 to test in a large, rigorous clinical trial whether this was indeed the case."

Fehrenbacher explained that although the data show that adding trastuzumab to standard adjuvant chemotherapy did not improve outcomes for patients with early-stage HER2-low breast cancer, it was vital to have conducted the study so that patients with this form of the disease can unequivocally know that trastuzumab is not a beneficial treatment for them. Trastuzumab treatment can cause serious adverse effects, including cardiotoxicity, so it is important to know that current guidelines defining HER2-positive status are valid and ensure that no patients are under- or overtreated, he said.

Fehrenbacher and colleagues enrolled 3,270 patients with that was either IHC 1+, IHC 2+, and/or ISH negative in the trial. The patients were randomized 1:1 to standard adjuvant chemotherapy with or without a year of trastuzumab.

After a median follow-up of 46.1 months, 264 patients had either recurrence of their original breast cancer, a diagnosis of a new , a diagnosis of new cancer outside the breast, or had died. These 264 events triggered analysis of the primary endpoint of the trial, invasive disease–free survival.

Among the 1,640 patients receiving trastuzumab, five-year invasive disease–free survival was 89.6 percent. It was 89.2 percent among the 1,630 patients who did not receive the HER2-targeted therapeutic. The findings did not differ if the patients were subdivided by HER2 IHC level, extent of lymph node involvement, or hormone receptor status.

In addition, five-year estimates for recurrence-free interval, distant recurrence–free interval, and overall survival were not statistically different for patients receiving trastuzumab compared with those not receiving trastuzumab.

Explore further: Adding a second HER2 blocker may lower chance of invasive breast cancer for some women

Related Stories

Adding a second HER2 blocker may lower chance of invasive breast cancer for some women

June 5, 2017
A phase III clinical trial of 4,805 women with HER2-positive breast cancer suggests adding a second HER2 targeted medicine, pertuzumab (Perjeta), to standard of care trastuzumab (Herceptin) after surgery may help, although ...

Study finds risk of recurrence low in smallest HER2+ breast cancer tumors

June 2, 2014
Patients with specific HER2+ breast cancer tumors had a low risk of the cancer recurring five years after diagnosis, even without chemotherapy or treatment with a common antibody, according to a Kaiser Permanente study published ...

Immune function marker does not predict benefit of trastuzumab in HER-2+ breast cancer

December 10, 2014
A marker of immune function that predicts for better outcomes in patients treated with chemotherapy for triple negative breast cancer is also linked to improved prognosis in patients treated with chemotherapy for HER2-positive ...

T-DM1 improved overall survival for heavily pretreated patients with HER2-pos breast cancer

December 11, 2015
Among patients with HER2-positive, metastatic breast cancer that had progressed despite treatment with two or more forms of HER2-targeted therapy (trastuzumab [Herceptin] and lapatinib [Tykerb]), median overall survival was ...

Researchers to present progression-free survival results

December 15, 2014
Results from the final analysis of progression-free survival, response rate, and safety for the randomized, phase III Breast Cancer Trials of Oral Everolimus-1 (BOLERO-1) are to be presented here at the 2014 San Antonio Breast ...

Researchers to present event-free and overall survival results from NeoALTTO trial

December 11, 2013
Results from the initial analysis of event-free and overall survival for patients enrolled in the randomized, phase III Neoadjuvant Lapatinib and/or Trastuzumab Treatment Optimization (NeoALTTO) trial are to be presented ...

Recommended for you

Cancer immunotherapy may work better in patients with specific genes

December 15, 2017
Cancer cells arise when DNA is mutated, and these cells should be recognized as "foreign" by the immune system. However, cancer cells have found ways to evade detection by the immune system.

Scientists pinpoint gene to blame for poorer survival rate in early-onset breast cancer patients

December 15, 2017
A new study led by scientists at the University of Southampton has found that inherited variation in a particular gene may be to blame for the lower survival rate of patients diagnosed with early-onset breast cancer.

'Bet hedging' explains the efficacy of many combination cancer therapies

December 14, 2017
The efficacy of many FDA-approved cancer drug combinations is not due to synergistic interactions between drugs, but rather to a form of "bet hedging," according to a new study published by Harvard Medical School researchers ...

Liquid biopsy results differed substantially between two providers

December 14, 2017
Two Johns Hopkins prostate cancer researchers found significant disparities when they submitted identical patient samples to two different commercial liquid biopsy providers. Liquid biopsy is a new and noninvasive alternative ...

Testing the accuracy of FDA-approved and lab-developed cancer genetics tests

December 14, 2017
Cancer molecular testing can drive clinical decision making and help a clinician determine if a patient is a good candidate for a targeted therapeutic drug. Clinical tests for common cancer causing-mutations in the genes ...

Scientists unlock structure of mTOR, a key cancer cell signaling protein

December 14, 2017
Researchers in the Sloan Kettering Institute have solved the structure of an important signaling molecule in cancer cells. They used a new technology called cryo-EM to visualize the structure in three dimensions. The detailed ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.