DESTINY-Breast04: What the Breast Cancer Trial Found

A group of patients who did not exist before this trial

For twenty years, breast cancer was sorted into two boxes for HER2. Either the tumor was HER2-positive and HER2 drugs were worth trying, or it was HER2-negative and they were not. DESTINY-Breast04 broke that split open. It showed that tumors with only a trace of HER2 can still respond to a HER2-targeted drug.

What "HER2-low" means on a pathology report

Pathologists stain tumor tissue for HER2 and grade it 0, 1+, 2+ or 3+. In this trial, HER2-low meant a score of 1+, or a score of 2+ with a negative result on a second test called in-situ hybridization. Those tumors had always been reported as HER2-negative. Roughly half of all breast cancers once labelled HER2-negative fall into this band.

How the trial was set up

557 people with HER2-low metastatic breast cancer took part. All had already had one or two rounds of chemotherapy. They were assigned 2 to 1 to receive either trastuzumab deruxtecan or a chemotherapy chosen by their doctor.

Most had hormone-receptor-positive disease: 494 people, or 88.7%. The other 63, or 11.3%, were hormone-receptor-negative. The main question was set in the hormone-receptor-positive group.

How much longer before the cancer grew

In the hormone-receptor-positive group, the cancer was held in check for a median of 10.1 months with trastuzumab deruxtecan and 5.4 months with chemotherapy. The hazard ratio was 0.51 (P<0.001) — close to half the risk of the disease growing or the person dying at any moment.

Survival moved too: 23.9 months against 17.5 months, hazard ratio 0.64 (P=0.003). Across the whole trial the pattern held, at 9.9 against 5.1 months to growth and 23.4 against 16.8 months of survival.

The lung risk that comes with the drug

Grade 3 or worse side effects were actually less common with trastuzumab deruxtecan than with chemotherapy: 52.6% against 67.4%. That is unusual and worth noting.

But the drug brings a risk that chemotherapy does not. Drug-related inflammation of the lungs — interstitial lung disease or pneumonitis — was confirmed in 12.1% of people who took it. In 0.8%, it was fatal. Teams watch for a new cough, breathlessness or fever, and they treat it early.

What this study cannot tell you

• It does not cover first-line use. Everyone had already had one or two chemotherapy regimens.
• The hormone-receptor-negative group was only 63 people. Those results are exploratory, not proof.
• HER2 staining was designed to separate positive from negative, not to grade faint signals. Repeating the test can move a tumor in or out of the HER2-low band.
• It tested one antibody-drug conjugate. It says nothing about others.

Questions a HER2-low result raises

• What exact HER2 score is on my pathology report, and was in-situ hybridization done?
• Would a fresh biopsy change that score?
• What symptoms of lung inflammation should make me call the team the same day?
• How often would my breathing be checked while I am on this drug?

Sources

This article was written from the sources below, which were checked on the source-check date shown above.

• NEJM: Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer (DESTINY-Breast04) (primary)

How this article was prepared

Prepared by Cancer Explained's AI-assisted editorial system and checked against the sources listed below. This article has not been reviewed by a healthcare professional unless a named reviewer is specifically shown.

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