HER2-Low Breast Cancer: — How Enhertu Created an Entirely New Patient Group

No, they are different drugs that both target HER2 in different ways. Herceptin (trastuzumab) is an antibody that blocks HER2 signalling and was designed for HER2-positive tumours — those with very high HER2 expression. Enhertu (trastuzumab deruxtecan) uses the same HER2-targeting antibody as a vehicle to deliver a chemotherapy payload directly into the tumour cell. Because it delivers its payload physically rather than blocking a signal, it can work at the lower HER2 levels that define HER2-low disease. The two drugs are used in different settings and are not interchangeable.

Yes. HER2-low is defined as IHC 1+ or IHC 2+ with a negative ISH result. A score of 2+ with a negative ISH means there is some HER2 protein on the tumour surface but the HER2 gene has not been amplified — which places you in the HER2-low category rather than HER2-positive. Your oncologist will have reviewed this alongside your hormone receptor status and other factors when planning your treatment. If you want to confirm this explicitly, ask your team to explain what your IHC and ISH results mean for your current options.

Based on the current evidence, Enhertu for HER2-low disease is established for patients who have already received prior lines of therapy in the metastatic setting — not as the very first treatment. DESTINY-Breast04 enrolled patients who had received prior chemotherapy. Your oncologist will explain where Enhertu fits in the treatment sequence for your situation, because what you have already had, and how your cancer responded, determines which line it is most appropriate at. Guidelines from NCCN and ESMO reflect this sequencing.

Interstitial lung disease, or ILD, is inflammation of the lung tissue. In the context of Enhertu, it is a known side effect that occurs in a proportion of patients. Most cases are mild and resolve with corticosteroids and a pause or stop of treatment. A smaller proportion are more serious, and in rare cases it can be life-threatening. This is why your oncology team will ask at every visit about new breathlessness, a dry cough, or fever. Do not wait for your next appointment if you notice any of those — contact your team the same day. Early reporting is what makes the difference in how well it can be managed.

There is no fixed number of cycles set at the start of treatment. You continue as long as the cancer is responding and you are tolerating it without unacceptable side effects. Your team will assess response periodically using scans and clinical review, and the decision to continue, pause, or stop is made at those review points. Some patients remain on Enhertu for an extended period; others move to a different treatment if the disease progresses or a side effect requires a change. Your oncologist will explain the review schedule at your first appointment.

HER2-low status reflects the biology of your individual tumour — it is not an inherited trait passed down in families the way BRCA mutations are. Your family members do not need HER2 testing because of your result. A conversation about hereditary risk may be relevant if your cancer type or family history raises those questions, but that is a separate assessment from your HER2 score. If you are unsure whether a genetic counselling referral applies to your family, ask your oncologist.