Who this is for
Small HER2-positive breast cancer can have an excellent prognosis with modern treatment.
You have been diagnosed with a HER2-positive breast cancer measuring 26 mm or less, with no cancer found in the lymph nodes, and you have been told that your cancer is “aggressive”.
Hearing the words ‘aggressive breast cancer’ is frightening. Many patients immediately assume this means they have a poor prognosis.
However, modern HER2-targeted treatment has transformed outcomes.
For carefully selected patients with small, node-negative HER2-positive breast cancer, the long-term prognosis can now be excellent.
Clinical observation
A lady recently came to see me after surgery for a 26 mm HER2-positive breast cancer.
Fortunately, her lymph nodes were completely clear.
Her surgeon had explained that chemotherapy would be recommended because HER2-positive breast cancer behaves aggressively under the microscope.
She came to me for a second opinion with one important question.
“Do I really need the strongest chemotherapy available?”
A 26 mm tumour was within the size range included in the APT trial.
However, it was close to the upper end of that range, so the decision could not be based on tumour size alone.
Hormone receptor status, tumour grade, lymphovascular invasion, heart health and the patient’s preferences also needed to be considered.
Her greatest concern was the possibility of receiving anthracycline chemotherapy—the so-called “red chemotherapy”—because she had read about the small risk of long-term or potentially irreversible heart muscle damage.
This is a conversation I have regularly in my breast cancer clinic.
The goal is not simply to cure the cancer.
The goal is to cure the cancer while avoiding unnecessary long-term toxicity whenever possible.
What surprised me
When I was a medical student, HER2-positive breast cancer was regarded as one of the more concerning forms of breast cancer.
That was before trastuzumab.
Today, the story has changed dramatically.
For carefully selected patients with small, node-negative HER2-positive breast cancer who receive appropriate treatment, long-term outcomes can be excellent.
What surprised me most was not simply that treatment improved.
It was that a cancer once defined by its higher risk could become one of the clearest examples of successful targeted treatment.
Hormone receptor-positive and HER2-positive breast cancers also have different recurrence patterns.
HER2-positive breast cancer has historically carried more of its recurrence risk earlier. Hormone receptor-positive breast cancer may behave more slowly but can retain a small risk of recurrence for many years.
Neither subtype is automatically “better”.
What matters is the stage, biology and treatment of the individual cancer.
Why small HER2-positive breast cancer can have an excellent prognosis
One of the most important studies influencing my practice is the APT (Adjuvant Paclitaxel and Trastuzumab) Trial.
Rather than giving every patient intensive chemotherapy, investigators asked an important question:
Could patients with small HER2-positive cancers receive a simpler treatment while still achieving outstanding long-term outcomes?
The results were highly reassuring.
This study has changed how many breast oncologists around the world treat carefully selected patients.
Background
Approximately 15–20% of breast cancers are HER2-positive.
Before HER2-targeted therapy became available, these cancers had one of the highest risks of recurrence.
The introduction of trastuzumab completely changed the natural history of this disease.
The pioneering work of Dennis Slamon and many international investigators established HER2 as one of the most successful targeted treatments in oncology.
Today, HER2-positive breast cancer represents one of the greatest advances in modern cancer medicine.
Methodology
Study
APT Trial
Number of patients
406 patients
Who was included?
- HER2-positive breast cancer
- Tumours measuring up to 3 cm
- Mainly included patients whose lymph nodes were clear.
- Surgery completed
Treatment
- Weekly paclitaxel for 12 weeks
- Trastuzumab for a total of 1 year
The study deliberately avoided anthracycline chemotherapy.
The researchers wanted to know whether a simpler, anthracycline-free treatment could provide excellent long-term cancer control for carefully selected patients.
It is important to understand that APT was a single-arm study.
Everyone received the same treatment, so the trial did not directly compare this regimen with a stronger chemotherapy program.
Key results
The results were remarkable.
After approximately ten years of follow-up:
- Most patients remained free from invasive breast cancer events.
At 10 years, approximately 91.3% of patients were alive without an invasive breast cancer recurrence, a new invasive breast cancer or death. - The chance of the original breast cancer returning was very low.
The 10-year recurrence-free interval was approximately 96.3%. - Breast cancer-specific survival was excellent.
At 10 years, approximately 98.8% of patients had not died from breast cancer. Put another way, among just over 400 patients, only a small number died from breast cancer during long-term follow-up. - Overall survival remained high.
Approximately 94.3% of patients were alive at 10 years. - Distant metastatic recurrence was uncommon.
Only a small number of patients developed cancer that had spread to distant organs.
In simple terms, carefully selected patients with small, node-negative HER2-positive breast cancer had excellent long-term outcomes after treatment with paclitaxel and trastuzumab.
For a cancer once considered highly aggressive, these are extraordinary results.
Why I often consider an anthracycline-free approach
One of the biggest changes in breast oncology has been recognising that more chemotherapy is not always better chemotherapy.
Anthracyclines are effective chemotherapy drugs.
They remain important and can save lives.
However, they also carry a small risk of long-term and sometimes irreversible heart muscle damage.
When anthracyclines are used as part of a trastuzumab-containing treatment plan, the risk of heart problems can be higher than with a non-anthracycline regimen.
For carefully selected patients with:
- an 8 mm tumour,
- a 15 mm tumour,
- or even a 26 mm node-negative HER2-positive breast cancer,
I may consider an anthracycline-free approach.
The APT trial included tumours measuring up to 3 cm and showed excellent long-term outcomes with paclitaxel and trastuzumab.
However, every patient is different.
Age, hormone receptor status, tumour grade, heart function, patient preference and whether cancer cells are seen in small blood or lymph vessels all influence treatment decisions.
This is why a personalised treatment discussion is so important.
How does this compare with hormone receptor-positive breast cancer?
Many people assume hormone receptor-positive breast cancer always has the best prognosis.
That is not necessarily true.
Large international studies have shown that hormone receptor-positive breast cancer can carry a continuing risk of recurrence for up to 20 years after diagnosis, even after completing five years of endocrine therapy.
The risk does not disappear completely.
I remember a lady diagnosed more than twenty years earlier with a relatively small hormone receptor-positive breast cancer involving only one lymph node.
She enjoyed many healthy years.
Then, more than two decades later, the cancer returned.
It had spread throughout the peritoneum, the thin lining covering the abdominal organs, causing widespread metastatic disease.
This illustrates that very late recurrence can occur in hormone receptor-positive breast cancer.
By comparison, in the APT trial, distant recurrence remained uncommon at approximately 10 years among patients with small, node-negative HER2-positive breast cancer who received modern HER2-targeted treatment. Longer follow-up is needed to understand recurrence beyond this period.
What does this mean for you?
If your cancer is:
- HER2-positive,
- measures 26 mm or less,
- and has not spread to the lymph nodes,
There is a genuine reason to be optimistic.
Modern HER2-targeted treatment has dramatically changed the outlook.
Carefully selected patients may achieve excellent long-term outcomes with an anthracycline-free treatment program, while reducing exposure to potential long-term heart toxicity.
Every patient deserves an individual treatment recommendation based on the biology of their cancer rather than a one-size-fits-all approach.
For patients with small HER2-positive breast cancer, there is genuine reason to be optimistic.
Key takeaways
- Small, node-negative HER2-positive breast cancer can have an excellent prognosis
Modern HER2-targeted treatment has transformed the outlook for carefully selected patients. - More chemotherapy is not always better chemotherapy
Some patients may achieve excellent long-term outcomes using an anthracycline-free treatment approach. - Treatment must be personalised
Tumour size, lymph nodes, hormone receptors, tumour grade, heart health and patient preferences all matter. - The goal is cure while minimising unnecessary long-term toxicity
The right treatment is not simply the strongest treatment. It is the treatment that offers the best balance of benefit and risk for the individual patient.
Key evidence
- Tolaney SM, Tarantino P, Graham N, et al. Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer: final 10-year analysis of the open-label, single-arm, phase 2 APT trial. Lancet Oncol. 2023;24(3):273-285. doi:10.1016/S1470-2045(23)00051-7
- Tolaney SM, Barry WT, Dang CT, et al. Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer. N Engl J Med. 2015;372(2):134-141. doi:10.1056/NEJMoa1406281
- Romond EH, Perez EA, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005;353(16):1673-1684. doi:10.1056/NEJMoa052122
- Slamon DJ, Leyland-Jones B, Shak S, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001;344(11):783-792. doi:10.1056/NEJM200103153441101
- Pan H, Gray R, Braybrooke J, et al. 20-year risks of breast-cancer recurrence after stopping endocrine therapy at 5 years. N Engl J Med. 2017;377(19):1836-1846. doi:10.1056/NEJMOA1701830
Frequently asked questions (FAQs)
- Does HER2-positive breast cancer still have a poor prognosis?
Not necessarily. Modern HER2-targeted therapies have transformed outcomes, particularly for small, node-negative cancers.
- Do I always need the strongest chemotherapy?
No. Many patients with small node-negative HER2-positive breast cancer may be candidates for an anthracycline-free regimen, although treatment should always be individualised.
- Why are doctors concerned about anthracyclines?
Anthracyclines are highly effective drugs but can increase the risk of long-term heart damage, particularly when combined with trastuzumab.
- Should I seek a second opinion?
If you have HER2-positive breast cancer and are uncertain about your chemotherapy plan, a specialist second opinion can help you understand the benefits and potential risks of each treatment option.
- Is trastuzumab chemotherapy?
No. Trastuzumab is a targeted antibody treatment that recognises the HER2 protein. In the APT regimen, it is given with the chemotherapy drug paclitaxel.
- Will my heart be monitored during trastuzumab?
Usually, yes. A heart scan is generally performed before treatment and repeated during treatment because trastuzumab can affect heart function in a small number of patients.
Dr Dilanka De Silva
MBBS, MRCP(UK), MRCP(UK SCE Oncology), FRACP, PhD
Medical Oncologist & Cancer Genetics Physician
Memorial Sloan Kettering Cancer Center Fellow (New York, USA)