For many patients with metastatic breast cancer, chemotherapy has long been part of the first line of treatment. It can control cancer effectively, but its side effects can also make everyday life difficult.
A small US trial suggests that some patients with a particular form of breast cancer may eventually have another option.
Researchers led by the Icahn School of Medicine at Mount Sinai tested four medicines that target specific weaknesses in cancer cells. None is traditional chemotherapy. Together, the drugs produced long periods of cancer control in many of the patients who took part.
The treatment was developed for breast cancers described as HR-positive and HER2-positive. HR stands for hormone receptor, meaning the cancer can use hormones to support its growth. HER2 is a protein on cells that can send powerful signals encouraging cancer cells to multiply.
Some breast tumors have both of these features. This gives doctors two important biological targets, but it also makes treatment more complicated because the cancer can rely on more than one growth pathway. Researchers have been exploring whether blocking both pathways strongly enough could reduce the need for chemotherapy.
The new study used four drugs: anastrozole, palbociclib, trastuzumab and pertuzumab. Anastrozole lowers estrogen production, reducing the hormone signal that can feed the tumor. Palbociclib interferes with proteins involved in cancer-cell division.
Trastuzumab and pertuzumab both target the HER2 system. Although they act on the same general target, they bind in different ways and can provide a stronger blockade when used together. The four-drug strategy therefore attacks the cancer from several directions at once.
This approach was tested in the ASPIRE trial, an early phase 1/2 clinical study conducted at five sites affiliated with Mount Sinai, NYU Langone Health and Columbia University.
The researchers first determined how much palbociclib could be used safely in the combination. They then studied the full regimen in 29 people with previously untreated HR-positive, HER2-positive metastatic breast cancer.
Metastatic means that cancer cells have spread from the breast to distant parts of the body. Although modern treatments have helped many patients live much longer, metastatic breast cancer is generally not considered curable. Doctors often use a series of treatments to keep the disease under control for as long as possible.
The ASPIRE findings were published in the Journal of the National Cancer Institute. The researchers reported that 97% of participants experienced clinical benefit during the first six months. In practical terms, nearly everyone in the small study had cancer that either shrank or remained controlled during that period.
Patients went a median of almost 25 months before their cancer worsened. This measure is known as progression-free survival and is commonly used in cancer trials to show how long a treatment keeps disease from advancing. Some people benefited for much longer than the median.
One participant had continued receiving the regimen for more than six years. Long-lasting responses like this are particularly interesting in metastatic cancer because patients may need continuous treatment. However, one exceptional response cannot predict what will happen for most patients.
The researchers also reported encouraging survival data. After patients had been followed for a median of roughly 39 months, almost 93% were still alive. Median overall survival had not been reached because more than half of the participants remained alive at the time researchers analyzed the results.
A major goal of the strategy is to avoid some of chemotherapy’s burden. Chemotherapy attacks rapidly dividing cells, which includes cancer cells but can also include healthy cells in the hair, digestive system and bone marrow. This explains many familiar chemotherapy effects, such as hair loss, nausea and reduced blood cell counts.
Targeted therapies are more selective, but they can still cause significant side effects. In the ASPIRE trial, the most common problems included neutropenia, which means having too few infection-fighting neutrophils, as well as other low white blood cell counts, diarrhea and anemia. Patients therefore still required medical monitoring.
Only one patient stopped treatment because of side effects, and researchers reported no deaths caused by the treatment. Senior author Dr. Amy Tiersten described the safety profile as manageable for many patients. The team believes this balance between disease control and tolerability deserves further investigation.
First author Dr. Rima Patel highlighted patients who may have difficulty tolerating chemotherapy, including some older adults and people living with other medical conditions. For them, an effective targeted approach could be particularly useful. Treatment that relies more heavily on oral medicines and injections may also be easier to fit into daily life.
Quality of life is an important issue in metastatic cancer. Because patients may receive therapy for long periods, even moderate side effects can become a major burden over time. A treatment that provides similar cancer control with fewer disruptive effects could therefore be valuable even if it does not dramatically extend survival.
Yet the study cannot show that this regimen is as good as the current standard treatment. The full combination was tested in only 29 patients, and everyone received the experimental approach. There was no second group receiving standard HER2-targeted therapy plus chemotherapy for a direct comparison.
This is the biggest weakness of the research. A high response rate can look impressive, but outcomes may partly reflect which patients were enrolled, their general health or the biology of their cancers. Only a larger randomized study can fairly determine whether removing chemotherapy improves, maintains or reduces treatment effectiveness.
The study should therefore be viewed as a strong reason to conduct more research, not as evidence that patients should avoid chemotherapy now.
Current treatments are supported by much larger bodies of evidence and remain important for many people with HER2-positive metastatic breast cancer. Treatment decisions also depend on where the cancer has spread, previous therapies, symptoms and individual health.
Even with these limitations, the trial demonstrates an important direction in cancer medicine. As scientists learn more about the signals that tumors depend on, treatment may increasingly focus on combining precise drugs rather than automatically using broad chemotherapy.
For the right patients, this could eventually mean controlling cancer while reducing some of the physical burden of treatment.
The investigators are planning additional studies comparing the four-drug approach with established first-line care. If larger randomized trials reproduce the long periods of cancer control seen here while showing good quality of life, the strategy could become a meaningful alternative for selected patients. For now, the results are encouraging, but confirmation is essential.
Source: Icahn School of Medicine at Mount Sinai.
