Survival rates for early stage or localised breast cancer are high, thanks to improved detection and treatment. But once breast cancer has spread to other parts of the body, the focus moves to urgently stopping the cancer from growing any further and adding priceless months or years to a patient’s life.

Now, an international study, including Australian patients, has shown that a new combination of medication gives patients with an aggressive type of metastatic breast cancer more than a year of extra time before their cancer progresses.

The new treatment regime promises to benefit up to 10% of people with metastatic breast cancer, says senior medical oncologist Professor Elgene Lim, who led the Australian arm of the study.

Researchers examined whether the drug palbociclib, which blocks proteins that promote the division of cancer cells, can delay cancer growth in people with metastatic breast cancer that is both hormone receptor (HR) positive and human epidermal growth factor receptor 2 (HER-2) positive.

The PATINA trial was conducted by Breast Cancer Trials and involved 496 participants, including 49 patients from Australia and New Zealand.

Results presented at the San Antonio Breast Cancer Symposium showed that adding the palbociclib inhibitor to a patient’s standard drug therapy extended their progression-free survival for an average of 15 months.

Professor Lim said that difference was clinically significant. “That means patients stay, on average, 15 months longer on this treatment before the cancer progresses and they need to change therapies,” he said.

Professor Lim said the new treatment regime could change clinical practice and become the new standard of care. However, the drug is not yet funded through the Pharmaceutical Benefits Scheme.

Metastatic HR-positive, HER-2-positive breast cancer has traditionally been treated with three therapies: the anti-HER2 medications trastuzumab and pertuzumab, plus endocrine therapy. In the PATINA study, half the patients received the traditional gold standard treatment plan, while half were also given palbociclib, which blocks proteins that promote the division of cancer cells.

The research found that patients who took palbociclib plus a combination of anti-HER2 treatment and endocrine therapy did not experience any growth in their cancer for an average of 44.3 months, compared with 29.1 months among patients who did not take palbociclib.

The quadruple therapy was also well tolerated, with only 7.5% of patients discontinuing treatment due to side effects. “The vast majority were able to continue the therapy, and the side effects were manageable,” Professor Lim said. The incidence of adverse events was similar in both patient groups.

Professor Lim said patients with HR positive, HER-2 positive breast cancer account for 7.5% to 10% of all breast cancer patients. “There is a significant minority of breast cancer patients who will benefit from this therapy,” he said.

Publication

Patina – ANZ 1701/AFT-38: PATINA. Metzger O, Mandrekar S, DeMichele A, Gianni L, Gligorov J, Lim E, Ciruelos E, Loibl S, Dockter T, Gonzalez Farre X, Francis P, Lynce F, Lanzillotti J, DuFrane C, Drop I, Vaz-Luis I, Valagussa P, Tripathy D, Soi S, Prat A, Goetz M, Escriva-de-Romani S, Porter D, Spoenlein J, Saresai S, Heudel P, Koehler M, Huang Bartlett C, Hoynskyj A, Copalakrishna P, Gauthier E, Liu Y, Slaloge S, Miller K, Winer E, Partridge A, Goel S, Carey L. AFT-38 PATINA: A Randomized, Open Label, Phase III Trial to Evaluate the Efficacy and Safety of Palbociclib + Anti-HER2 Therapy + Endocrine Therapy vs. Anti-HER2 Therapy + Endocrine Therapy after Induction Treatment for Hormone Receptor-Positive (HR+)/HER2-Positive Metastatic Breast Cancer. SABCS 2024. https://www.breastcancertrials.org.au/media-releases/patina-study-results/

Two drugs targeting the same molecule in a fast-growing type of breast cancer are better than one, even in women with earlier stage disease.

The international APHINITY study, published in the Journal of Clinical Oncology in 2024, involved more than 4,800 people with HER-2-receptor positive breast cancer, which accounts for about one in five cases of breast cancer.

The study investigators – including researchers from Breast Cancer Trials in Australia – were asking whether using two drugs to target the HER2 receptor could improve survival in women with early-stage disease.

When the study launched, there was already evidence that treating advanced HER2-receptor-positive breast cancer with two different drugs targeting the HER2 receptor – trastuzumab (Herceptin) and pertuzumab (Perjeta) – in combination with chemotherapy made a big difference to survival.

The APHINITY study looked at whether those same benefits would occur in women with earlier stage disease, before the cancer had spread.

Half the participants were randomised to get the two HER2-receptor-targeting drugs plus chemotherapy, and the other half received trastuzumab only plus chemotherapy and a placebo infusion.

The study found that the combination of the two HER2-receptor-targeting drugs did improve survival in earlier stage disease, but only in women whose tumour had spread to their lymph nodes.

In those participants, the combination of trastuzumab and pertuzumab was linked to a nearly 5% greater likelihood of having no recurrence of their cancer at eight years after starting treatment, compared to the participants only treated with trastuzumab.

This translates to nearly five fewer women in every 100 with this type of cancer would have their disease return in the eight years after treatment

But in the people whose cancer hadn’t spread to their lymph nodes, adding pertuzumab to trastuzumab didn’t make a significant difference to their disease-free survival rates.

“I would describe APHINITY as a bridge between when the standard was just chemotherapy and trastuzumab, by saying that adding pertuzumab is a little bit better, at least in more advanced disease,” said Associate Professor Nicholas Wilcken, the Breast Cancer Trials study chair of APHINITY.

It has also paved the way for this combination treatment to be used before surgery, which, for some patients, can mean less extensive surgery. “Now there’s an emphasis on giving the chemotherapy before the surgery, not after the surgery,” Prof Wilcken said. “It does two things: one is it shrinks the tumour; and, the other is it gives you a test run to see how well your treatment works. We now know that if there’s still some residual tumour at surgery after the two targeted drugs, a change in drug treatment leads to better survival.”

Publication

Loibl, S et al. (2024) Adjuvant Pertuzumab and Trastuzumab in Early Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer in the APHINITY Trial: Third Interim Overall Survival Analysis With Efficacy Update. Journal of Clinical Oncology, 42 (31), P **-**. https://doi.org/10.1200/JCO.23.02505

A new study supported by Breast Cancer Trials is helping doctors better understand how to personalise treatment for people with early-stage breast cancer.

The human epidermal growth factor receptor 2, or HER2, protein is a well-established drug target in some breast cancers where it promotes cancer cells to grow. Cancers with high levels of HER2 are treated with targeted therapies designed to block this growth. More recently, new drugs also work in cancers with lower levels of the HER2 protein. These therapies – known as antibody-drug conjugates, which deliver chemotherapy directly to cancer cells – have expanded treatment options and created a newly defined category called ‘HER2-low breast cancer’, which is now used to help determine who would benefit from these newer drugs.

But what does HER2-low really mean for people with early stage, hormone receptor-positive breast cancer – the most common breast cancer subtype? And is it truly different enough from other types of breast cancer to justify its own treatment approach?

To explore this, a team led by Dr Stephen Luen from the Peter MacCallum Cancer Centre and the University of Melbourne, analysed tumour samples from about 1,800 women who participated in two large international clinical trials: BIG 1-98 and SOFT. These years-long trials collected detailed clinical and biological data, providing a rich resource to explore questions of tumour behaviour and treatment response. All participants had breast cancers that tested negative for high HER2 levels, but were grouped by the researchers as either HER2-low or HER2-zero, based on the amount of HER2 protein present in the tumour.

The researchers compared outcomes between the two groups, including how the cancers behaved over time and how likely they were to return. They also examined tumour characteristics and patterns of gene mutations. The findings showed no meaningful differences. HER2-low tumours did show slightly more expression of the HER2 gene, but this difference was small and unlikely to influence how the cancer responds to treatment.

“Our findings suggest that the HER2-low category isn’t a discrete type of breast cancer in its early stages,” said Dr Luen. “That matters because it raises questions about how we currently use HER2 test results to make treatment decisions.”

This research suggests that HER2 expression exists on a spectrum, rather than in fixed categories. It highlights the need for better tools to identify who will benefit most from HER2-targeted therapies, so that treatment decisions are based on meaningful differences, not on arbitrary thresholds.

Publication

Luen, S. J., Brown, L. C., van Geelen, C. T., Savas, P., Kammler, R., Dell’Orto, P., Biasi, O., Coates, A. S., Gelber, R. D., Thürlimann, B., Colleoni, M., Fleming, G. F., Francis, P. A., Regan, M. M., Viale, G., Loi, S. (2025). Genomic characterization and prognostic significance of human epidermal growth factor receptor 2–low, hormone receptor–positive, early breast cancers from the BIG 1-98 and SOFT clinical trials. JCO Precision Oncology, 9, e2400599. https://doi.org/10.1200/PO-24-00599

Since 2000, women diagnosed with breast cancer are about 20 percent less likely to have their tumour come back or spread, compared to those diagnosed in the 1990s.

A study published in the Lancet in 2024 analysed data from a massive database of 151 clinical breast cancer trials involving more than 155,000 people with early-stage breast cancer. The aim was to determine how the risk of breast cancer spreading, or metastasizing, had changed over time.

Women with breast cancer that is sensitive to oestrogen are known to have an increased risk of their disease returning for at least 20 to 30 years after treatment, even with use of therapies that block hormones. But less is known about the long-term recurrence rate in women with breast cancer that isn’t sensitive to hormones.

Given the many recent advances in treatment of both oestrogen receptor-positive and oestrogen receptor-negative, researchers in the Early Breast Cancer Trialists’ Collaborative Group were interested in how that recurrence rate in both cancer types might have changed over time.

They did what’s called a ‘pooled analysis’ of all the relevant clinical trial data from their database, which enabled them to analyse all the participants in those studies as one enormous group, to see how the risk of recurrence had changed between 1990 and 2009, and what factors might have played a role in those changes.

Overall, they found that the recurrence rates for both types of breast cancer had gone down over time. This was due not only of improved treatments, but also to improved diagnostic technology and screening programs, which meant cancer was being detected and treated earlier which increased the likelihood of survival and a cure.

There have also been advancements in tailoring treatments to an individual cancer.

One of the trials included in the analysis was the TailorX study, which tried to work out whether hormone-sensitive breast cancers that had an intermediate risk of recurrence – based on genetic analysis – would benefit from more intensive treatment with chemotherapy on top of hormone-blocking therapy.

Associate Professor Nicholas Wilcken was a member of the Breast Cancer Trials Scientific Advisory Committee when the TailorX trial was running.

“TailorX essentially showed that, at least for post-menopausal women, the chemotherapy did not make any difference, so you were just as well off having only hormone-blockers alone,” Prof Wilcken says. That finding was significant because it meant many women could avoid chemotherapy and its side-effects, which not only improved outcomes but also quality of life, without increasing their risk of the cancer coming back.

Publication

Early Breast Cancer Trialists’ Collaborative Group (2024). Reductions in recurrence in women with early breast cancer entering clinical trials between 1990 and 2009: a pooled analysis of 155 746 women in 151 trials, Lancet 404: 1407-18. doi: 10.1016/S0140-6736(24)01745-8

Suppressing the production of oestrogen from the ovaries can significantly improve survival in some premenopausal women with breast cancer that is sensitive to estrogen. But, ovarian-function suppression is associated with some unpleasant side effects.

A study published in JAMA Oncology in 2024 found a way to identify which premenopausal women were most likely to benefit from ovarian-function suppression as part of their cancer treatment, and who was unlikely to benefit and should avoid that treatment.

Researchers used tumour samples from 1,687 premenopausal people with breast cancer, which were collected as part of the original Suppression of Ovarian Function Trial (SOFT), and applied a genetic test called the Breast Cancer Index (BCI) that looked at the activity levels of 11 genes known to play important roles in hormone-sensitive breast cancer.

Their theory was that those women with a cancer that exhibited a high score on this test would be more likely to benefit from the addition of hormone-suppressing therapy than to the standard treatment options of either tamoxifen or exemestane.

Surprisingly, they found the opposite: those with a lower score on the genetics test were the ones who benefited the most in terms of freedom from breast cancer recurrence during the 12 years of follow-up.

“It may be that those patients with a BCI low score have more sensitivity to the maximum endocrine blockade, and therefore that high endocrine sensitivity leads to them getting more of a benefit from getting rid of all of the estrogen,” said Dr Nicholas Zdenkowski, a medical advisor with Breast Cancer Trials and medical oncologist at Hunter Valley Oncology.

The difference was significant. Participants with a low BCI score who were treated with ovarian suppression and exemestane had about half the risk of their breast cancer returning, and those given ovarian suppression and tamoxifen had a 31% lower risk, compared to those treated with tamoxifen alone.

In contrast, those in the trial with a high BCI score had no benefits from the additional ovarian-suppressing treatment.

The original SOFT trial, which demonstrated the additional benefit of ovarian suppression, was practice-changing, as it led to the standard use of ovarian suppression in premenopausal women with hormone-sensitive breast cancer, and saw those drugs listed on the Pharmaceutical Benefits Scheme in Australia.

While the BCI test isn’t routinely available, Dr Zdenkowski said it could also have an impact on clinical practice if it becomes more widely used.

“If we had access to this test, then we could use it to help refine our decision-making about who specifically might get most benefit from ovarian suppression,” he said.

Publication

O’Regan RM, Zhang Y, Fleming GF, Francis PA, Kammler R, Viale G, Dell’Orto P, Lang I, Bellet M, Bonnefoi HR, Tondini C, Villa F, Bernardo A, Ciruelos EM, Neven P, Karlsson P, Muller B, Jochm W, Zaman K, Marino S, Geyer CE, Jerzak KJ, Davidson NE, Coleman RI, Ingle JN, van Mackelenbergh MR, Loi S, Colleoni M, Schnabel CA. Breast cancer index in premenopausal women with early-stage hormone receptor-positive breast cancer. JAMA Oncology. 2024; epub 15 August 2024; doi:10.1001/jamaoncol.2024.3044

One of the largest, and longest, worldwide studies into breast cancer, the ALTTO trial, is continuing to reap benefits. The trial was designed to test the effectiveness of different treatment strategies on those with HER2-positive breast cancer. More than 8,000 women from 44 countries participated.

Dr Janine Lombard is a medical oncology specialist at Calvary Mater in Newcastle and Breast Cancer Trials researcher, and has been involved in ALTTO for 18 years. She says the trial has not only greatly increased our understanding of ideal treatments for the roughly 20% of breast cancer tumours that overexpress the HER2 (human epidermal growth factor receptor 2) protein, but it has also created a rich biobank of tumours.

“This is one of the biggest studies ever done in breast cancer and it was done across the entire world, so it has this absolutely unique collection of tumours,” Dr Lombard says. “It has helped advance a lot of understanding about HER2-positive breast cancers.”

Dr Lombard was the principal investigator in the ALTTO trial for Australia and New Zealand, where 223 women participated. “There was a good representation of Oceania, which at the time was often underrepresented in international studies.”

The latest publication from the trial was a 10-year comparison of 6,281 patients who had HER2-positive breast cancer. Too much HER2 protein is thought to cause cancer cells to grow and divide quicker.

“The study was designed with the premise that hopefully a combination of two drugs [trastuzumab and lapatinib] would improve outcomes,” Dr Lombard says. Because the two drugs work differently, it was hoped – based on previous evidence – that a combination would prevent the cancer from returning and possibly spreading to the brain. “However, the 10-year data supports an earlier publication that showed that was not to be the case,” she says.

Standard therapy is now trastuzamab alone, or in combination with another drug that has been developed since the study started, pertuzumab.

But far from being a ‘negative’ study, Dr Lombard says the ALTTO trial provides many grounds for optimism. “The thing we’ve understood in this decade and a half is that with treatment, outcomes for individuals with HER2-positive breast cancer are excellent,” she says. “Ten-year survival rates are close to 90% and that’s a huge improvement compared to before we had these anti-HER2 drugs. Because the survival rates are so good, it encourages us to think, as clinicians, ‘is there a group of women who we can give less chemotherapy to?’”

Dr Lombard says the breast cancer treatment landscape has changed a lot since the ALTTO trial started. Along with the development of next-generation drugs, treatment protocols now often recommend chemotherapy before surgery, whereas all the patients in the trial had surgery before chemotherapy.

Publication

Final analysis of the ALTTO trial: adjuvant trastuzumab in sequence or in combination with lapatinib in patients with HER2-positive early breast cancer [BIG 2-06/NCCTG N063D (Alliance)] de Azambuja, E. et al. ESMO Open, Volume 9, Issue 11, 103938. https://doi.org/10.1016/j.esmoop.2024.103938

A shorter, smarter treatment could bring new hope to people with early stage, triple-negative breast cancer (TNBC). Driven by the need to limit toxic side effects, researchers from Breast Cancer Trials designed the Neo-N study to see if combining a powerful immunotherapy drug with a shorter, focused course of chemotherapy before surgery could control tumours as effectively as longer treatments.

TNBC lacks the hormone and HER2 receptors that many targeted therapies attack. It often grows faster, spreads sooner, and strikes younger women more severely, leaving few treatment options. While standard chemotherapy can shrink tumours, its high doses and long schedules can lead to fatigue, nerve damage, and even heart problems years later.

In Neo-N, 108 women at 14 hospitals in Australia, New Zealand, and Italy received 12 weeks of pre‑surgery treatment combining nivolumab – a therapy that awakens the immune system – with two common chemotherapy drugs. The trial deliberately omitted a class of medicines called anthracyclines, which are linked to lasting heart risks and other side effects.

To test timing, participants were split into two groups. One began nivolumab alone for two weeks, then added chemotherapy. The other started all drugs together. After 12 weeks, each woman had surgery to remove the treated tumour and nearby lymph nodes.

The results were striking. 57 of 108 women (53%) had no detectable cancer at surgery – a ‘complete response’ matching rates seen with much longer, more intensive regimens. “This 12‑week chemo‑immunotherapy treatment combination is a promising new treatment option that has been very effective at eradicating the cancer in those patients,” says Professor Sherene Loi, medical oncologist at the Peter MacCallum Cancer Centre, who led the study.

Neo-N also highlighted two simple lab tests that predicted who would benefit most. Women whose tumours contained at least 30% immune cells saw a 67% complete-response rate, while those whose tumours displayed the PD‑L1 protein reached 71%. These markers could help doctors tailor treatment to each patient’s tumour biology.

Importantly, the shorter plan proved generally well tolerated. Serious side effects affected 65% of women – mainly low white-blood cells, anaemia and mild liver changes – but these were managed promptly with standard supportive medications, and did not force most participants to stop treatment. No one died from therapy, and the vast majority completed the full course.

Researchers stress that larger phase 3 trials are now needed – and Neo-N participants will remain under observation for up to three years to track any recurrence, long‑term survival, and late effects.

By pairing immunotherapy with a shorter, heart-safer chemotherapy regimen, Neo-N points toward a future where some people can beat early-stage TNBC with fewer treatments, less toxicity, and a better quality of life.

Publication

Zdenkowski N, Kuper‑Hommel MJJ, Niman SM, et al. Timing of nivolumab with neoadjuvant carboplatin and paclitaxel for early triple-negative breast cancer (BCT1902/IBCSG 61–20; Neo-N). Lancet Oncol. 2025;26(3):367–77. doi:10.1016/S1470-2045(24)00092-4