Young age at diagnosis of HER2-positive early breast cancer, irrespective of hormone receptor status, does not have prognostic or predictive value in women treated with modern adjuvant anticancer therapies.

While younger women are at higher risk of developing biologically aggressive breast cancer phenotypes, results from an exploratory analysis of the APHINITY trial demonstrate that age per se in the HER2-positive group is not a reason to prescribe more aggressive therapies or to expect a different treatment benefit.

The international RCT, investigating the addition of pertuzumab to adjuvant chemotherapy plus trastuzumab, included 768 women ≤40 years and 4,036 women >40 years.

Younger women had a slightly higher rate of ER and/or PgR hormone receptor positive disease (71.7% v 64.9%; p = 0.003).

The study, published in the Journal of the National Cancer Institute, found the primary endpoint, invasive disease-free survival (IDFS) was observed in 11.2% of younger women and 10.5% of older women over a median follow-up of 74 months.

“At the univariate and multivariable Cox proportional hazard models, age was not prognostic neither as a dichotomous (vs. older cohort: unadjusted HR 1.06; 95% CI 0.84-1.33; adjusted HR 1.07; 95% CI 0.84-1.35) nor as a continuous (unadjusted HR 1.00; 95% CI 1.00-1.01) variable(,” the study said.

“The lack of prognostic effect of age was observed irrespective of hormone receptor status and administered anti-HER2 treatment.”

The study found the addition of pertuzumab improved IDFS in both age groups.

“Results of this analysis support prior findings from the HERA trial showing lack of prognostic or predictive value of young age in patients with HER2-positive early breast cancer treated with chemotherapy alone or with sequential trastuzumab.”

They said the larger sample size and longer follow-up of the present analysis “allows for the first time to add important prognostic and predictive information for young patients with HER2-positive breast cancer according to the hormone receptor status of the disease.”

“Although many studies has shown that young age at diagnosis is a poor prognostic factor in breast cancer, with a better biological characterisation of breast cancer and the availability of more effective targeted therapies, the importance of age with regard to prognosis is expected to diminish and potentially disappear,” it said.

“This is an important information to reassure young patients at diagnosis and possibly to avoid overtreatment based solely on age considerations.”

Local perspective

Commenting on the study for the limbic, Professor Prue Francis said the large APHINITY trial was a good source for information on the question of age and especially as there hadn’t been much data in HER2-positive breast cancer.

“It’s a good way to get a reasonable number of patients with well annotated follow-up. From that perspective it is a good trial to look at it. It’s an interesting study and good to have this sort of data available.”

Professor Francis, Clinical Head of Breast Medical Oncology at the Peter MacCallum Cancer Centre in Melbourne, said another strength of this study was the longer follow-up than studies such as the HERA trial.

“It’s certainly reassuring because these women sometimes haven’t completed childbearing and they are young… the fact that they can still have good outcomes is good information.”

“It’s saying that on the face of it, if they have a HER2-positive tumour they can still have a good outcome and you shouldn’t overtreat them just because they are young.”

“It’s obviously important with any patients, but particularly with young patients, that the margins are nice and clear so that they don’t end up getting local recurrences.”

She said the only issue from the analysis that wasn’t totally clear was whether young women need ovarian suppression or not.

“We know from ER-positive HER2-negative [breast cancer] that it looks like if you add ovarian suppression into the mix, that may be helpful for those very young patients.”

“So in the APHINITY analysis, they talk about the fact that some of them did get ovarian suppression as part of their treatment… but they didn’t really break it down to say if that mattered in terms of outcomes.”

“On the face of it, it all looks fine. I think they are saying they look like they are doing as well as the older ones but we don’t know how much of that is definitely influenced by the ovarian suppression or not.”