In the staging group with the largest number of patients, T1N0, the percentage of 10-year local recurrence declined from 4.6% at diagnosis to 0.5% in the last year. For 10-year regional recurrence, the risk declined from 2.3% at diagnosis to 0.2% in the last year. For 10-year distant metastases, it ranged from 7.8% at diagnosis to 0.6% in the last year.

And, as noted previously, even risk declined across the group of patients determined to be at the highest risk, those in the T2N1 stage group: risk declined from 6.2% to 0.8% for local recurrence, from 5.2% to 0.4% for regional recurrence, and from 19.6% to 1.5% for distant metastases.

There were 6267 patients with complete known breast cancer subtype whom were available for analysis. Breast cancer subtypes were defined as follows: luminal A (ER- or PR-positive, HER2-negative and grade 1 or grade 2), luminal B (ER- or PR-positive, HER2-positive, or HER2-negative with grade 3), HER2-positive (ER- and PR-negative and HER2-positive) and triple-negative (ER-, PR-, and HER2-negative).

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Of these 6267 patients, at 10-years from diagnosis, 81.4% of the patients with luminal A disease were still alive, compared with 77.3%, 76.4%, and 70.0% in luminal B, HER2-positive and triple-negative breast cancers, respectively.

Clinical Applicability

Conditional disease-free survival reflects changes over time. Because traditional disease-free survival is estimated from the date of diagnosis, a known downside is its limitation to predict risk of recurrence in patients who have been disease free.2 Dr van Maaren noted no studies had previously been performed that investigated the conditional risk of local recurrence, regional recurrence, and distant metastases in patients with breast cancer.

What is remarkable, Dr van Maaren and coauthors noted, was that at diagnosis, clear differences between the subgroups were observed regarding recurrences, “which attenuated as more years passed.”1 Being disease-free at 1 to 9 years following diagnosis increased the chance of being free of disease at 10 years following diagnosis.

“Our study has shown that the conditional risk on recurrences declines over the years, becoming as low as only a few percent in the last years. Whether this small risk may contribute to the described excess mortality rates beyond 10 years is unclear. In our study, we showed that RS rates in the 10th year following diagnosis ranged between 96.5% and 98.0% for the different T and N subgroups, confirming a small but persistent excess mortality compared to the general Dutch population,” the group wrote.

They did acknowledge, however, that the study used data from the pre-trastuzumab era, “which may have led to higher recurrence rates for these patients” compared with those diagnosed and treated more recently, after trastuzumab was approved by the European Medicines Agency in 2000 for certain patients with breast cancer.

These findings may help personalize follow-up and may contribute to the increased awareness of lower recurrence risks over time, the authors said.

A similar study evaluated 205,827 women diagnosed with stage I to stage III breast cancer from 1989 to 2008 from the same cancer registry, and calculated the conditional 5-year relative survival rates for breast cancer patients, for each subsequent year survived up to 15 years after primary diagnosis.

For stage I, the conditional 5-year relative survival remained approximately 95% up to 15 years after diagnosis (a stable 5-year excess mortality rate of 5%). For stage II, excess mortality remained 10% for those aged between 15 years to 44 years, or those aged between 45 years to 59 years, and 15% for those aged between 60 years to 74 years. For patients with stage III cancer, excess mortality decreased from 35% at diagnosis to 10% at 15 years for those aged between 15 years to 44 years, or aged between 45 years to 59 years, and from  approximately 40% to 30% for those aged at least 60 years. Authors of that paper also advocated for more personalized follow-up, noting caregivers “can use this information to better inform (especially disease-free) cancer survivors about their actual prognosis.”3

References

  1. Van Maaren MC, Strobbe LJA, Smidt ML, Moossdorff M, Poortmans PMP, Siesling S. Ten-year conditional recurrence risks and overall and relative survival for breast cancer patients in the Netherlands: taking account of event-free years. Eur J Cancer. 2018;102:82-94.
  2. Paik H-J, Lee SK, Ryu JM, et al. Conditional disease-free survival among patients with breast cancer. Medicine (Baltimore). 2017;96(1):e5746.
  3. Janssen-Heijnen MLG, van Steenbergen LN, Voogd AC, et al. Small but significant excess mortality compared with the general population for long-term survivors of breast cancer in the Netherlands. Ann Oncol. 2014;25(1):64-68.