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Disease-Free Interval

Patients with de novo MBC are used in studies of prognosis, despite the difficulty of
extrapolating results from this population to the entire MBC population, because the disease-
free interval—the time between the initial diagnosis and the metastatic diagnosis—doesn’t exist
in this subgroup and need not be considered. Because the length of time before breast cancer
recurs has been confirmed as an independent predictive factor known to impact duration of
survival, studies relying on these data can be misleading.

Tevaarwerk et al. [110] demonstrated the effect of the disease-free interval in their 2013 analysis
of long-term patient outcomes across 11 phase 3 adjuvant chemotherapy trials completed by
the Eastern Cooperative Oncology Group over approximately 30 years (1978–2010). In this
study of 13,785 breast cancer patients who received adjuvant chemotherapy, 3447 patients
(25%) developed distant MBC; the overall median survival after relapse was 20 months. The
factor that best predicted duration of survival was disease-free interval, which was 2.44 times
higher among patients with relapse 6 or more years after initial diagnosis as compared with
those with relapse after 3 or fewer years. By contrast, TN or ER− tumors (vs. ER+ tumors), any
Modest increase involved lymph nodes (vs. none), and black race (vs. other) were much weaker (but statistically
in survival has significant) predictors of survival.
been observed
mainly in ER+ and/ In fact, when this study’s results were stratified to take disease-free interval into account, the
or HER2+ MBC and increased survival benefit over time all but disappeared—except among ER− MBC patients who
is attributable to
the wide use of had relapse within 5 years after adjuvant treatment. The exception was probably due to the
targeted therapies. approval of trastuzumab (Herceptin) in 1998.
No survival benefit
has been found in
TN MBC. Summary

Recent studies on duration of survival of de novo and recurrent MBC generally demonstrate 3
findings:

• Over the past few decades, the duration of survival after metastatic diagnosis has
The disparity increased modestly—by a matter of months, not years. Hospital-based studies generally
between survival report a larger survival benefit than population-based studies.
among black
women with MBC • The modest increase in survival has been observed mainly in ER+ and/or HER2+ MBC
and non-Hispanic and is attributable to the wide use of targeted therapies. No survival benefit has been
white women with found in TN MBC.
MBC appears to
be increasing as • The disparity between survival among black women with MBC and non-Hispanic white
treatments improve. women with MBC appears to be increasing. According to SEER data, non-Hispanic white
patients with de novo MBC have a survival benefit that is not found in black patients. It is
unclear how much of the observed disparity in outcome is related to access to care and
related socioeconomic concerns and how much is related to the greater incidence of
TN MBC among black women.

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