Some women with more advanced stages of breast cancer may experience worse outcomes when chemotherapy is delayed after surgery, according a retrospective review of 6,827 patients with stage I to III disease at a single center.
However, overall, there were no differences in outcomes among the cohorts of women (all stages of disease) who started chemotherapy either 0 to 30 days, 31 to 60 days, or more than 60 days after surgery.
The outcomes included overall survival (OS), relapse-free survival (RFS), and distant-relapse-free survival (DRFS).
But there were differences seen in subgroups of women—namely those with stage II and III disease and poorer prognosis subtypes, report the authors, led by Debora de Melo Gagliato, MD of the University of Texas M.D. Anderson Cancer Center in Houston
Specifically, among patients with stage II disease, the authors found a detrimental effect in RFS and DRFS when chemotherapy started more than 60 days after surgery.
Also, among patients with stage III disease, they also found a detrimental effect in RFS, DRFS, and OS associated with a start time after 60 days.
Furthermore, the authors discovered that patients with triple negative disease and patients with HER2-positive disease treated with trastuzumab ( Herceptin; Genentech/Roche) had a worse OS if chemotherapy was started 60 days or more after surgery.
Most of the patients in the study got their treatment in a timely fashion (before 60 days) — only 16.4% started chemotherapy beyond that time.
The findings were published online in the Journal of Clinical Oncology.
There is no standard as to when to start adjuvant chemotherapy, observe the authors.
"For most patients, adjuvant chemotherapy starts within a few weeks from surgery," they write.
The problem is that no one knows whether delaying the treatment is harmful. "It is unclear whether a delay in initiation of therapy is associated with adverse outcomes," say the authors.
In an editorial accompanying the new study, a pair of experts downplay the importance of timing.
"Evolving evidence indicates that it is unlikely that early commencement of chemotherapy makes a difference for the
majority of patients," write Marco Colleoni, MD of the European Institute of Oncology, Milan, Italy and Richard D. Gelber, MD of the Dana-Farber Cancer Institute, Boston, Massachusetts. Both are members of the International Breast Cancer Study Group.
The study authors acknowledge that the "majority" of other studies on this topic "did not show any detrimental effect in postponing chemotherapy."
However, they pursued their new study because the evidence has been mixed; furthermore, it is uncertain what the impact of breast cancer subtypes is on outcomes.
The editorialists find much to fault with the current study, calling its evidence "weak due to the potential biases and inconsistent outcomes."
The new results can only be regarded as "hypothesis generating." Further, new data would be needed before any changes to practice, they add.
They have a variety of concerns including the statistical strength of a study in which "multiple subgroups analyses and endpoints [are] considered."
Amid other concerns, the pair of editorialists point out that, among patients with triple-negative disease, there was a difference in outcome with respect to OS, but no impact of chemotherapy timing on RFS or DRFS. These findings "raise concerns that at least some of the OS differences are due to patient selection."
Despite their litany of complaints, Dr. Colleoni and Dr. Gelber ultimately say that "unnecessary delay" in starting chemotherapy may be "unwise" in those patients with more advanced disease in whom "the effect of chemotherapy is expected to be significant."
In other words, the editorialists are in some agreement with the study authors. .
The authors conclude their paper by saying: "Among patients with stage II and III breast cancer, triple negative breast cancer, and HER2-positive tumors, every effort should be made to avoid postponing the initiation of adjuvant chemotherapy."
Deciding May Cause Delay
Current guidelines from the European Society of Medical Oncology on adjuvant chemotherapy for breast cancer indicate that treatment should start preferably within 2 to 6 weeks, observe the editorialists.
They also point out that despite such guidelines, in the last 10 years, there has been a "significant" increase in time between surgery and the start of the first adjuvant treatment, including chemotherapy.
For instance, in a large, multi-institutional cohort of women with breast cancer, the mean time from diagnosis to start of adjuvant chemotherapy increased from 10.8 to 13.3 weeks between 2003 and 2009 (J Natl Cancer Inst. 2013;105:104-112).
What is going on?
The increase in delay, in this earlier study, was "mainly associated with diagnostic evaluations such as use of a multigene assay and therapeutic interventions such as immediate post-mastectomy reconstruction and re-excision for adequate surgical margins," they say.
The new study, at the very least, puts the spotlight on a subject that largely goes unnoticed, suggest the editorialists. The matter of timing of adjuvant chemotherapy "has not received much recent attention from physicians and patients," they write.
The authors and editorialists have disclosed no relevant financial relationships.
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου