Breast cancer chemotherapy more effective when started within 1 month of surgery


Chemotherapy after surgery (called adjuvant chemotherapy) for breast cancer should not be delayed for more than 60 days. Such delays significantly increased the odds of premature death and distant metastasis, in a review of almost 7,000 cases.

As compared with starting adjuvant therapy within 30 days of surgery, initiating chemotherapy at 61 days or later was associated with a 19% increase in the risk of premature death. In the subgroup of patients with stage 3 disease, the mortality risk increased by 76%. Relapse-free survival (RFS) and distant relapse-free survival (DRFS) worsened regardless of stage at diagnosis, according to Mariana Chavez-MacGregor, MD, of the University of Texas MD Anderson Cancer Center in Houston, and colleagues.

Patients with high-risk breast cancer (triple negative, HER2-positive, or stage 3) seemed most susceptible to the adverse effects of delayed chemotherapy, as reported online in the Journal of Clinical Oncology.

"The adverse outcomes occurred when chemotherapy was delayed ≥61 days, which in most circumstances, gives medical oncologists enough time to initiate adjuvant chemotherapy," the authors concluded.

"Among patients with stage 2 and 3 breast cancer, triple-negative breast cancer, and HER2-positive tumors, every effort should be made to avoid postponing initiation of adjuvant chemotherapy. This may lead to an improvement in outcomes for these subsets of patients."

Multiple studies have documented survival benefits associated with adjuvant chemotherapy in early breast cancer. Equally well recognized is the heterogeneity of breast cancer, affecting both risk and the benefit of adjuvant chemotherapy.

In most instances, adjuvant chemotherapy begins within a few weeks of surgery. However, the potential impact of a delay in initiation of therapy is unclear, although mathematical models have suggested deleterious effects, in particular, an increased likelihood that treatment-resistant micrometastases would emerge, the authors noted.

Moreover, little information exists relative to the impact of time to chemotherapy on outcomes in different breast cancer subtypes.

In an attempt to fill in some of the information gaps, Chavez-MacGregor and colleagues retrospectively reviewed medical records of 6,827 patients treated for early breast cancer at MD Anderson from 1997 to 2011 and followed for a median duration of 59.3 months.

Patients with stage 1-2 disease accounted for 84.5% of the study population, and the remaining 15.5% of patients had stage 3 disease at diagnosis. The study group comprised 2,716 (39.8%) patients who started therapy within 30 days of surgery, 2,994 (43.8%) who initiated adjuvant therapy 31 to 60 days after surgery, and 1,117 (16.4%) who initiated treatment ≥61 days after surgery.

The cohort had a 5-year overall survival (OS) of 84%, 5-year RFS of 69%, and DRFS of 72%. Not unexpectedly, patients with larger tumors and greater nodal involvement had worse OS, RFS, and DRFS, the authors noted.

Analysis of factors that influenced outcomes of interest showed no difference in OS, RFS, or DRFS in patients with hormone receptor-positive or HER2-positive tumors, regardless of when they initiated therapy.

The 5-year OS estimate did differ among HER2-positive patients who received trastuzumab (Herceptin), as better survival was observed in patients who started therapy within 30 days of surgery (88%) compared with 31 to 60 days (87%) or ≥61 days (75%). Statistically speaking, the difference between ≥61 days and ≤30 days translated into a hazard ratio of 3.09 (95% CI 1.49-6.39).

Similarly, patients with triple-negative breast cancer had a 5-year OS estimate of 70% when they started chemotherapy within 30 days, 59% for therapy starting between 31 and 60 days, and 67% for therapy ≥61 days after surgery (P=0.005). Comparing the latest and earliest initiation times resulted in a hazard ratio of 1.54 (95% CI 1.09-2.18).

Neither relapse-free survival (RFS) nor distant relapse-free survival (DRFS) differed by time to chemotherapy in patients with stage 1 disease. Among patients with stage 2 disease, the hazard for DRFS increased by 18% to 20% when chemotherapy was started more than 30 days after surgery.

The subgroup of patients with stage 3 disease had a 76% increase in mortality risk if they started chemotherapy ≥61 days after surgery versus 30 days or less (Hazard Ratio of 1.76, 95% CI 1.26-2.46). Risks associated with RFS and DRFS increased by 34% and 36%, respectively.

The study is consistent with other reports in the literature, said Jim Biagi, MD, of Queen's University in Kingston, Ontario, and continued to state that "The study adds to the available literature suggesting that delays may be detrimental to a patient's cancer outcome. Indeed, patients who had the highest-risk features for breast cancer recurrence, and who would thus derive the greatest benefit from adjuvant chemotherapy, were the most vulnerable to this effect."

"While discrepancies in their results limit our ability to make a strong statement about delays, the study is an important addition to our understanding of the impact delays might have on patient outcomes. It seems to me that if we are asking our patients to undergo 4 to 6 months of chemotherapy, that we offer the treatment in a timely manner."

Biagi participated in a meta-analysis of studies evaluating the impact of time to chemotherapy on survival in colorectal cancer and found a significant association between increasing time to therapy and worse OS and overall survival and disease-free survival. However, in another study Biagi was involved in, an analysis of time to chemotherapy showed no significant effect on survival in non-small-cell lung cancer.


Source: MedPage Today:

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