For Breast Cancer Treatment, Timing May Be Everything

For the approximately 232,670 women in the United States who will be diagnosed with breast cancer this year, findings from a new Phase 3 clinical trial are shedding light on the best way to administer treatments. These finding have the potential to change the way oncologists will use adjunctive chemotherapy in the future.
The use of chemotherapy following primary treatment for breast cancer has significant potential to extend lives. For patients with early-stage breast cancer, adjuvant intervention is particularly important for halting illness progression and barring future recurrence of disease. However, oncologists have yet to determine the dose and schedule of chemotherapy that will yield optimal outcomes in mortality. The new trial offers first steps toward changing that.

Fine-Tuning Frequencies

Oncology researchers from the North American Breast Intergroup, which includes Cleveland Clinic and other medical centers across the United States and Canada, recently collaborated on a novel study to better determine the optimal dose and frequency of commonly administered chemotherapies for breast cancer. Findings from the trial, which was supported by the National Cancer Institute, were released in the online edition of the Journal of Clinical Oncology.

The study looked at no new drugs but rather at the best way of administering medications oncologists have given to patients with breast cancer for some time.

“Previous studies had shown that it appeared to be better to give some chemotherapies every two weeks as opposed to every three weeks, and in the case of Taxol, to give it weekly as opposed to every three weeks,” explains George Thomas Budd, MD, staff physician in the Taussig Cancer Institute and lead author on the paper. “This study looked at giving all chemotherapies weekly or every two weeks.”

In most of the 3,000-plus patients enrolled, the schedule of chemotherapies tested — doxorubicin (Adriamycin®), cyclophosphamide (Cytoxan®) and paclitaxel (Taxol®) — had no significant effect on outcomes of survival and time to recurrence. For instance, Taxol given on a weekly basis had no effect on mortality but resulted in more doctors’ visits but fewer side effects. But in a small subset of patients with so-called triple-negative disease (that is, individuals whose tumors tested negative for the presence of estrogen, progesterone and HER2 hormone receptors) results supported giving chemotherapies every two weeks.

“From a practical point of view, that means that most patients can be treated with Adriamycin and Cytoxan every two weeks and Taxol weekly, but for patients with triple-negative breast cancer, it might be better to give all the treatments every two weeks,” says Dr. Budd, adding that because the findings in the triple-negative group came from unplanned statistical analyses, they should be interpreted with caution.

Implications for Patients

The study’s results suggest that, in the future, it may be beneficial to tailor chemotherapy to an individual’s type of breast cancer, particularly for whether or not the tumor is hormone-receptor positive or negative. Further studies will need to explore if different cancers would best be treated with different doses and schedules of chemotherapies.

Dr. Budd warns against making assumptions about survival. One unusual finding from the study indicated an improvement in overall survival for patients in the “every two weeks” schedule but no improvement in disease-free survival, meaning time from diagnosis to recurrence. However, this might reflect differential effects from triple-negative breast cancer, which has a worse prognosis after recurrence. It also may be due to random differences between the study groups that have nothing to with the treatment, he notes.

Additional trials are needed to more definitively inform potential changes in treatment approaches.
“The next steps will include genetic studies looking at the side effects experienced by patients enrolled in this trial and also molecular studies of the tumors of these patients in order to gain insight into how best to treat breast cancer,” Dr. Budd summarizes.

Photo Credit: Russell Lee