Women diagnosed with stage I to stage III HER2-negative breast cancer who received less than 85% of the planned total dose of chemotherapy had worse survival than women who received 85% or more of the planned dose, according to a study.
The research was published in the August 2019 issue of the Journal of the National Comprehensive Cancer Network. Read “Impact of Cumulative Chemotherapy Dose on Survival With Adjuvant FEC-D Chemotherapy for Breast Cancer.”
How the study was done
The study included 1,302 women from the Canadian province of Alberta who were diagnosed with stage I to stage III HER2-negative breast cancer between 2007 and 2014. After breast cancer surgery, all the women received between four and six cycles of the chemotherapy regimen FEC-D:
- Ellence (chemical name: epirubicin)
- Cytoxan (chemical name: cyclophosphamide)
- followed by at least one dose of Taxotere (chemical name: docetaxel)
Doctors call treatments given after surgery adjuvant treatments.
The women’s ages ranged from 24 to 77. About 65% of the women were diagnosed with stage II breast cancer. About 83% of the cancers were hormone-receptor-positive and 17% were hormone-receptor-negative. About 40% of the women had lumpectomy and about 60% had mastectomy.
The researchers looked at the women’s medical records and calculated the total amount of chemotherapy each woman received for cycles one to six, which the researchers called the total cumulative dose. The researchers also looked to see when a dose was reduced. The researchers then compared the total cumulative dose of chemotherapy each woman received to the planned dose each woman should have received and calculated whether a woman received 85% or more of her planned dose or less than 85% of her planned dose.
The researchers noted that a landmark 1995 study found that women diagnosed with early-stage breast cancer who received 85% or more of the total cumulative dose of an older chemotherapy regimen — Cytoxan, methotrexate, and fluorouracil — had better survival than women who received less than 85% of the total cumulative dose of chemotherapy. The researchers wanted to see if this 85% threshold applied to a newer chemotherapy regimen commonly used today.
Overall, 1,100 women received 85% or more of their planned doses of chemotherapy and 202 women received less than 85% of their planned doses of chemotherapy.
Women who received 85% or more of their planned chemotherapy doses were more likely to be younger, premenopausal, and have a lower number of other diseases.
At 5 years, disease-free survival rates were:
- 85.9% for women who received 85% or more of their planned chemotherapy doses
- 79.2% for women who received less than 85% of their planned chemotherapy doses
The disease-free survival rate is how many women were alive without the cancer coming back.
At 5 years, overall survival rates were:
- 88.8% for women who received 85% or more of their planned chemotherapy doses
- 80.7% for women who received less than 85% of their planned chemotherapy doses
The overall survival rate is how many women were alive, whether or not the cancer had come back.
Both of these differences were statistically significant, which means they were likely because of the difference in chemotherapy doses and not just due to chance.
The researchers also found that when chemotherapy doses were reduced early in chemotherapy treatment, survival was worse compared to when chemotherapy doses were reduced later in chemotherapy treatment. This difference was not statistically significant, but it was a trend that continued through the data.
"What surprised us the most was how dramatically early reductions in chemotherapy affect survival compared to later modifications," said lead author Zachary Veitch, M.D., of the University of Toronto, in a statement. "This became even more apparent when patients were further separated based on chemotherapy dose cutoffs. Often the first cycle of chemotherapy can be difficult for patients, and oncologists must convey the need for maintaining initial dose intensity, while using other medications to control side effects and manage comorbidities."
What this means for you
If you’ve been diagnosed with early-stage HER2-negative breast cancer and chemotherapy will be part of your treatment plan, this study strongly suggests that receiving 85% or more of your planned dose of chemotherapy can improve your survival.
Chemotherapy destroys cancer cells because the medicines target rapidly dividing cells. But healthy cells in your blood, mouth, intestinal tract, nose, nails, vagina, and hair also divide rapidly. So chemotherapy affects them, too, and can cause a variety of side effects.
While the researchers who did this study were not able to find out why the women in the study received a lower than planned dose of chemotherapy, they did note that dose reductions are often related to side effects.
If you’re receiving chemotherapy and are having unacceptable side effects, it’s important to tell your doctor and oncology nurse right away. There are medicines available to control these side effects. If you’re already taking medicine to ease chemotherapy side effects and they’re not working, speak up and your doctor or nurse can help you find something that does work.
In some cases, you may be able to change the medicines in your chemotherapy regimen to ones that cause fewer or different side effects.
For more information on chemotherapy, including regimens and side effects, visit the Breastcancer.org Chemotherapy pages.
Written by: Jamie DePolo, senior editor
Reviewed by: Brian Wojciechowski, M.D., medical adviser