Do All Breast Cancer Patients Benefit From Chemotherapy?
Breast cancer is the most common cancer in women both in the United States and beyond. There is about a 1 in 8 chance that a woman in the U.S. will be diagnosed with breast cancer in her lifetime. Sadly, nearly 42,170 American women will likely die in 2020 as a result of breast cancer.
But there is good news: breast cancer research has led to breakthrough treatments that extend patient survival.
Researchers are not only discovering new ways to treat breast cancer, but are also becoming extremely skilled at predicting how patients will respond to these treatments.
For instance, take a look at this recent breast cancer study.
The study looked at the 21-gene breast cancer assay to determine which breast cancer patients benefited from endocrine therapy alone, or endocrine therapy combined with chemotherapy, also known as adjuvant chemotherapy.
Oftentimes, adjuvant chemotherapy, which is chemotherapy given in addition to treatments like radiation and surgery, reduces the risk of breast cancer recurrence. Studies have shown that the method is even more effective in younger women. It seems that nodal status, grade, or the use of endocrine treatment had little effect on the success of adjuvant chemotherapy.
So, because several patients seemed to benefit from adjuvant chemotherapy, the official suggestion from a National Institutes of Health consensus board is to go ahead and give the adjuvant chemotherapy to most patients.
It’s true that this method is correlated with a decrease in the breast cancer death rates, but does that mean every patient benefits from the adjuvant chemotherapy?
Or is it possible that many receive the harsh treatment without really needing it?
This is what The Trial Assigning Individualized Options for Treatment (TAILORx) sought to uncover.
So what is the 21-gene recurrence score assay?
The 21-gene recurrence score assay (developed by Oncotype DX, Genomic Health) is a way of predicting patient outcome in hormone-receptor-positive breast cancer. The score ranges from 0 to 100, and estimates the benefit of chemotherapy. A score is considered high usually at 31 or higher. A low score is from 0-10, and predicts only a 2% rate of recurrence at 10 years. This outcome is not believed to be changed by adjuvant chemotherapy.
The issue with the 21-gene recurrence score assay is that most patients score in the mid-range. Adjuvant chemotherapy is recommended for these patients even though doctors aren’t positive that they’ll even benefit from or need it.
So TAILORx set out to see whether or not chemotherapy is the best choice for women who score in the mid-range (11-25). The ultimate goal would be to avoid adjuvant chemotherapy if it isn’t necessary.
The trial also sought to officially confirm that a low recurrence score (1-10) is indeed correlated with a low rate of distant recurrence when patients only receive endocrine therapy.
The trial was a prospective clinical trial, meaning it produces quality evidence to show how useful a biomarker is. It was sponsored by the National Cancer Institute and coordinated by the Eastern Cooperative Oncology Group (ECOG) – eCOG- American College of Radiology Imaging Network (ACRIN) Cancer Research Group.
Women enrolled in the study were between 18 and 75 years of age, and they all had hormone-receptor-positive, human epidermal growth factor receptor (HER2)- negative axillary node-negative breast cancer.
The women in the study were placed into four separate treatment groups based on their 21-gene recurrence score.
Women with a score of 10 or lower received endocrine therapy only.
Women with a score of 26 or higher received chemotherapy plus endocrine therapy (chemoendocrine therapy.)
Women with a midrange score between 11-25 were randomly assigned either endocrine therapy alone or chemoendocrine therapy.
A total of 10,273 women were originally registered in the study between April 7, 2006 and October 6, 2010. The 9,719 patients who had follow-up information are included in the final results of the study.
Of these 9,719 patients,
6,711 (69%) had a recurrence score between 11 and 25
1619 (17%) had recurrence score of 10 or lower
1389 (14%) had recurrence score of 26 or higher
The median duration of follow-up in the group of patients with a median recurrence score of 11 to 25 was 90 months of survival without any invasive disease and 96 months for overall survival.
There were a total of 836 incidences of invasive disease recurrence, second primary cancer, or death in the 2 random treatment groups. 338 of these were recurrences of breast cancer as the first event, while 199 were distant recurrences.
So what did the study reveal?
Among the 6,711 patients who had a midrange recurrence score between 11 and 25, endocrine therapy was not inferior to chemoendocrine therapy.
This means that adjuvant chemotherapy did not benefit these patients!
This result also stands in opposition to previous biomarker validation studies done on tumor specimens. This prior study showed that a combination of chemotherapy and endocrine therapy had a significant benefit in patients with a recurrence score of 26 or higher in preventing distant recurrence.
The 9-year rate of distant recurrence in women with a score between 11 and 25 in this trial was about 5% — regardless of chemotherapy use.
40% of women 50 years or younger had a recurrence score of 15 or lower. This correlated with a low rate of recurrence with endocrine therapy by itself. The study also showed that chemotherapy had some effect for women 50 years or younger who had a recurrence score of 16 to 25. There was a greater effect with adjuvant chemotherapy in younger women.
How will this study benefit breast cancer patients?
Since the release of this study, doctors have lessened the use of adjuvant chemotherapy significantly. The study allowed researchers to better assess the benefits of adding chemotherapy to a treatment regimen in women with certain 21-gene assay recurrence scores.
The 21-gene assay can determine up to 85% of women with early breast cancer who don’t need adjuvant chemotherapy!
This is especially true in patients who are older than 50 and have a recurrence score of 25 or lower, and in patients 60 or younger with a recurrence score of 15 or lower.
Why does this matter?
Chemotherapy can be an effective treatment for many cancers in many patients, but it is not without its debilitating effects. The side effects can be extreme and may lower the overall quality of life and health for the patient. By more precisely predicting which patients may actually benefit from the added chemotherapy, doctors can now spare patients the debilitating effects of the treatment if they don’t actually need the treatment.