Study: Some women with early-stage breast cancer forego chemotherapy

IN-DEPTH REVIEW OF RESEARCH

Study background:

Oncotype DX is a test to predict whether chemotherapy will benefit a patient with hormone receptor-positive breast cancer. Recurrence scores are based on RNA expression of 21 genes. Recurrence scores range from 0 to 100. Scores of 31 and higher (or 26 and higher in some studies) are associated with chemotherapy benefit. Low recurrence scores (0-10) are associated with a very low risk of recurrence that chemotherapy is not likely to lower any further. While many experts recommend the use of the Oncotype DX tumor test as a predictor of recurrence and to guide chemotherapy recommendations, it was uncertain whether those who had mid-range recurrence scores would benefit from adjuvant chemotherapy.

Researchers of this study wanted to know:

Whether they could further tailor treatment of hormone receptor-positive breast cancer for patients with mid-range Oncotype DX recurrence scores.

Study design:

The phase III, prospective study enrolled women who were 18 to 75 years of age, had hormone receptor-positive, HER2-negative, axillary node-negative breast cancer who met National Comprehensive Cancer Network guidelines for the consideration of adjuvant chemotherapy.

10,273 women registered for the study between October 6, 2010, and April 7, 2016.

There were 9,716 patients with follow-up information who were assigned therapy based on their Oncotype DX recurrence score:

• 6,711 (69%) had an Oncotype DX recurrence score of 11-25 and were randomly assigned to receive either endocrine therapy alone or endocrine therapy plus chemotherapy.
• 1,619 (17%) had an Oncotype DX recurrence score of 10 or lower and were assigned to receive endocrine therapy alone.
• 1,389 (14%) had an Oncotype DX recurrence score of 26 or higher and were assigned to receive chemotherapy plus endocrine therapy.

Median length of endocrine therapy was 5.4 years. The most common chemotherapy regimens among patients were docetaxel-cyclophosphamide (56%) and anthracycline-containing regimens. Hormonal therapies among postmenopausal women most commonly included an aromatase inhibitor (91%) and among premenopausal women either tamoxifen alone or tamoxifen followed by an aromatase inhibitor (78%). Suppression of ovarian function was used in 13% of premenopausal women.

Study findings:  

Results of the TAILORx trial were presented on June 3, 2018, at the annual American Society of Clinical Oncology meeting in Chicago, Illinois and published in the New England Journal of Medicine.

• In patients with Oncotype DX recurrence scores ranging from 11 to 25, chemotherapy did not improve invasive disease-free survival (iDFS) when added to adjuvant endocrine therapy.
  • For endocrine therapy alone versus endocrine therapy plus chemotherapy:
    • Nine-year iDFS rates were 83.3% and 84.3%.
    • Freedom from recurrence of breast cancer at a distant site were 92.2% and 92.9%.
    • Freedom from recurrence of breast cancer at a distant or local-regional site were 93.9% and 93.8%.
    • Overall survival was 93.9% and 93.8% respectively.
• Women with Oncotype DX scores of 26 or higher had poorer outcomes with higher with higher even rates despite the addition of chemotherapy to endocrine therapy.
• Younger women (50 years or under) with a recurrence score of 16 to 25 saw some benefit with adjuvant chemotherapy (slightly less than half of women in this age group had scores in this range).
  • Women 50 or younger with recurrence scores of 16 to 20 who had adjuvant chemotherapy had fewer distant recurrences.
  • Women 50 or younger with recurrence scores of 21 to 25 who received adjuvant chemotherapy had 7% fewer distant recurrences.

Limitations:

While chemotherapy had some benefit for women 50 years of age or younger with recurrence scores of 16 to 25, it is not clear why. It is possible that this observation is due a lowering of estrogen from chemo-induced menopause, but the researchers did not collect data on that. It remains unclear whether similar benefits could be achieved with ovarian suppression coupled with an aromatase inhibitor for these women.

Conclusions:

In the early 2000s, most patients with breast cancer who were hormone receptor-positive and node-negative received chemotherapy, but most did not benefit from it. The results of the TAILORx trail, the largest breast cancer treatment trial ever conducted, suggest that the Oncotype DX tumor test could identify up to 85% of women with early breast cancer who can forego adjuvant chemotherapy, especially women older than 50 with a recurrence score of 25 or less and women 50 years of age or younger with a recurrence score of 15 or less. This trial, as well as other smaller trials, have generated new data that can guide adjuvant chemotherapy use for patients.  More studies are needed to clarify those women who need more of some therapies and less of other therapies.

Posted 7/20/18

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