Hormone Therapy-Chemo Combo Reduces Risk of Tumor Return in Highly Recurrent Breast Cancer, Phase 3 Trial Shows

Using chemotherapy in combination with hormone therapy in women with highly recurring forms of breast cancer reduces the likelihood of disease returning elsewhere in the body over nine years compared with hormone therapy alone, a Phase 3 trial shows.

The research, “Clinical Outcomes by Chemotherapy Regimen in Patients with RS 26-100 in TAILORx,” was presented at the recent European Society for Medical Oncology (ESMO) 2019 Congress, in Barcelona, Spain, and also published in JAMA Oncology.

TAILORx (NCT00310180) is a Phase 3 study sponsored by the National Cancer Institute (NCI) and led by the ECOG-ACRIN Cancer Research Group. It was designed to determine the best course of treatment for women with highly recurring forms of breast cancer, as defined by the Oncotype DX Breast Recurrence Score test. With more than 1,200 trial sites from six countries, TAILORx is the largest breast cancer treatment trial ever conducted.

Oncotype DX, developed by Genomic Health, uses a tumor biopsy to examine the activity of 21 genes in a patient’s breast tumor, scoring it from 1 to 100 for the risk of cancer returning. It is intended for women newly diagnosed with breast cancer that’s still at an early phase (I-IIIa), and is positive for estrogen receptors (ER-positive) but has no excess levels of the growth-promoting protein HER2 (HER2-negative).

One of TAILORx’s goals was to determine if adding chemotherapy to hormone (or endocrine) therapy would lower the likelihood of cancer recurrence in a sub-group of 1,389 women (median age of 56 years) with the most common form of early breast cancer — hormone receptor-positive (having estrogen and progesterone receptors) but HER2- and axillary node-negative (no cancer spreading to the axillary lymph nodes) — and deemed at high risk of disease recurrence (Oncotype DX score of 26 to 100) and likely to respond well to chemo.

Results indicated that women receiving chemotherapy and hormone therapy had a 91% chance of remaining cancer-free in the breast, and a 93% chance of having no signs of cancer recurrence elsewhere in the body within five years. The different chemotherapy combinations were associated with a higher-than-90% likelihood of no cancer recurrence at a distant site, with the exception of the CMF regimen (cyclophosphamide / methotrexate / 5-fluorouracil), which had a likelihood of 88.5%.

However, if on hormone therapy alone, the likelihood of no cancer recurrence in a different region of the body within the same period was reduced to 78.8%.

Estimations of cancer recurrence within nine years followed the same trend, with women receiving chemotherapy together with hormone therapy expected to have higher chances of remaining cancer-free (86.8%) compared to those treated with hormone therapy alone (65.4%).

“These findings were highly consistent with a comparable population with ERBB2 [HER2]-negative disease in the B20 trial,” the investigators wrote. B20 had shown that, unlike women with low recurrence scores (0–10), those with high scores (26 or more) could benefit from add-on chemotherapy.

Previous TAILORx findings had supported the usefulness of the Oncotype DX test to identify patients more likely to respond well to treatment. Women with an intermediate risk score (11–25) showed no benefit from adding chemo to hormone therapy, meaning that they can be spared from this aggressive treatment. More recent data showed that adding an assessment of a woman’s clinical risk to the Oncotype DX score may spare more young women from undergoing chemotherapy after surgery.

“Last year, TAILORx established the highest level of evidence and unprecedented precision supporting the use of the Oncotype DX Breast Recurrence Score test to guide adjuvant chemotherapy treatment for women with early-stage breast cancer,” Joseph A. Sparano, MD, associate director for clinical research at the Albert Einstein Cancer Center and Montefiore Health System in New York, vice chair of the ECOG-ACRIN Cancer Research Group and lead author of the study, said in a news release.

“This new analysis provides the largest dataset on outcomes in patients with high Recurrence Score results, and confirms the importance of using the test to identify the patients who will receive a significant benefit from adding adjuvant chemotherapy,” Sparano added. 

Steven Shak, MD, chief scientific officer of Genomic Health, commented: “We’re pleased to see that the landmark TAILORx trial continues to receive global recognition, as evidenced by this fourth peer-reviewed publication.”

“TAILORx established that the Oncotype DX test definitively identifies the vast majority of women with early-stage breast cancer who receive no benefit from chemotherapy and the important minority for whom chemotherapy can be life-saving. The additional insight from this new analysis is consistent with, and further supports, the conclusion that the Recurrence Score predicts which patients benefit from chemotherapy and which patients do not, giving them the standard of care they deserve,” Shak added.

Over the last few months, data from TAILORx and the Oncotype DX Breast Recurrence Score test have contributed to updates to treatment guidelines from the American Society of Clinical Oncology, the National Comprehensive Cancer Network, ESMO, as well as the new St. Gallen International Breast Cancer Guidelines. The cost of Oncotype DX is now reimbursed in Lombardy (Italy) and Germany.