Results from the prospective, randomized phase III MINDACT study indicate that a subset of women with early-stage breast cancer can forego adjuvant chemotherapy. Investigators hope this eventually changes clinical practice, because unnecessary treatment places many women at risk of long-term side effects, such as cardiac toxicity, secondary cancers, and early menopause.

MINDACT, a prospective, randomized phase III study of women with early-stage breast cancer, has identified a subset who can forego adjuvant, or postsurgery, chemotherapy. Data from the trial were presented by Martine Piccart, MD, PhD, head of medicine at the Jules Bordet Institute in Brussels, Belgium, at the American Association for Cancer Research Annual Meeting 2016 in New Orleans, LA.

“Because advanced breast cancer is largely incurable, oncologists tend to prescribe adjuvant therapy to most women with early-stage disease, with the goal of eradicating micrometastases,” Piccart said. However, many women who receive this additional treatment face long-term risks, such as cardiac toxicity, secondary cancers, and early menopause, with little chance of prolonging their lives.

MINDACT compared the ability of two different assays to calculate the risk of breast cancer recurrence: MammaPrint (Agendia), a 70-gene signature developed by researchers at the Netherlands Cancer Institute in Amsterdam; and Adjuvant! Online, a computerized tool that uses common clinical factors such as tumor stage and grade. The study enrolled 6,693 women from 112 centers in nine countries who had undergone surgery for early-stage breast cancer. All patients had their risk of disease recurrence assessed with both tools.

Piccart and her colleagues identified two groups of women with discordant results: The first was categorized as high risk, genomically, by MammaPrint but low risk, clinically, by Adjuvant! Online (G-high/C-low). The second group had the opposite results—low risk by MammaPrint but high risk with Adjuvant! Online (G-low/C-high). Patients in both groups were randomly assigned to receive adjuvant chemotherapy or no treatment.

The investigators paid particular attention to the 644 women classified as G-low/C-high who did not receive adjuvant chemotherapy. For MammaPrint to outperform Adjuvant! Online and reduce the use of chemotherapy without compromising survival, researchers determined that 92% of the women would need to be metastasis-free after 5 years. The actual outcome was 94.7%.

“We're pretty confident that these particular women can be spared adjuvant chemotherapy,” Piccart said—a move that would effectively halve the use of chemotherapy in a population otherwise thought to be at high risk through traditional clinical assessments of disease recurrence.

Harold Burstein, MD, PhD, of Dana-Farber Cancer Institute in Boston, MA, lauded Piccart's team for their “heroic effort” in carrying out this large study. “It successfully demonstrates that integrating genomic features with pathology is a powerful strategy for improving breast cancer prognosis and tailoring treatment for women so that many can avoid chemotherapy,” he said.

Piccart is hopeful that the results of MINDACT will eventually change clinical practice. Meanwhile, the study has “played a major educational role in Europe, popularizing the concept of biology-driven treatment,” she said. In addition, the logistics are now in place “to collect and freeze tumor materials in a quality-controlled fashion,” she added, which will enable the researchers to build “an invaluable biobank for future research that allows us to gain a much better understanding of breast cancer.” –Alissa Poh

©2016 American Association for Cancer Research.
2016
American Association for Cancer Research.