Refining Post-Surgical Therapy for Women with Lymph Node-Positive Breast Cancer
Name of the Trial
Tamoxifen Citrate, Letrozole, Anastrozole, or Exemestane with or without Chemotherapy in Treating Patients with Invasive RxPONDER Breast Cancer. See the protocol summary.
Official title: A Phase III, Randomized Clinical Trial of Standard Adjuvant Endocrine Therapy with or without Chemotherapy in Patients with 1-3 Positive Nodes, Hormone Receptor-Positive and HER2-Negative Breast Cancer with Recurrence Score (RS) of 25 or Less (SWOG-S1007).
Dr. Kevin Michael Kalinsky, SWOG (formerly Southwest Oncology Group)
Why This Trial Is Important
The term “breast cancer” encompasses several distinct cancers that are defined by their genetic and molecular characteristics in addition to their location in the body. The individual types of breast cancer may respond differently to treatments such as endocrine therapy, chemotherapy, and biologic or drug therapies that target certain receptor proteins on the cell surface, including the receptor protein HER2. Scientists have made substantial progress in classifying the different types of breast cancer by their molecular features and are creating new treatments that target those features.
Early-stage breast cancer is usually treated with surgery, followed by radiation therapy. In addition, many women with breast cancer have cancer cells that express estrogen and progesterone hormone receptors; such cancers are referred to as hormone receptor (HR) positive. These women typically receive post-surgical, or adjuvant, endocrine therapy with tamoxifen or an aromatase inhibitor.
If a woman has HR-positive breast cancer that is determined to have a higher risk of recurrence, she may receive adjuvant chemotherapy with cytotoxic drugs for up to 6 months before starting endocrine therapy. One common determinant of higher recurrence risk is the presence of cancer cells in the lymph nodes closest to the tumor (node-positive disease). Currently, all women with HR-positive breast cancer that has spread to the lymph nodes receive chemotherapy, unless it is contraindicate d.
Genetic tests developed in recent years are helping to better identify women likely to experience a recurrence. The 21-gene signature recurrence score test, Oncotype DX™, examines the expression of 21 genes—16 known to play a role in breast cancer and 5 reference genes—to generate a recurrence score between 1 and 100. For women with HR-positive breast cancer that has not spread to the lymph nodes (node-negative disease), the test can accurately predict the likelihood of recurrence better than traditional predictors of recurrence, such as patient age and tumor size. Using the test, doctors are now able to determine which patients are most likely to need chemotherapy in addition to endocrine therapy because of a high likelihood of recurrence, thereby allowing women with low recurrence scores to avoid the toxic side effects and other costs of chemotherapy.
To see if the test might also be useful for women with node-positive disease, researchers retrospectively analyzed tumor tissue taken from women with HR-positive, node-positive breast cancer who participated in a previous clinical trial of endocrine therapy with or without adjuvant chemotherapy. Results from this analysis suggest that the 21-gene recurrence score test can help identify women who will benefit from chemotherapy and those who may safely skip it. The current clinical trial will prospectively evaluate the test in a similar patient population.
In this phase III trial, women with HER2-negative, HR-positive breast cancer and 1 to 3 positive lymph nodes will be tested to determine their recurrence score. Women with recurrence scores of 25 or lower will discuss their score with their physicians, and, if they decide to continue in the study, they will be randomly assigned either to undergo adjuvant chemotherapy before starting endocrine therapy or to begin endocrine therapy without chemotherapy. The primary objectives of the study are to see if those women with low recurrence scores can safely skip chemotherapy and if there is a specific score above which there is a consistent benefit from chemotherapy.
“We estimate that about two-thirds of the 9,400 women who will be tested in this study will have a recurrence score of 25 or less, and those are the patients we would consider low risk and hypothesize that chemotherapy has no benefit for,” said Dr. Gonzalez-Angulo. “So, our main purpose is to see if we can spare these women from 6 months of toxic therapy that they may not need and may get no benefit from.
“If we can demonstrate that there is a score below which chemotherapy has no benefit, then for those women we can do away with the risks of long-term toxicity, including cardiac toxicity and leukemias, and the costs associated with chemotherapy, not just in terms of direct costs of the drugs but also those associated with hospitalization for complications of chemotherapy treatment,” she added.