The San Antonio Breast Cancer Symposium (SABCS) 2024 showcased groundbreaking clinical trial results, offering new hope and refined treatment strategies for breast cancer patients. Several studies presented at the symposium highlighted potential shifts in the standard of care for various subtypes and stages of the disease.
Novel Therapies for Metastatic Breast Cancer
The EMBER3 trial (NCT04975308) evaluated imlunestrant, a next-generation selective estrogen receptor degrader (SERD), in patients with estrogen receptor (ER)-positive, HER2-negative advanced breast cancer previously treated with endocrine therapy. Dr. Komal Jhaveri of Memorial Sloan Kettering Cancer Center presented the findings, which suggest that while imlunestrant monotherapy improved progression-free survival (PFS) in patients with ESR1 mutations (median PFS of 5.5 months versus 3.8 months for chemotherapy), the combination of imlunestrant and abemaciclib showed enhanced PFS across all patients, regardless of ESR1 mutation status (9.4 months).
The phase 3 PATINA trial (NCT02947685) investigated the addition of palbociclib to standard anti-HER2 therapy and endocrine therapy in patients with hormone receptor (HR)-positive, HER2-positive metastatic breast cancer. Dr. Otto Metzger of the Dana-Farber Cancer Institute presented the results, demonstrating a greater than 15-month improvement in PFS for patients receiving palbociclib (median PFS of 44.3 months versus 29.1 months in the control arm), representing a 26 percent reduction in the risk of progression.
Impact of Risk-Reducing Surgeries in BRCA Mutation Carriers
An international, multicenter study presented by Dr. Matteo Lambertini of University of Genova-IRCCS Policlinico San Martino Hospital analyzed data from 5,290 patients ages 40 or under diagnosed with BRCA1- or BRCA2-mutated, stage 1 to 3 invasive breast cancer. The study found that patients who underwent risk-reducing mastectomy experienced a 35 percent reduction in the risk of death and a 42 percent reduction in the risk of breast cancer recurrence or a second primary malignancy. Oophorectomy was associated with a 42 percent reduction in the risk of death and a 32 percent reduction in the risk of breast cancer recurrence or a second primary malignancy. The survival benefit of oophorectomy varied by BRCA mutation type, with a greater reduction in risk of death in patients with BRCA1 mutation (56 percent) compared to the BRCA2-mutated group (15 percent).
Long-Term Benefits of Olaparib in High-Risk HER2-Negative Breast Cancer
Dr. Judy E. Garber, BCRF Scientific Director, presented updated results from the phase III OlympiA trial (NCT02032823), which evaluated olaparib as adjuvant therapy in patients with germline BRCA1/BRCA2 pathogenic variants and high-risk stage 2-3 HER2-negative breast cancer. After a median follow-up of 6.1 years, olaparib reduced the risk of death by 28 percent and reduced both the risk of invasive breast cancer recurrence and the risk of distant disease recurrence by 35 percent, compared to placebo.
Promising Results for Novel Antibody-Drug Conjugate in Early-Stage Breast Cancer
Dr. Mafalda Oliveira of Vall d’Hebron Institute of Oncology presented primary results of SOLTI-VALENTINE (NCT05569811), a phase 2 study testing HER3-deruxtecan (HER3-Dxd) alone or in combination with letrozole in previously untreated, high-risk HR-positive/HER2-negative early breast cancer. The study demonstrated that treatment with HER3-DXd, both with and without letrozole, had similar overall response rate and pathological complete response as chemotherapy, but with lower incidence rates of grade 3 adverse events.
FDA Approvals Based on Clinical Trial Success
Dr. Eric Winer, BCRF investigator and Scientific Advisory Board member, detailed the clinical trial results behind recent FDA approvals. The NATALEE trial (NCT03701334) results led to expanded approval for ribociclib for treating early, high-risk breast cancer. The INAVO120 trial (NCT04191499) investigated inavolisib in combination with palbociclib and fulvestrant for patients with endocrine-resistant, HR-positive, HER2-negative locally advanced or metastatic breast cancer with PIK3CA mutations, leading to its approval as a targeted therapeutic option.
Active Monitoring for Low-Risk DCIS
In the primary analysis of the COMET trial, researchers found that active monitoring patients with low-risk DCIS was comparable to treating patients upfront with surgery. Researchers also found that patients with low-risk DCIS who underwent active monitoring reported similar physical, emotional, and psychological outcomes to patients who received upfront treatment.
Obesity and Breast Cancer Outcomes
An analysis of data from 206,904 women with early breast cancer has found that elevated BMI (Body Mass Index) increases the risk of breast cancer mortality and recurrence. The research was undertaken by the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG), who found that there is an increased risk of breast cancer recurrence and risk of mortality regardless of age, tumour, type, year of diagnosis and hormone receptor status.
DECRESCENDO Trial
The DECRESCENDO researchers aimed to find out if a shorter duration of chemotherapy with trastuzumab and pertuzumab before surgery would lead to outcomes that were just as good as if a more intense treatment were used, but without as many side effects. Patients with lymph node negative, hormone receptor negative, HER2-positive early breast cancer were given treatment prior to surgery. The findings reported a very high 86% complete clearance of cancer cells by the time of surgery.
SUPREMO Trial
The SUPREMO trial aimed to find out if some patients might be able to be spared radiotherapy without any detriment to their long term outcomes. Eligible patients were randomly assigned after their mastectomy to receive either chest wall radiotherapy, or no radiotherapy, and were followed up for an average of 10 years. The trial found equivalent overall survival in both groups, without any differences according to lymph node involvement or oestrogen receptor status.
