Alliance E-News - December 2025
Spotlight on Scientific Meetings
At the 48th Annual San Antonio Breast Cancer Symposium (SABCS), taking place December 9-12, researchers from the Alliance for Clinical Trials in Oncology and Alliance Foundation Trials, LLC (AFT) will showcase their latest research. SABCS convenes an international community of academic and community-based clinicians and scientists to share leading-edge advances spanning breast cancer biology, prevention, detection, treatment, and premalignant breast disease.
Alliance investigator Sara M. Tolaney, MD, MPH, will receive the 2025 AACR Outstanding Investigator Award for Breast Cancer Research, which is supported by the Breast Cancer Research Foundation. Dr. Tolaney, Chief of the Division of Breast Oncology and Associate Director of the Susan F. Smith Center at the Dana-Farber Cancer Institute, and Associate Professor at Harvard Medical School, is being honored for her pioneering work in targeted therapies for HER2-positive breast cancer. This includes the Adjuvant Paclitaxel and Trastuzumab (APT) trial, which established a less intensive paclitaxel-trastuzumab regimen for early-stage disease, and her advancement of biomarker-driven, personalized approaches such as CDK4/6 inhibitors in both early and metastatic settings.
Frederick Howard, MD, an Alliance investigator, is one of four recipients of the 2025 SABCS® Rising Stars Award, a distinction that honors early-career researchers whose work shows exceptional promise in advancing breast cancer science and improving patient outcomes. Dr. Howard is an Assistant Professor of Medicine in the Section of Hematology/Oncology at UChicago Medicine, where he specializes in breast cancer care and clinical research. His work focuses on improving outcomes through biomarker development, advanced imaging and pathology techniques, and the use of artificial intelligence to better predict treatment response. [Rising Stars Session: December 9, 4:15 PM CST]
At this year’s meeting, Alliance and AFT will present 17 research abstracts, including:
GENERAL SESSION
GS2-07: Effect of preoperative breast MRI staging on local regional recurrence (LRR) in early stage breast cancer: Alliance A011104/ACRIN 6694
Lead Author: Isabelle Bedrosian, University of Texas MD Anderson Cancer Center
Alliance trial: A011401 | Abstract #:1668
Summary: Doctors sometimes order a breast MRI after a new breast cancer diagnosis to look for cancer that might not appear on a mammogram or ultrasound. The idea is that finding any additional disease could help guide surgery and lower the chance that the cancer returns in the breast or nearby lymph nodes. However, it has not been clear whether MRI actually leads to better outcomes.
This study included 319 people with early-stage triple-negative or HER2-positive breast cancer who were eligible for breast-conserving surgery. Participants were randomly assigned to either receive an MRI or continue with standard imaging only. All patients went on to receive usual treatments such as surgery, chemotherapy, and radiation when appropriate.
After about five years of follow-up, the study found no difference in how often the cancer came back locally between the two groups. Local recurrence rates were very low overall, whether or not an MRI was performed. There were also no differences in the chances of the cancer spreading or in overall survival.
For these patients, adding a breast MRI did not improve cancer control compared with standard imaging alone.
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POSTER SPOTLIGHT
PD2-03: Basal-like residual disease after neoadjuvant chemotherapy is immunologically cold and associated with poor prognosis in triple negative breast cancer CALGB 40603 (Alliance)
Lead Author: Patrick D. Rädler, University of North Carolina at Chapel Hill
Alliance trial: CALGB-40603
Summary: In early-stage triple-negative breast cancer (TNBC), patients with residual disease (RD) after chemotherapy have a higher risk of poor outcomes. This study found that prognostic features in RD tumors differ from pre-treatment tumors, especially in basal-like TNBC, which showed low immune activity and high oncogenic signals. Preclinical testing suggests that these high-risk, immune-cold tumors may respond to antibody-drug conjugates (ADCs) like sacituzumab govitecan or trastuzumab deruxtecan, offering a potential new treatment option for patients whose tumors do not fully respond to standard chemotherapy.
PD8-01: Weight trajectories in the Breast Cancer Weight Loss (BWEL) trial (Alliance)
Lead Author: Chao Cao, Dana-Farber Cancer Institute
Alliance trial: A011401
Summary: The BWEL study is testing whether a structured weight-loss program can improve outcomes for women with stage II–III breast cancer who have a higher body weight. More than 1,500 women in the weight-loss program used Fitbit scales to track their weight over two years. On average, participants lost about 6% of their weight by 40 weeks and kept off about 4% at two years. Most women had a moderate amount of weight loss, a smaller group lost a large amount, and about one in five did not lose weight. Certain factors—like menopause status, race, and health history—were linked to how much weight women lost. The results show that large-scale digital weight tracking is practical and that women respond differently to weight-loss programs, which may help tailor future support.
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POSTER SESSION
PS1-08-07: Final results from the randomized phase II study of Z-endoxifen and tamoxifen in endocrine refractory, estrogen receptor positive, HER2 negative metastatic breast cancer (Alliance A011203)
Lead Author: Matthew P. Goetz, Mayo Clinic
Alliance trial: A011203
Summary: In postmenopausal women with ER-positive/HER2-negative metastatic breast cancer, the study compared Z-endoxifen to tamoxifen. Overall, Z-endoxifen did not significantly improve the time patients lived without disease progression. However, in patients who had not previously received CDK4/6 inhibitors, Z-endoxifen extended progression-free survival by over six months compared to tamoxifen. Patients who switched from tamoxifen to Z-endoxifen after progression also showed clinical benefit, supporting further development of this therapy.
PS1-13-17: RNA-based immune features associated with benefit from distinct microtubule inhibitor therapy for metastatic HER2-negative breast cancer: a post hoc analysis of the CALGB 40502 (Alliance) phase III randomized clinical trial
Lead Author: Elijah Blige, The Ohio State University
Alliance trial: CALGB-40502
Summary: Microtubule-targeting chemotherapy, like paclitaxel, nab-paclitaxel, and ixabepilone, is commonly used for HER2-negative metastatic breast cancer (MBC). The CALGB (Alliance) 40502 trial compared these drugs as first-line therapy. Previous analysis suggested nab-paclitaxel may work less well in hormone receptor-positive (HR+)/HER2-negative MBC. In this trial, researchers looked at stromal tumor-infiltrating lymphocytes (sTILs)—immune cells in the tumor—and RNA-based immune markers to see if immune activity affected outcomes differently depending on the chemotherapy used. Researchers found that sTILs were linked to outcomes differently depending on breast cancer type. High immune activity improved survival in triple-negative breast cancer but was associated with worse outcomes in younger patients with HR+/HER2- disease. High T-cell signatures also predicted poorer outcomes with nab-paclitaxel in HR+/HER2- patients, highlighting that the effect of immune cells depends on cancer subtype and treatment.
PS2-07-13: Prognostic and predictive role of RBsig and CCNE1/RB1 gene-expression signatures for patients with early breast cancer treated with endocrine therapy with or without palbociclib in the PALLAS trial (ABCSG-42, AFT-05, BIG 14-03)
Lead Author: Luca Malorni, Hospital of Prato, Azienda USL Toscana Centro
Alliance trial: AFT-05
Summary: In the PALLAS/AFT-05 trial, higher levels of two gene signatures, RBsig and CCNE1/RB1, were linked to a higher risk of recurrence and worse survival in early-stage HR+/HER2- breast cancer. However, these markers did not predict benefit from adding palbociclib to hormone therapy. RBsig may help identify patients who could benefit more from chemotherapy, highlighting its potential use in guiding treatment decisions.
PS3-01-30: Change in mammographic density (MD) with metformin use: Alliance A211201, A companion study to NCIC study MA.32
Lead Author: Marie E. Wood, University of Colorado
Alliance trial: A211201
Summary: This study tested whether metformin, a common diabetes drug, could reduce breast density—a factor linked to higher breast cancer risk—in women treated for estrogen receptor–negative breast cancer. After one year, breast density decreased only slightly and similarly in both the metformin and placebo groups. Because the study enrolled fewer women than planned and breast density was lower than expected, it may have been harder to detect a difference. Overall, metformin did not significantly reduce breast density, though future studies in higher-risk groups may still be useful.
PS3-07-14: Predictors of early discontinuation of adjuvant palbociclib in early HR+/ HER2- breast cancer: Final analysis of the PALLAS trial integrating patient-reported outcomes
Lead Author: Marcus Vetter, Cantonal Hospital Baselland
AFT trial: AFT-05
Summary: In the PALLAS/AFT-05 trial, more than 40% of patients stopped adjuvant palbociclib early, mostly for reasons other than disease progression. Older age, lower nodal stage, lower quality of life, and financial difficulties were key factors linked to early discontinuation. Many patients also required dose reductions due to side effects. These findings highlight the importance of monitoring patient-reported outcomes and providing symptom management, social support, and financial counseling to help patients complete oral targeted therapies.
PS3-07-27: Identifying premenopausal patients with early-stage hormone receptor–positive node-negative breast cancer at minimal risk of recurrence by breast cancer index
Lead Author: Ruth M. O'Regan, University of Rochester
Alliance trial: IBCSG-24-02 (SOFT-TEXT)
Summary: The adjusted Breast Cancer Index can identify premenopausal patients with hormone receptor-positive, node-negative breast cancer who have a very low 10-year risk of distant recurrence (less than 5%). This helps doctors and patients make more informed decisions about whether intensive endocrine therapy with ovarian suppression is necessary, potentially sparing some patients from unnecessary treatment and side effects.
PS3-07-28: Prognostic performance of Breast Cancer Index in patients with early-stage HR+ HER2+ breast cancer (BC) treated with adjuvant trastuzumab: NCCTG N9831 (Alliance)
Lead Author: Saranya Chumsri, Mayo Clinic in Florida
Alliance trial: NCCTG-N9831
Summary: The Breast Cancer Index (BCI) can help predict the risk of distant recurrence in patients with hormone receptor-positive (HR+) HER2-positive early breast cancer treated with chemotherapy and trastuzumab. In this study, patients classified as low-risk by BCI had very high 10-year recurrence-free survival, while high-risk patients had a higher chance of recurrence. These findings suggest BCI may help guide decisions about adjuvant hormone therapy in HR+ HER2+ breast cancer.
PS3-08-13: Exploratory analysis of palbociclib benefit in the PALLAS trial by SETERPR index and prior chemotherapy regimens (ABCSG-42/AFT-05/BIG-14-13)
Lead Author: Otto Metzger, Dana-Farber Cancer Institute
AFT trial: AFT-05
Summary: In the PALLAS/AFT-05 trial, adding palbociclib to hormone therapy helped some patients with stage II-III HR+/HER2- breast cancer, especially those who had prior anthracycline-paclitaxel chemotherapy. Tumors with moderate hormone receptor activity (not too low or too high) appeared to benefit the most. These results are preliminary and need more research to confirm.
PS4-09-29: Variation in weight loss and intervention engagement in the Breast Cancer Weight Loss (BWEL) trial by language and ethnicity
Lead Author: Ashley Odai-Afote, Dana-Farber Cancer Institute
Alliance trial: A011401
Summary: Hispanic women with breast cancer often have higher rates of obesity, yet they are not well represented in weight-loss research. The BWEL study tested a two-year, telephone-based weight-loss program for women with stage II–III breast cancer. Earlier results showed that Hispanic participants lost less weight than White participants after one year. This analysis looked at whether differences in program engagement—such as number of coaching calls or use of tracking tools—might explain this gap.
Among women in the weight-loss program, those who preferred Spanish were younger and had a lower starting weight than English-speaking Hispanic and non-Hispanic women. After 12 months, Spanish-speaking Hispanic participants lost the least weight. They also took part in fewer coaching calls and used their activity monitors and scales less often. However, they received more shipments of meal-replacement shakes. Dropout rates and call length were similar across groups.
These findings suggest that Spanish-speaking Hispanic women may face barriers to fully engaging in weight-loss programs, even when delivered in their preferred language. More work is needed to design programs that are accessible, culturally relevant, and effective for diverse patient communities.
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RAPID FIRE SESSION
RF1-02: Surgical outcomes in the ALTERNATE trial (Alliance A011106) - A randomized phase 3 neoadjuvant endocrine therapy (NET) trial in postmenopausal women with clinical stage II/III estrogen receptor positive (ER+) and HER2 negative (HER2-) breast cancer
Lead Author: A. Marilyn Leitch, UT Southwestern Medical Center
Alliance trial: A011106
Summary: This study looked at how breast cancer surgery is performed after women receive hormone therapy before surgery (neoadjuvant endocrine therapy, or NET). Unlike chemotherapy, NET rarely eliminates all cancer, so the best approach to lymph node surgery is less clear.
More than 900 women in the ALTERNATE trial received six months of NET. After treatment, about 70% were able to have breast-conserving surgery (lumpectomy), including nearly half who were not candidates before NET. Lymph node involvement was still common, but many women had only 1–2 positive nodes.
Surgeons often used a less invasive lymph node procedure (sentinel lymph node biopsy) for women having lumpectomy, following current guidelines, but were more likely to perform full lymph node removal for women having mastectomy.
Overall, NET helped many women become eligible for breast-conserving surgery, and the limited number of positive nodes seen suggests that avoiding full lymph node removal may be appropriate for some patients after NET.
RF2-02: Pooled analysis of the BrighTNess, CALGB 40603 (Alliance), and GeparSixto clinical trials identifies the impact of neoadjuvant carboplatin on pCR and survival in early-stage triple-negative breast cancer
Lead Author: Brooke Marie Felsheim, University of North Carolina at Chapel Hill
Alliance/AFT trials: CALGB-40603, AFT-04
Summary: Adding carboplatin to neoadjuvant chemotherapy in early-stage triple-negative breast cancer (TNBC) improves the chance of completely eliminating the tumor (pCR) and increases event-free survival (EFS), especially in patients with BRCA1/2 mutations. However, it does not significantly improve overall survival. Immune-related gene signatures help predict patient outcomes but do not specifically indicate who benefits from carboplatin. These results of this pooled analysis support including carboplatin in standard neoadjuvant treatment for stage II-III TNBC.
RF3-04: Tumor-informed circulating tumor DNA analysis to assess molecular residual disease for prognosis and prediction of benefit from palbociclib in the PALLAS trial
Lead Author: Heather Parsons, Fred Hutchinson Cancer Center
AFT trial: AFT-05
Summary: The PALLAS/AFT-05 trial tested adding two years of palbociclib to standard hormone therapy in patients with early-stage HR+/HER2- breast cancer. Researchers are using circulating tumor DNA (ctDNA) to detect molecular residual disease (MRD) and identify patients at highest risk of recurrence. This ongoing analysis will show how MRD status relates to recurrence risk over seven years and how it may differ between patients treated with palbociclib plus endocrine therapy versus endocrine therapy alone—the first such evaluation in a randomized phase III trial.
RF4-01: Central nervous system outcomes from the phase III PATINA trial (AFT-38)
Lead Author: Otto Metzger, Dana-Faber Cancer Institute
AFT trial: AFT-38
Summary: In this secondary analysis, researchers found that in patients with HER2-positive metastatic breast cancer, adding palbociclib to anti-HER2 and hormone therapy reduced the risk of cancer spreading to the brain. At three years, fewer patients on palbociclib developed new central nervous system (CNS) metastases compared to standard therapy (13% vs. 19%). These results suggest palbociclib may help delay or prevent brain metastases in this setting.
RF7-07: Adjuvant palbociclib for ER+ breast cancer in the PALLAS trial (ABCSG-42/AFT-05/PrE0109/BIG-14-13): Post-recurrence treatment and overall survival
Lead Author: Angela DeMichele, University of Pennsylvania
AFT trial: AFT-05
Summary: The PALLAS/AFT-05 trial tested adding two years of palbociclib to standard hormone therapy in patients with early-stage HR+/HER2- breast cancer. After seven years, overall survival was similar between the groups, but patients who relapsed after adjuvant palbociclib had delayed or reduced access to CDK4/6 inhibitors for metastatic disease, which affected survival. These findings suggest that patients may still benefit from CDK4/6 inhibitors if used at the time of metastatic recurrence.
