SABCS 2022 Takeaways and Highlights

Investigators shared notable findings on antibody-drug conjugates, the tumor microenvironment, and much more

It was another impactful San Antonio Breast Cancer Symposium (SABCS) this past December filled with exciting results and meaningful discussions. SABCS, the largest international meeting dedicated to breast cancer research, serves as a gateway for conversations and collaborations that fuel advancements, and BCRF investigators and BCRF-funded studies were once again prominent. Here, we recap this year’s major highlights and promising research.

BCRF researchers recognized

Three BCRF investigators received awards in honor of their stellar achievements in breast cancer research. Dr. Norman Wolmark received the Brinker Award for Scientific Distinction in Clinical Research for his contributions to advancing and improving patient care. Dr. Geoffrey Wahl was honored with the Brinker Award for Scientific Distinction in Basic Science for his cutting-edge research in identifying the genetic drivers of breast cancer. For his groundbreaking discoveries in cancer genomics and work translating them to clinical practice, Dr. Charles Perou was awarded The AACR Distinguished Lectureship in Breast Cancer Research.

Read more about these awards

Antibody-drug conjugates continue their winning streak

On the heels of recent practice-changing results with antibody-drug conjugates (ADCs), the excitement continued at SABCS as follow-up studies from the DESTINY trials (Breast02, 03, and 04) revealed more encouraging data. In particular, T-DXd (fam trastuzumab deruxtecan/Enhertu®) continued to benefit patients with advanced HER2-positive breast cancer (DESTINY-Breast02 and DESTINY-Breast03) and HER2-low metastatic breast cancer (DESTINY-Breast04). Furthermore, the most common side effect, interstitial lung disease, was not significantly worse after two- or three-year follow-up.

Among the notable presentations on ADCs:

Presenter Dr. Ian Krop, on behalf of the DESTINY-Breast02 study team, confirmed the positive benefit of T-DXd seen in DESTINY-Breast01 and demonstrated that it is sustained over three years with no additional adverse effects.
In a two-year follow-up on the DESTINY-Breast03 clinical trial, T-DXd significantly reduced patients’ risk of death and extended progression-free survival four times longer than observed for another ADC, T-DM1 (ado trastuzumab emtansine/Kadcyla®).
The DESTINY-Breast04 study team found that T-DXd’s significant benefits held up over a two-year follow-up compared to chemotherapy (physician’s choice).

Additionally, in patients with advanced estrogen receptor (ER)–positive/HER2-negative breast cancer, sacituzumab govitecan-hziy (SG/Trodelvy®) sustained its benefits regardless of Trop-2 levels on the tumor cells. Dr. Hope Rugo presented these results from the 10- to 12-month follow-up on TROPiCS-02.

Clinical trial highlights

BCRF researchers also presented updates from the BCRF-supported, ongoing TAILORx and RxPONDER studies that assess long-term outcomes and delve into possible explanations for observed racial disparities.

From a 12-year follow-up of TAILORx, Dr. Joseph Sparano reported that recurrence events in study participants (patients with ER–positive/HER2-negative breast cancer) were 50 percent higher in those with an intermediate risk of breast cancer compared to low and high-risk groups (based on the Oncotype Dx® score). Additionally, early recurrence rates were different between Black and white women—the implications of which are being investigated.

Recent RxPONDER analysis looked at the clinical outcomes of participants by race and ethnicity and found that, despite having similar recurrence scores, non-Hispanic Black women with HR-positive/HER2-negative, lymph node–positive breast cancer had worse outcomes than Asian, Hispanic, and non-Hispanic white women.

The BCRF-supported POSITIVE clinical trial yielded promising news for patients with breast cancer wanting to get pregnant. Dr. Ann Partridge led the study in women 42 and younger with HR-positive breast cancer (stages 1-3) who were previously treated with endocrine therapy. Initial analysis revealed that temporary pausing endocrine therapy to attempt pregnancy does not impact short-term disease outcomes; 74 percent of the women had at least one pregnancy with no significant increase in adverse outcomes for women or their babies.

Researchers reported the results from the CAPItello-291 clinical trial that tested the AKT inhibitor capivasertib in advanced HR-positive/HER2-negative breast cancer. AKT is a key component of the most-mutated pathway in breast cancer. Inhibiting this pathway with capivasertib, combined with fulvestrant treatment, improved survival in the study group. These encouraging results may lead the FDA to approve the first-ever AKT inhibitor for clinical use and in breast cancer.

Additionally of note, updated results from the phase 3 EMERALD trial demonstrated a statistically significant improvement in progression-free survival with the selective estrogen degrader SERD), elacestrant/Orserdu®, compared to physician’s choice endocrine therapy in patients with ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer. The women and men in this study had progressed after treatment with endocrine therapy plus CDK4/6 inhibitors, a major therapeutic concern for patients with this breast cancer subtype. Elacestrant has the potential to fill this therapeutic gap and is the first SERD other than fulvestrant to show promise. Indeed, the results of this trial led the FDA to approve elacestrant for treating this breast cancer population in January.

Tumor microenvironment as a mediator of breast cancer progression

The area surrounding a tumor (the tumor microenvironment or TME) is composed of many different factors that influence how the tumor behaves. Researchers are focusing on these factors to understand their role in cancer progression and identify actionable ways to influence the TME to improve patient outcomes. Several presentations at SABCS highlighted the TME in recurrence and metastasis:

Two types of cells in the TME interact with tumor cells to create a “doorway” that provides passage for them to leave the initial site and migrate to distant sites or metastasize. A team including Dr. Sparano confirmed this observation and found that in ER-positive/HER2-negative breast cancer this phenomenon occurs disproportionately in Black women compared to white women. This may contribute to the higher rates of recurrence and metastasis experienced by Black women.
A team of researchers identified a molecule, srGAP1, that hijacks components of the TME to enter and stay in a dormant state—allowing tumor cells to stop dividing and remain hidden until triggered to resume growing and recur. Researchers will explore whether this process can be targeted to prevent cells from becoming dormant.
BCRF investigators Drs. Perou, Mafalda Oliviera, Aleix Prat, and their colleagues found that an immune component of the TME and immune gene expression was correlated with patients’ poor response to immune checkpoint inhibitors in HR–positive/HER2-negative breast cancer. Further studies are exploring ways to exploit this finding to improve immunotherapy outcomes.
In laboratory studies, researchers used triple-negative breast cancer models and showed that the novel agent (AMUN-003) almost completely halted tumor progression. Further, the combination of AMUN-003 and immune checkpoint inhibitors delayed tumor growth and controlled metastatic spread. These findings may lead investigators to test AMUN-003 in future clinical trials.

Results presented at SABCS this year provide a snapshot of the many angles and strategic approaches researchers are using to advance our understanding of breast cancer and gain insight into new avenues for treatment. Meetings such as SABCS enable the free flow of information and ideas today that will spur the investigations of tomorrow—ultimately moving the entire field forward.

Highlights and Key Takeaways from SABCS 2022