Key Takeaways from the 2023 San Antonio Breast Cancer Symposium

Investigators presented compelling advances in treatment (including for metastatic breast cancer), updates on emerging therapies, and more

The San Antonio Breast Cancer Symposium (SABCS) is the world’s largest conference solely devoted to breast cancer research. Participants include basic and clinical scientists, patient advocates, students, and industry representatives who were there to hear the latest developments in breast cancer research, share ideas, and forge collaborations.

Here, we highlight a few of the many insights presented at SABCS this year—including those from BCRF investigators.

Developments in the metastatic setting

Metastatic breast cancer (MBC) affects approximately 168,000 women in the U.S. With no cure, MBC research remains a priority not only for patients and their families but for the research community. There have been encouraging advancements in new drugs and exciting research in recent years including these highlights from SABCS.

Dr. Mafalda Oliveira presented the phase 3 results of the CAPItello 291 study that examined patient-reported outcome data. Previously reported results from CAPItello 291 showed improved progression-free survival with capivasertib in combination with fulvestrant versus fulvestrant alone for hormone receptor (HR)–positive, HER2-negative locally advanced or metastatic breast cancer with one or more PIK3CA/AKT1/PTEN alterations. This led to recent FDA approval for the first-in-class AKT inhibitor, capivasertib (Truqap®). Phase 3 of the study involved a series of quality-of-life evaluations from patients and assessment of side effects. As reported by patients, the research team found that capivasertib had little impact on their overall sense of wellbeing and was well tolerated with manageable side effects that were minimized presumably by the dosing schedule of capivasertib, providing further support for its use in this strategy.

Elacestrant (Orserdu®), a novel selective estrogen receptor degrader (SERD), was FDA approved on January 27, 2023, for treating postmenopausal women or adult men with estrogen receptor (ER)–positive, HER2-negative, ESR1-mutated advanced or MBC with disease progression following at least one line of endocrine therapy. Approval was based on a series of clinical trials, notably the EMERALD trial (NCT03778931) presented by BCRF investigator Dr. Aditya Bardia.

Although it was FDA approved in 2022, researchers continue to assess the antibody-drug conjugate (ADC) trastuzumab deruxtecan (T-DXd/Enhertu®) in long term follow-up studies. After 32 months, it was reported to maintain its efficacy with no new side effects. This sustained clinical benefit may assure clinicians and patients of the long-term advantages of T-DXd treatment for MBC.

Refining ADC treatments

ADCs continued to be a hot topic at this year’s SABCS meeting. ADCs are targeted therapies that deliver chemotherapy drugs directly to cancer cells while limiting toxicity to normal cells. As such, they are increasingly recognized as an important addition to breast cancer treatment regimens.

Even with their success in clinical trials, however, there are still unanswered questions about using these relatively new breast cancer treatments in a real-world setting, and more data is needed to identify the most appropriate treatment protocols. The Translational Breast Cancer Research Consortium (TBCRC), partially supported by BCRF, is investigating some of these questions in studies focused on treating HER2-low advanced or metastatic breast cancer. A prospective trial will examine study data and compare the sequencing of sacituzumab govitecan (SG) and T-DXd. In addition, TBCRC will initiate the TRADE-DXd trial to optimize sequencing of T-DXd and datopotamab deruxtecan (dato-DXd).

Researchers are constantly seeking new and more effective therapies for breast cancer. The development of ADC technology has opened a wide area of study to identify novel antibody targets or more efficient drug components. Thus far, only ADCs targeting the HER2 and Trop2 proteins have been approved for treating breast cancer. But there are several novel ADCs in the pipeline and several molecules beyond HER2 have surfaced as possible novel targets for treating cancer:

HER3, a member of the HER family of proteins, acts in concert with HER2 to influence cell signaling and cell growth. BCRF investigator Dr. Ian Krop reported the positive results from a clinical trial testing a novel, first-in-class, HER3-directed antibody-drug conjugate, patritumab deruxtecan (HER3-DXd).

Nectin-4 is a new tumor-associated antigen and demonstrated reliable marker for breast cancer. In fact, it is not detected in normal breast cells but is highly expressed in breast tumors, making it an attractive target for therapy.

LIV1, first identified as an estrogen-inducible gene in breast cancer, mediates metastatic progression. It is expressed in ER-positive hormone-treated tumors (both primary and metastatic sites) and triple-negative breast cancers.

B7-H4, a protein found on immune cells in the breast tumor microenvironment, is also hypothesized to mediate metastatic progression.

AXL is a novel tyrosine kinase overexpressed or mutated in many tumors, including breast cancer. As a member of the large family of tyrosine kinases, AXL mediates communication from the cell surface into the cell and potentially contributes to all stages of malignant breast cell transformation.

Radiation can safely be skipped by certain patient populations

Results from the IDEA study (NCT02400190) showed that in some breast cancer patients who have received neoadjuvant chemotherapy, radiation after surgery may not be needed. The IDEA study centered on three patient populations with ER-positive, HER2-negative breast cancer: patients with low-risk ductal carcinoma in situ (DCIS); postmenopausal patients ages 50-69 with early-stage breast cancer and low recurrence risk; and patients whose lymph nodes were cancer-free following neoadjuvant chemotherapy. The researchers found that, for all three groups, recurrence rates remained low compared to patients who did undergo radiation. Read more about the study here.

BCRF investigator Dr. Seema Khan presented exciting results from the BCRF-supported E4112, a study to determine whether the Oncotype DX Breast DCIS Score test could identify patients with DCIS who could forego radiotherapy following breast conserving surgery. After a median follow-up of five years after surgery, 5.1 percent of the 82 patients with low-risk DCIS and 4.5 percent of the 89 patients with high-risk DCIS experienced disease recurrence in the same breast as their primary DCIS.

This was the first prospective study to evaluate the utility of genomic testing to personalize treatment decisions regarding radiation for patients with DCIS. Follow-up will continue to ten years, but these results offer strong evidence to prevent excessive treatment for patients with low-risk DCIS. Read more about the study here.

Benign breast disease with calcification increases breast cancer risk

Benign breast disease (BBD) can cause changes in the breast and is not cancerous. But research presented at SABCS showed that BBD accompanied by calcifications increases the five-year risk of developing breast cancer. The study analyzed 5.3 million mammograms from 1.3 million women with no prior history of breast cancer who participated in the Breast Cancer Surveillance Consortium from 1996 to 2019—the largest study of future breast cancer risk to date.

The researchers sought to develop more accurate risk classifications for BBD associated with the lower-risk categories called non-proliferative or proliferative without atypia (PWoA). Within those classified as PWoA, they asked if future risk of invasive breast cancer differs by breast density or by the presence of calcifications. They found that calcification increases risk regardless of breast density.

This study demonstrated that imaging could provide information beyond the nature of the lump and is an important step toward refining risk stratification and precision breast cancer prevention for patients with BBD.

Other highlights

BCRF investigators Drs. Alana Welm, Jack Cuzick, and Kornelia Polyak received awards acknowledging their contributions to breast cancer research. In addition, Dr. Charles Swanton was chosen to give a plenary lecture on his groundbreaking work in chromosomal instability and its role in cancer formation.

At SABCS, presenters noted the highly collaborative nature of the breast cancer research community. This is evidenced by the development of several current resources that have recently been made available to the community at large: the Breast Cancer Single-Cell Atlas, which was developed to enhance our understanding of breast cancer subtypes and to personalize treatments; and a robust series of patient-derived organoids developed by Dr. Welm to imitate breast tumors in the lab. Access to these cutting-edge resources can help accelerate advancements in breast cancer research, ultimately bringing laboratory results to the clinic to impact patients with the disease.