The annual American Association for Cancer Research (AACR) is one of the world’s largest cancer research conferences. Attendees present their findings in basic science and translational and clinical research across the spectrum of all cancers. The meeting inspires clinicians to collaborate with laboratory scientists and gives researchers focused on one cancer a forum to hear from experts on others. This year, more than 22,000 researchers from around the world gathered in San Diego to hear about recent scientific breakthroughs, participate in discussion forums, and more.
BCRF investigators chaired and spoke in a wide variety of sessions and received top honors at this year’s meeting. Find highlights below.
BCRF investigators were once again recognized by their peers for their contributions to the field.
Dr. Titia de Lange received the Pezcoller Foundation–AACR International Award for Extraordinary Achievement in Cancer Research. A BCRF investigator since 2003, Dr. de Lange was recognized for her invaluable discoveries in telomere research—an area that has been supported directly by BCRF. Her research has increased our understanding of cancer development and genome maintenance.
Dr. Joseph Sparano, a BCRF investigator since 2012, received the AACR–Joseph H. Burchenal Award for Outstanding Achievement in Clinical Cancer Research for his illuminating clinical cancer research that has improved treatment options for breast cancer and HIV-associated cancers. He led the landmark BCRF-supported TAILORx clinical trial that transformed the standard of care for women with early-stage estrogen receptor–positive breast cancer, sparing many patients from unnecessary chemotherapy regimens. Read BCRF’s coverage of TAILORx’s groundbreaking findings here.
Additionally, BCRF investigators Drs. Lori Pierce, Silvia Formenti, and Johanna Joyce were inducted into the 2024 class of AACR Academy fellows for their scientific achievements that have improved our understanding of cancer and how it’s treated.
AACR’s annual meeting highlights potential new targets and treatments for cancer—and the fundamental research needed to get them to patients. This year’s opening plenary session showcased basic science leading to clinical breakthroughs and emphasized the importance of multidisciplinary research.
PARTNER Trial
BCRF investigator Dr. Hope Rugo discussed updates from the PARTNER trial, a phase II–III, randomized controlled clinical trial that enrolled patients with triple-negative breast cancer (TNBC) and/or germline BRCA 1 or BRCA2 mutations. Patients were randomized to receive neoadjuvant carboplatin–paclitaxel with or without the PARP inhibitor olaparib (Lynparza®). The primary endpoint—an event or outcome that is measurable and indicates if the intervention the trial is testing is successful—was pathological complete response (pCR; no sign of tumor at time of surgery). Secondary endpoints included event-free survival (EFS; time on treatment without progression) and overall survival.
Study investigators presented two analyses in 559 patients with non-BRCA-mutated TNBC and in 86 patients with germline BRCA-mutated breast cancer. They investigated the impact of a staggered olaparib dosing schedule (48-hour delay after starting chemotherapy) to avoid bone marrow toxicity observed when combining with carboplatin, which can limit the dose or duration of treatment. In the TNBC group, the addition of olaparib had no added benefit at any timepoint. These results were published in the journal Nature.
In the study of patients with germline BRCA mutations, however, the 48-hour delay of olaparib after chemotherapy resulted in a significant improvement in pCR, EFS, and overall survival. These results need to be confirmed in a larger study, and translational studies are ongoing to provide insights into the biology of BRCA-driven breast cancer. But these results demonstrate the importance of genetic testing in patients with a breast cancer diagnosis to identify personalized targeted therapies and move the field forward in managing BRCA-driven breast cancer.
PETRA Trial
The PETRA trial is a phase I/IIA trial testing the safety and efficacy of a second-generation PARP inhibitor called saruparib. Saruparib acts by selectively targeting PARP1 and was found to be less toxic than dual PARP1/2 inhibitors in preclinical studies. The trial is open and enrolling patients with advanced solid tumors with DNA repair defects because of germline mutations in BRCA1, BRCA2, PALB2, or RAD51C/D. In early results presented at AACR, saruparib was found to be safe and effective at doses exceeding those of first-generation PARP inhibitors.
DTP Trial
For patients with high-risk HER2-enriched early breast cancer, the standard treatment is neoadjuvant (prior to surgery) chemotherapy along with HER2 targeted therapy. The DTP trial, a multicenter phase II trial, is testing a chemotherapy alternative by combining the immunotherapy drug durvalumab (Imfinzi®), with dual HER2-targeted therapy trastuzumab (Herceptin®) and pertuzumab (Perjeta®) prior to surgery. Trial data illustrated that the combination therapy produced pCR rates of 49 percent, which increased to 57 percent when those who did not initially respond to the chemotherapy-free treatment received the standard chemotherapy regimen. This study seeks to improve patient response and personalize treatment strategies to prevent overtreatment.
The last few decades have seen an expansion in precision medicine and therapies that target specific molecular alterations of tumors. Today, researchers are finding more druggable targets, designing better treatments more efficiently, and applying the same principles of precision medicine in early disease and early detection. Progress in this space was another major focus of this year’s meeting.
BCRF investigator Dr. David Rimm led a session focused on biomarkers to find cancer earlier and to detect progression, including a presentation from BCRF investigator Dr. Charles Swanton who gave an overview of results from the Circulating Cell-free Genome Atlas (CCGA) Study showing that a noninvasive cell-free DNA-based blood test for early detection of more than 50 cancer types improves outcomes for patients followed over four years, particularly when their cancer is fast-growing.
BCRF investigator Dr. Geoffrey Lindeman discussed prevention strategies for patients with BRCA1 and BRCA2 mutations, highlighting emerging studies targeting two proteins (mTORC1 and RANKL) that are involved in cell proliferation. In laboratory studies, targeting mTORC1 or RANKL slowed tumor growth in BRCA1 and BRCA2 breast cancer models, respectively. Additional studies suggest that inhibiting RANKL, which is associated with breast density in premenopausal women, may be a promising target to preventing breast cancer in high-risk women with dense breasts.
Sessions at this year’s AACR meeting underscore the fact that, despite breast cancer’s complexity, our fundamental understanding of the disease is accelerating as new technologies and innovations catalyze discoveries. BCRF investigators are leading the charge to discover new treatments and keep pushing our knowledge of the disease forward.
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