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ASCO 2022: Early-Stage Breast Cancer Updates

By BCRF | July 15, 2022

The 58th annual meeting of the American Society for Clinical Oncology featured several important presentations in this area

At the American Society of Clinical Oncology’s (ASCO) annual meeting, BCRF investigators and other leading breast cancer researchers presented recent findings from the field—highlighting a banner year for advancements to improve diagnosis, treatment, and prognoses for patients.

This year’s meeting included notable developments in early-stage breast cancer, that which has not spread beyond the breast or nearby lymph nodes and can be classified as stage 0 to 3A. While it generally has a good prognosis, researchers are steadily working to improve outcomes and match the right treatments to patients for the most benefit.

Here we highlight some of these noteworthy presentations on early-stage breast cancer.

Tailoring adjuvant therapy

Some women with low-risk, early-stage breast cancer may forego radiation therapy after surgery. The phase 3 LUMINA study (NCT01791829) evaluated recurrence risk in women with luminal A [hormone receptor (HR)–positive/HER2-negative] low-grade, early-stage breast cancer who have undergone breast-conserving surgery and were treated with adjuvant endocrine therapy alone, without radiation.

Study findings revealed a very low rate of five-year local recurrence at 2.3 percent, suggesting that certain patients with low-risk breast cancer may be able to avoid adjuvant radiation. Read more here.

Immunotherapy improves response in patients with early-stage TNBC

Triple-negative breast cancer (TNBC) remains a challenging disease to treat, but a type of immunotherapy called checkpoint blockade has emerged as a promising treatment for some patients. At ASCO, BCRF investigator Dr. Lajos Pusztai presented an exploratory analysis from the KEYNOTE 522 (NCT03036488) study. It demonstrated that patients with stage 2/3 TNBC receiving the immunotherapy drug pembrolizumab (KETRUDA®) plus chemotherapy had a superior response compared to those receiving chemotherapy alone prior to surgery.

Those with residual tumor at the time of surgery continued to receive the combination or chemotherapy alone. All patients benefitted from pembrolizumab including patients with residual tumor at the time of surgery who continued to receive pembrolizumab after surgery. Pembrolizumab was the first immunotherapy drug approved for early-stage breast cancer and these findings further confirm and extend its benefit to some TNBC patients.

Tumor molecular profiling for predicting treatment response in early-stage HER2-positive breast cancer

The I-SPY2 study, supported in part by BCRF, is a uniquely designed clinical trial testing novel agents in the neoadjuvant (pre-surgical) setting to identify drugs that are most likely to show a significant benefit in phase 3 studies of early-stage breast cancer.

At ASCO, I-SPY2 investigators presented results from one study that found five new molecular subtypes of HER2-positive breast cancer—the presence of which predicted the likelihood of pathologic complete response to a variety of agents including immunotherapies. The five categories were based on gene signatures—groupings of gene expression profiles related to specific cell functions. Because HER2-positive breast cancer is a diverse set of diseases, these findings could help doctors select the right drugs for patients.

New test identifies patients with estrogen receptor (ER)–positive breast cancer most likely to benefit from chemotherapy

The SET2,3 test developed with BCRF support by Dr. W. Fraser Symmans is a gene-based assay that measures the level of estrogen-induced gene activation in breast cancer cells. Presenting results from the phase 3 CALGB 9741 study, Dr. Otto Metzger of Dana-Farber Cancer Institute reported that 86 percent of patients with high SET2,3 measures were disease-free at five years versus 69 percent of patients with low SET2,3 measures. The prognostic value of SET2,3 remained significant at 10 years with nearly 78 percent of SET2,3 high patients being disease-free versus 58 percent of SET2,3 low patients. Low SET2,3 levels, however, were found to be predictive of response to dose-dense chemotherapy—identifying patients most likely to benefit from this therapy and sparing those less likely to benefit.

Elderly patients with early-stage breast cancer may forego chemotherapy

Presenting results from the phase 3 ASTOR 70s trial (NCT01564056), Dr. Etienne Brain of Institut Curie reported that adding adjuvant chemotherapy to endocrine therapy in patients 70 years or older with ER-positive/HER2-negative breast cancer did not significantly improve outcomes, even in tumors with a high genomic grade index—a predictor of poor outcomes.

Commenting on the study, BCRF investigator and Scientific Advisory Board member Dr. Nancy Davidson called the trial a tour de force for its focus on elderly people with breast cancer, inclusive eligibility criteria, and expansive biological samples for future correlative studies. Read more here.

Osteoporosis drug decreases bone fractures and improves outcomes in patients receiving AI therapy

Aromatase inhibitors (AI) are a standard-of-care for post-menopausal women with ER-positive breast cancer, but side effects include bone loss and increased risk of fractures. Bisphosphonates are a class of drugs use to prevent bone loss due to osteoporosis and are also given in conjunction with AIs.

The ABCSG-18 trial (NCT00556374) had previously shown that the bisphosphonate drug Denosumab (XGEVA®) significantly reduced fractures and improved disease-free survival in women taking AIs. In the current analysis presented by Dr. Michael Gnant of the Medical University of Vienna, these findings were not only confirmed, but researchers found that  denosumab notably reduced the risk of bone metastases and improved overall survival compared to placebo.

With a median of eight years of follow-up, denosumab’s effects were judged to be durable. These findings suggest an affordable and low-impact option—denosumab is inexpensive, only requires injection every 6 month, and has a low toxicity—to manage AI-related bone loss. Read more here.

Conferences like ASCO’s annual meeting provide an opportunity for cancer researchers to share results and, through thoughtful discussions, gain inspiration or added perspective from their peers. This year’s gathering was no exception, particularly for breast cancer researchers, as they reported findings that steadily advance the field and improve outcomes for all aspects of the disease—rom early-stage breast cancer to metastatic disease. BCRF investigators play an integral role in these advancements.