Significant Gaps Still Remain in The Treatment of Breast Cancer

Hope S. Rugo, MD, FASCO

Novel treatment approaches and a growing portfolio of approved agents have significantly improved outcomes for patients with breast cancer. However, many opportunities to improve the standard of care for these patients remain, according to Hope S. Rugo, MD, FASCO.

“I think back to less than 30 years ago when my mother had metastatic breast cancer, how few tools we had compared with what we have now,” said Rugo, adding that that was a catalyst for her to switch careers from bone marrow transplant to breast cancer research. “It’s been an incredible ride to see what has happened in the past 23 years that I’ve been a breast cancer oncologist.”

In the Giants of Cancer Care® lecture delivered during the 40th Annual CFS®, Rugo focused on the priorities for breast cancer research in 2022 and beyond, tackling key questions raised by her colleagues. Rugo, a professor of medicine and director of breast oncology and clinical trials education at the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, was the 2020 Giants of Cancer Care® award winner in the education category.

A theme throughout was communication. Continued discussions with colleagues, patients, nursing staff, and the community are key to accelerating and optimizing treatments.

Escalation, de-escalation, and optimization of therapy

The use of escalation and de-escalation is not favored by the advocate community, Rugo said, adding that these therapeutic adjustments should instead be referred to as “optimizing treatment for tumor biology and treatment response. [In some ways] escalating and de-escalating [imply] intensity of treatment and even toxicity, and that is not the objective. [Rather,] the objective is not to have more [therapy]—it’s to have smarter therapy.”

Speaking about approaches to developing smarter therapies, Rugo noted that understanding the tumor biology and understanding biomarkers and gene signatures are vital components of progress. “We have new study platforms, which are helping us to look [at] better ways to understand the efficacy of different combination treatments,” she said, adding that the search for new biomarkers is a continual one.

Immunotherapy

A focus on refining the use of checkpoint inhibitors across populations of women with breast cancer will include looking at clinicopathologic variables for women with hormone receptor–positive disease and refining treatment strategies for those with triple-negative disease. “We’ve made improvements [with] immunotherapy, and we’re refining the use of checkpoint inhibitors and trying to understand whether we can expand the use of immunotherapy within and beyond triple-negative breast cancer,” Rugo said. “Are there subsets of women with hormone receptor–positive, HER2-negative disease who benefit from the addition of immunotherapy?” Efforts tackling this question include the phase 3 KEYNOTE-756 (NCT03725059) and the phase 3 KEYNOTE-B49 (NCT04895358) trials, both evaluating pathological complete response (pCR) with pembrolizumab (Keytruda).

For patients with TNBC, areas of further exploration include balancing risk and toxicity. Identifying those who will most benefit from treatment and the optimal thresholds of checkpoint inhibition once pCR is achieved and further refining sequencing of post-neoadjuvant therapies, remain areas of unmet need in this space.

ADCs: the new chemotherapy

Sacituzumab govitecan-hziy (Trodelvy) and trastuzumab deruxtecan-nxki (Enhertu) have made waves for patients with breast cancer, and Rugo said that antibody-drug conjugates (ADCs) may very well be the next chemotherapy mainstays for these patients. “We’ve seen remarkably positive data in triple-negative and hormone receptor–positive disease with the Trop-2 ADC sacituzumab govitecan and amazing data in HER2-positive and HER2-low [disease] with trastuzumab deruxtecan, just earth-shattering information.”

The next steps are to better understand HER2 status in the phase 3 DESTINY-Breast06 trial (NCT04494425) and evaluate the use of trastuzumab deruxtecan in the first-line setting in the phase 3 DESTINY-Breast05 study (NCT04622319). For sacituzumab govitecan, Rugo noted that first-line studies are also underway, including the phase 3 ASCENT-04 trial (NCT05382286) and the planned phase 3 Optimice-RD trial (NCT04595565).

Preventing brain metastases

Advances in drug development have not only led to strides in the treatment of primary tumors but also tackled an unfortunate complication of breast cancer—brain metastases. “This is a very discouraging area,” Rugo said. “You have patients with phenomenal response [to breast cancer treatment], and they have leptomeningeal disease before they can even get to surgery for locally advanced TNBC. Our goal is to try to use more effective therapies so we can prevent these metastases.”

Overcoming disparities in cancer care worldwide

Rugo concluded by noting the slow progress in resolving disparities in cancer care. “There is a global initiative to improve breast cancer outcomes, [as] most patients in the world do not have access to the therapies that patients [in the United States] do,” she said, adding that the problem of access hits close to home as well. “Even within the US, many patients don’t have access; they are the silent minority.” Rugo cited a patient who discontinued her treatments because of the financial implications, without reaching out for help.

“We need to reach out to our patients,” Rugo said. “We need to be vocal about tackling disparities in cancer care in the United States and worldwide.”