The San Antonio Breast Cancer Symposium was a virtual event this pandemic year, allowing thousands of breast cancer researchers, oncologists and patient advocates from around the world to log in for four full days of science and resilience writ large.
Researchers from Fred Hutchinson Cancer Research Center and the Fred Hutch/University of Washington Cancer Consortium presented findings in a number of areas, from new clinical protocols to the impact of the COVID-19 pandemic on cancer patients, to the first trial using CAR T-cell therapy. Read on for a few highlights.
As in years past, the de-escalation of toxic treatment was a subject of huge interest, with preliminary findings from RxPONDER, a large new clinical trial conducted by the SWOG Cancer Research Network, announced in a late-breaking abstract.
Dr. Julie Gralow, a breast cancer researcher and oncologist with the Hutch and its clinical-care partner Seattle Cancer Care Alliance, an executive officer with SWOG and an RxPONDER co-investigator, discussed the trial at a large patient advocate session.
In the TAILORx trial, announced in 2018, researchers used a 21-gene recurrence score assay (with a scale from 1 to 100) to demonstrate that early stage patients with ER+/HER2- breast cancer and an intermediate recurrence score of 11 to 25 did not need chemotherapy if their cancer has not spread to the lymph nodes. In this assay, those with a score of 26 to 100 have a high risk of recurrence and chemotherapy is recommended.
The new international RxPONDER trial used the same assay to determine if early stage patients with the same type of cancer that had spread into one to three lymph nodes could safely skip chemotherapy, as well.
"Early findings showed that for postmenopausal women in this group — women over 50 — there was no hint of a benefit from chemo if they had a recurrence score of 25 or less,” Gralow said. “Even with one to three lymph nodes showing signs of cancer, there’s not a whiff of benefit. They don’t need chemo. They don’t need the side effects and they will do very well with just endocrine therapy alone."
For premenopausal women — those under 50 — it’s fuzzier.
RxPONDER showed a benefit from chemotherapy in premenopausal women no matter what their recurrence score was, Gralow said, although it’s not clear “if it’s about chemo or the effects of chemo, which is that it temporarily or permanently shuts down the ovaries.”
“We’re still doing the analysis and we need to do additional research and try and sort this out,” she said. “But starting tomorrow, we feel a lot more comfortable omitting chemo from postmenopausal patients with one to three lymph nodes that are positive with a low-to-intermediate recurrence score.”
Hutch/SCCA breast cancer oncologist and researcher Dr. Jennifer Specht’s trial of the first CAR T-cell therapy for patients with breast cancer (which is still experimental) was featured in the SABCS20 poster session.
The Phase 1 trial, which is ongoing, is a collaboration between the Hutch, the SCCA immunotherapy program and Minerva Biotechnologies.
“This is one of the few studies of CAR T cells enrolling breast cancer patients,” said Specht. “It’s a study of adoptive immunotherapy for patients with advanced MUC1* positive breast cancer.”
The cleaved form of the gene MUC-1, MUC1* is expressed in all subtypes of breast cancer and higher expression is found in high-grade breast cancers. CAR T-cell therapy uses an infusion of the patient’s own T cells which have been genetically modified with a chimeric antigen receptor, or CAR, to destroy cancer cells.
Specht stressed this form of treatment is “completely different” from other forms of treatment but said that doesn’t necessarily mean there won’t be side effects.
“The unique toxicities of CAR T-cell therapy may include cytokine release syndrome and neurotoxicity,” Specht said. “But a single infusion of MUC1* CAR T cells may persist for a long period of time.”
The poster outlined the study background, objectives, schema and process for continued enrollment. The study’s primary objective at this point is safety.
“We are enrolling patients in the dose-escalation part of this Phase 1 trial,” Specht said.
Once the T-cell dose is determined, additional patients will be enrolled. More information on the trial can be found at the National Cancer Institute's clinical trials website, clinicaltrials.gov.
Data on the characteristics and outcomes of COVID-19 infection in breast cancer patients was shared in a poster presented by the COVID-19 and Cancer Consortium, or CCC19.
It marked the largest study to date to report outcomes related to COVID-19 in patients with this type of invasive cancer.
Hutch physician-scientist Dr. Gary Lyman is a founding member of CCC19 and actively involved in many of its major research efforts, including studying the impact of COVID-19 on patients with breast cancer. The poster was presented by Hutch and UW clinical researcher Dr. Ali Khaki. Co-authors from the Hutch/UW include Drs. Petros Grivas and Shaveta Vinyak.
“Patients with a cancer diagnosis have been identified as a population at high risk of adverse outcomes, but specific information on patients with breast cancer has been limited,” Khaki explained in his oral presentation.
The CCC19 group found that out of a total of 846 COVID-19 patients with active breast cancer or a history of breast cancer, nearly half — 48%, or 403 people — were hospitalized, and 9% (or 76 people) died within 30 days of their COVID-19 diagnosis.
Factors associated with worst outcomes included older age, a higher ECOG performance status (on the ECOG scale, 0 is fully active and 5 is dead), more comorbidities and active, progressing cancer, the researchers found.
Interestingly, recent breast cancer treatment — defined as within three months — was not associated with hospitalizations, Khaki said.
But Lyman cautioned that there was “limited power” to address the risk associated with specific cancer treatments.
“Patients on treatment should receive appropriate supportive care to minimize any risk,” he said, adding that new findings will be published as they become available.
In the realm of imaging, two scientific posters outlined novel imaging agents that could benefit patients with the subtypes lobular and HER2-positive breast cancer.
Researchers out of the United Kingdom shared findings from the first study of a new "affibody" tracer for HER2-positive breast cancer in hopes it will provide a less-invasive method for determining this type of disease. Currently, HER2 status is determined via biopsy. Affibody molecules are small proteins engineered to bind to larger target proteins.
In a study of 13 patients with metastatic HER2-positive disease, the new affibody PET tracer — designed to bind to the HER2 receptor — successfully differentiated between HER2-positive and HER2-negative disease. Researchers concluded the imaging tracer was well-tolerated by patients and felt it “showed promise for imaging of HER2-positive breast cancer.”
Lobular breast cancer is often difficult to image due to its unconventional growth pattern. In lieu of lumps, the cancer cells often travel in single file, like tree branches. The disease can also metastasize to uncommon sites like the peritoneum, gastrointestinal tract and ovaries. Linden and Manohar are trying to find better ways to detect and track this cancer, which is usually driven and fueled by estrogen.
Manohar presented findings from a new study that compared traditional glucose-based tracer (FDG) with the estrogen-based tracer (FES) in 38 metastatic lobular breast cancer patients. The retrospective study used data from studies performed at the institutions between the years 1995 and 2015.
“When the tracer is glucose as in FDG-PET, it’s measuring glucose uptake and corresponding activity,” Manohar explained. “We expect in cancer cells, that the SUV — the standardized uptake volume — will be higher compared to surrounding tissue, because they are more metabolically active and use up more glucose.”
But FDG-PET is not specific to cancer, she said. It can also show uptake in infection or inflammation. FES is more precise. It’s an estradiol (estrogen) tracer so the SUV is picking up activity of tissue that is using estradiol only. The FES tracer was recently approved by the Food and Drug Administration and should be available for use in 2021.
“It’s more specific for breast cancer,” Manohar said. “And, most importantly, a surrogate way to measure estrogen receptor expression, which we believe is both prognostic and predictive.”
The study demonstrated that the FES estrogen tracer did just as well as the FDG glucose tracer in lighting up metastatic lobular lesions. Both had value in detecting lobular histology. At higher SUV values, however, Manohar said there was indication that the FES-PET could be additionally informative.
“One of our hypotheses is that FES tracer can detect disease in the peritoneum, where other imaging is lacking,” Manohar said. “We didn’t quite see this in the retrospective data set we examined. But at higher SUV uptake, there does appear to be discordance. The fact that at higher values we are seeing a difference shows us that the two tests are telling us something different and giving us more information to work with (in this case, likely predicting response to endocrine therapy). We’re reviewing this now. Stay tuned.”
Another big advantage of the FES-PET tracer?
Manohar said it might be used to offer patients and clinicians “a whole-body understanding” of their disease without the need for “biopsying every lesion.”
What was it like attending a virtual version of SABCS? Manohar called it “a whole new beast.”
“I’ve been part of two virtual meetings so far: ASCO [American Society of Clinical Oncology] and the ASCO Quality Care Symposium,” she said. “I’m still learning to navigate virtual meetings.”
The biggest drawback is the lack of collaboration, she said.
“It’s hard to meet people and discuss ideas on a virtual platform, but safety is paramount and we are all very grateful to be part of a community that takes responsibility for public health and creates a safe environment for discussion.”
Specht, too, said she missed the interactions and conversations that happen in real life.
“The best and most productive parts of attending meetings are the conversations that occur at poster sessions and informally,” she said. “Those are difficult to impossible to recreate in an online or virtual format.”
The virtual format didn’t hurt attendance, though, and may have even boosted it.
“Attendance at virtual conferences seems to be high — and perhaps even higher than in person,” Specht said. “Not needing to travel is nice. But missing the opportunity to see colleagues is huge and a big loss.”
Diane Mapes is a staff writer at Fred Hutchinson Cancer Center. She has written extensively about health issues for NBC News, TODAY, CNN, MSN, Seattle Magazine and other publications. A breast cancer survivor, she blogs at doublewhammied.com and tweets @double_whammied. Email her at email@example.com. Just diagnosed and need information and resources? Check out our patient treatment and support page.
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