Clinical trials — the treatments of tomorrow, today — took top billing at the fourth annual Northwest Metastatic Breast Cancer Conference held September 7 at the Amazon Meeting Center in Seattle.
Scientists from Fred Hutchinson Cancer Research Center shared new treatments; National Cancer Institute experts and patient advocates offered up snazzy searchable trial registries and resources; and a Clinical Trials Fair let patients and caregivers learn about the latest cancer trials at treatment centers in Seattle and across the country.
It wasn’t quite cancer trial speed dating, but it was about hooking patients up with the trials, treatments and tools that might work for them and keep them alive longer. The full-day event also honored patient advocates; highlighted gaps in cancer recurrence data; exposed access issues with the NCI’s less-than-intuitive trial site, ClinicalTrials.gov, and offered special breakouts on common sites of metastasis and tumor biology. There were even sessions in Spanish and a few yoga classes.
Co-chair Teri Pollastro in her opening remarks credited a breast cancer vaccine clinical trial with extending her life but acknowledged, “Before I was involved in a trial, I had many misconceptions.”
“One of the goals for this conference is that we better understand clinical trials and dispel the myths around them,” said Pollastro, a Fred Hutch research advocate and current patient at the Hutch’s clinical-care partner, Seattle Cancer Care Alliance. “We also want to help clinicians understand why patients don’t participate in trials."
Created for patients by patients, the conference drew nearly 300 participants to Seattle’s bioscience hub to hear the latest on precision therapies, immunotherapies, translational research and other hot topics in metastatic and lobular breast cancer.
Livestreamed sessions beamed the information to many more watching from home (last year’s views topped 35,000). The grassroots, patient-driven event was sponsored and supported by Susan G. Komen Puget Sound, Amazon Web Services, Swedish Cancer Institute, SCCA and others, including Fred Hutch.
Hope and help for metastatic breast cancer patients
“Our whole mission is to give you help and hope for what you’re dealing with, what we’re all dealing with,” said Lynda Weatherby, a stage 4 patient who co-founded the conference as a way to help people better understand metastatic disease. “I hope you can use today to connect with others who really get it. And connect with the information you need.”
Hutch clinical researcher and SCCA breast cancer oncologist Julie Gralow, MD, kicked things off with a fast-paced overview of genetics, genomics and targeted therapies.
“All cancer is due to changes in genes, all cancer is genetic,” she said, going on to explain that only a small portion of cancers — perhaps 5% to 10% — are caused exclusively by inherited or germline genes. “The rest are acquired over our lifetime. These are somatic or sporadic gene changes.”
Driven by external exposures (think chemicals or radiation) or internal exposures from hormones or lifestyle (think smoking or too much booze), these changes cause alterations in genes (and the proteins they create) that control cell growth, cell invasion and spread.
The good news for cancer patients?
"Understanding an individual patient’s genetics and genomics can offer new possibilities for the treatment of metastatic breast cancer,” she said.
The hunt for mutations … and treatment targets
The most common targets include the estrogen receptor (ER-positive cancers feed on estrogen) and the human epidermal growth factor receptor 2 (HER2-positive breast cancers produce too much of this protein), but there are many more.
Oncologists utilize these targets when they treat a cancer, often shrinking the tumor. But a few genes may mutate in response to the treatment, allowing the cancer to become resistant and continue to grow. A new treatment may kill most of the cancer again until there’s another mutation, another resistance.
Gralow said this cycle of mutation, resistance and metastatic spread means there can be a mix of many mutations within one patient, i.e., a HER2-positive met in the lung and a HER2-negative met in the liver. It also means your tumors can acquire mutations in cancer-driving genes like BRCA1 or 2.
"Even if you didn’t inherit a BRCA mutation from your parents, your tumor can acquire a BRCA1 or 2 mutation,” she said. “The list is getting longer and longer at all the things we’re looking for in breast cancer.”
Gralow demonstrated her point by sharing slides of a patient’s genomic profiling — delineating all of the gene amplifications or deletions that might point to possible therapies — as well a multitude of DNA repair genes beyond BRCA1 or 2, that might contribute to cancer’s growth. The list reads like a deadly alphabet soup: CHEK2, ATM, P53, PALB2, RAD51D, BARD1, ATR, FAM175, etc.
Cancer’s mutational shapeshifting means targeted therapies for people with metastatic disease need to constantly be informed by the genomic profiling of tumor tissue, Gralow said. And oncologists need to constantly keep an eye out for the actionable genomic alterations, i.e., cancer mutations that can be targeted with treatment.
“We’ve got to know what’s in the genome and we’ve got to know how it changes over time,” Gralow said. “I want to stress the importance of getting the tumor tissue — serially, over time — to know what we’re treating.”
Testing tumor tissue means biopsies, which Gralow and others acknowledged are neither painless nor without complications. Liquid biopsies, using a patient’s blood to find all the various mutations that could lead to treatment, are getting close but aren’t quite ready for prime time.
Fred Hutch and SCCA physician-scientist V.K. Gadi, MD, PhD, emphasized the role of precision medicine in oncology, likening “old school” cancer genomics to a paper roadmap and precision medicine to a GPS-enabled phone app.
Oncologists, he said, are now working with biotech partners to create cancer avatars and tumor organoids — biological models of disease grown on the backs of mice or in dishes — to determine the best therapy for each patient’s cancer. And this practice will only increase as time goes on.
“We can now grab cancer cells out of a patient, grow them in a petri dish and literally have them behave as if they were still in a human being,” Gadi said. “We can massively test drugs and combinations of drugs and generate a report from that. This is the next generation of what’s going on with how we interrogate cancer cells for their sensitivity for precision medicines."
Gadi talked about all the strategies he and other scientists are exploring to squelch cancer before it can spread, giving updates on drugs that target DNA repair pathways, PARP inhibitors, antibody-drug conjugates and CDK4/6 inhibitors. He also encouraged patients to “absolutely” bring new findings and potential trials to the attention of their oncologist.
“We’re moving away from the simple genomics,” Gadi said. “What we really need is a 360-degree view of the … biology of the cancer and the biology of the human, including the immune system. In the future, we’re going to get more of these molecular medicines — and when we do use chemotherapy, we’re getting smarter about how we deliver it. All of that’s going on.”
Breast cancer clinical trials and tribulations
Hutch/SCCA physician-scientist Jennifer Specht, MD, gave an in-depth presentation on immunotherapy, which, in addition to surgery, chemotherapy and radiation, has become what she termed “the fourth pillar” of cancer treatment.
Hutch translational researcher and SCCA breast oncologist Kevin Cheung, MD, talked about tumor cell clusters and how these clumps of cells break off from a tumor and cooperate to actively promote metastasis, a process he’s trying to stymie with his new TARGET-CLUSTER trial.
Hannah Linden, MD, also of the Hutch and SCCA, led a Lobular Lunch and Learn with a deep dive into this sneaky ER+ subtype and how its growth pattern and metastatic spread differs from the more-common ductal breast cancer.
“Unlike ductal, lobular tumors may line the organs,” said Linden. “It may line the outside of the lungs or you’ll see caking on the surface inside of your belly. It’s sometimes difficult to see by imaging but not always. We’re doing work with estrogen-receptor imaging now that seems to be useful.”
Larisa Korde, MD, current head of the breast cancer trials at the NCI-sponsored National Clinical Trials Network, explained the phases and basic framework of all trials and agreed with advocates in the audience that the master list of all clinical trials in the country, NCI’s ClinicalTrials.gov, could be “amazingly difficult to navigate.”
“I don’t know of any efforts to bring it into the 21st century but I agree that it’s incredibly important,” Korde said.
Patient advocates then shared their own efforts to do just that.
Christine Hodgdon of Baltimore presented her MBC clinical trial and news database, TheStormRiders.org, where patients can search for current trials or promising new drugs. BreastCancerTrials.org, introduced by its program director Elly Cohen, lets patients search for trials and also translates the scientific ClinicalTrials.gov descriptions into more lay-friendly language. Patients were also encouraged to sign up for MBC Connect, a registry that matches MBC patients to open trials, and MBC Project, an open science, patient-partnered research initiative designed to accelerate understanding of the disease.
Connecting with info, and others
Most of all, people connected — with information, with resources, with potential trials and with each other. Barista Sandra Partida, 45, a triple-negative breast cancer patient from Bellevue, Washington, was thrilled to make a new friend with the same cancer subtype.
“There were cancer support groups over in Bellevue, but no one was triple negative,” she said. “Today, I found a woman who lives on Bainbridge [Island, also in the Seattle area] who’s triple negative. We’re going to get together.”
Other patients came away with possible treatments or specific questions for their oncologists.
“I got quite a bit out of this,” said Peggy Bissell, 68, from Bow, Washington, who is currently on her ninth line of MBC treatment. “I’ve had a lot of bad news over the years but this was very helpful.”
Even patients from the United Kingdom lobbied for the government’s National Health Service to tune in and take note, via Twitter.
Linden, the lobular expert, praised the conference for helping to “close the loop” between patients and the data they need.
“People give their time to participate in a trial but they may not know the results,” she said. “Or how that trial impacts others in the future. This conference gives that information back to the patients, it closes that loop, so they’re better informed about breast cancer and about cancer trials.
“This is just such a good opportunity. We’ve got to keep doing this.”
This article was originally published on September 12, 2019, by Hutch News. It is republished with permission.