What's new in breast cancer research: #SABCS19 edition
From new therapies to better imaging, the 42nd San Antonio Breast Cancer Symposium, held last week in Texas, was packed full of new research insights for people with all types of breast cancer.
The largest scientific breast cancer conference in the world, SABCS drew close to 8,000 attendees to hear 1,000-person plenaries and spotlight talks on clinical trials large and small, and view thousands of posters on emerging therapies from around the world.
Most of the buzz this year was reserved for highly anticipated national clinical trials of new anti-HER2 drugs. This class of drugs targets breast cancer that overexpresses, or produces too much of, the HER2 growth receptor.
In Seattle Genetics’ HER2CLIMB trial, overall survival at two years was nearly 45% with an experimental new three-drug combination. The new treatment was especially significant for women with brain metastases: progression-free survival, or PFS, for patients who took the drug combo was 24.9% at one year and zero in the placebo group (PFS means the patient is still alive and the cancer has not gotten any worse).
The Phase 2 DESTINY trial tested another experimental anti-HER2 drug, trastuzumab deruxtecan, in metastatic breast cancer patients who’d developed resistance to multiple drugs (the median was six). One hundred twelve of 184 patients (61%) responded, with a median PFS of 16.4 months, nearly double or triple what other drugs have been able to offer patients who’d tried (and been failed by) multiple other drugs.
But there was much more, including a promising “Baby Tam” (or a mini-dose of tamoxifen) trial. Herewith, your SABCS19 wrap-up.
Combined hormone therapy still a risk
Results from a 19-year follow-up of the 27,000 women who participated in the large prevention-focused Women’s Health Initiative randomized controlled trial of hormone use in menopausal women, led by breast oncologist Dr. Rowan Chlebowski from Harbor-UCLA Medical Center and Fred Hutchinson Cancer Research Center public health researchers Drs. Garnet Anderson and Ross Prentice, were also announced at the conference. Fred Hutch houses the WHI Clinical Coordinating Center.
In 2002, and again this year, the researchers found that menopausal women who took CHT, which contains both estrogen and progestin, had an increase of breast cancer, a risk that remained strong even after they discontinued CHT. But women who’d had full hysterectomies (removal of uterus and ovaries) and took estrogen alone experienced the opposite effect: The hormone had a protective effect which, again, lasted long after they’d discontinued use. In fact, the majority of women diagnosed with breast cancer in the estrogen-alone trial were taking placebo.
“There’s no debate that CHT elevates risk of breast cancer — it elevates it quite substantially — but there’s been recent debate about the use of estrogen alone and whether it also increases risk,” Prentice said. “The results for breast cancer between the two regimens are definitely disparate. For estrogen alone, they’re favorable significantly, and for estrogen plus progestin, they’re unfavorable significantly.”
Prentice was quick to acknowledge that it’s a “complicated picture” and one that the WHI will continue to illuminate.
“We do have prior publications that show the more favorable results of estrogen alone may depend how long the women were from menopause when they first started hormone therapy,” he said. “In earlier publications and in continuing work, the relationship between these findings for both hormonal preparation and timing from menopause to starting hormone therapy appear to be important considerations.”
“We’re trying to find out what is going on with these lobular tumors and how they are different. Our study demonstrated that there are potentially specific pathways differentially activated between lobular and ductal breast cancers dependent on the type of hormone exposure."
Fred Hutch breast cancer researcher Dr. Jamie Guenthoer
Long-awaited results on large collaborative trials
Researchers also presented findings from several large collaborative trials at the annual meeting. In the international MONALEESA-3 trial, metastatic patients with estrogen-receptor positive, or ER+, HER2-negative disease did better when they took ribociclib plus fulvestrant as opposed to fulvestrant alone.
The Phase 2 ATEMPT trial showed a new biologic therapy (Kadcyla) for people with early-stage HER2+ breast cancers caused significantly fewer toxicities than the chemo agent Taxol plus Herceptin, the current standard of care.
The large, collaborative Phase 3 SOPHIA trial looked at a new agent, margetuximab, in combination with chemotherapy in more than 500 women with HER2+ metastatic breast cancer who’ve been treated with prior anti-HER2 therapies.
Margetuximab plus chemotherapy offered a small but statistically significant improved PFS versus Herceptin plus chemo. Women who took the new experimental drug had a median PFS of 5.7 months compared to women who took Herceptin, who gained 4.4 months. While there was no overall survival benefit, the trial did identify subgroups whose cancers might be more responsive to the drug. Also, unlike many other breast cancer clinical trials, this one included women with brain metastases.
Dr. Lupe Salazar of Seattle Cancer Care Alliance, who helped design the trial, said she was pleased by the experimental drug’s performance and anticipated it would soon receive Food and Drug Administration approval.
“This can be just as impactful as Herceptin for patients with metastatic breast cancer,” she said.
Hormones, anti-hormones and adherence
Drs. Julie Gralow and Joe Unger and others from the Hutch participated in a large national trial sponsored by the SWOG Cancer Research Network that explored why breast cancer patients often stop taking their anti-hormone drugs. The researchers drilled down into baseline patient-reported outcomes, or PROs, and found that women who had preconceived negative beliefs about medication and higher levels of pain and other side effects (think hot flashes, weight gain, poor sleep) were more likely to stop.
“In this way, PROs can act like biomarkers,” said study lead Dr. Dawn Hershman of Columbia University. “They can predict outcomes and be used to personalize treatment.”
Gralow said the finding will lead to better identification of patients at high risk of having trouble tolerating and/or staying on their anti-hormone therapy long term.
“That will let us focus efforts — including future trials — on strategies to help them,” she said.
Dr. Jamie Guenthoer, a researcher who focuses on breast cancer biology, presented a poster on exogenous steroid hormone exposure (that is, hormones from sources outside the body) and the biology of lobular breast cancer, a “discovery project” conducted with other lobular experts from the Hutch, including Drs. Nancy Davidson, Christopher Li and Peggy Porter.
Previous research has shown that women who take CHT have a much higher risk of lobular breast cancer. But, as Guenthoer pointed out, “there are women who are not taking hormone replacement therapy who still get lobular.”
The researchers measured the activity of around 1,000 genes that represent known cancer-promoting pathways, or molecular mechanisms, and steroid hormone-associated pathways to determine the relationship between CHT use and pathway alterations in two ER+ subtypes: lobular and ductal.
“We’re trying to find out what is going with these lobular tumors and how they are different,” she said. “Lobular is understudied and surprisingly so. Our study demonstrated that there are potentially specific pathways differentially activated between lobular and ductal breast cancers dependent on the type of hormone exposure.
“[We] focused on tumor molecular pathways modulated in response to HRT use, but steroid hormone exposure can come from multiple sources,” she said. “The results of this study can provide insights into hormonally driven breast cancers that develop with excess estrogen and/or progesterone exposure.”
Powerful posters on PET scans
A type of PET scan called FES-PET effectively picks up estrogen and can be used to measure tumor estrogen levels throughout the body to better predict response to endocrine (hormone) therapy.
Hutch/SCCA research docs Drs. Poorni Manohar, Hannah Linden and others analyzed two types of PET scans performed between 1996 and 2015 in women with metastatic lobular breast cancer.
Previously, they showed FES-PET can pick up lobular breast cancer, which is notoriously difficult to find with conventional imaging. This year, they looked at bone metastases and found both FES and another type of PET, called FDG, (which picks up glucose in tumor cells) lit up bones and bone marrow infiltrated by cancer.
But the FES scan lit up significantly more in patients with more bone marrow uptake. Those patients also had longer PFS (1.3 years versus 0.57 years).
“This challenges the conventional belief that bone marrow involvement is an aggressive feature and provides insight into the biology and spread of lobular breast cancer,” Manohar said.
The major takeaway, per the researchers: FES-PET is more promising than FDG-PET in the detection of metastatic lobular breast cancer, especially cancers with bone involvement. And it may be available in the U.S. in a matter of months.
"FES-PET has been approved and is available in Europe," Manohar said. "We are expecting it may be commercially available in the U.S. as soon as next summer."
Are FES-PET scans cost effective, though? And better than biopsy?
Using mathematical modeling and a hypothetical cohort of 60-year-old breast cancer survivors with suspected metastasis, Manohar, Linden and Hutchinson Institute for Cancer Outcomes Research colleague Dr. Josh Roth found FES-PET to be a “potentially high-value strategy” to identify patients who could benefit from estrogen therapy compared with biopsy, the standard for detecting mets and guiding choice of treatment.
“Our study found that FES-PET could be cost effective depending on the treatment selection,” Manohar said. "We have data showing that FES-PET in combination with FDG-PET could help determine low-risk patients, who could get endocrine therapy only; intermediate risk patients, who could receive endocrine therapy plus a CDK4/6 inhibitor; and high-risk patients, who need chemo.”
Overall, she said, FES-PET will help oncologists treat patients with the treatment they need: aggressive care only for those who require it and no unnecessary treatment for those who will do fine just with endocrine therapy.
“This type of risk stratification and personalized medicine is very much needed in metastatic breast cancer,” she said.
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 dmapes@fredhutch.org. Just diagnosed and need information and resources?
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