Trio of studies to evaluate metastatic breast cancer care

Hutch researcher awarded grants to study the use of biopsy to drive therapy choices and test new type of PET scan to stage lobular
Photograph of two female scientists standing in front of a poster at a breast cancer conference
Dr. Poorni Manohar, right, with her mentor Dr. Hannah Linden at the San Antonio Breast Cancer Symposium in December 2019. Photo courtesy of Dr. Poorni Manohar

Dr. Poorni Manohar, a health services researcher with the Fred Hutchinson Cancer Research Center’s HICOR institute, was recently awarded three grants to fund research designed to ensure patients with metastatic, or stage 4 breast cancer, are consistently getting the current standard of care.

A senior fellow at the Hutch and University of Washington and a trainee in breast oncology at Seattle Cancer Care Alliance, Manohar partnered with the Hutchinson Institute for Cancer Outcomes Research (HICOR) to study real-world practice patterns and the disparities in health outcomes that can arise from them. HICOR’s research and interventions are often used to make changes in policy and clinical practice.

Manohar’s work in this area was acknowledged with a Young Investigator Award from Conquer Cancer, the ASCO Foundation. ASCO is the American Society of Clinical Oncology; its Young Investigator Awards are supported, in part, by the Breast Cancer Research Foundation.

The $50,000 award will be used to review the real-world use of biopsy in metastatic breast cancer recurrence to make sure these patients are receiving the appropriate treatment.

Metastatic biopsies: are they being done?

“In early breast cancer, hormone status is a defining factor in choosing therapy,” Manohar said. “But when there’s a metastatic recurrence, national guidelines call for another biopsy. This is because 20-30% of the time there’s a mismatch in hormone status between early and advanced, or metastatic cancer.”

Metastatic breast cancer is not in the breast, but in other organs of the body like the liver, the lungs, the bones, the peritoneum (in the case of lobular) and/or the brain. It’s treatable — targeted treatments are key — but incurable.

Manohar wants to determine if second biopsies are being performed when patients recur because if clinicians are relying on the original biopsy or pathology report to select treatment for a new metastatic tumor, they could be hitting the cancer with the wrong targeted treatment. In other words, patients might be receiving a chemo that’s not doing any good. Or not receiving an anti-hormone pill that would be more beneficial.

Manohar and colleagues will drill down into HICOR’s data sets — private and public insurance data and clinical records from Washington state — to determine who received second biopsies and who didn’t before being put on a therapy for their newly metastatic disease.

If clinicians aren’t following the guidelines, Manohar and team will dig into the data to find answers as to why. Are there disparities in terms of insurance status? Is the institution that’s providing the care in an urban or rural area? Does that influence whether they perform a biopsy?

“Certain institutes may not be as experienced as others,” she said. “The study will look at whether we’re practicing good quality care for patients, using NCCN guidelines.” National Comprehensive Cancer Network guidelines are considered the gold standard for cancer care.

The study will include both newly diagnosed MBC patients as well as those who recurred in the past and may still be in treatment or deceased. They’ll determine if a second biopsy was done on recurrence to ascertain both ER and HER2 receptor status and then see if treatment was based on that information.

One challenge that Manohar readily acknowledged: Biopsies can be difficult to obtain. Not because of the expense (Manohar said they cost on average around $200 to perform), but the logistics.

“The location can be challenging, especially in bone,” she said. “But it’s important to do these biopsies because there can be so much variability in hormone and HER2 status in tumor sites. Also, a bone site could have a different biology than a lung site. And even within a bone site, you can find different biology. There can be varied heterogeneity in both inter- and intra-tumor sites.”

Manohar said if she finds patients are not receiving a secondary biopsy upon metastatic diagnosis, the HICOR team will try to figure out why and work to improve the guidelines.

Or better yet, they’ll try to “create an alternate for biopsy in the metastatic setting.” More on this later.

Are MBC patients receiving the latest therapies?

A second grant, this one for $100,000 from the pharmaceutical maker Pfizer Inc., will allow her to examine the treatment choices oncologists have made in those diagnosed with metastatic breast cancer, to make sure patients are receiving the most current therapies recommended by national cancer care guidelines.

“We’re interested in who is prescribing what and why,” she said. “The guidelines are nebulous. There are so many first-line recommendations on preferred therapy.”

Manohar said there’s strong support for using CDK4/6 inhibitors, which have shown “amazing progression-free survival for patients.” But data show many clinicians are still using chemotherapies, which can have a severe impact on a patient’s quality of life. She wants to determine if patients are getting new drugs or other treatments like a “double-agent chemotherapy.” Pfizer, which is funding the study, makes a type of CDK4/6 inhibitor known as Ibrance or palbociclib.

The FDA granted approval to palbociclib for metastatic breast cancer patients in March 2017. There are currently three CDK4/6 Inhibitors that are FDA approved.

Since these targeted drugs are still fairly new, Manohar said there may be cancer centers unfamiliar with them.

“That could be one of the issues we find,” she said. “If so, we can do more education and outreach to improve treatment in these areas. We’ll look at the institutions, whether they’re urban or rural, and whether the choices they make are causing any kind of disparities in care.”

The team will also look at barriers — socioeconomic, cultural, geographical, financial, etc. — that prevent patients from receiving the latest standard of care. Again, they’ll use HICOR’s oncology informatics database that integrates cancer registry and health insurance claims to produce data-driven improvements in patient care. 

pull quote photo

“There’s a lot of promise for FES-PET, but it has to be defined before we start using it widely. In lobular, we often miss a lot of the cancer with conventional imaging ... FES could be an alternative way to stage this type of breast cancer.”

Fred Hutch / UW researcher Dr. Poorni Manohar

A better staging tool for lobular BC

A third award of $20,000, via a Roger E. Moe Fellowship in Interdisciplinary Breast Cancer Care through the University of Washington, will allow Manohar to investigate whether a new type of PET scan might be a better alternative to biopsy.

In late May, the FDA approved the use of FES imaging agent for PET scans in patients with recurrent or metastatic breast cancer as an adjunct to biopsy, thanks in large part to research done by Manohar and her mentor Dr. Hannah Linden of Fred Hutch/UW.

FES stands for fluoroestradiol F 18, a new type of estrogen-analogue tracer (a traceable injected fluid) that’s used in PET scans to detect estrogen-receptor binding in tumors. Most breast cancers are estrogen receptor-positive (ER+), particularly the subtype lobular. FES-PET scans pick up the function of estrogen receptors, lighting up the presence of ER+ breast cancer.

“This enables clinicians to help patients select appropriate and effective treatment,” she said. 

Manohar believes FES-PET scans might also be used to great effect in detecting lobular breast cancer, which is notoriously hard to image with current technology like traditional PETs, CTs and mammograms. Lobular is almost always ER+.

Her previous research proved FES-PET can detect lobular bone “mets” and lights up more in bone marrow, a finding that may have an implication for treatment response and prognosis.

Using a FES-PET scan, she believes, could help doctors “gain the same information when a biopsy is not feasible.”

“In some ways, it surpasses biopsy because it’s going to give you both intra- and inter-tumor heterogeneity, she said. “It looks at multiple tumor sites simultaneously.”

Since the tracer was just approved — and these new PET scans will likely be expensive — Manohar said it’s crucial to figure out the best use for the tool now.

“There’s a lot of promise for FES, but it has to be defined before we start using it widely,” she said. “In lobular, we often miss a lot of the cancer with conventional imaging. Then we have to backtrack and upstage patients surgically. FES could be an alternative way to stage this type of breast cancer. And it has potential to be cost-effective. We will know more when the cost of FES has been determined.”

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 and tweets @double_whammied. Email her at Just diagnosed and need information and resources? Visit our Patient Care page.

Read more about Fred Hutch achievements and accolades.

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