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Positron Emission Tomography and De-Escalation of Breast Cancer Treatment: What Emerging Research Reveals


In a lecture at the Society of Nuclear Medicine and Molecular Imaging (SNMMI) conference, Matthew F. Covington, M.D., discussed key findings from recent studies that emphasize the possible prognostic role of positron emission tomography (PET) in de-escalating treatment for breast cancer.

Positron emission tomography (PET) may play an increasingly larger role in the de-escalation of breast cancer treatment, according to emerging research discussed by Matthew F. Covington, M.D., during a lecture at the Society of Nuclear Medicine and Molecular Imaging (SNMMI) conference in Chicago.

In a recent study presented earlier this month at the American Society of Clinical Oncology (ASCO) conference, Dr. Covington said Javier Cortes, M.D., Ph.D., and colleagues examined the use of PET and a pathologic complete response (pCR)-adapted model for assessing treatment effectiveness in human epidermal growth factor receptor 2 (HER2)-positive women with breast cancer.1 The researchers found that a significant three-year invasive disease-free survival (iDFS) rate was associated with the PET-based, pCR-adapted approach and that one-third of HER2-positive women with early breast cancer (EBC) could avoid chemotherapy.

Dr. Covington said additional studies have shown the potential viability of fluorodeoxyglucose (FDG)-PET/CT as a biomarker for predicting pCR in women on HER2-directed treatment with some researchers suggesting that it could predict pCR in as little as two weeks after the initiation of HER2-directed therapy.

“Two weeks. Think about that. Maybe we don’t have to wait six months or 12 months to know how people will respond (to HER2-directed therapy). Maybe FDG-(PET/CT) can provide some of that information,” noted Dr. Covington, who is affiliated with the Huntsman Cancer Institute Center for Quantitative Cancer Imaging and the University of Utah Department of Radiology and Imaging Sciences.

In another study, presented recently at the American Roentgen Ray Society (ARRS) conference, Dr. Covington said researchers from MD Anderson Cancer Center compared FDG-avid nodal disease versus nodal ultrasound at initial presentation in patients with inflammatory breast cancer (IBC) and the impact of the findings on overall survival rates.

Positron Emission Tomography and De-Escalation of Breast Cancer Treatment: What Emerging Research Reveals

Positron Emission Tomography and De-Escalation of Breast Cancer Treatment: What Emerging Research Reveals

While the detection of axillary adenopathy and ipsilateral supraclavicular adenopathy was similar between the two diagnostic modalities, the researchers noted that PET/CT had a higher detection rate for ipsilateral internal mammary node (IMN) adenopathy (16.8 percent versus 10.3 percent for ultrasound). They also noted that contralateral IMN adenopathy was not routinely assessed on ultrasound and ultrasound wasn’t performed at all for contralateral supraclavicular adenopathy. Yet patients with contralateral supraclavicular and axillary adenopathy on PET/CT had a 3.1 hazard ratio and a median overall survival rate of 2.96 years, according to the study. For those with contralateral supraclavicular adenopathy, Dr. Covington noted the median overall survival rate was 1.51 years in comparison to 3.99 years for those without contralateral supraclavicular adenopathy.

“Perhaps we should go to FDG PET very early with inflammatory breast cancer, even perhaps as early as initial diagnosis. The authors suggest that maybe we skip ultrasound entirely. Once you’re diagnosed with inflammatory breast carcinoma, you go immediately to FDG-PET/CT. (Given the aggressive nature of a good proportion of inflammatory breast cancer), you would get an FDG-PET scan eventually. This could make a lot of sense to just get there from the start,” suggested Dr. Covington in his SNMMI lecture.

For patients who have recurrence or metastasis for estrogen receptor (ER)-positive breast cancer, Dr. Covington noted the National Comprehensive Cancer Network (NCCN) recently recommended 18F-fluoroestradiol (FES) PET, for systemic staging in this patient population under certain circumstances.

“That is actually a huge step to have something other than FDG addressed in the NCCN guidelines,” added Dr. Covington.

Covington added that criteria for appropriate use of 18F-FES PET in the imaging of patients with ER-positive breast cancer was published earlier this year.2 Based on this guidance, Covington said 18F-FES PET may be employed in this patient population when treating physicians are considering endocrine treatment or for assessment of the ER status of lesions that may prohibit biopsy or lead to inconclusive results with other imaging modalities.

In a recent pilot study he co-authored on the use of 18F-FES PET in patients with invasive lobular carcinomas (ILCs), Dr. Covington and colleagues found greater than 60 percent abnormal FES uptake in ILC sites.3 They also noted that 17 percent of histologically confirmed ILC sites were identified only with FES PET/CT in comparison to four percent only identified with FDG PET/CT, and FES PET/CT led to clinical staging changes in 18 percent of patients with ILC.

By demonstrating whether estrogen receptors are still present and able to bind to estradiol, the use of 18F-FES PET can help determine candidacy for endocrine therapy, according to Dr. Covington. He suggested that future use of 18F-FES PET may be able to show therapeutic blockade of ERs and possibly enable individually tailored dosing of anti-ER agents.

Dr. Covington also noted seven ongoing clinical trials examining the potential of theranostic agents, ranging from Ga Bombesin PET/CT (NeoB) imaging to 177Lu-DOTATATE and Radium-223 dichloride, for breast cancer.

“Radium-223 dichloride is commonly used for prostate metastases in the bone. I’ve always wondered why aren’t we using this for breast cancer bone metastases? Perhaps this study will get us a step closer,” suggested Dr. Covington.


1. Cortes J, Perez-Garcia JM, Ruiz-Borrego M, et al. 3-year invasive disease-free survival (iDFS) of the strategy-based, randomized phase II PHERGrain trial evaluating chemotherapy (CT) de-escalation in human epidermal growth factor receptor 2-positive (HER2(+)) early breast cancer (EBC). Presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, May 31-June 4, 2023, Chicago. Available at: https://meetings.asco.org/abstracts-presentations/219848 . Accessed June 24, 2023.

2. Ulaner GA, Mankoff DA, Clark AS, et al. Summary: appropriate use criteria for estrogen receptor-targeted PET imaging with 16a-18F-fluoro-17B-fluoroestradiol. J Nucl Med. 2023;64(3):351-354.

3. Covington MF, Hoffman JM, Morton KA, et al. Prospective pilot study of 18F-fluoroestradiol PET/CT in patients with invasive lobular carcinomas. AJR Am J Roentgenol. 2023 Jun 21;1-12. doi: 10.2214/AJR.22.28809. Online ahead of print.

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