Lugano, Switzerland, May 8, 2021 – The finding that breast tumors can develop in order to express low levels of HER2 may increase the number of patients who can benefit from new test agents, typically novel antibody-drug conjugate therapies are currently in clinical trials for HER2. low tumors.
The first study of its kind to look at how breast cancer changes from primary to recurrent tumor found that nearly 30% of breast cancer patients convert from the 2-low human epidermal growth factor receptor (HER) status. Specifically, the study found that 14% of triple negative breast cancers with HER2-negative expression (also known as HER2-0) in the primary tumor were converted to HER2-low expression in the recurrent tumor, potentially offering an option for such severe disease. Treat tumors.
Traditionally, breast cancers are divided into the following categories: hormone receptor positive (HR +) / HER 2 negative (also known as luminal-like), HER2 positive or triple negative (negative for estrogen receptors, progesterone receptors and excess HER2 protein). . HER2-low refers to HER2-negative tumors with low HER2 biomarker expression. About half of breast cancers classified as HER2-negative show low HER2 expression.
Dr. Federica Miglietta, School of Oncology, University of Padua, Italy, presents the results at this year’s ESMO Virtual Breast Cancer Congress. (1) “The results provide a whole new perspective on the development of HER2-low tumors as a subset and may challenge the current dichotomy between HER2-positive and HER2-negative breast cancer,” she said. “Our results underscore the importance of retesting HER2 expression in tumor recurrence, as this could open up new therapeutic options that are currently under study and hopefully in the clinic in the near future.” Several clinical trials of HER2-low breast cancer are ongoing.
Overall, 29% of recurrent breast cancer biopsies showed conversion to or from HER2-low expression. In primary and relapsing tumors, HER2-low expression was observed in 34% and 38% of the tumors, respectively. A total of 15% HER2-negative tumors switched to HER2-low tumors and 14% HER2-low tumors switched to HER2-negative.
The study also confirmed that low HER2 expression was more common in HR + / HER2-negative tumors than in triple negative tumors (47% versus 36% for primary tumor samples, 54% versus 36% for relapse samples). In addition, the change from HER2-negative to HER2-low in primary to recurrent tumors was 21% compared to 14% in lumen-like or triple negative tumors.
Commenting on the results, Professor Aleix Prat, Head of Medical Oncology at the Barcelona Hospital Clinic, Spain: “These changes in low HER2 levels are significant. There could be a biological or a technical rationale for this, as there is currently no standardization for determining levels of the HER2 biomarker in metastatic biopsies that are biopsied from skin, liver, or bone that could provide different results. ”
“We need to find out how HER2 status determines response to therapy. Is HER2 status important in the primary tumor or in the metastatic biopsy? Perhaps some patients have low HER2 expression in metastatic tumors and respond now when they haven’t before, and this could change over time and cause more relapses. ”
“All of this suggests a much greater need to biopsy metastatic tumors. The important thing is that we need to find out who will benefit from the treatments for HER2-low, as patients will soon be asking the clinic if the study results are positive, ”said Prat.
Notes for editors
Please make sure to use the official name of the meeting in your reports: ESMO Breast Cancer Virtual Congress 2021
Official congress hashtag: # ESMOBreast21
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2 Abstract 4MO_PR ‘HER2-low breast cancer: development from primary breast cancer to relapse.’ will be presented by Federica Miglietta during Mini Oral Session 2 on Saturday, May 8th, 12:45 pm-2:00pm (CEST). Annals of Oncology, Volume 32, Supplement 2, May 2021
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4MO_PR – HER2-low breast cancer: development from primary breast cancer to relapse. ??
F. Miglietta1, G. Griguolo1, M. Bottosso1, T. Giarratano2, M. Lo Mele3, M. Fassan4, M. Cacciatore5, E. Genovesi1, D. De Bartolo4, G. Vernaci2, PF Conte1, V. Guarneri1, MV Dieci1
1 Department of Surgery, Oncology and Gastroenterology (DISCOG), University of Padua, Padua, Italy, 2Dipartimento di Oncologia 2, IOV – Istituto Oncologico Veneto IRCCS, Padua, Italy, Department 3 Surgical Pathology, University Hospital Padua, Padua, Italy, 4 Department of Medicine (DIMED), Department of Surgical Pathology and Cytopathology, University of Padua, Padua, Italy, 5 Department of Pathology and Molecular Genetics, Treviso General Hospital, Treviso, Italy
Background: Around half of breast cancers traditionally classified as HER2 negative show low HER2 expression (IHC 1+ or IHC 2+ and ISH negative), which new antibody-drug conjugates can target. There are no data on the development of HER2-low status from primary tumor to relapse.
METHODS: Patients with matching primary and recurrent breast cancer specimens from two facilities (IOV-IRCCS Padova and Treviso Hospital) were included. HER2 was assessed according to the ASCO / CAP recommendations in force at the time of diagnosis. Cases diagnosed between 2007 and 2013 were reviewed by IHC to meet the cutoff of> 10% cells stained for HER2 positivity. In addition, 100 random samples were reviewed by a blinded pathologist: agreement with the original report was 80%. HER2 neg cases were classified as HER2 low (IHC 1+ or IHC 2+ and ISH not amplified) or HER2-0 (IHC 0).
Results: 575 patients were included. The primary tumor phenotype was: 59% luminal (HR + / HER2-neg), 25% HER2-pos, 16% triply negative. The proportion of HER2-low cases was 34% in the primary tumor and 38% in the relapse samples. Among HER2-neg cases, the HER2-low status was more common in lumen-like than in triple negative tumors (47% versus 41% for primary tumor samples, p = 0.268; 54% versus 40% for relapse samples, p = 0.006). . The overall rate of HER2 discordance was 38% (Table 1), mainly represented by the HER2-0 switch to HER2-low (15%) and HER2-low switch to HER2-0 (14%). A minority (9%) of the cases lost or acquired HER2 positivity. In patients with a primary HER2 neg? Tumor, the HER2 discordance rate was higher in luminal and triple negative cases (45% versus 35% p = 0.080). This difference was mainly due to cases of switching from HER2-0 to HER2-low: 40% of the luminal / HER2-0 patients versus 24% of the triple negative / HER2-0 patients (p = 0.088).
Conclusions: Low HER2 expression is very unstable during disease development. A relapse biopsy for a primary HER2-0 tumor can open up new treatment options in a relevant proportion of patients.
Legal person responsible for the study: the authors
Funding: Has not received funding
Disclosure: M.Fassan: Advice, research grant / funding (institution), outside of the submitted work: Astellas Pharma; Advice outside of the submitted work: Diaceutics; Advice outside of the submitted work: Tesaro; Research grant / funding (institution) outside of the submitted work: QED Therapeutics. PF Conte: Research grant / funding (institution) outside of the submitted work: Merck; Fees (self), research grant / funding (institution), outside of the submitted work: Roche; Fees (self), outside of the submitted work: Novartis; Fees (self), outside of the submitted work: Lilly. V. Guarneri: fees (self), research grant / funding (institution), outside of the submitted work: Roche; Fees (self), outside of the submitted work: Novartis; Fees (self), outside of the submitted work: Eli Lilly. MV Dieci: Honoraria (self), outside of the submitted work: Genomic Health; Honoraria (self), outside of the submitted work: Eli Lilly; Fees (self), outside of the submitted work: Celgene. All other authors have indicated no conflicts of interest.