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Breast experts work together to discuss the treatment decision after multiple rapid progression of advanced breast cancer with low HR+/HER2 expression
On July 1, 2024, the ninth issue of the "Big Coffee Style Multidisciplinary Diagnosis and Treatment Interactive Column for Breast Cancer" was officially launched online. In this meeting, the MDT team from Fudan University Cancer Hospital and the MDT team from the Fourth Hospital of Hebei Medical University were invited to demonstrate in-depth analysis and discussion on a difficult case of HR+/HER2 low expression breast cancer, aiming to further standardize the MDT pattern of HER2 low expression advanced breast cancer and promote the precision treatment of breast cancer. The important contents of the conference are summarized as follows for the benefit of readers.
At the beginning of the meeting, the chairman of the conference, Professor Shao Zhimin from Fudan University Cancer Hospital, first delivered an opening speech and introduced the participating teams.
Professor Shao Zhimin from Fudan University Cancer Hospital delivered a speech
MDT Member
Sharing of treatment decisions based on multiple changes in molecular typing in advanced breast cancer cases
The case sharing session was chaired by Professor Geng Cuizhi from the Fourth Hospital of Hebei Medical University, and Professor Zhang Lina from the Fourth Hospital of Hebei Medical University reported a difficult case of advanced breast cancer with low HR+/HER2 expression. In April 2014, the female patient underwent modified radical resection of right breast cancer, and the postoperative pathology showed ER (90% strong positive), PR (70% strong positive), HER2 (1+), Ki-67 (20%), and then adjuvant chemotherapy with pirarubicin + cyclophosphamide (AC regimen) for 6 cycles, and tamoxifen (TAM) adjuvant endocrine therapy for 5 years. During this period, he underwent surgery for papillary thyroid adenocarcinoma in 2017, and the disease-free survival (DFS) was 8 years and 4 months. The first recurrence occurred in August 2022, pathology showed ER (90% strong positive), PR (3% weak positive), HER2 (2+), Ki-67 (10%), FISH (HER2 no amplification), CDK4/6 inhibitor (CDK4/6i) + letrozole first-line treatment, rated as disease progression (PD), progression-free survival (PFS) of 2 months; After progression, the patient received CDK4/6i+fulvestrant second-line treatment in other hospitals, and the efficacy was evaluated as PD and PFS was 2 months. After improving the relevant treatment, we enrolled in a clinical trial in June 2023, and underwent third-line SYHX2011/nab-paclitaxel chemotherapy, with PD and PFS for 2 months. Although trastuzumab (T-DXd) had excellent efficacy in the treatment of patients with low HER2 expression, combined with the patient's wishes, he was enrolled in a clinical trial to receive SHR-A1811 as fourth-line therapy, with PD and PFS for 6 months. After disease progression, the fifth-line treatment was treated with rekang satuzumab (SKB264), and the PD was evaluated, and the PFS was 2 months.
Professor Geng Cuizhi of the Fourth Hospital of Hebei Medical University
Professor Zhang Lina from the Fourth Hospital of Hebei Medical University
Case MDT discussion
The case discussion session was chaired by Professor Fan Lei from Fudan University Cancer Hospital, and the two MDT teams analyzed and discussed the timing of polygenic testing, postoperative adjuvant therapy strategies, and the treatment selection of ADC drugs in patients with HR+/HER2 low expression breast cancer who had progressed multiple times since the first recurrence.
- In terms of pathology, Professor Zhao Meng summarized the results of the patient's 3 needle biopsies, and said that the molecular biological characteristics of the patient before and after treatment were relatively stable. Professor Shui Ruohong also pointed out that the breast cancer phenotype of the patient's first primary lesion was consistent with that of the second recurrence lesion, and there was no temporal and spatial heterogeneity.
- In terms of imaging, Professor Xiao Qin said that pleural lesions are unmeasurable lesions, and the clinical evaluation of non-target lesions should be strictly controlled. Professor Wang Lijia pointed out that in the process of regular re-examination of patients, if the patient's condition is stable, chest and abdomen CT detection can be performed; PET-CT is indicated if the patient has abnormal laboratory parameters but normal routine CT results.
- In terms of postoperative adjuvant therapy, Professor Huang Liang said that the T2N0 patient underwent AC regimen for 6 cycles and adjuvant TAM therapy for 5 years, at this time, if 21 gene testing was performed to assess the risk, low-risk patients could be exempted from chemotherapy, and intermediate-risk patients could be treated with chemotherapy, such as AC regimen. Postoperative adjuvant therapy clinically recommends ovarian function suppression (OFS) + TAM for premenopausal patients, and whether to prolong endocrine therapy is still controversial.
- In terms of first-line treatment selection strategies, Professor Yang Chao pointed out that patients receiving 1st and 2nd lines of endocrine therapy have shorter PFS, and in view of this, genetic testing can be recommended for patients to explore whether they are accompanied by gene mutations. After that, for patients enrolled in clinical trials and undergoing two PDs, the selection of ADC drugs in clinical practice should first consider whether the cytotoxic drugs carried by different ADC drugs are conflicting in mechanism, and if there is no cross-resistance, T-DXd therapy can be selected in the future, or bring better efficacy to patients. Secondly, for patients with low HER2 expression in clinical practice, the results of the DB04 study should be referred to, that is, patients with HR+ breast cancer have progressed on 2nd line of endocrine therapy, or at least 1 line of chemotherapy should be treated with T-DXd. In addition, at this year's ASCO Annual Meeting, the DB06 study was announced, and its enrollment population is HR+ endocrine-refractory patients who have not received advanced chemotherapy before, which is more frontline than the DB04 study. It is believed that with the publication of the results of the DB06 study, it is expected to advance the front-line application of T-DXd treatment regimens, so that eligible patients with advanced breast cancer can benefit from T-DXd treatment as soon as possible.
- Regarding the timing of polygenic testing and radiotherapy for luminal breast cancer, Professor Dong Qian suggested that multi-gene testing such as PAM pathway can be performed for HR+ patients after disease progression, and it is expected that Fudan typing can provide further guidance for the treatment of this patient. Professor Kong Deyou said that in view of the patient's first recurrence, if the systemic treatment of the T2N0M1 patient is effective, radiotherapy can be used; In the case of disease progression with pleural metastases, radiation therapy may be indicated after symptoms have been controlled, i.e., the tumor has shrunk and stabilized for 3 to 6 months. Professor Ma Jinli also said that for patients with recurrent breast cancer with distant metastasis, the value of radiotherapy is relatively limited. When metastases interfere with the patient's quality of life, topical therapy may be considered.
- Regarding the deployment of ADC drugs for HER2-low expression breast cancer, Professor Huang Liang pointed out that for HR+ breast cancer, when accompanied by low HER2 expression, it is recommended to treat T-DXd first, and its efficacy is better than that of gosatuzumab (SG); When HER20 is expressed, SG is optional. For the sequential treatment of different ADC drugs, if the target is the same, ADCs with different drug loads should be selected; If the targets are different, ADC therapy with different targets is selected. In addition, the Breast Cancer Precision Therapy Collaboration (BCTOP) also has relevant clinical studies to provide guidance for subsequent treatment strategies.
- Regarding the patient's current treatment decision, Professor Zhang Lina said that the patient is currently receiving anti-angiogenic drugs. Professor Zhang Wenjuan pointed out that the establishment of the POST-ADC and POST-CDK4/6i platforms in Fudan University Cancer Hospital may provide relevant strategies for the treatment of patients with advanced breast cancer with low HR+/HER2 expression and bring more treatment opportunities. Professor Fan Lei also said that at present, the patient has not tried a variety of chemotherapy drugs and endocrine therapy drugs, and can be tested by PAM pathway, in order to obtain chemotherapy + targeted therapy, or other ADC drug treatment opportunities.
- Professor Geng Cuizhi summarized the case again, questioned whether the pleural metastases could be used as a target lesion, and consulted whether the patient could undergo Fudan tetramorphic treatment strategies and related detection methods.
Professor Fan Lei from Fudan University Cancer Hospital
Case Discussion Specialist
Subsequently, Professor Shao Zhimin concluded that the RTK-driven (SNF4) type of luminal breast cancer is characterized by primary drug resistance, and the first-line endocrine therapy effect of this patient is not good. Second, the patient can be treated with a PAM pathway inhibitor. At present, most of the patients enrolled in the Fudan POST-CDK4/6i platform are patients who have been treated with 1-2 lines of chemotherapy, and all of them have achieved good therapeutic efficacy. In addition, patients can also try other ADC drugs, and it is expected that the POST-ADC and POST-CDK4/6i platforms can bring better treatment opportunities to more patients.
At the end of the meeting, Professor Shao Zhimin said that this conference promoted the academic exchanges and cooperation between the two MDT teams, provided valuable experience and ideas for the standardized diagnosis and treatment of breast cancer, and looked forward to discussing and analyzing more difficult cases through the series of meetings of big coffee style, providing an important reference for the diagnosis and treatment of breast cancer and clinical research, and helping the clinical diagnosis and treatment of breast cancer in mainland China to be more accurate and standardized.
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