Radiotherapy For Breast Cancer Research Articles

Deep Inspiration Breath Hold in Left-Sided Breast Radiotherapy: A Balance Between Side Effects and Costs

BackgroundDeep inspiration breath hold (DIBH) is an effective technique for reducing heart exposure during radiotherapy for left-sided breast cancer. Despite its benefits, cost considerations and its impact on workflow remain significant barriers to widespread adoption. ObjectivesThis study aimed to assess the cost-effectiveness of DIBH and compare its operational, financial, and clinical outcomes with free breathing (FB) in breast cancer treatment. MethodsTreatment plans for 100 patients with left-sided breast cancer were generated using both DIBH and FB techniques. Dosimetric data, including the average mean heart dose, were calculated for each technique and used to estimate the cardiotoxicity of radiotherapy. A state-transition microsimulation model based on SCORE2 (Systematic Coronary Risk Evaluation) algorithms projected the effects of DIBH on cardiovascular outcomes and quality-adjusted life-years (QALYs). Costs were calculated from a provider perspective using time-driven activity-based costing, applying a willingness-to-pay threshold of €40,000 for cost-effectiveness assessment. A discrete event simulation model assessed the impacts of DIBH vs FB on throughput and waiting times in the radiotherapy workflow. ResultsIn the base case scenario, DIBH was associated with an absolute risk reduction of 1.72% (95% CI: 1.67%-1.76%) in total cardiovascular events and 0.69% (95% CI: 0.67%-0.72%) in fatal cardiovascular events over 20 years. Additionally, DIBH was estimated to provide an incremental 0.04 QALYs (95% CI: 0.05-0.05) per left-sided breast cancer patient over the same time period. However, DIBH increased treatment times, reducing maximum achievable throughput by 12.48% (95% CI: 12.36%-12.75%) and increasing costs by €617 per left-sided breast cancer patient (95% CI: €615-€619). The incremental cost-effectiveness ratio was €14,023 per QALY. ConclusionsDespite time investments, DIBH is cost-effective in the Belgian population. The growing adoption of DIBH may benefit long-term cardiovascular health in breast cancer survivors.

Role of AURKB Inhibition in Reducing Proliferation and Enhancing Effects of Radiotherapy in Triple-Negative Breast Cancer.

Breast cancer is a leading cause of cancer-related deaths in females. Triple-negative breast cancer (TNBC) subtype is the most aggressive form of breast cancer that lacks biomarkers and effective targeted therapies. Its high degree of heterogeneity as well as innate and acquired resistance to treatment creates further barriers in achieving positive clinical outcomes in TNBC. Thus, development of novel treatment approaches in TNBC is of high clinical significance. Multimodality approaches with targeted agents and radiotherapy (RT) are promising for increasing efficacy of treatment and circumventing resistance. Here we examined anticancer effects of the Aurora Kinase B (AURKB) inhibitor AZD1152 as a single agent and in combination with RT using various TNBC cell lines, MDA-MB-468, MDA-MB-231 and SUM-159. We observed that AZD1152 alone effectively inhibited colony formation in TNBC cell lines. The combination of AZD1152 at IC50 concentrations together with ionizing radiation further reduced colony formation as compared to the single agent treatment. Our data support the notion that inhibition of the AURKB pathway is a promising strategy for treatment and radiosensitization of TNBC and warrants further translational studies.

Construction and validation analysis of a risk factor and risk prediction model for radiation dermatitis in patients undergoing postoperative radiotherapy for early stage breast cancer

Construction and validation analysis of a risk factor and risk prediction model for radiation dermatitis in patients undergoing postoperative radiotherapy for early stage breast cancer

Correlation of new two-dimensional geometrical parameters to lung and heart dose-volume parameters in breast cancer radiation therapy.

To develop new two-dimensional geometric parameters for pulmonary and cardiac dose estimation in left-sided breast cancer radiation therapy without dose-volume histogram (DVH). On the CT image of 90 patients with left breast cancer, treatment planning was performed using two opposed tangent fields with/without supraclavicular. The field-in-field technique and 6MV photons were used. From DVH dosimetric parameters of mean dose, Vx (x (Gy) =5, 10, 15, 20, 30, 40, 50) were calculated, and from heart and lung outlines on the beam's eye view, new geometric parameters of percent of lung area in tangent and supraclavicular fields (%area of the lung in the tangent (ALT), %ALS) and percent of heart in tangent field (%area of the heart in the tangent (AHT)) were measured. Correlation, regression, and diagnostic performance by receiver operating characteristic curve (ROC) were investigated for statistical analysis. The Pearson coefficient between %ALT and Vx (x = 10, 15, 20, 30, 40) show strong correlation in patient treatment with only opposed tangents (>0.85) and weaker in treatment by opposed tangents with supraclavicular (0.56-0.88), the %ALS indicate weak correlation (<0.5) and %AHT show strong correlation (0.93-0.98). The regression analysis shows a positive relation between %ALT and mean dose (R2 = 0.8), V20Gy (R2 = 0.9) in the lung (tangent treatment), and between %AHT and mean dose (R2 = 0.9), V20Gy (R2 = 1.0) in the heart. The ROC analysis shows by %ALT <20.3 for treatment by just opposed fields, %ALT <22.1% for treatment tangents with supra, and %AHT <11.6%, practical lung and heart dose constraints are addressed. The proposed geometric parameters could replace previous one-dimensional maximum and central distances for predicting doses to lung and heart. This study presents simple geometric parameters that could estimate pulmonary and cardiac dose in left breast cancer treatment from a 2D radiograph.

Ultrahypofractionation in postoperative radiotherapy for breast cancer: A single-institution retrospective cohort series.

The 'FAST-forward', study published in April 2020, demonstrated the effectiveness of an extremely hypofractionated radiotherapy schedule, delivering the total radiation dose in five sessions over the course of 1 week. We share our department's experience regarding patients treated with this regimen in real-world clinical settings, detailing outcomes related to short-term toxicity and efficacy. A descriptive observational study was conducted on 160 patients diagnosed with breast cancer. Between July 2020 and December 2021, patients underwent conservative surgery followed by a regimen of 26 Gy administered in five daily fractions. The median age was 64 years (range: 43-83), with 82 patients (51.3%) treated for left-sided breast cancer, 77 patients (48.1%) for right-sided breast cancer, and 1 instance (0.6%) of bilateral breast cancer. Of these, 66 patients had pT1c (41.3%), 70.6% were infiltrative ductal carcinomas, and 11.3% were ductal carcinoma insitu. Most tumours exhibited intermediate grade (41.9%), were hormone receptor positive (81.3%), had low Ki-67 (Ki-67 < 20%; 51.9%) and were Her 2 negative (85%). The majority of surgical margins were negative (99.4%). Among the patients, 72.5% received hormonotherapy, and 23.8% received chemotherapy. Additionally, 26 patients (16.3%) received an additional tumour boost following whole breast irradiation (WHBI) of 10 Gy administered in five sessions of 2 Gy over a week. The median planning target volume (PTV) was 899 cm3 (range: 110-2509 cm3). Early toxicity was primarily grade I radiodermatitis, affecting 117 patients (73.1%). During a median follow-up of 15 months (range: 3.9-28.77), only one patient experienced a local relapse, which required mastectomy. The implementation of this highly hypofractionated regimen in early-stage breast cancer appears feasible and demonstrates minimal early toxicity. However, a more extended follow-up duration would be required to evaluate long-term toxicity and efficacy accurately.

Hypofractionated versus Conventional Postmastectomy Irradiation for Breast Cancer: Comparison of Acute Skin Toxicity.

Breast cancer is the leading cause of cancer mortality among women. Radiotherapy can reduce recurrence and prolong survival of patients accepting breast-conserving surgery (BCS). This study aims to compare acute skin reactions in patients receiving hypofractionated versus conventional radiotherapy at a single institution and to summarize the relevant influencing factors. This study analyzed 152 patients who underwent either hypofractionated or conventional whole-breast irradiation (WBI) after BCS. Acute skin toxicity was assessed according to the Radiation Therapy Oncology Group (RTOG) criteria. Predictive factors for acute skin toxicity were identified using multivariate analysis and visualized using a forest spot. Grade 0 reactions occurred in 75.34% vs 70.89%, grade 1 in 16.44% vs 15.19%, grade 2 in 8.22% vs 12.66%, and grade 3 in 0% vs 1.27% of patients receiving hypofractionated and conventional WBI, respectively. There was no statistically significant difference in acute skin reaction in patients treated with hypofractionated radiation compared with conventional radiation (P = 0.62). Multivariate analysis revealed that metastatic lymph nodes (P = 0.021), whole-breast planning target volume (PTV-WB) (P < 0.001), and tumor bed planning target volume (PTV-TB) (P = 0.002) were significantly correlated with higher rates of acute skin toxicity. Hypofractionated WBI demonstrated similar acute skin adverse reactions compared to conventional WBI. These findings indicate that hypofractionated radiotherapy offers comparable tolerance, equivalent curative effect, convenience, andeconomic benefits, supporting its clinicalpromotion.

INCIDENTAL BONE METASTASIS FINDING FROM CT SIMULATION FOR BREAST CANCER RADIOTHERAPY

Breast cancer has the highest tendency for bone metastasis. This study aimed to evaluate bone metastasis using computed tomography (CT) simulation for breast cancer radiotherapy. We retrospectively reviewed the patient's CT images from September 2022 to February 2023. The median age was 48 (34–80), and almost half of the patients had T3-4 and N2-3 disease. Nine out of 53 patients (17%) had bone metastasis, and 8 had multiple lesions. The vertebral spine was the predominant site of bone metastasis. Due to the high rate of bone spreading, bone evaluation is mandatory during CT simulation for more appropriate treatment. Keywords: Bone metastasis, computed tomography, breast cancer

Evaluating Danish Breast Cancer Group locoregional radiotherapy guideline adherence in clinical treatment data 2008–2016: The DBCG RT Nation study

Background and purposeGuideline adherence in radiotherapy is crucial for maintaining treatment quality and consistency, particularly in non-trial patient settings where most treatments occur. The study aimed to assess the impact of guideline changes on treatment planning practices and compare manual registry data accuracy with treatment planning data. Materials and methodsThis study utilised the DBCG RT Nation cohort, a collection of breast cancer radiotherapy data in Denmark, to evaluate adherence to guidelines from 2008 to 2016. The cohort included 7448 high-risk breast cancer patients. National guideline changes included, fractionation, introduction of respiratory gating, irradiation of the internal mammary lymph nodes, use of the simultaneous integrated boost technique and inclusion of the Left Anterior Descending coronary artery in delineation practice. Methods for structure name mapping, laterality detection, detection of temporal changes in population mean lung volume, and dose evaluation were presented and applied. Manually registered treatment characteristic data was obtained from the Danish Breast Cancer Database for comparison. ResultsThe study found immediate and consistent adherence to guideline changes across Danish radiotherapy centres. Treatment practices before guideline implementation were documented and showed a variation among centres. Discrepancies between manual registry data and actual treatment planning data were as high as 10% for some measures. ConclusionNational guideline changes could be detected in the routine treatment data, with a high degree of compliance and short implementation time. Data extracted from treatment planning data files provides a more accurate and detailed characterisation of treatments and guideline adherence than medical register data.

Impact of the COVID-19 Pandemic on Hypofractionated Radiation Therapy Use for Breast Cancer in Japan: A Nationwide Study

Purpose: Hypofractionated radiotherapy was recommended for several cancer sites to reduce outpatient visits during the coronavirus disease 2019 pandemic. This study aimed to identify the impact of the pandemic on hypofractionated radiotherapy for breast cancer in Japan. Methods and Materials: The monthly number of courses for hypofractionated and conventional radiotherapy was counted using sample datasets from the National Database of Health Insurance Claims and Specific Health Checkups of Japan, a nationwide database accumulating insurance claims data comprehensively. Changes in the number of hypofractionated and conventional radiotherapies were estimated using an interrupted time series analysis. Results: The number of hypofractionated radiotherapy courses gradually increased before the pandemic in contrast to that of conventional radiotherapy courses, which gradually decreased. However, conventional radiotherapy remained outnumbered by hypofractionated radiotherapy throughout the observation period. After the outbreak of the pandemic, the use of hypofractionated radiotherapy significantly increased in April 2020 (1,312 courses; 95% confidence interval: 801 to 1,823) but decreased in October 2020 (-601; 95% confidence interval: -1,111 to -92). Subgroup analysis by age and the number of beds in medical institutions revealed similar trends. Conclusions: Although conventional radiotherapy for breast cancer has been gradually replaced by hypofractionated radiotherapy, it remains predominant. The use of hypofractionated radiotherapy increased briefly early in the coronavirus disease 2019 pandemic; however, this increase was not sustained, unlike in other countries. Considering the benefits of hypofractionated radiotherapy for breast cancer, its use should be encouraged in Japan.

Sequelae of Adjuvant Irradiation of Breast Cancer on the Shoulder Region (Influence of Different Doses and Techniques)

Sequelae of Adjuvant Irradiation of Breast Cancer on the Shoulder Region (Influence of Different Doses and Techniques)

Dosimetric analysis of six whole-breast irradiation techniques in supine and prone positions

In breast cancer radiation therapy, minimizing radiation-related risks and toxicity is vital for improving life expectancy. Tailoring radiotherapy techniques and treatment positions can reduce radiation doses to normal organs and mitigate treatment-related toxicity. This study entailed a dosimetric comparison of six different external beam whole-breast irradiation techniques in both supine and prone positions. We selected fourteen breast cancer patients, generating six treatment plans in both positions per patient. We assessed target coverage and organs at risk (OAR) doses to evaluate the impact of treatment techniques and positions. Excess absolute risk was calculated to estimate potential secondary cancer risk in the contralateral breast, ipsilateral lung, and contralateral lung. Additionally, we analyzed the distance between the target volume and OARs (heart and ipsilateral lung) while considering the treatment position. The results indicate that prone positioning lowers lung exposure in X-ray radiotherapy. However, particle beam therapies (PBTs) significantly reduce the dose to the heart and ipsilateral lung regardless of the patient’s position. Notably, negligible differences were observed between arc-delivery and static-delivery PBTs in terms of target conformity and OAR sparing. This study provides critical dosimetric evidence to facilitate informed decision-making regarding treatment techniques and positions.

Dosimetric risk factors for radiation esophagitis in patients with breast cancer following regional nodal radiation

BACKGROUND Radiation esophagitis (RE) is one of the most common clinical symptoms of regi-onal lymph node radiotherapy for breast cancer. However, there are fewer studies focusing on RE caused by hypofractionated radiotherapy (HFRT). AIM To analyze the clinical and dosimetric factors that contribute to the development of RE in patients with breast cancer treated with HFRT of regional lymph nodes. METHODS Between January and December 2022, we retrospectively analysed 64 patients with breast cancer who met our inclusion criteria underwent regional nodal intensity-modulated radiotherapy at a radiotherapy dose of 43.5 Gy/15F. RESULTS Of the 64 patients in this study, 24 (37.5%) did not develop RE, 29 (45.3%) developed grade 1 RE (G1RE), 11 (17.2%) developed grade 2 RE (G2RE), and none developed grade 3 RE or higher. Our univariable logistic regression analysis found G2RE to be significantly correlated with the maximum dose, mean dose, relative volume 20-40, and absolute volume (AV) 20-40. Our stepwise linear regression analyses found AV30 and AV35 to be significantly associated with G2RE (P &lt; 0.001). The optimal threshold for AV30 was 2.39 mL [area under the curve (AUC): 0.996; sensitivity: 90.9%; specificity: 91.1%]. The optimal threshold for AV35 was 0.71 mL (AUC: 0.932; sensitivity: 90.9%; specificity: 83.9%). CONCLUSION AV30 and AV35 were significantly associated with G2RE. The thresholds for AV30 and AV35 should be limited to 2.39 mL and 0.71 mL, respectively.

Concurrent Use of Abemaciclib and Radiotherapy in Metastatic Breast Cancer Patients: A Single-Center Experience.

There is little evidence regarding the safety and efficacy of the combination of abemaciclib plus radiotherapy (RT). The majority of studies investigated the combination of RT with palbociclib or ribociclib reporting that hematological toxicity is common. Given the unique toxicity profile of abemaciclib with greater gastrointestinal toxicity compared to hematological toxicity, we wanted to evaluate the toxicity of the combination with RT in metastatic breast cancer (BC) patients. Patients with histologically proven metastatic or locally advanced BC treated with RT and concurrent abemaciclib were selected. Toxicity was assessed according to the NCI-CTCAE V4.0. Thirty-two metastatic sites were treated in 19 patients and analyzed. All patients received abemaciclib during the RT course. A total of 68% of patients received a full dose of abemaciclib during RT. Also, 71.9% of patients received a palliative intent (median dose = 30 Gy, range = 8-30 Gy), and 26.3% were treated for 9 oligo-metastatic or oligo-progressive sites of disease with stereotactic body RT (median dose = 30 Gy, range 21-30 Gy, given in 3-5 fractions). Overall, the rate of G3 toxicity was 15.7%. The rate of G3 hematological toxicity was 10.6% (2/19 patients, one G3 neutropenia and one G3 anemia). No patient presented diarrhea, including those treated for RT sites close to the bowel. One patient developed G3 skin toxicity. Pain significantly improved after RT (mean value NRS pre-RT = 3.9, SD = 3.07; mean value NRS after RT = 0.9, SD = 0.46; p &lt; 0.0001). Abemaciclib and concomitant RT seem well tolerated showing acceptable toxicity.

Evaluating Operative Times for Intraoperative Conversion of Axillary Node Biopsy to Axillary Lymph Node Dissection with Immediate Lymphatic Reconstruction.

Lymphedema can occur in patients undergoing axillary lymph node dissection (ALND) and radiation for breast cancer. Immediate lymphatic reconstruction (ILR) is performed to decrease the risk of lymphedema in patients after ALND. Some patients who ultimately require ALND are candidates for attempted sentinel lymph node biopsy (SLNB) or targeted axillary excision. In those scenarios, ALND can be performed (1) immediately if frozen sections are positive or (2) as a second operation following permanent pathology. The purpose of this study is to evaluate immediate ALND/ILR following positive intraoperative frozen sections to guide surgical decision-making and operative planning. A single-center retrospective review was performed (2019-2022) for breast cancer patients undergoing axillary node surgery with breast reconstruction. Patients were divided into two groups: immediate conversion to ALND/ILR (Group 1) and no immediate conversion to ALND (Group 2). Demographic data and operative time were recorded. There were 148 patients who underwent mastectomy, tissue expander (TE) reconstruction, and axillary node surgery. Group 1 included 30 patients who had mastectomy, sentinel node/targeted node biopsy, TE reconstruction, and intraoperative conversion to immediate ALND/ILR. Group 2 had 118 patients who underwent mastectomy with TE reconstruction and SLNB with no ALND or ILR. Operative time for bilateral surgery was 303.1 ± 63.2 minutes in Group 1 compared with 222.6 ± 52.2 minutes in Group 2 (p = 0.001). Operative time in Group 1 patients undergoing unilateral surgery was 252.3 ± 71.6 minutes compared with 171.3 ± 43.2 minutes in Group 2 (p = 0.001). Intraoperative frozen section of sentinel/targeted nodes extended operative time by approximately 80 minutes in patients undergoing mastectomy with breast reconstruction and conversion of SLNB to ALND/ILR. Intraoperative conversion to ALND adds unpredictability to the operation as well as additional potentially unaccounted operative time. However, staging ALND requires an additional operation.

Evaluation of Ovary Radiation Dose in Breast Cancer Radiotherapy with Modern Techniques: A Prospective Pilot Study

Evaluation of Ovary Radiation Dose in Breast Cancer Radiotherapy with Modern Techniques: A Prospective Pilot Study

Integrated Transcriptome Analysis of Radioresistant Cells Revealed Genes and Pathways Predictive Of Tumor Response to Radiotherapy and Chemotherapy in Breast Cancer

AbstractBreast cancer cells exposed to radiotherapy frequently develop radiation resistance through molecular and phenotypic changes. While there is evidences of pathways controlling radioresistance, the evolution of diverse cell phenotypes and transcriptional changes as mediators of radioresistance in breast cancer are restricted. Moreover, the effectiveness of the chemotherapy on radioresistant cells remains uncertain. In this work, an isogenic model of radioresistant breast cancer cells (RR cells) is used to study this phenotype. RR cells show high survival rates after radiation, moreover, RR cells of the triple negative breast cancer (TNBC) subtype show a significantly advanced invasiveness phenotype. Notably, RR cells are significantly sensitive to chemotherapy by inhibit cell survival and promote apoptosis. Transcriptomics and gene co‐expression network analysis identify differentially expressed genes (DEGs) and hub genes related to survival and apoptosis pathways in the RR cells of luminal subtype, while in TNBC subtype, cell migration, cell differentiation, and immune pathways are enriched. Hub genes predict the failure of radiotherapy in breast cancer patients, but they are also related to pathological complete response after chemotherapy. Transcriptome changes during acquired radioresistance uncover genes and pathways associated to radio and chemotherapy response. These results demonstrate that radioresistant pathways may converge to develop collateral chemo‐sensitivity.

ASO Visual Abstract: Impact of Neoadjuvant Chemoimmunotherapy on Surgical Outcomes and Time to Radiation in Triple-Negative Breast Cancer.

ASO Visual Abstract: Impact of Neoadjuvant Chemoimmunotherapy on Surgical Outcomes and Time to Radiation in Triple-Negative Breast Cancer.

Ultra-hypofractionated adjuvant radiation therapy for breast cancer (UK FAST-Forward trial): A real life scenario analysis in a developing country.

e12501 Background: Selected patients showed non-inferior outcomes after conservative surgery for early breast cancer in the FAST-Forward UK (26Gy in 5 fractions) when compared to standard to date treatment. This study triggered an important change in radiation therapy routines across the world. We aimed to establish a pattern of treatment related events at a third-world country cancer center. Methods: We retrospectively analyzed all patients treated with 26Gy in 5 fractions (1 week) from January 2020 to June 2023. All data was exported and analyzed for demographics. A clinical profile was traced, dosimetric parameters and side effects assessed based on individual inquiries to each patient, per and post treatment. A strict medical record was kept in order to understand patterns of side effects and results. Results: 101 individuals were identified. Mean age was 64 years, 48 (47%) patients experienced radiation dermatitis of any grade, 33 (32%) grade 1, 9 (8%) grade 2, 6 grade 3 or 4 (5%). Patients older than 60 years showed to be a significant factor for dermatitis development (34 over a total of 48 - 70%) and 8 (53%) over 15 had grade 2 or higher dermatitis. 27 (26%) developed radiation dermatitis during sessions. 21 (20%) took 7 or less days to heal; 27 (26%) had a recovery longer than one week at an average age of 65 years - being the majority of dermatitis grade 1. Reported toxicities were sharp pain 31 (30%), burning pain 24 (23%), edema 17 (16%) and pruritus 5 (4%). At the time of this study was completed, 3 reported deaths (2%) were reported - with a 97% rate of survival. Conclusions: The FAST-Forward trial regimen has 3 years since its publication. Our study shows that in a selected group of breast cancer patients, this novel model has shown to be a safe alternative for adjuvant radiation therapy following breast conservative surgery, results corroborating with published data. To the best of our knowledge, this is the largest single center group analyzed and published.

Cancer therapy-related cardiac dysfunction (CTRCD) after radiation therapy for breast cancer: Results of the French BACCARAT study

Cancer therapy-related cardiac dysfunction (CTRCD) after radiation therapy for breast cancer: Results of the French BACCARAT study

Efficacy and Safety of Chidamide in Combination with PD-1 Inhibitor and Radiotherapy for HER2-Negative Advanced Breast Cancer: Study Protocol of a Single Arm Prospective Study.

As one of the most important breakthroughs in cancer therapy, immune checkpoint inhibitors have greatly prolonged survival of patients with breast cancer. However, their application and efficacy are limited, especially for advanced HER2-negative breast cancer. It has been reported that epigenetic modulation of the histone deacetylase (HDAC) inhibitor chidamide, as well as immune microenvironment modulation of radiotherapy are potentially synergistic with immunotherapy. Thus, the combination of chidamide, radiotherapy and immunotherapy is expected to improve prognosis of patients with advanced HER2-negative breast cancer. This is a single-arm, open, prospective clinical trial investigating the efficacy and safety of the combination of HDAC inhibitor chidamide, anti-PD-1 antibody sintilimab, and the novel immuno-radiotherapy, which aims to enhance efficacy of immunotherapy, in subsequent lines of therapy of HER2-negative breast cancer. Our study will include 35 patients with advanced breast cancer that has failed endocrine therapy and first-line chemotherapy. Participants will receive 30 mg of chidamide twice a week, 200 mg of sintilimab once every 3 weeks, combined with immuno-radiotherapy. Radiotherapy will be centrally 8 Gy for at least one lesion, and at least 1 Gy for the other lesions. We will complete three fractions of radiotherapy in one cycle. The primary endpoint is progression-free survival, and secondary endpoints are objective response rate, disease control rate and safety. Moreover, biomarkers including cytokines and lymphocyte subgroups will be explored. As a single-arm clinical trial, the analysis of the influence of each single treatment is limited. Besides, our study is an open study, which involves neither randomization nor blinding. In spite of the abovementioned limitations, this prospective clinical trial will give an insight into subsequent lines of therapy of HER2-negative advanced breast cancer, prolong the survival or achieve long remission for these participants, and identify potential responders.