Receptor 2-positive Breast Cancer Patients Research Articles

Treatment with trastuzumab deruxtecan in patients with HER2-positive breast cancer and brain metastases and/or leptomeningeal disease (ROSET-BM)

Therapeutic options for breast cancer patients with brain metastases (BM)/leptomeningeal carcinomatosis (LMC) are limited. Here, we report on the effectiveness and safety of trastuzumab deruxtecan (T-DXd) in human epidermal growth factor receptor 2-positive breast cancer patients with BM. Data were analyzed for 104 patients administered T-DXd. Overall response rate (ORR), progression-free survival (PFS), overall survival (OS), intracranial (IC)-ORR, and IC-PFS were evaluated. ORR by investigator assessment was 55.7% (total population). Median PFS was 16.1 months; 12-month OS rate was 74.9% (total population). Median time-to-treatment failure was 9.7 months. In 51 patients with BM imaging, IC-ORR and median IC-PFS by independent central review were 62.7% and 16.1 months, respectively. In 19 LMC patients, 12-month PFS and OS rates were 60.7% and 87.1%, respectively. T-DXd showed effectiveness regarding IC-ORR, IC-PFS, PFS, and OS in breast cancer patients with BM/active BM, and sustained systemic and central nervous system disease control in LMC patients.Trial Registration: UMIN000044995.

Absolute Lymphocyte Count Changes During Neoadjuvant Chemotherapy are Associated With Prognosis of Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer Patients

ntroduction/BackgroundSome reports have shown that absolute lymphocyte count (ALC) is associated with prognosis in breast cancer; however, the impact of ALC changes remains unclear. This study aimed to investigate the relationship between ALC changes during neoadjuvant chemotherapy for human epidermal growth factor receptor-2 (HER2)-positive breast cancer patients and disease prognosis. Patients and MethodsThis retrospective cohort study January 2010 to September 2020) included patients diagnosed with HER2-positive breast cancer and treated with trastuzumab-based neoadjuvant chemotherapy. The ALC ratio was defined as the ALC value after administration of the anti-HER2 drug divided by the ALC value before administration. The optimal ALC ratio cut-off value was identified using the receiver operating characteristic curve analysis and Youden's index. The relationship between the ALC ratio and disease-free survival was assessed using the Kaplan–Meier method. Univariate and multivariate analyses were performed using the Cox proportional hazards model. ResultsData from a total of 100 HER2-positive breast cancer patients were analyzed. The cut-off value of the ALC ratio was set as 1.142. The median follow-up period was 52.0 (range: 5.1-123.7) months. The 5-year disease-free survival rates were 88.4% and 60.9% in the high-and low-ALC ratio groups, respectively, and were significantly higher in the high-ALC ratio group (p = .0031). The ALC ratio was an independent prognostic factor in multivariate Cox proportional hazards analysis (p = .0032). ConclusionHER2-positive breast cancer patients with a higher ALC ratio during trastuzumab-based neoadjuvant chemotherapy may have a better prognosis than their counterparts.

Crossover in Adjuvant Trastuzumab Trials: Sparing Toxicity in Patient Care.

Design and reporting of randomized control trials for drug therapies in the adjuvant setting require a nuanced consideration of patient crossover. Adjuvant trials can be susceptible to the misuse of crossover and may distort the interpretation of findings. We sought to investigate and describe crossover and/or postprogression access to trastuzumab within adjuvant trastuzumab randomized control trials for human epidermal growth factor receptor 2-positive breast cancer patients. Seven clinical trials for adjuvant trastuzumab in human epidermal growth factor receptor 2-positive breast cancer were identified through a meta-analysis published in the Lancet . Primary study publications were located through MEDLINE, Google Scholar, and trials were identified, when possible, using Clincialtrials.gov. Sixteen publications, describing 7 studies, were reviewed. Four (57%) trials reported offering patients within the control arm the opportunity to crossover and receive trastuzumab in the adjuvant setting. Two (29%) trials did not report nor discuss crossover within the publication. Five (71%) trials reported the total number of patients who crossed over among the control arms. No trials specified the proportion of control patients who received trastuzumab at recurrence. Trials for adjuvant trastuzumab did not disambiguate between crossover (1) in the adjuvant setting or (2) at recurrence. Due to the low reported rate of crossover, it is questionable if participants received the standard of care.

Abstract P5-13-31: Pik3ca mutations and myc amplification are associated with pathological complete response in human epidermal growth factor receptor 2-positive breast cancer patients receiving pyrotinib combined with trastuzumab neoadjuvant treatment

Abstract Background: Our previous study reported a good efficacy and safety of pyrotinib combined with trastuzumab neoadjuvant treatment in human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients. We further explored the potential biomarkers for the efficacy of pyrotinib combined with trastuzumab neoadjuvant treatment in HER2-positive breast cancer patients. Methods:To date, a total of 162 patients with early-stage breast cancer were enrolled for the neoadjuvant pyrotinib combined with trastuzumab treatment clinical trial (ChiCTR1900022293). By the method of 425 genes next-generation sequencing (NGS), the genomic characteristics of them were evaluated for the potential correlation with postoperative pathological complete response (pCR). Results:. Among the cohort of 162 cases, a total of 43 patients have completed the whole therapy as well as final surgery and acquired qualified sequencing analysis report, and 25 of them achieved total pCR. The most frequently mutated driver genes were TP53 (80%), PIK3CA (46%), ERBB2 (10%), NF1 (8%), NBN (8%), ATRX (8%), respectively. In terms of somatic copy number alterations, the most frequent alterations are gain or amplification of ERBB2 (66%), MYC (24%), CKD12 (14%), CCND1 (12%) and ZNF217 (12%), respectively. The median tumor mutation burden (TMB) was 4.76 mut/Mb (0.00-29.61). Compared with pCR populations, non-pCR populations had higher median TMB but not statistically significant (5.29 vs 3.85 mut/Mb, P=0.141). In addition, the pCR rate of patients with wild-type PIK3CA is significantly higher than that of patients with mutated PIK3CA (80.0% vs 27.8%, P = 0.001), and those with amplified MYC are more likely to achieve pCR (22.2% vs 67.6%, P = 0.023). Conclusions:Preliminary results suggested that HER2-positive breast cancer patients with activating mutations in PIK3CA and amplified MYC are less likely to benefit from pyrotinib combined with trastuzumab neoadjuvant therapy, which need larger sample size to validate. Citation Format: Qiyun Shi, Juncheng Xuhong, Jia Ge, Feng Liu, Yang Lan, Yi Zhang, Luo Tao, Xiuwu BIan, Xiaowei Qi, Jun Jiang. Pik3ca mutations and myc amplification are associated with pathological complete response in human epidermal growth factor receptor 2-positive breast cancer patients receiving pyrotinib combined with trastuzumab neoadjuvant treatment [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-13-31.

Retrospective Analysis of Preferred Hepatectomy Combined with Systemic Drug Therapy for Breast Cancer Liver Metastases

To understand the efficacy and safety of preferred hepatectomy combined with postoperative systemic drug therapy for breast cancer liver metastases is the objective of the study. We retrospectively analyzed 3 patients with liver metastases included in the initial metastatic sites after breast cancer surgery that preferred hepatectomy and postoperative systemic drug therapy in our department between October 2016 and November 2019, combined with literature review to share our experience. All patients were estrogen receptor and/or human epidermal growth factor receptor-2 positive with good performance status and no obvious drug resistance but still had some unfavorable factors. Patient 1 was 73 y old; patient 2 developed 8 liver metastases after only 7 mo after breast surgery and patient 3 had the largest (6.3 cm) liver metastatic lesion and simultaneous extra-hepatic lymph nodes metastases. They all underwent radical (R0) resection of hepatectomy without complications, combined with systemic drug therapy including timely postoperative chemotherapy, sequential targeted therapy and endocrine therapy. During 28-64 mo of follow-up, they all have eventually achieved clinically complete remission of tumor in the whole body with good quality of life. The longest progression-free survival has been above 64 mo. Preferred hepatectomy combined with postoperative systemic drug therapy was safe and may benefit for estrogen receptor and/or human epidermal growth factor receptor-2 positive breast cancer patients with liver included in the initial metastatic sites who had good performance status, no drug resistance, potential R0 resection, limited and controllable extrahepatic metastasis.

Tumor mutation burden and PIK3CA mutations are associated with pathological complete response in human epidermal growth factor receptor 2-positive breast cancer patients receiving pyrotinib combined with trastuzumab neoadjuvant treatment.

e12610 Background: Our previous study reported a good efficacy and safety of pyrotinib combined with trastuzumab neoadjuvant treatment in human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients. We further explored the potential biomarkers for the efficacy of pyrotinib combined with trastuzumab neoadjuvant treatment in HER2-positive breast cancer patients. Methods: To date, a total of 96 patients with early-stage breast cancer were enrolled for the neoadjuvant pyrotinib combined with trastuzumab treatment clinical trial (ChiCTR1900022293). By the method of 425 genes next-generation sequencing (NGS), the genomic characteristics of them were evaluated for the potential correlation with postoperative pathological complete response (pCR). Results: Among the cohort of 96 cases, a total of 32 patients have completed the whole therapy as well as final surgery and acquired qualified sequencing analysis report, and 18 of them achieved total pCR. The most frequently mutated driver genes were TP53 (75%), PIK3CA (44%), NBN (9%), RUNX1 (9%), FANCD2 (9%), ATRX (9%), MAP3K1 (9%) and NF1 (9%), respectively. In terms of somatic copy number alterations, the most frequent alterations are gain or amplification of ERBB2 (63%), MYC (22%), CCND1 (19%), CDK12 (16%) and FGF19 (16%), respectively. The median tumor mutation burden (TMB) of the 36 patients was 4.23 mut/Mb (0.00-29.61). Compared with pCR populations, non-pCR populations had significantly higher median TMB (5.29 vs 3.17 mut/Mb, P = 0.025). In addition, the pCR rate of patients with wild-type PIK3CA is significantly higher than that of patients with mutated PIK3CA (88.9% vs 14.3%, P < 0.001). Conclusions: Preliminary results suggested that HER2-positive breast cancer patients with higher TMB and activating mutations in PIK3CA are less likely to benefit from pyrotinib combined with trastuzumab neoadjuvant therapy, which need larger sample size to validate. *Qiyun Shi and Juncheng Xuhong contributed equally. #Co-corresponding author (Dr. Jun Jiang, jcbd@medmail.com.cn; Dr. Xiaowei Qi, qxw9908@foxmail.com). Clinical trial information: ChiCTR1900022293.

Biomarkers for the identification of recurrence in human epidermal growth factor receptor 2-positive breast cancer patients.

This review discusses the mechanisms of anti-human epidermal growth factor receptor 2 (HER2) resistance in breast cancer patients, detailing possible predictive biomarkers of therapy benefit that could implement novel therapeutic strategies. Despite a remarkable improvement in survival over the past two decades, up to 30% of early-stage HER2+ breast cancer patients exhibit de-novo or acquired resistance to targeted therapy, underlying the need of developing predictive biomarkers. The role of HER family receptor redundancy, p95HER2 expression, and phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin downstream pathway activation in counteracting the inhibitory effects of anti-HER2 targeted therapy has been addressed. We also discuss the possible inconsistencies in the definition of HER2 positivity according to American Society of Clinical Oncology/College of American Pathologists guidelines or molecular intrinsic subtypes, and address the role played by tumor heterogeneity and evolutionary clonal selection on therapy selective pressure. Finally, the interplay between adaptive immunity and anti-HER2 targeted therapy is extensively discussed, focusing on its putative predictive and prognostic role.

Severe thrombocytopenia after trastuzumab retreatment: a case report

BackgroundTrastuzumab prolongs survival of human epidermal growth factor receptor 2-positive breast cancer patients in both the adjuvant and metastatic settings. Currently toxicity data are not available on retreatment of metastatic breast cancer patients who relapse after adjuvant trastuzumab. We report one patient with metastatic breast cancer who developed acute thrombocytopenia after trastuzumab infusion. This patient had trastuzumab treatment in the adjuvant setting.Case presentationA 70-year-old Caucasian woman received a diagnosis of metastatic breast cancer four years after her initial diagnosis of locally advanced, hormone receptors-positive, human epidermal growth factor receptor 2-positive breast cancer. Trastuzumab retreatment was planned. Less than 24 hours after trastuzumab infusion, the patient was admitted to the hospital for the appearance of diffuse petechial hemorrhages and ecchymosis. The patient was confirmed to have a severe trastuzumab-induced thrombocytopenia. A rapid and complete recovery was observed after high-dose intravenous corticosteroids and immunoglobulin. No trastuzumab retreatment was attempted.ConclusionAmong the reported cases of trastuzumab-induced thrombocytopenia, this is the first report in the literature occurring in a patient retreated with trastuzumab after adjuvant therapy.

Obesity increases the incidence of distant metastases in oestrogen receptor-negative human epidermal growth factor receptor 2-positive breast cancer patients

BackgroundObesity is a major negative determinant of breast cancer outcome. However, there are contrasting data on the differential impact of obesity on specific breast cancer subtypes. In particular, very little is known on human epidermal growth factor receptor 2-positive (HER2+) tumours. Patients and methodsWe assessed the prognostic role of increased body mass index (BMI) on a consecutive series of non-metastatic HER2+ patients treated at our institution before the introduction of adjuvant Trastuzumab. We separately analysed oestrogen receptor-positive (ER+) and -negative (ER−) HER2+ cases. ResultsIn ER−/HER2+ tumours we observed a significantly worse overall survival (Hazard ratio (HR) 1.79, p-value 0.041) and cumulative incidence of distant metastases (HR 2.03, p-value 0.019) in obese (BMI>30) versus normal/underweight (BMI<25) patients. Local relapses appeared to be non-significantly reduced in obese patients, masking the overall effect on disease-free survival. Outcome in ER+ tumours, instead, was not significantly different between BMI groups. ConclusionsObesity significantly correlates with worse overall survival and cumulative incidence of distant metastases in ER−/HER2 positive breast cancer. Differences in the biology of breast tumours may determine individual susceptibility to obesity. The biology of the underlying tumour should be taken into account in the design of dietary intervention trials in breast cancer.

The Croatian government is to pay for early-stage human epidermal growth factor receptor 2-positive breast cancer patients to receive Roche's Herceptin

The Croatian government is to pay for early-stage human epidermal growth factor receptor 2-positive breast cancer patients to receive Roche's Herceptin