Impressive Objective Response to Nab-Paclitaxel plus Trastuzumab as Fifth Line Therapy in an Elderly HER-2 Positive Breast Cancer Patient

Background: Agent targeting HER-2 pathway plus chemotherapy has represented a major progress in the management of patients with breast cancer. However, the role of late-line treatment in heavily pretreated patients is still largely unclear. In the last decade, nab-paclitaxel has shown significant activity and good toxicity profile in metastatic breast cancer. Case Presentation: We report the case of a 76-year-old Caucasian woman with metastatic HER-2 positive ductal infiltrating breast carcinoma treated with a combination of weekly nab-paclitaxel and trastuzumab as fifth-line therapy. She had previously received first-line paclitaxel and trastuzumab, second-line vinorelbine and trastuzumab, third-line TDM1 and fourth-line oral capecitabine and lapatinib. Clinical and radiological staging showed progression at bone, skin and soft-tissue. The patient received weekly nab-paclitaxel plus trastuzumab. Massive objective response was clinically and PET documented which lasted 8 months. Tolerance to treatment was fairly good as well as cardiac safety. Conclusion: To the best of our knowledge, this is the first reported case of efficacy of nab-paclitaxel in combination with trastuzumab as fifth-line of treatment in a patient with metastatic HER-2 positive breast cancer.

CORRELATION BETWEEN SERUM HER-2 ONCOPROTEIN AND PATIENTS WITH BREAST CANCER

To detect serum HER-2 oncoprotein levels in patients with operable and metastatic breast cancers, and to study the correlations between serum HER-2 level and lymph node status as well as other clinical parameters. Methods A total of 120 women were studied consisting of 10 healthy volunteers, 31 benign breast disease, 53 operable breast cancer, and 26 metastatic breast cancer patients. The levels of serum HER-2 were measured using an enzyme-liked im-munosorbent assay (ELISA). Results The mean serum HER-2 levels were 9.6 ± 1.5 ng/mL in healthy volunteers, 11.9 ± 1.6 ng/mL in benign breast disease, 13.2 ± 4.2 ng/mL in operable breast cancer, and 30.5 ± 30.8 ng/mL in metastatic breast cancer patients. The former is much lower than the latter three (P = 0.02, 0.001, 0.03, respectively). If using 15 ng/mL as a normal baseline, elevated serum HER-2 levels were observed in none of the healthy volunteers as well as patients with benign disease, but in 18.9% (10/53) operable breast cancer patients and 61.5% (16/26) metastatic patients. In patients with operable breast cancer, there was a positive correlation between serum concentrations of HER-2 and the size of primary tumor (P < 0.05), whereas there was no correlation between serum concentration and axillary lymph node or estrogen receptor status. In patients with metastatic dise-ase, there was no correlation with site of metastases (P > 0.05). Conclusion Serum HER-2 level was strongly correlated with tumor loads and clinical stages, thus acting as a promising predictor of cancer recurrence in breast cancer patients.

Comparison of Fluorescence in situ Hybridization and Immunohistochemistry for Assessment of HER-2 Status in Breast Cancer Patients

The accurate assessment ofa proto-oncogene, human epidermal growth factor receptor-2 gene （HER-2）, is extremely important for the therapy and prognosis of breast cancer. Currently, immunohistochemistry （IHC） is the method widely used for the detection of HER-2 protein. Fluorescence in situ hybridization （FISH） has been suggested to be a golden standard assay for HER-2 amplification. This study examined the expression and amplification of HER-2 in paraffin-embedded sections of breast cancer tissues, and compared the two methods on the measurement of HER-2 status. HER-2 gene and protein were determined in breast cancer samples from 52 Chinese women by FISH and IHC respectively. The findings indicated that the HER-2 gene amplification was found in 18 cases （34.6%） by FISH and the HER-2 protein over-expression （score 3＋） in 15 cases （28.8%） by IHC. hnmunohistochemically, 28.6% of the cases scored as 2＋ and 93.3% of the cases scored as 3＋ were HER-2-positive by FISH. There was a significant correlation between the HER-2 gene amplification and HER-2 protein over-expression in breast cancer （P〈0.005）. No correlation was noted between the HER-2 gene amplification and any of the clinicopathological parameters examined, including age, menopausal status, menarche age, tumor size, histological tumor type, histological grade, lymph node status, and the expression of ER and PR. It was concluded that the detection of HER-2 gene amplification in breast cancer by FISH is valuable and can compare with HER-2 protein detection by IHC.

Increased Mortality Risk among Early Stage Hormone Receptor Positive Breast Cancer Patients Who Did Not Receive Adjuvant or Neoadjuvant Therapy

Background: Hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) is the most common biologic subtype of breast cancer. Although adjuvant therapy has demonstrated a survival benefit in clinical trials, its use is poorly understood in the real-world among elderly breast cancer patients since age is a barrier to receiving adjuvant therapy. An examination of treatment patterns and outcomes associated with receipt of adjuvant/neoadjuvant therapy among elderly HR + HER2-breast cancer patients was undertaken. Methods: There were 18,470 HR + HER2-breast cancer patients from the linked SEER-Medicare database. Patients were diagnosed with stage I-III disease between 1/1/2007-12/31/2011, ≥66 years, enrolled in Medicare Parts A, B and D, and underwent breast cancer surgery after diagnosis. Time-varying Cox proportional hazards regression assessed overall survival. Results: There were 13,670 (74%) patients treated with adjuvant/neoadjuvant therapy and 4800 (26%) untreated. Compared to treated patients, untreated patients were older, had earlier stage, lower grade, smaller tumors, poorer performance, higher comorbidity score, and less use of a 21-gene recurrence score (RS) assay (p < 0.0001). In the survival model, increasing age, stage, tumor size, tumor grade, comorbidity score and poor performance were significantly associated with higher mortality risks, while use of an RS assay was associated with lower risks. The Cox model showed a 48% higher risk of death in untreated compared to treated patients. In a subset of 8967 patients with stage I disease, tumor size < 2.0 cm and grade 1/2;untreated patients had a 22% higher risk of death compared to treated patients. Conclusions: Older patients with favorable clinical characteristics (earlier stage, smaller tumor, lower grade) are less likely to be treated and have a higher risk of death compared to adjuvant/neoadjuvant treated patients. An unmet need among older breast cancer patients persists.

Cancer risk in relatives of BRCA1/2 pathogenic variant carriers in a large series of unselected patients with breast cancer

Objective:The spectrum and risk of cancer in relatives of BRCA1/2 pathogenic variant carriers in the Chinese population have not been established.Methods:A family history of cancer in 9903 unselected breast cancer patients was retrospectively analyzed.BRCA1/2 status was determined for all patients and relative risks(RRs)were calculated to evaluate cancer risk in relatives of the patients.Results:The incidences of breast cancer in female relatives of BRCA1 carriers,BRCA2 carriers,and non-carriers were 33.0%,32.2%,and 7.7%,respectively.The corresponding incidences of ovarian cancer were 11.5%,2.4%,and 0.5%,respectively.The incidences of pancreatic cancer in male relatives of BRCA1 carriers,BRCA2 carriers,and non-carriers were 1.4%,2.7%,and 0.6%,respectively.The corresponding incidences of prostate cancer were 1.0%,2.1%,and 0.4%,respectively.The risks of breast and ovarian cancers in female relatives of BRCA1 and BRCA2 carriers were significantly higher than female relatives of non-carriers(BRCA1:RR=4.29,P<0.001 and RR=21.95,P<0.001;BRCA2:RR=4.19,P<0.001 and RR=4.65,P<0.001,respectively).Additionally,higher risks of pancreatic and prostate cancers were noted in male relatives of BRCA2 carriers than non-carriers(RR=4.34,P=0.001 and RR=4.86,P=0.001,respectively).Conclusions:Female relatives of BRCA1 and BRCA2 carriers are at increased risk for breast and ovarian cancers,and male relatives of BRCA2 carriers are at increased risk for pancreatic and prostate cancers.

Current status of PI3K-mTOR inhibition in hormone-receptor positive, HER2-negative breast cancer

Breast cancer (BC) is the most common cancer in women and second only to lung cancer in terms of mortality. Among the three different BC subtypes, the oestrogen receptor positive represents nearly 70% of all cases and it is usually treated with anti-oestrogen drugs. However, the majority of hormone receptor positive metastatic BC patients develop resistance to anti-oestrogen treatments.The need for more down-stream therapies brought to the development of therapeutic strategies inhibiting the phosphatidylinositol 3-kinase-mammalian target of rapamycin (mTOR) pathway. Inhibitors of the mTOR have been tested in different clinical trials; everolimus has been Food and Drug Administration approved for the treatment of oestrogen receptor positive/human epidermal growth factor receptor 2 negative BC patients in combination with exemestane in patients who have progressed to anastrozole or letrozole after the encouraging results coming from BOLERO-2 trial. Similar results were obtained by the TAMRAD investigatory study testing tamoxifen in combination with everolimus in advanced BC. This editorial focuses on the results from BOLERO-2, BOLERO 4 and BOLERO-6, which tested the clinical importance of mTOR inhibition. We comment also on the role of phosphatidylinositol 3-kinase-mTOR inhibition as reported in the BELLE-2 and BELLE-3 trials and the future directions for the inhibition of this tumour metabolic axis.

Tyrosine kinase inhibitors and human epidermal growth factor receptor-2 positive breast cancer

The body of evidence investigating human epidermal growth factor receptor-2(HER2)directed therapy in patients with breast cancer(BC)has been growing within the last decade.Recently,the use of tyrosine kinase inhibitors(TKIs)has been of particular interest in the treatment of human malignancies.This literature commentary is intended to highlight the most recent findings associated with the widely-studied TKI agents and their clinical significance in improving the outcomes of HER2 positive BC.

Downregulation of wild-type p53 protein by HER-2/neu mediated PI3K pathway activation in human breast cancer cells: its effect on cell proliferation and implication for therapy

Overexpression and activation of HER-2/neu (also known as c-erbB-2), a proto-oncogene, was found in about 30% of human breast cancers, promoting cancer growth and making cancer cells resistant to chemo- and radio-therapy. Wild-type p53 is crucial in regulating cell growth and apoptosis and is found to be mutated or deleted in 60-70% of human cancers. And some cancers with a wild-type p53 do not have normal p53 function, suggesting that it is implicated in a complex process regulated by many factors. In the present study, we showed that the overexpression of HER-2/neu could decrease the amount of wild-type p53 protein via activating PI3K pathway, as well as inducing MDM2 nuclear translocation in MCF7 human breast cancer cells. Blockage of PI3K pathway with its specific inhibitor LY294002 caused Gl-S phase arrest, decreased cell growth rate and increased chemo- and radio-therapeutic sensitivity in MCF7 cells expressing wild-type p53. However, it did not increase the sensitivity to adriamycin in MDA-MB-453 breast cancer cells containing mutant p53. Our study indicates that blocking PI3K pathway activation mediated by HER-2/neu overexpression may be useful in the treatment of breast tumors with HER-2/neu overexpression and wild-type p53.

GENISTEIN INHIBITS EXPRESSION OF VASCULAR ENDOTHELIAL GROWTH FACTOR IN HER-2/NEU TRANSFECTED HUMAN BREAST CANCER MCF-7 CELLS

Objective： our previous studies have demonstrated that HER-2/neu gene expression in human breast cancer MCF-7 cells promotes angiogenesis in MCF-7 cells xenograft tumors, and genistein inhibits angiogenesis in MCF-7 cells with HER-2/neu expression xenograft tumors. Here, the effects of genistein on the expression of vascular endothelial growth factor （VEGF） in MCR-7 cells with HER-2/neu expression were further studied for exploring the molecular mechanism of anti-angiogenesis in HER-2/neu-overexpressing breast cancer by genistein. Methods： HER-2/neu-overexpressing MCF-7 cells （MCF-7/HER-2） were established by transfecting HEg-2/neu gene into HER-2/neu negative expression breast cancer MCF-7 cells. Immunocytochemical staining, western blot and reverse transcription-polymerase chain reaction （RT-PCR） were adopted to measure the expression of VEGF in MCF-7/HER-2 cells treated by genistein for 24, 48 and 72h. Results： HER-2/neu expression up-regulated VEGF mRNA and protein in MCF-7 cells, genistein decreased VEGF mRNA and protein level in MCF-7/HER-2 cells in a time-dependent manner. Conclusion： These results suggest that VEGF plays an important role in HER-2/neu gene expression promoted antiogenesis in breast cancer and genistein induced down-regulation of the expression of VEGF may be one of the molecular mechanisms of its anti-angiogenesis in HER-2/neu-overexpressing breast cancer.

HER-2 expression after neoadjuvant chemotherapy of the breast cancers

Objective:The aim of this study was to study changes of HER-2 expression after neoadjuvant chemotherapy in the breast cancer cases.Methods:One hundred and thirty-seven female patients with primary breast cancers,who received neoadjuvant chemotherapy,underwent core needle puncture and Mammotome biopsy before chemotherapy,and the biopsy results were used as the basis of histological diagnosis,fluorescence in situ hybridization (FISH) was performed to test HER2 status of tumor tissues before and after chemotherapy.All patients underwent FEC,TE,or AC neoadjuvant chemotherapy of 2-6 cycles before surgery.Results:Twenty-two patients were positive according to FISH test among 137 preoperative patients,8 patients achieved pathological complete remission after chemotherapy (three HER-2 positive patients and five negative patients),91 patients achieved partial remission,24 patients were stable,and 14 cases were invalid.Twenty-two patients were positive according to FISH test (8 patients with pathological complete remission did not undergo test),and positive patients still expressed positively after chemotherapy before neoadjuvant chemotherapy.Three negative patients were converted to be positive,and changes before and after chemotherapy had no statistical difference (P>0.05).Conclusion:Neoadjuvant chemotherapy makes no influence on patients with HER-2 positive expression,while patients with negative expression can be converted to be positive,but without significant difference.

HER-2,P53 and Hormonal Receptors Protein Expression as Predictive Factors in Breast Cancer Prognosis

OBJECTIVE Breast cancer is a heterogeneous disease with vari-able biological and clinical characteristics.We conducted a studyto evaluate P53,HER-2/neu and hormonal receptor expression aspredictors of prognosis in breast cancer.METHODS In a prospective study,we recruited 81 consecutivepatients with primary operable breast cancer who were treatedwith mastectomy followed by locoregional radiotherapy or che-motherapy and studied the presence of P53,HER-2/neu andhormonal receptors (ER/PR) expression in tumor tissues by im-munohistochemical staining.Associations between these markersexpression and clinical outcomes,including local and regionalrecurrence and metastasis were evaluated.Statistical analysis wasperformed with the SPSS software.RESULTS The mean time of follow-up was (47.3±4.6) months.Expression of P53,HER-2/neu,Estrogen receptors and progester-one receptors were observed in 31.1%,38.5%,31.8% and 51.7% ofthe patients,respectively.P53,HER-2/neu and Negative ER statuswere potent predictors of local-regional recurrence (P=0.034,0.038,0.044,respectively).Also HER-2/neu,Negative ER and NegativePR status were strong predictors of metastasis (P=0.001,0.042,0.054,respectively).CONCLUSION P53 and HER-2/neu expression and also steroidreceptors status (ER/PR status) have an important role in predict-ing the outcome of breast cancer and thus may be of value in se-lecting suitable therapeutic strategy and determining prognosis inthese patients.

Human epidermal growth factor receptor 2 positive rates in invasive lobular breast carcinoma: The Singapore experience

BACKGROUND Invasive lobular carcinomas(ILC)form 5%-10%of breast cancer and rarely show overexpression of human epidermal growth factor receptor 2(HER2).AIM To describe the prevalence and prognostic factors of HER2 positive(HER2+)ILC in an Asian population.METHODS A retrospective review of patients with ILC seen between January 1985 and March 2018 at various SingHealth medical institutions was conducted.Demographic and clinical data were collected from medical records.We examined clinicopathological characteristics and survival in relation to HER2 status.RESULTS A total of 864 patients were included.Prevalence of HER2 positivity was 10.1%(87 patients).Compared with HER2 negative(HER2-)ILC,HER2+ILC was associated with a higher proportion of estrogen receptor negative(24.4%vs 5.9%,P<0.001),progesterone receptor negative(PR-)(40.2%vs 24%,P=0.002)and grade 3 tumours(Grade 3,29.0%vs 10.2%,P<0.001).Overall survival rate was poorer in patients with HER2+compared to HER2-ILC(56.7%vs 72.9%alive at 10 years;hazard ratio 1.87,95%confidence interval:1.21-2.90,P=0.004).Based on multivariate analysis,negative prognostic factors for overall survival included HER2 positivity,PR negativity,older age,Indian ethnicity and higher tumour stage.CONCLUSION Prevalence of HER2+ILC was 10.1%.HER2+ILC was more likely to have poorer prognostic features such as estrogen receptor negative,PR-and higher tumour grade,and have a poorer survival.

Research of vitamin E succinate combined with paclitaxel on the apoptosis of Her-2 over-expressing breast cancer cells

Objective： The aim of this study was to detect apoptosis rates of Her-2 overexpression breast cancer cells, which were administrated with vitamin E succinate （VES） combined with paclitaxel at different dosages, or administrated alone; to discuss the mechanism of their actions. Methods： Using immunohistochemical method to detect Her-2 expression of MDA- MB-453 cells. Using TUNEL assay to detect apoptosis rates of MDA-MB-453 ceils, with the concentrations at 10, 20 mg/L of VES and 50, 100 nmol/L of paclitaxel, and also combined together for 24 or 48 h. Then compared apoptosis action of various combinations. Results： The expression rate of 95% Her-2 was interval （63.32%, 69.60%）; VES and paclitaxel both induced apoptosis of MDA-MB-453 cells, and it is dose to time dependence. It was strongest in apoptosis at 10 mg/L VES and 100 nmol/L paclitaxel in MDA-MB-453 cells 48 h later. Conclusion： VES and paclitaxel both induced apoptosis of MDA-MB-453 cells. It is stronger when the two drugs are administrated together. The mechanism is probably related to reduction of bcl-2 expression, so as to be more sensitive to paclitaxel. Synergistic effect is also possible for the two drugs influence tumor cells in different growing phases.

Relationship between expression of ER, PR, Her-2, Ki-67 and neoadjuvant chemotherapy effect in breast cancer

Objective: The purpose of the study was to investigate the relationship between the expression of estrogen receptor(ER), progestogen receptor(PR), human epidermal growth factor receptor(Her-2), Ki-67 and the effect of neoadjuvant chemotherapy in breast cancer. Methods: The expression of ER, PR, Her-2 and Ki-67 in 45 breast cancers which received neoadjuvant chemotherapy was detected by immunohistochemistry. Results: The effective rates in ER negative and PR negative groups were higher than those in ER positive and PR positive groups(83.3% vs 59. 4%, 82.4% vs 60.6%). There was no significant difference of the effective rate between Her-2 overexpressed group and Her-2 non-overexpressed group(81.8% vs 64.1%), and the same thing happened between Ki-67 negative group and Ki-67 positive group(67.7% vs 63.2%). Conclusion: In the patients with breast cancer, ER, PR negative ones were more sensitive to neoadjuvant chemotherapy. These patients may get more benefits from chemotherapy. ER, PR could be feasible markers for predicting the effective rate of neoadjuvant chemotherapy.

Detection of HER-2/neu Amplification on Fine Needle Aspirates of Breast Cancer Using Fluorescence in Situ Hybridization

The accuracy of diagnostic assays for HER-2/neu in breast cancer is extremely important as HER-2/neu status is essential in tailoring adjuvant and/or neoadjuvant treatment in every patient. FNAC is widely practiced in Egypt in preoperative diagnosis of breast cancer for its low cost and high diagnostic accuracy. Since the determination of HER-2/neu protein expression on cytological preparations was previously found to be unreliable for clinical use, we opted for the assessment of HER-2/neu status in fine needle aspirates using FISH. The main objective of this study was to evaluate the reliability of HER-2/neu status assessment by FISH on fine needle aspirates of breast cancers by comparing the results with IHC and FISH on FFPE tissue sections obtained from corresponding surgically resected specimens. Fine needle aspirates from 40 breast cancer patients with pathologically confirmed breast cancer were included in the study. They were submitted for HER-2/neu evaluation by FISH. After surgery, the corresponding FFPE sections were evaluated for HER-2/neu by FISH and by IHC. FNAs from 11 cases proved to be amplified by FISH, while 29 cases were not amplified. Apart from two cases that showed lack of signals, all specimens evaluated by FISH on the corresponding FFPE sections showed matched results. The Measurement of Agreement between FISH on FNAs and FISH on FFPE sections was 86.7%, while that between FISH on FNAs and IHC was 72.5%. The high concordance rate in the present study between FISH evaluation of HER-2/neu gene amplification on FNAC samples and their corresponding FFPE samples indicate that FISH may be a reliable technique for HER-2/neu assessment on FNAs. Furthermore, FISH on FNAs gave us better hybridization signals than their corresponding FFPE tissue sections. Finally, we also conclude that all score (2+) cases by IHC should be reevaluated by FISH which is crucial for the patient management.

Evaluation of Tobacco Use and Her-2 Receptor Expression in Breast Cancer in an Ethnically Diverse Inner-City Population

Background: Tobacco is linked to most cancers however despite overwhelming biological plausibility and decades of epidemiological studies, no association has been established between tobacco and breast cancer. Although estrogen receptor status has been looked at as a variable there has been no evaluation of the role of Her-2 and smoking in breast cancer. Methods: Review of records from patients treated at the University of Miami/Jackson Memorial Hospital from 1998-2012. The incidence of smoking and Her-2 expression in1255 women was evaluated. Data was analyzed by age, race, ethnic group, menopausal status, tumor stage, and ER/PR/Her-2 receptor status. Results: 1255 charts were analyzed with 1094 having full information. Overall rate of Her-2 expression 18.1%. The rate of Her-2 expression was 21.4% in smokers and 17.0% in non-smokers (p = 0.10). The rate of Her-2 expression was 10.8% in Caucasian smokers and 9.8% in Caucasian non-smokers (p = 0.88);24.5% in smokers of African descent and 17.3% in non-smokers of African descent (p = 0.24);22.9% in Latino smokers and 17.4% in Latino non-smokers (p = 0.10). The rate of Her-2/ER expression was 9.4% in smokers and 7.9% in non-smokers (p = 0.42);5.4% in Caucasian smokers and 4.9% in Caucasian non-smokers (p = 0.916);12.2% in smokers of African descent and 5.9% in non-smokers of African descent (p = 0.11);9.5% in Latin smokers and 8.8% in Latin non-smokers (p = 0.77). Conclusions: We found non-statistically significant positive associations in all analyses between Her-2 expression with or without ER expression and tobacco exposure when analyzed by ethnicity.

Inetetamab combined with sirolimus and chemotherapy for the treatment of HER2‐positive metastatic breast cancer patients with abnormal activation of the PI3K/Akt/mTOR pathway after trastuzumab treatment

Background:We explored the efficacy and safety of inetetamab combined with sirolimus and chemotherapy for the treatment of human epidermal factor receptor 2(HER2)‐positive metastatic breast cancer patients with abnormal activation of the PI3K/Akt/mTOR(PAM)pathway after trastuzumab treatment.Methods:For this prospective multicenter clinical study,HER2‐positive metastatic breast cancer patients with PAM pathway mutations confirmed by histology or peripheral blood genetic testing were enrolled from July 2021 to September 2022.Patients were randomly assigned to a trial or control group.The patients in the trial group received inetetamab combined with sirolimus and chemotherapy,while the control group patients received pyrotinib and chemotherapy.The RECIST v1.1 standard was used to evaluate efficacy.Descriptive statistics were used to summarize the clinicopathological features,and the Kaplan–Meier method was used to generate survival curves.The log‐rank test was used to compare progression‐free survival(PFS)between the two groups.Results:A total of 59 HER2‐positive metastatic breast cancer patients with abnormal activation of the PAM pathway were included,of which 37 received inetetamab combined with sirolimus and chemotherapy treatment and 22 received pyrotinib and chemotherapy treatment.The median PFS was 4.64 months in the inetetamab group and 5.69 months in the pyrotinib group,with no statistically significant difference(p=0.507).The objective response rates were 27.3%for the inetetamab group and 29.4%for the pyrotinib group.The safety assessment indicated that the adverse event(AE)incidences were 86.1%(31/36)in the inetetamab group and 78.9(15/19)in the pyrotinib group,with 9(25%)and four(21.1%)Grade 3/4 AEs in the inetetamab and pyrotinib groups,respectively.Conclusions:For metastatic HER2‐positive breast cancer patients with abnormal PAM pathway activation and previous trastuzumab treatment,the combination of inetetamab with sirolimus and chemotherapy is equivalent to the combination of pyrotinib and chemotherapy.Therefore,this regimen could be a treatment option for PAM pathway‐activated metastatic HER2‐positive breast cancer patients.

曲妥珠单抗新辅助化疗治疗HER-2阳性乳腺癌中体重指数与病理完全缓解的关系

目的 分析体重指数(BMI)与人表皮生长因子受体2(HER-2)阳性乳腺癌曲妥珠单抗新辅助化疗病理完全缓解(pCR)的关系。方法 收集2018年5月至2022年6月曲妥珠单抗新辅助治疗HER-2阳性乳腺癌患者136例临床资料,分析不同BMI的HER-2阳性乳腺癌临床病理特征,采用单因素及多因素Logistic分析BMI与pCR的关系。结果 136例HER-2阳性乳腺癌患者中,获得pCR 43例(31.62%)。BMI≥24组T分期(Ⅲ~Ⅳ期)、孕激素受体(PR)(阳性)、细胞核增殖抗原(Ki-67)(≥14)、淋巴结转移(阳性)高于BMI<24组(P<0.05)。pCR组与非pCR组年龄、月经状态、Ki-67比较(P>0.05);pCR组T分期(Ⅲ~Ⅳ期)、ER(阴性)、PR(阴性)、淋巴结转移(阳性)、BMI(≥24)低于非pCR组(P<0.05)。孕激素受体(PR)、淋巴结转移、BMI是影响ER-2阳性乳腺癌pCR的危险因素(P<0.05)。结论 曲妥珠单抗新辅助化疗治疗HER-2阳性乳腺癌pCR与PR、淋巴结转移、BMI明显相关,结合BMI与HER-2阳性乳腺癌临床病理特征的关系,BMI是HER-2阳性乳腺癌曲妥珠单抗新辅助化疗pCR的独立危险因素。

乳腺超声造影预测HER-2阳性乳腺癌曲妥珠单抗化疗敏感性的价值

目的研究乳腺超声造影预测人类表皮生长因子受体2(HER-2)阳性乳腺癌患者对曲妥珠单抗化疗敏感性的价值。方法回顾性分析2023月1月至2024年1月湛江中心人民医院诊疗的187例HER-2阳性乳腺癌患者的临床和影像资料,所有患者均接受曲妥珠单抗治疗,按照治疗第1个周期(3周)的疗效分为不敏感组122例和敏感组65例,所有患者在治疗第1个周期结束后均接受乳腺超声造影检查,比较两组患者治疗第1个周期结束后的乳腺超声造影表现。结果治疗敏感组患者病灶的最大径为(2.91±0.33)cm,明显小于不敏感组患者的(4.67±0.75)cm,差异有统计学意义(P<0.05);治疗不敏感组患者的高增强率、快进增强模式、增强后肿物不清晰、增强后肿块形态不规则、周围有穿行血管的占比分别为100.00%、100.00%、79.51%、86.07%、100.00%,明显高于治疗敏感组患者的83.08%、60.00%、63.08%、69.23%、80.00%,差异均有统计学意义(P<0.05)。结论乳腺超声造影在预测HER-2阳性乳腺癌曲妥珠单抗治疗敏感性中有一定价值,可指导临床治疗。

酪氨酸激酶抑制剂治疗Her-2阳性乳腺癌脑转移疗效的单臂meta分析

目的探讨酪氨酸激酶抑制剂(TKIs)在Her-2阳性乳腺癌脑转移(BCBM)中的疗效。方法检索从建库至2022年4月11日数据库(PubMed、Cochranelibrary、Embase)中TKIs治疗Her-2阳性BCBM的临床研究,采用STATA 17.0进行meta分析。结果纳入15项研究,其中3项关于TKIs单药治疗,12项关于联合治疗,meta分析显示TKIs单药治疗的疗效欠佳,与未使用TKIs治疗相比总生存期(OS)差异不显著(P>0.05),但TKIs联合治疗的疗效改善,与未使用TKIs治疗、未使用抗Her-2治疗或仅基于曲妥珠单抗治疗相比,OS差异有统计学意义(P<0.05);中枢神经系统(CNS)进展为TKIs单药或联合药物治疗的主要进展方式,发生率为59.0%~82.2%,而TKIs联合放疗的CNS复发率降低为22.9%。结论基于TKIs的联合治疗能够改善Her-2阳性BCBM的预后,但CNS复发率仍然很高,TKIs联合放疗能够降低CNS复发率,但相关的前瞻性临床研究较少,需更多前瞻性临床研究进一步确定最佳治疗策略。