Changes of HER2 low expression status in primary and recurrent/metastatic breast cancer / 中华病理学杂志

Objective: To investigate the evolution and clinical significance of HER2 low expression status in HER2 negative patients in primary and recurrent/metastatic breast cancers. Methods: The data and archived sections of 259 breast cancer patients with recurrence/metastasis and HER2-negative primary foci were collected from January 2015 to January 2022 at the Fourth Hospital of Hebei Medical University, and the HER2 status of primary and recurrence/metastasis foci was determined by immunohistochemistry (IHC), among which IHC 2+patients were subject to fluorescence in situ hybridization (FISH). The HER2 status was classified as HER2-0 group; patients with IHC 1+, IHC 2+and no FISH amplification were classified as HER2 low expression group; and patients with IHC 3+, IHC 2+and FISH amplified were classified as HER2-positive group. The changes of HER2 status in patients with HER2 low expression in primary versus recurrent/metastatic breast cancer foci were compared, and their clinicopathologic characteristics and prognosis were analyzed. Results: The overall concordance rate between primary and recurrent/metastatic HER2 status in breast cancer was 60.6% (157/259, κ=0.178). A total of 102 patients (102/259, 39.4%) had inconsistent primary and recurrent/metastatic HER2 status; 37 patients (37/259, 14.3%) had HER2-0 at the primary foci and HER2-low expression at the recurrent/metastatic; and 56 patients (56/259, 21.6%) had HER2-low expression in the primary foci and HER2-0 in the recurrent/metastatic. The recurrent/metastatic foci became low-expressing compared with the recurrent/metastatic foci which remained HER2-0 patients, with longer overall survival time, higher ER and PR positivity, lower Ki-67 positivity index, and lower tumor histological grade; all with statistically significant differences (all P<0.05). In the primary HER2-low group, patients with recurrent/metastatic foci became HER2-0 while those with recurrent/metastatic foci remained low expression; there were no statistically significant differences in clinicopathological features and overall survival time (all P>0.05). Conclusions: Unstable HER2 status in patients with HER2-0 and low expression in primary versus recurrent/metastatic breast cancer foci, and HER2-0 in the primary foci but low HER2 expression status in recurrence/metastasis is associated with favourable prognosis, and testing HER2 status in recurrence/metastasis can provide more treatment options for such patients.

Survival status and influencing factors of HIV/AIDS on highly active anti-retrovial therapy in Shandong province / 中华流行病学杂志

Objective: To understand the survival status and influencing factors for HIV/AIDS patients on highly active anti-retroviral therapy (HAART) in Shandong province. Methods: Both Kaplan-Meier (K-M) method and cumulative incidence function (CIF) were used to calculate the cumulative incidence of AIDS-related death respectively, and Fine-Gray model was used to identify the influencing factors related to survival time. Results: Through K-M method, a higher AIDS-related cumulated death rate than the CIF, was estimated. Among all the HIV/AIDS patients who initiated HAART from 2003 to 2015 in Shandong, 5 593 of them met the inclusion criteria. The cumulative incidence rate for AIDS-related death was 3.08% in 1 year, 4.21% in 3 years, 5.37% in 5 years, and 7.59% in 10 years respectively by CIF. Results from the F-G analysis showed that HIV/AIDS patients who were on HAART, the ones who had college degree or above (HR=0.40, 95%CI: 0.24-0.65) were less likely to die of AIDS-associated diseases. However, HIV/AIDS patients who were on HAART and living in the western areas of Shandong (HR=1.33, 95%CI: 1.01-1.89), diagnosed by medical institutions (HR=1.39, 95%CI: 1.06-1.80), started to receive care ≥1 year after diagnosis (HR=2.02, 95%CI: 1.30-3.15), their CD(4) cell count less than 200 cells/μl (HR=3.41, 95%CI: 2.59-4.59) at the time of diagnosis, with NVP in antiviral treatment (ART) regime (HR=1.36, 95%CI: 1.03-1.88), at Ⅲ/Ⅳ clinical stages (HR=2.61, 95%CI: 1.94-3.53) and CD(4) cell count less than 350 cells/μl (HR=5.48,95%CI: 2.32-12.72) at initiation of HAART ect., were more likely to die of AIDS-associated diseases. Conclusions: With the existence of competing risks, the cumulative incidence rate for AIDS-related death was overestimated by K-M, suggesting that competing risk models should be used in the survival analysis. Measures as early diagnoses followed by timely care and early HAART could end up with the reduction of AIDS-related death.

Association between maternal body height and risk of preterm birth / 中华流行病学杂志

Objective: To investigate the association between maternal body height and risk of preterm birth. Methods: A total of 11 311 pregnant women who gave birth of live singletons were recruited from the Healthy Baby Cohort Study in Hubei province, China from September 2012 to October 2014. Finally 11 070 pregnant women were selected as study subjects. Data were collected by using questionnaires, their prenatal care records and medical records. The women were divided into 4 groups according to the quartiles distribution (<158 cm, 158- cm, 160- cm, and >164 cm). Gestational age was estimated according to maternal last menstrual time. Preterm birth was defined as delivering a live singleton infant at 28-37 weeks' gestational age. Logistic regression was used to calculate the odds ratios (OR) and 95% confidence intervals (CI) for the association between body height and preterm birth. Results: Among the 11 070 pregnant women, the incidence of preterm birth was 5.9%. Logistic regression analysis indicated that women in group with body height <158 cm had 46% (OR=1.46, 95%CI: 1.16-1.83) higher risk of giving preterm birth than those in group with body height >164 cm after adjustment for potential confounders. Every 1- cm increase in body height was associated with 3% lower risk of preterm birth (OR=0.97, 95%CI: 0.95-0.99). Conclusion: Shorter body height was a risk factor for preterm birth. It is necessary to strengthen the monitoring in pregnant women with short body height to reduce the risk of preterm birth.

Lead time bias and its control in observational studies for clinical outcomes / 中华流行病学杂志

Lead time bias might exist in observational study for clinical outcomes. This paper summarizes the concept of lead time bias, causes and control of lead time bias by using the studies of influences of screening diagnostic test on cancer patients'survival and highly active antiretroviral therapy on HIV/AIDS patients' survival as examples for the purpose of providing thinking and methods in the control of lead time bias for the accurate evaluation of the effects of interventions, such as test and treatment, on the diseases with multi courses or phases.

Related factors on secondary drug resistance in HIV infected persons receiving antiretroviral therapy in Shandong province: a case-control study / 中华流行病学杂志

Objective: To explore the causes of secondary drug resistance among HIV infected persons who were receiving antiretroviral therapy in Shandong province, and provide evidence for the improvement of antiretroviral therapy strategy. Methods: A case-control study was designed with 1∶2 matching on case and control groups. Household and face-to-face interview were conducted in October, 2015. All the study subjects were screened from both the drug resistant database of antiretroviral therapy of Shandong provincial laboratory and national comprehensive HIV/AIDS database in Shandong. The sample size was estimated as 330 cases including 110 drug resistant and 220 non-drug resistant cases. Subjects were people living with HIV/AIDS (PLWHA) aged 15 or older and received antiretroviral therapy for more than 6 months with records of virus load (VL). Subjects who presented VL above 1 000 copies/ml would receive drug resistance testing. Subjects who were confirmed resistant to with secondary drug, were selected as case group, the rest subjects with non-secondary drug resistance would form the control group. EpiData 3.1 software and SPSS 22.0 software were used to establish a database. Related influencing factors were analyzed with non- conditional stepwise logistic regression model. Results: A total of 288 cases were enrolled, including 103 in the case and 185 cases in the control groups, with average age as (37.62±1.06) years and (37.90±0.74) years old, respectively. Most of them were male, married/cohabitant, with education level of junior/senior high school or below and under Han nationality. Results from the multivariate logistic regression model showed that ORs (95%CI) of receiving antiretroviral therapy for 1-3 years, or more than 3 years were equal to 8.80 (3.69-21.00), 3.00 (1.20-7.53), compared with receiving antiretroviral therapy less than one year, respectively. OR (95%CI) of Among the PLWHA that with missing rate above 25.0% on medication, the OR appeared as 15.41(4.59-51.71), compared with not missing medication. OR (95%CI) among those who took the medicine themselves was 0.22 (0.07-0.74). Conclusions: Factors as duration of treatment, missing rate on medication and taking medicine by oneself were of influence on secondary drug resistance. Other factors as duration on antiretroviral therapy longer than 1 year, missing rate above 25.0% on medication, were related to the risk on secondary drug resistance. However, if the medicine was taken by oneself, it served as a protective factor for secondary drug resistance. It is necessary to strengthen the intervention and health education programs related to antiretroviral therapy.