Li Ma

Background: Adjuvant chemotherapy is a major adjuvant treatment modality for hormonal receptor (HR)-positive and HER2-negative early breast cancer, but only 2%-20% of patients derive practical benefits. How to balance its potential benefits and risks becomes a challenging clinical problem. The purpose of this study was to assess whether RecurIndex assay could serve as an aid for adjuvant chemotherapy decisions in Chinese patients with HR-positive HER2-negative early breast cancer.Methods: The tissue samples of pT1-2N0 HR-positive HER2-negative breast cancer from multiple centers were detected using RecurIndex assay, based on which the patients were assigned into low- and high-risk groups. The survival outcomes of low- and high-risk patients including those with and without adjuvant chemotherapy were compared, and the risk factors for recurrence and metastasis were identified.Results: Totally 445 patients were eligible for analysis. By contrast to high-risk patients, low-risk patients represented better 7-year recurrence-free survival (RFS), distant recurrence-free survival (DRFS) and local recurrence-free survival (LRFS) rates. For low-risk patients, no significant differences were shown between those with and without adjuvant chemotherapy in 7-year RFS, DRFS and LRFS rates. These differences were also inapparent between high-risk patients with and without adjuvant chemotherapy. The multivariate model revealed high-risk patients had a significantly elevated risk of recurrence and metastasis than those at low risk.Conclusion: HR-positive HER2-negative early breast cancer patients at low risk stratified by RecurIndex assay might be exempt from adjuvant chemotherapy. Whether adjuvant chemotherapy may derive survival benefits for high-risk patients still needs larger cohorts to verify.

Background: Circadian clock genes play a crucial role in physiological and pathological processes, and their aberrant expressions were involved in various human cancers. The objective of this study was to investigate the expression level of Period circadian regulator 1 (PER1), an important circadian clock gene, and its biological roles in the development and progression of breast cancer. Methods: The expression level of PER1 in breast cancer samples was analyzed using the Oncomine database, and the correlation between PER1 expression and clinicopathologic parameters was assessed by bc-GenExMiner v4.5. In addition, Kaplan–Meier plotter database was used to determine the prognostic significance of PER1 expression for breast cancer patients. The expressions of PER1 in breast cancer tissues and cells were validated by Western blot. The loss-or-gain assay of PER1 was conducted to investigate the effects of its expression on cell proliferation, migration and invasion of breast cancer. The relationship between PER1 expression and epigenetic modifications was further explored by Western blot. Results: The results of the bioinformatics analysis revealed that the expression level of PER1 was markedly reduced in breast cancer tissues (P< 0.001), and patients with high expression of PER1 had a better overall survival (HR:0.78, 95% CI:0.63– 0.97, P=0.026) and recurrence-free survival (HR:0.83, 95% CI:0.75– 0.93, P=0.001) than those with low expression. The assay of gene loss-or-gain indicated that downregulation of PER1 expression markedly promoted cell proliferation, migration and invasion (P< 0.05), whereas these malignant phenotypes of breast cancer cells were inhibited by PER1 overexpression (P< 0.05). Further studies showed that trichostatin A (TSA), a histone deacetylase inhibitor, induced the expression of PER1 protein in breast cancer cells (P< 0.05). Conclusion: PER1 functions as a tumor suppressor in the development and progression of breast cancer, and its expression silencing might be regulated by epigenetic modifications.

Rationale: The incidence of pregnancy-associated breast cancer (PABC) is increasing nowadays, and its diagnosis and treatment remain complicated due to the consideration of the fetus. The available data on PABC are primarily derived from case reports since there are ethical restrictions on conducting randomized clinical trials. In the present work, we reported a case of the human epidermal growth factor receptor 2 (HER2)-positive PABC and described the diagnosis and treatment for such type of breast cancer. Patient concerns: A 27-year-old patient was admitted to our hospital with the complaints of right breast mass for 3 days, and she was a first-time pregnant woman with a single live intrauterine fetus at 26 + 3 weeks of gestation. Physical examination of the right breast revealed a palpable and hard mass with obscure boundaries (5.0 cm x 4.0 cm) in the upper outer quadrant. Significant axillary lymph nodes (2.0 cm) were also present. Diagnosis: PABC. Intervention: To protect the fetus, breast ultrasonography was used to test her breast mass, a core needle biopsy was adopted to confirm the diagnosis, and abdominal ultrasound and chest X-ray were used to evaluate the metastasis. The patient was scheduled for neoadjuvant therapy using bi-weekly pirarubicin in combination with cyclophosphamide (AC) without anti-HER2 therapy for consideration of the fetus's safety. After 4 cycles of AC, the patient delivered a healthy male infant. After the delivery, all the treatments were carried out according to the standard recommendation for HER2 + breast cancer as non-pregnant patients. Outcomes: After the surgery, the disease-free survival for the patient was 12 months until brain metastasis was diagnosed. She was still undergoing second-line anti-HER2 therapy and currently in a stable situation. Besides, the child was also healthy so far. Lessons: The methods for the diagnosis and treatment of PABC that result in teratogenesis should be avoided to protect the fetus. Mammogram and chest X-ray were safe approaches for the fetus. Moreover, chemotherapy-based on pirarubicin in combination with cyclophosphamide had no risk to the fetus.

The aim of this study was to clarify the clinicopathological outcome and prognostic significance of metastasis-associated gene 2 (MTA2) in esophageal squamous cell carcinoma (ESCC). Immunohistochemical staining for MTA2 was performed on surgical specimens obtained from 162 patients with ESCC. Relationships between MTA2 expression and clinicopathological factors, including prognosis, were analyzed. Significant correlations were noted among MTA2 overexpression and TNM clinical classification staging, depth of invasion, presence of regional lymph node metastasis, presence of distant metastasis, lymphatic invasion, blood-vessel invasion and the 5-year survival rates. The expression of MTA2 protein was correlated with tumour progression. Patients with MTA2 overexpression tended to have poor prognosis compared to patients with MTA2 underexpression.