Efficacy and safety of oral pyrotinib in HER2 positive metastatic breast cancer: real-world practice / 北京大学学报(医学版)

OBJECTIVE@#Pyrotinib, a novel irreversible pan-ErbB receptor tyrosine kinase inhibitor, showed promising antitumor activity and acceptable tolerability in phase II and phase III randomized clinical trials. We assessed the activity and safety of oral pyrotinib for human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer patients in the real world.@*METHODS@#We retrospectively analyzed 72 HER2 positive metastatic breast cancer (MBC) patients who received oral pyrotinib based regimens at Beijing Cancer Hospital and other four hospitals (Peking University First Hospital, China-Japan Friendship Hospital, General Hospital of PLA, Peking University Third Hospital) from August 2018 to September 2019. Progression free survival (PFS), objective response rate (ORR), adverse events (AE) of pyrotinib were investigated.@*RESULTS@#Seventy-two patients with HER2 positive MBC were enrolled. The median age of the patients was 55 years (range: 32-79 years). Sixty-nine (95.8%) patients had received anti-HER2 treatment in the metastatic and/or (neo) adjuvant settings; 61 (84.7%) patients had received anti-HER2 treatments in the metastatic setting in terms of trastuzumab 56 (77.8%) patients, lapatinib 36 (50.0%) patients, and T-DM1 4 (5.6%) patients. Among these 72 patients who received oral pyrotinib based regimens, 62 (86.1%) patients received pyrotinib (±trastuzumab) in combination with chemotherapy, 6 (8.3%) patients received pyrotinib (± trastuzumab) in combination with endocrine therapy and 4 (5.6%) patients received pyrotinib (±trastuzumab). Sixty-five (90.3%) patients received 400 mg pyrotinib once daily as initial dose, and 7 (9.7%) patients received 320 mg. OBJECTIVE response and safety to pyrotinib based therapy were evaluable in all the 72 patients. One (1.4%) patient achieved complete response (CR), 18 (25.0%) patients achieved partial response (PR), 41 (56.9%) patients had stable disease (SD), and 12 (16.7%) patients had progressive disease (PD). The ORR (CR+PR) was 26.4% and the median PFS was 7.6 months (95%CI: 5.5-9.7 months). Among the 36 patients with prior lapatinib therapy, the median PFS was 7.9 months (95%CI: 4.1-11.7 months). Among the 15 patients with brain metastasis, the median PFS was 6.0 months (95%CI: 2.2-9.8 months). The main toxicities related to pyrotinib were diarrhea in 57 (79.2%) cases, and 48 (66.7%) cases with grade 1-2 as well as 9 (12.5%) cases with grade 3.@*CONCLUSION@#Pyrotinib based therapy is an effective treatment for patients with HER2 positive MBC, including patients with lapatinib treatment failure and brain metastasis, and the toxicities can be tolerated.

Prediction of recurrence risk in early breast cancer using human epidermal growth factor 2 and cyclin A2 / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Human epidermal growth factor 2 (HER2) is one of the most important prediction factors, but only 25% - 30% of breast cancer patients HER2 are positive. It is unknown whether there are other molecular markers that could be used to predict prognosis and recurrence in HER2 negative patients. This study investigated correlations of cyclin A2 and HER2 levels with clinical outcomes in 281 patients with invasive breast cancer in order to identify whether cyclin A2 can serve as a prognostic factor in HER2 negative patients.</p><p><b>METHODS</b>Immunohistochemical staining was used to detect cyclin A2 and HER2 expression in 281 patients. Cyclin A2 and HER2 gene amplifications were analyzed using gene analysis and RT-PCR in 12 patients. Risk and survival estimates were analyzed using Log-rank, Kaplan-Meier, and Cox regression analysis; cyclin A2 and HER2 consistency with survival were analyzed using Kappa analysis.</p><p><b>RESULTS</b>Patients with higher cyclin A2 and HER2 expressions had significantly shorter disease-free survival periods (P = 0.047 and P = 0.05, respectively). Kappa analysis performed that cyclin A2 and HER2 showed a low Kappa index (kappa = 0.37), allowing us to conclude that cyclin A2 and HER2 detect different pathologies. Gene analysis and RT-PCR showed that cyclin A2 was upregulated in patients with early relapse; the average increase was 3.69 - 2.74 fold.</p><p><b>CONCLUSIONS</b>Cyclin A2 and HER2 are associated with proliferation and high recurrence, particularly when combined. Cyclin A2 is easily detected by nuclear staining and might be a useful biomarker for recurrence risk in HER2 negative patients.</p>

Observation and clinical significance of adjuvant chemotherapy-induced amenorrhea in premenopausal breast cancer patients / 中华肿瘤杂志

<p><b>OBJECTIVE</b>A retrospective analysis of 160 pre-menopausal breast cancer patients was carried out to elucidate the the menstrual outcome in those cases who had undergone adjuvant chemotherapy after surgery, and evaluate the relationship between chemotherapy-induced amenorrhea (CIA) and recurrence of the disease.</p><p><b>METHODS</b>160 pre-menopausal breast cancer patients were collected, 62/159 (39.0%) of them were node positive, 91/158 (57.6%) were ER positive, and 95/155 (61.3%) were PR positive. 111 cases had infiltrative ductal carcinoma, 26 cases had infiltrative lobular carcinoma, and 22 cases with others. In 152 cases data were collected by face-to-face interview and 8 cases by phone conversation. Types and cycles of chemotherapy regimen as well as menstrual abnormalities were recorded before, during, and after chemotherapy completion. Follow up duration was 12-72 months after chemotherapy completion for all patients.</p><p><b>RESULTS</b>107 (66.9%) developed CIA, 24 cases returned to normal menses (22.4%), 83 cases continued CIA during more than 12-month follow up (77.6%). The rate of CIA increased with age (P < 0.01). During the follow up, disease free survival (DFS) rate was 85.9% in CIA group and 79.2% in non-CIA group, with no statistically significant difference. But in hormonal receptor positive patients, DFS was 80.0% in non-CIA and 90.1% in CIA, respectively (P = 0.04), showing a significant difference. Because of the small number of died cases, no analysis of the overall outcome was carried out.</p><p><b>CONCLUSION</b>Adjuvant chemotherapy causes ovarian function suppression, and may further leading to amenorrhoea. Women who experienced amenorrhoea after chemotherapy had a significantly better disease-free survival (DFS) rate showed by univariate analysis than women who continued normal menstruation. Chemotherapy is insufficient therapy for very young patients who are in high risk with hormone responsive disease, particularly when chemotherapy fails to induce amenorrhea. Further research is needed to evaluate interventional chemotherapy to improve the quality of life in women with early stage breast cancer who experienced ovarian toxicity. The post-chemotherapy menstruation status is a clinically valuable, objective and salient marker for sufficient endocrine effect of chemotherapy in ER/PR-positive premenopausal patients.</p>