Trastuzumab and fulvestrant combination therapy for women with advanced breast cancer positive for hormone receptor and human epidermal growth factor receptor 2: a retrospective single-center study.

BACKGROUND: Trastuzumab and fulvestrant combination therapy is one of the treatment options for patients with hormone receptor- and human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer; however, there are limited studies evaluating the efficacy of this combination therapy. METHODS: We retrospectively reviewed the data of women with hormone receptor- and HER2-positive metastatic breast cancer who received trastuzumab and fulvestrant combination therapy between August 1997 and August 2020 at the Cancer Institute Hospital. The primary endpoint of this study was progression-free survival, and the secondary endpoints were response rate, overall survival and safety. RESULTS: We reviewed the data of 1612 patients with recurrent or metastatic breast cancer, of which 118 patients were diagnosed with hormone receptor- and HER2-positive breast cancer. Of these, 28 patients who received trastuzumab and fulvestrant combination therapy were eligible for this study. The median treatment line for advanced breast cancer was 6 (range, 1-14), the median progression-free survival was 6.4 months (95% confidence interval [CI], 3.46-8.17), and the median overall survival was 35.3 months (95% CI, 20.0-46.7). Of the 28 patients, partial response was observed in 1 (4%), stable disease in 17 (61%), and progressive disease in 10 (36%) patients. The disease control rate was 64%. Adverse events of grade ≥ 3 were not observed. CONCLUSIONS: Trastuzumab and fulvestrant combination therapy showed moderate clinical efficacy and no severe toxicity after standard anti-HER2 treatment, which is a reasonable treatment option for patients with hormone receptor- and HER2-positive metastatic breast cancer. These data contribute to understanding the efficacy of trastuzumab and fulvestrant combination therapy as control data for further development of anti-HER2 agents plus hormone therapy.

Endoscopic thoracic sympathectomy as a novel strategy for vasospastic angina refractory to medical treatments.

Although vasospastic angina (VSA) is usually controlled by medications, refractory or lethal cases are occasionally encountered. We performed bilateral endoscopic thoracic sympathectomy (ETS) in 5 male patients with refractory VSA. Prior to ETS, stellate ganglion blockade was performed in 4 patients to reduce VSA attacks and to confirm the effect of sympathetic blockade. Under endoscopic guidance, the second to fourth thoracic sympathetic ganglia were ablated with a YAG-laser. No patient had complications after ETS, including major sweating abnormalities. In 4 of 5 patients, ETS relieved all VSA symptoms. ST-segment elevation often detected before ETS was absent on repeated ambulatory 24-h Holter monitoring after ETS. ETS is an effective strategy for the treatment of refractory VSA.

An appropriate indication for the initiation of beta-blocker therapy in dilated cardiomyopathy.

BACKGROUND: Although long-term treatment with beta-blockers has been shown to improve morbidity and mortality in dilated cardiomyopathy (DCM), patient responses are heterogeneous. METHODS: To establish the appropriate indication for the initiation of beta-blocker therapy, we retrospectively analyzed 38 DCM patients treated with beta-blockers (metoprolol or carvedilol) and examined differences in baseline profiles between patients who could continue the therapy (responders) and those who could not (non-responders). RESULTS: In 13 non-responders, the duration from onset of symptoms to beta-blocker initiation was longer (p < 0.05), systolic blood pressure was lower (p < 0.001), serum sodium concentration was lower (p < 0.05), left ventricular posterior wall thickness was thinner (p < 0.05), left ventricular end-diastolic pressure was higher (p < 0.05) and left ventricular wall stress was lower (p < 0.05) than in 25 responders. In 19 patients receiving carvedilol, 5 non-responders showed higher levels of human atrial natriuretic peptide (p < 0.05) and brain natriuretic peptide (p < 0.01) than 13 responders. Discriminant analysis with a linear discriminant function showed the following equation predicted response to beta-blocker therapy: h = 0.004 x systolic blood pressure - 0.002 x brain natriuretic peptide + 0.667 (R2 = 0.67, p < 0.001). The probability of predicting the response was 94.1% with h > or = 0.5. CONCLUSION: We conclude that h > or = 0.5 is the appropriate indication for the initiation of beta-blocker therapy in DCM.

Comparison of changes in circulating platelet-derived microparticles and platelet surface P-selectin expression after coronary stent implantation.

Platelet-derived microparticles (PDMPs) are released from activated platelets and may participate in the inflammatory process in response to vessel wall injury. This study was designed to compare the clinical significance of circulating PDMPs with that of P-selectin on the platelet membrane surface. In 20 patients with stable angina undergoing coronary stent implantation, circulating PDMPs were serially measured by enzyme-linked immunosorbent assay, and P-selectin expression on the surface of platelets was simultaneously analyzed by flow cytometry. PDMPs increased 24-48 h after coronary stenting in the coronary sinus (8.7 +/- 8.9 to 31.8 +/- 19.8 U/ml, P < 0.001) with a maximum at 48 h. In contrast, the mean channel fluorescence intensity for P-selectin increased 15 min after coronary stenting in the coronary sinus (19.5 +/- 5.6 to 25.2 +/- 7.5, P < 0.01) and remained elevated for 48 h; the changes were less striking in peripheral blood. The relative increase in PDMPs was not correlated with the increase in P-selectin expression at 15 min or 24 h after coronary stenting, but was correlated at 48 h (R = 0.48, P < 0.05). Both circulating PDMPs and P-selectin expression were enhanced in association with stent-induced platelet activation; however, the time course of changes in these two platelet activation markers was different. Therefore, the clinical relevance of circulating PDMPs may differ from that of P-selectin expression on the platelet membrane surface.