Shin‐Cheh Chen

Purpose Abemaciclib, a cyclin-dependent kinase 4 and 6 inhibitor, demonstrated efficacy as monotherapy and in combination with fulvestrant in women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer previously treated with endocrine therapy. Methods MONARCH 3 is a double-blind, randomized phase III study of abemaciclib or placebo plus a nonsteroidal aromatase inhibitor in 493 postmenopausal women with HR-positive, HER2-negative advanced breast cancer who had no prior systemic therapy in the advanced setting. Patients received abemaciclib or placebo (150 mg twice daily continuous schedule) plus either 1 mg anastrozole or 2.5 mg letrozole, daily. The primary objective was investigator-assessed progression-free survival. Secondary objectives included response evaluation and safety. A planned interim analysis occurred after 189 events. Results Median progression-free survival was significantly prolonged in the abemaciclib arm (hazard ratio, 0.54; 95% CI, 0.41 to 0.72; P = .000021; median: not reached in the abemaciclib arm, 14.7 months in the placebo arm). In patients with measurable disease, the objective response rate was 59% in the abemaciclib arm and 44% in the placebo arm ( P = .004). In the abemaciclib arm, diarrhea was the most frequent adverse effect (81.3%) but was mainly grade 1 (44.6%). Comparing abemaciclib and placebo, the most frequent grade 3 or 4 adverse events were neutropenia (21.1% v 1.2%), diarrhea (9.5% v 1.2%), and leukopenia (7.6% v 0.6%). Conclusion Abemaciclib plus a nonsteroidal aromatase inhibitor was effective as initial therapy, significantly improving progression-free survival and objective response rate and demonstrating a tolerable safety profile in women with HR-positive, HER2-negative advanced breast cancer.

BACKGROUND: Restoring the continuity of lymphatic drainage by lymphaticovenous or lymphaticolymphatic anastomosis was observed in the short term to be patent but eventually occluded because the elevated interstitial pressure will cause obliteration of these tiny, thin-walled, low-pressure lumens. The purpose of this study was to evaluate the outcome of vascularized groin lymph node transfer using the wrist as a recipient site in patients with postmastectomy upper extremity lymphedema. METHODS: Between January of 1997 and June of 2005, 13 consecutive patients with a mean age of 50.69 +/- 11.25 years underwent vascularized groin lymph node transfer for postmastectomy upper extremity lymphedema. A vascularized groin lymph node nourished by the superficial circumflex iliac vessels was harvested and transferred to the dorsal wrist of the lymphedematous limb. The superficial radial artery and the cephalic vein were used as the recipient vessels. Outcome was assessed by upper limb girth, incidence of cellulitis, and lymphoscintigraphy. RESULTS: All flaps survived, and one flap required reexploration, with successful salvage. No donor-site morbidity was encountered. At a mean follow-up of 56.31 +/- 27.12 months, the mean reduction rate (50.55 +/- 19.26 percent) of the lymphedematous limb was statistically significant between the preoperative and postoperative groups (p < 0.01). The incidence of cellulitis was decreased in 11 patients. Postoperative lymphoscintigraphy indicated improved lymph drainage of the affected arm, revealing decreased lymph stasis and rapid lymphatic clearance. A hypothesis was proposed that the vascularized groin lymph node transfer might act as an internal pump and suction pathway for lymphatic clearance of lymphedematous limb. CONCLUSION: Vascularized groin lymph node transfer using the wrist as a recipient site is a novel and reliable procedure that significantly improves postmastectomy upper extremity lymphedema.

BACKGROUND: Vascularized groin lymph node flap transfer is an emerging approach to the treatment of postmastectomy upper limb lymphedema. The authors describe the pertinent flap anatomy, surgical technique including different recipient sites, and outcome of this technique. METHODS: Ten cadaveric dissections were performed to clarify the vascular supply of the superficial groin lymph nodes. Ten patients underwent vascularized groin lymph node flap transfer for postmastectomy upper limb lymphedema using the wrist (n=8) or elbow (n=2) as a recipient site. Ten patients who chose to undergo physical therapy were used as controls. Intraoperatively, indocyanine green was injected subcutaneously on the flap margin to observe the lymph drainage. Outcomes were assessed using improvement of circumferential differentiation, reduction rate, and decreased number of episodes of cellulitis. RESULTS: A mean 6.2±1.3 groin lymph nodes with consistent pedicles were identified in the cadaveric dissections. After indocyanine injection, the fluorescence was drained from the flap edge into the donor vein, followed by the recipient vein. At a mean follow-up of 39.1±15.7 months, the mean improvement of circumferential differentiation was 7.3±2.7 percent and the reduction rate was 40.4±16.1 percent in the vascularized groin lymph node group, which were statistically greater than those of the physical therapy group (1.7±4.6 percent and 8.3±34.7 percent, respectively; p<0.01 and p=0.02, respectively). CONCLUSIONS: The superficial groin lymph nodes were confirmed as vascularized with reliable arterial perfusion. Vascularized groin lymph node flap transfer using the wrist or elbow as a recipient site is an efficacious approach to treating postmastectomy upper limb lymphedema. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

PURPOSE: We investigated the incidence of cardiac adverse events in patients with early breast cancer in the Herceptin Adjuvant (HERA) trial who were treated with 1 year of trastuzumab after completion of (neo)adjuvant chemotherapy. PATIENTS AND METHODS: The HERA trial is a three-group, randomized trial that compared 1 year or 2 years of trastuzumab with observation in women with human epidermal growth factor receptor-2 (HER2) -positive early breast cancer. Eligible patients had normal left ventricular ejection fraction (LVEF; >or= 55%) after completion of (neo)adjuvant chemotherapy with or without radiotherapy. Cardiac function was monitored throughout the trial. This analysis considers patients randomly assigned to 1 year of trastuzumab treatment or observation. RESULTS: There were 1,698 patients randomly assigned to observation and 1,703 randomly assigned to 1 year of trastuzumab treatment; 94.1% of patients had been treated with anthracyclines. The incidence of discontinuation of trastuzumab because of cardiac disorders was low (5.1%). At a median follow-up of 3.6 years, the incidence of cardiac end points remained low, though it was higher in the trastuzumab group than in the observation group (severe CHF, 0.8% v 0.0%; confirmed significant LVEF decreases, 3.6% v 0.6%) In the trastuzumab group, 59 of 73 patients with a cardiac end point reached acute recovery; of these 59 patients, 52 were considered by the cardiac advisory board (CAB) to have a favorable outcome from the cardiac end point. CONCLUSION: The incidence of cardiac end points remains low even after longer-term follow-up. The cumulative incidence of any type of cardiac end point increases during the scheduled treatment period of 1 year, but it remains relatively constant thereafter.