Long-Term Disease Control with Lapatinib and Capecitabine in a Heavily Pretreated Patient with ErbB2-Positive Metastatic Breast Cancer

BACKGROUND: The optimal sequence of systemic palliative chemotherapy in metastatic breast cancer is unknown. CASE REPORT: We report the course of disease in a patient aged 24 years at the onset of disease, who was treated over 17 years for her metastatic ErbB2-positive breast cancer. Seventeen years ago, the patient was diagnosed to have invasive ductal breast cancer and underwent surgical treatment. She received 6 cycles of adjuvant chemotherapy with CMF (cyclophosphamide, methotrexate, 5-fluorouracil). Twenty-eight months after the primary surgery, the patient developed a histologically verified lung metastasis, and subsequently received 8 different lines of chemotherapy, including high-dose cytotoxic therapy and stem cell support as well as trastu-zumab. In addition, she received 5 different types of antihormonal treatment. Due to the recent progression of her lung metastasis, 27 cycles of lapatinib and capecitabine were administered. A long-term partial response in the lung was observed. CONCLUSIONS: Individualized systemic treatment with the tyrosine kinase inhibitor lapatinib and capecitabine in heavily pretreated patients with Her2-positive metastatic breast cancer may lead to effective palliation for almost 2 years despite extensive pretreatment.     

A Retrospective Analysis of the Activity and Safety of Oral Etoposide in Heavily Pretreated Metastatic Breast Cancer Patients

Metastatic breast cancer (MBC) patients derive benefit from chemotherapy, but options become limited after several prior chemotherapeutic regimens. Oral etoposide (VP‐16) has previously been found to be clinically active in MBC patients in phase II trials. However, with increasing availability of other drugs, etoposide use has declined in spite of its unfavorable toxicity profile probably being overestimated. We therefore evaluated the clinical benefit and safety of oral etoposide in a population of MBC patients who had failed multiple regimens of currently used therapies. Sixty‐six patients with MBC previously treated with a median of eight (range 2–13) regimens of therapy were eligible for the study. Patients received 50 mg/day oral etoposide in 20‐day cycles with 1‐week of rest. All patients were evaluated for clinical benefit (clinical benefit rate [CBR], complete response, partial response, and disease stabilization >24 weeks), progression‐free survival (PFS), overall survival (OS), and toxicities. Median PFS was 4 months, CBR was 18% (overall response rate 4%), and median OS from the start of treatment was 11 months. Little clinically significant or high‐grade toxicity were observed. No patients withdrew from treatment due to etoposide‐induced toxicity. The favorable clinical response, low toxicity, and low cost of the drug suggest that etoposide is a viable option for patients with heavily pretreated MBC.     

Cytoreduction and Hyperthermic Intraperitoneal Chemoperfusion in Women with Heavily Pretreated Recurrent Ovarian Cancer

Background

Limited data are available on the use of cytoreductive surgery with hyperthermic intraperitoneal chemoperfusion (HIPEC) in patients with recurrent stage III ovarian cancer.

Methods

Patients with recurrent, heavily pretreated ovarian cancer were enrolled onto a phase II multimodal protocol consisting of extensive cytoreduction followed by HIPEC.

Results

Forty-two women were treated from October 2002 until January 2009. Chemoperfusion was performed with cisplatin in 59% and oxaliplatin in 41% of patients. A macroscopically complete resection was achieved in 50% of patients. No mortality occurred, and the major morbidity rate was 21%. After a mean follow-up of 21?months, median overall survival (OS) was 37?months (95% confidence interval 12.2?C61.8) and median progression-free survival was 13?months (95% confidence interval 6.9?C19.1). In univariate analysis, OS was influenced by completeness of cytoreduction, type of chemoperfusion drug, nodal status, and tumor grade. In a Cox regression model, only completeness of cytoreduction (hazard ratio 0.06?C0.8, P?=?.022) and tumor grade (hazard ratio 1.23?C12.6, P?=?.021) were independent predictors of OS.

Conclusions

In selected patients with heavily pretreated recurrent ovarian cancer, cytoreduction combined with HIPEC may provide a meaningful OS with acceptable morbidity. Optimal results are achieved in patients with a macroscopically complete resection and biologically favorable disease.     

An Initial Experience with Rapid Microwave Processing in the One-Stop Breast Clinic

Background  

Rapid microwave processing allows core biopsy results to be obtained within a 3- to 4-h time period. This study was designed to compare the accuracy and reporting time of microwave-processed breast biopsies with samples processed using traditional methods.     

Tattooing Breast Cancers Treated with Neoadjuvant Chemotherapy

Background In breast carcinomas treated with neoadjuvant chemotherapy, intraoperative identification of residual tumors may be difficult. A well-tolerated, low-diffusion charcoal suspension has been designed to tattoo breast tumors. In this study, we investigated whether this tattooing technique is efficient for localizing the tumor after treatment with chemotherapy. Methods In a series of 109 patients with large breast tumors, a 4% or 10% charcoal suspension was injected at the time of the initial biopsy before preoperative chemotherapy. Results Tolerance was good. After three or four cycles of chemotherapy, 91 patients underwent conservative treatment, and the surgical specimen was examined intraoperatively. The charcoal was detected in 94% of the cases. The charcoal was seen in the nodule or at the periphery in the surgical specimen without any acute inflammatory reaction or diffusion. Conclusions On the basis of these results, this micronized charcoal suspension at a defined granulometry and a concentration of 10% seems to be ideal for tattooing breast carcinomas over a period of 3 months in patients in whom neoadjuvant chemotherapy is planned.     

Intraoperative Ultrasound Localization of Nonpalpable Breast Cancers

Background Preoperative localization of nonpalpable breast cancers requires good coordination between imaging and surgery departments, and insertion of a guide wire can be traumatic for the patient. This study was designed to evaluate the efficacy of intraoperative ultrasound localization of nonpalpable breast cancers directly by the surgeon. Methods This prospective study was conducted from June 2006 to October 2006 in 70 patients who underwent surgery for nonpalpable invasive breast cancer. Ultrasound was performed in the operating room by the surgeon with the patient in the operative position. Tumor identification, the correlation with tumor diameter on preoperative ultrasound, analysis of resection margins, and the need to perform surgical re-excision were analyzed. Results Intraoperative ultrasound identified the target in 67 (95.7%) of 70 patients. Two of the three lesions not detected by intraoperative ultrasound were ≤5 mm in diameter in patients with a body mass index of ≥25 (normal range, 19–24). The correlation with diagnostic ultrasound for tumor dimensions was satisfactory (correlation coefficient r = .80). Resection margins free of invasive lesions were obtained in 66 cases (94.3%). Three patients (4.3%) required surgical re-excision, one mastectomy due to multifocal cancer, and two lumpectomy due to positive resection margins. Conclusions Intraoperative ultrasound localization of nonpalpable breast cancers is feasible and effective, with a sensitivity of 98.3% for tumors >5 mm. It spares the patient the discomfort of a radiological and/or supplementary examination with insertion of a guide wire. It also saves time and money for hospital teams.     

Characteristics of Multifocal and Multicentric Breast Cancers

Annals of Surgical Oncology - Multifocality and multicentricity are increasingly recognized in breast cancer. However, little is known about the characteristics and biology of these cancers and the...     

Initial Experience with Videoscopic Inguinal Lymphadenectomy

Background

Inguinofemoral lymphadenectomy is associated with frequent and marked incision-related morbidity. Our initial feasibility study of videoscopic inguinal lymphadenectomy (VIL) for melanoma showed appropriate nodal yield and anatomic dissection. Although a limited suprafascial dissection has been reported in the urologic literature, we report our growing experience with VIL applying a comprehensive approach to dissection.

Methods

Patients with inguinal metastases from varied malignancies were offered VIL. With institutional review board approval, procedures were performed via three ports: one at the apex of the femoral triangle, a second medial to the adductor, and a third lateral to sartorius. Femoral vessels were skeletonized, and all lymphatic tissue within the femoral triangle to 5 cm up onto the external oblique aponeurosis was resected. Specimens were removed through the apical port via a specimen bag. Clinicopathologic and perioperative outcome data were recorded.

Results

Forty-five VILs were performed in 32 patients: 19 had unilateral VILs, and 13 had bilateral VILs for neuroendocrine, extramammary Paget disease, or varied genitourinary malignancies. Nine procedures (20%) were performed in women. Median age was 61 (range 16–87) years. Median body mass index was 30 (range 19–53). Median operative time was 165 (range 75–245) minutes, median length of stay was 1 (range 1–14) day, and median drain duration was 15 days. Median number of collected nodes was 11 (range 4–24), and the largest node removed was 5.6 cm in size. Wound complications were observed in 8 cases (18%). Six patients (13%) developed cellulitis without any wound dehiscences, 1 patient developed a seroma, and 1 patient with diabetes had mild skin flap necrosis, which resolved with minimal local care.

Conclusions

VIL is an alternative approach to traditional open inguinal lymphadenectomy. In our growing experience, node retrieval is appropriate and wound complications are substantially fewer than reported via an open approach. Further comparative analysis of VIL and traditional inguinofemoral lymphadenectomy is being pursued in a randomized, prospective trial.     

Breast Cancers Found with Digital Breast Tomosynthesis: A Comparison of Pathology and Histologic Grade

To compare the pathology and histologic grading of breast cancers detected with digital breast tomosynthesis to those found with conventional digital mammography. The institutional review board approved this study. A database search for all breast cancers diagnosed from June 2012 through December 2013 was performed. Imaging records for these cancers were reviewed and patients who had screening mammography with tomosynthesis as their initial examination were selected. Five dedicated breast imaging radiologists reviewed each of these screening mammograms to determine whether the cancer was visible on conventional digital mammography or whether tomosynthesis was needed to identify the cancer. A cancer was considered mammographically occult if all five radiologists agreed that the cancer could not be seen on conventional digital mammography. The size, pathology and histologic grading for all diagnosed breast cancers were then reviewed. The Mann–Whitney U and Fisher exact tests were utilized to determine any association between imaging findings and cancer size, pathologic type and histologic grade. Sixty‐five cancers in 63 patients were identified. Ten of these cancers were considered occult on conventional digital mammography and detected with the addition of tomosynthesis. These mammographically occult cancers were significantly associated with Nottingham grade 1 histologic pathology (p = 0.02), were smaller (median size: 6 mm versus 10 mm, p = 0.07) and none demonstrated axillary nodal metastases. Breast cancers identified through the addition of tomosynthesis are associated with Nottingham grade 1 histologic pathology and prognostically more favorable than cancers identified with conventional digital mammography alone.     

Feasibility of Surgery After Systemic Treatment with the Humanized Recombinant Antibody Bevacizumab in Heavily Pretreated Patients with Advanced Epithelial Ovarian Cancer

Background  

The aim of this study was to assess operative feasibility and outcome after bevacizumab treatment (BT) in ovarian cancer (OC) patients.     

The Novel Application of Genomic Profiling Assays to Shorten Inactive Status for Potential Kidney Transplant Recipients With Breast Cancer

The concern about cancer recurrence has traditionally resulted in delaying kidney transplantation for 2–5 years after a cancer diagnosis in patients who are otherwise eligible for transplant. This period of inactive status to observe the tumor biology can result in significant morbidity and decreased quality of life for patients with end‐stage renal disease (ESRD). We reported the novel application of genomic profiling assays in breast cancer to identify low‐risk cancers in two patients with ESRD who were able to have the mandatory inactive status eliminated prior to kidney transplantation.     

Initial Japanese Experience with Intragastric Balloon Placement

Background

We introduced intragastric balloon placement in Japan and evaluated the initial data.

Methods

Between December 2004 and March 2008, intragastric balloons [BioEnterics® Intragastric Balloon (BIB®) system] were placed in 21 Japanese patients with obesity [six women, 15 men; mean age 40?±?9 years; mean body mass index (BMI) 40?±?9 kg/m²]. The inclusion criteria were morbid obesity (BMI?≥?35 kg/m²), the presence of obesity-related disorders, and failure with conventional treatments for at least 6 months. The balloon was routinely removed under endoscopy after 5 months.

Results

No serious complications occurred, but in two of the 21 patients (9.5%), early removal (within 1 week) of the balloon was required due to continuous abdominal discomfort. Two other patients (9.5%) could not control their eating behavior and were considered unresponsive to the treatment, and their balloons were also removed before 5 months. Seventeen of the 21 patients (81%) finished the treatment, and the average weight loss and percent excess weight loss (%EWL) at the time the balloons were removed were 12?±?5 kg and 27?±?9%, respectively. Eight patients were followed for 1 year without intervention of consecutive bariatric surgery, and at that time, four of these patients had kept more than 20% of %EWL. The other patients regained their weight in the first year.

Conclusions

Intragastric balloon placement is a safe and effective procedure in obese Japanese patients, and about half of the patients will maintain their weight loss after the balloon is removed.     

Initial Multi-institutional Experience with Transoral Robotic Surgery

Objective To assess the initial experience for transoral robotic surgery (TORS), as observed in the French TORS group. Study Design A multi-institutional prospective cohort study. Setting Seven tertiary referral centers. Subjects and Methods One hundred thirty consecutive patients who were scheduled for a TORS between October 2008 and March 2011 were included. The operative times, conversion rates, morbidity, and alternatives were described. The serious adverse effects encountered were analyzed, and recommendations for avoiding them are specified. Results Most of the patients (65%) had a laryngeal (supraglottic) and/or hypopharyngeal resection. Thirty-nine of the 130 patients receiving TORS would have had a transoral laser resection as their alternative surgery. The tumor exposure was suboptimal in 26% of the cases. Six of the 130 patients needed conversion to an open approach. There were 15 postoperative hemorrhages and 2 deaths due to posthemorrhage complications in patients with significant comorbidities at 9 and 18 days after the surgery. The median setup and procedure times were 52 ± 46 and 90 ± 92 minutes, respectively. The learning curve was characterized by better selection and management of potential patients. Conclusion The visualization offered by the robotic assistance allowed transoral resections of tumors that were difficult to resect or unresectable by laser surgery. Self-assessment of surgical exposure and a decrease in the need to convert to an open procedure over time suggested improvement in TORS-related surgical skills. Nevertheless, strict patient selection is essential. Even with a minimally invasive approach, some patients will need a tracheostomy for safety reasons.     

Genomic Alterations Associated with Early Stages of Breast Tumor Metastasis

Background  Molecular studies suggest that acquisition of metastatic potential occurs early in the development of breast cancer; mechanisms by which cells disseminate from the primary carcinomas and successfully colonize foreign tissues are, however, largely unknown. Thus, we examined levels and patterns of chromosomal alterations in primary breast tumors from node-negative (n = 114) and node-positive (n = 115) patients to determine whether specific genomic changes are associated with tumor metastasis. Methods  Fifty-two genetic markers representing 26 chromosomal regions commonly altered in breast cancer were examined in laser microdissected tumor samples to assess levels and patterns of allelic imbalance (AI). Real time-PCR (RT-PCR) was performed to determine expression levels of candidate genes. Data was analyzed using exact unconditional and Student’s t-tests with significance values of P < 0.05 and P < 0.002 used for the clinicopathological and genomic analyses, respectively. Results  Overall levels of AI in primary breast tumors from node-negative (20.8%) and node-positive (21.9%) patients did not differ significantly (P = 0.291). When data were examined by chromosomal region, only chromosome 8q24 showed significantly higher levels (P < 0.0005) of AI in node-positive primary tumors (23%) versus node-negative samples (6%). c-MYC showed significantly higher levels of gene expression in primary breast tumors from patients with lymph node metastasis. Conclusions  Higher frequencies of AI at chromosome 8q24 in patients with positive lymph nodes suggest that genetic changes in this region are important to the process of metastasis. Because overexpression of c-MYC has been associated with cellular dissemination as well as development of the premetastatic niche, alterations of the 8q24 region, including c-MYC, may be key determinants in the development of lymph node metastasis. Contact for reprints: Ms. Kerri Cronin, Clinical Breast Care Project, Walter Reed Army Medical Center, 6900 Georgia Avenue, NW Washington, DC 20307, Tel.: +1 (202) 782-0002, E-mail: kerri.cronin@amedd.army.mil.