Breast cancer prevention: lifestyle changes and chemoprevention.

Susceptibility to breast cancer is caused by a combination of genetic and environmental factors. Research is exploring which factors influence breast cancer risk, and by which mechanisms they exert their influence. Women should be informed about lifestyle factors influencing their life time breast cancer risk and encouraged by their physician to adapt changes in diet, physical activity, reproductive issues and use of hormone substitution after menopause, to minimize the risk. Patients identified as high risk to develop breast cancer can consider prophylactic surgery, chemo-preventive therapies and take part in personalized screening programs.

Neoadjuvant chemotherapy versus primary debulking surgery in advanced ovarian cancer.

Primary surgical cytoreduction followed by chemotherapy usually is the preferred management of advanced (stage III or IV) ovarian cancer. The presence of residual disease after surgery is one of the most important adverse prognostic factors for survival. Neoadjuvant chemotherapy has been proposed as an alternative approach to conventional surgery as initial management of bulky ovarian cancer, with the goal of improving surgical quality. Since 1989, we have been treating advanced epithelial ovarian cancer with neoadjuvant chemotherapy instead of primary cytoreductive surgery in approximately half of the patients with stage III-IV disease. Selection of neoadjuvant chemotherapy was based on disease-related characteristics (eg, metastatic tumor load, stage of disease, performance status). Since 1993, open laparoscopy also has been used to aid in evaluating operability. A retrospective analysis of 338 patients was conducted to compare outcomes during 1989 to 1998, when neoadjuvant chemotherapy was used, with those observed during 1980 to 1988, when all patients underwent primary cytoreductive surgery. Crude 3-year survival rates were higher and postoperative mortality rates were lower during the second time period compared with the first. Overall, the results suggest that neoadjuvant chemotherapy results in survival rates in selected patients with advanced ovarian cancer that are comparable with those associated with primary cytoreductive surgery. Patients with stage IV disease, total metastatic tumor load greater than 1,000 g, uncountable plaque-shaped peritoneal metastases, and/or a poor performance status are probably the best candidates for this alternative approach. A prospective randomized study of neoadjuvant chemotherapy and primary cytoreductive surgery is ongoing.

Interval debulking surgery: an alternative for primary surgical debulking?

Retrospective analyses suggest that a subgroup of patients with Stage III and IV ovarian carcinoma can be treated with neo-adjuvant chemotherapy followed by interval debulking surgery. The absolute indications for neo-adjuvant chemotherapy appear to be Stage IV disease (excluding pleural fluid) or metastases of more than 1 g at sites where resection is impossible. In patients with an estimated total metastatic tumor load of >100 g, the presence of at least two of the following relative indications for neo-adjuvant chemotherapy are considered to be necessary: 1) uncountable (>100) peritoneal metastases, 2) estimated metastatic tumor load of >1000 g, 3) presence of large (>10 g) peritoneal metastatic plaques, 4) large volume ascites, and 5) World Health Organization (WHO) status II or III. Interval debulking surgery in patients with suboptimal primary debulking surgery has been proven effective in increasing overall survival and progression-free survival in a large prospective, randomized trial of the European Organization for Research and Treatment of Cancer (EORTC). The strategy of neo-adjuvant chemotherapy, followed by interval debulking surgery, should be confirmed in a prospective randomized trial. The EORTC 55971 trial is currently addressing this issue. We will review the studies on primary chemotherapy, interval debulking surgery, and the indications for primary chemotherapy followed by interval debulking surgery, and ongoing trials.

Trocar implantation metastasis after laparoscopy in patients with advanced ovarian cancer: can the risk be reduced?

OBJECTIVE: The purpose of this study was to determine risk factors for trocar implantation metastasis after diagnostic laparoscopy in patients with primary or recurrent advanced ovarian cancer. STUDY DESIGN: Eighty-three women with primary advanced ovarian cancer and 21 women with recurrent ovarian cancer undergoing a laparoscopy for a tissue diagnosis and for assessment of operability were included in the study. The occurrence of implantation metastasis at the trocar incision scars was analyzed according to clinicopathologic characteristics. RESULTS: A recurrence developed at the trocar site in 7 (58%) of 12 patients undergoing a laparoscopy in which only the skin was closed at the end of the procedure and in 2 (2%) of 92 patients undergoing a laparoscopy with closure of all layers (odds ratio, 63; 95% confidence interval, 10.3-385; P <.001). The International Federation of Gynecology and Obstetrics stage at initial presentation, tumor histologic type, tumor differentiation, maximal tumor diameter at the time of diagnosis, estimated weight of the metastatic tumor, residual tumor after cytoreductive surgery, surgical characteristics, and type of chemotherapy were well balanced among both groups. Patients with implantation metastasis had significantly more ascites (median, 700 mL vs 300 mL; P =.032) and a longer interval between the start of platinum-based chemotherapy or cytoreductive surgery (median, 6 days vs 17 days; P <.01) compared with patients without abdominal wall recurrence. A palpable abdominal wall metastasis developed in none of the patients undergoing a laparoscopy with closure of all layers of the abdomen followed by cytoreductive surgery or chemotherapy within 1 week after the laparoscopy. Kaplan-Meier survival analysis showed that patients with abdominal wall implantation metastasis had a survival rate similar to that of the other patients. CONCLUSIONS: Laparoscopy with careful closure of the peritoneum, rectus sheath, and skin followed by chemotherapy or cytoreductive surgery with excision of the trocar trajectories within 1 week is safe in patients with disseminated ovarian cancer.

Neoadjuvant chemotherapy or primary debulking surgery in advanced ovarian carcinoma: a retrospective analysis of 285 patients.

OBJECTIVE: This study was aimed at comparison of neoadjuvant chemotherapy with primary debulking surgery in advanced ovarian carcinoma. METHODS: Retrospective analysis of 285 patients with advanced ovarian carcinoma treated between 1980 and 1997 was performed. RESULTS: In the period 1980-1988 all patients underwent primary debulking surgery and 82% were cytoreduced to less than 0.5 cm largest residual tumor mass (n = 112). Analysis of this group of patients showed that some subgroups of patients (e.g., Stage IV disease or a total metastatic tumor load of more than 1000 g prior to debulking surgery) had a poor survival despite cytoreduction to no or less than 1 g of total residual tumor load. The complication rate was high especially in the group with unfavorable prognosis (postoperative mortality, 6%). In the period 1989-1997 (n = 173) the patients were surgically evaluated to receive primary chemotherapy (43%) or primary debulking surgery (57%). Prognostic variables were similar for both treatment periods. The actuarial crude survival was higher in the second time period (3-year crude survival of 26% +/- 4. 3 and 42% +/- 4.6 for the first and second time periods, respectively; P = 0.0001). The postoperative mortality was 0% during the second time period. From 1993 on, the decision to give neoadjuvant chemotherapy or to perform primary debulking surgery in patients with clinically obvious metastatic disease was made with the help of an open laparoscopy (n = 77). Median duration of the laparoscopy, blood loss, and hospital stay due to this procedure were 25 min, 10 ml, and 2 days. Primary and interval debulking surgery was performed in 36 and 63% of this subgroup of patients, respectively. CONCLUSION: In this retrospective analysis over two different time periods, crude survival was higher when treating about half of the patients with advanced ovarian carcinoma with primary chemotherapy instead of primary debulking surgery. The role of neoadjuvant chemotherapy should be evaluated in a prospective randomized study.

The feasibility of open laparoscopy in gynecologic-oncologic patients.

Gynecologic-oncologic patients are at increased risk for complications with closed laparoscopy. Open laparoscopy eliminates the steps of blind insufflation and trocar insertion. This study is the first large series of open laparoscopies to assess the feasibility and safety of the open laparoscopy technique in patients with gynecologic malignancies. We performed 90 open laparoscopies in 89 oncologic patients with previous major surgery (65%) and/or radiotherapy (17%) or a large omental cake (18%). Complications due to the laparoscopic access technique occurred in one patient (1%) for whom a laparotomy was performed for a small bowel perforation. The incidence of complications of the open laparoscopy technique (1%) is favorable compared to the complication rate of closed laparoscopy in gynecologic-oncologic patients. It is concluded that open laparoscopy is a safe and feasible technique in gynecologic-oncologic patients.