American Society of Clinical Oncology 1998 update of recommended breast cancer surveillance guidelines.

OBJECTIVE: To determine an effective, evidence-based, postoperative surveillance strategy for the detection and treatment of recurrent breast cancer. Tests are recommended only if they have an impact on the outcomes specified by American Society of Clinical Oncology (ASCO) for clinical practice guidelines. POTENTIAL INTERVENTION: All tests described in the literature for postoperative monitoring were considered. In addition, the data were critically evaluated to determine the optimal frequency of monitoring. OUTCOME: Outcomes of interest include overall and disease-free survival, quality of life, toxicity reduction, and secondarily cost-effectiveness. EVIDENCE: A search was performed to determine all relevant articles published over the past 20 years on the efficacy of surveillance testing for breast cancer recurrence. These publications comprised both retrospective and prospective studies. VALUES: Levels of evidence and guideline grades were rated by a standard process. More weight was given to studies that tested a hypothesis directly relating testing to one of the primary outcomes in a randomized design. BENEFITS, HARMS, AND COSTS: The possible consequences of false-positive and -negative tests were considered in evaluating a preference for one of two tests providing similar information. Cost alone was not a determining factor. RECOMMENDATIONS: The attached guidelines and text summarize the updated recommendations of the ASCO breast cancer expert panel. Data are sufficient to recommend monthly breast self-examination, annual mammography of the preserved and contralateral breast, and a careful history and physical examination every 3 to 6 months for 3 years, then every 6 to 12 months for 2 years, then annually. Data are not sufficient to recommend routine bone scans, chest radiographs, hematologic blood counts, tumor markers (carcinoembryonic antigen, cancer antigen [CA] 15-5, and CA 27.29), liver ultrasonograms, or computed tomography scans. VALIDATION: The recommendations of the breast cancer expert panel were evaluated and supported by the ASCO Health Services Research Committee reviewers and the ASCO Board of Directors.

The need to consider survival, outcome, and expense when evaluating and treating patients with unknown primary carcinoma.

BACKGROUND: Patients who present with unknown primary carcinomas represent 10% to 15% of the patients with cancer who present to medical centers. Despite data in the literature indicating minimal success in determining the location of primary carcinomas, these patients continue to be evaluated exhaustively. Additionally, identification of the location of primary carcinomas does not often affect treatment. Clinical treatment and prognosis are only affected if a reevaluation of the pathologic findings yields a potentially curative diagnosis of an undifferentiated lymphoma, germ cell tumor, or a hormonally sensitive carcinoma. METHODS: Tumor registry files from January 1, 1990, through December 31, 1992, were retrospectively retrieved to identify adult patients who presented with metastasis of an unknown primary site at the H. Lee Moffitt Cancer Center and Research Institute, a 162-bed tertiary care cancer center specialty hospital affiliated with the University of South Florida College of Medicine, Tampa. Medical records were reviewed for age, sex, histologic findings of previous malignant growth, types and duration of symptoms, and mode of presentation. Fifty-six of the 199 patients were included in the study; 31 were men (55.4%) and 25 were women (44.6%), with ages ranging from 33 to 83 years. Diagnostic evaluations were reviewed and included data from procedures conducted at both the H. Lee Moffitt Cancer Center and at outside facilities. Diagnostic studies performed included barium swallow; intravenous pyelogram; mammogram; abdominal ultrasound; chest x-ray film; bone scan; magnetic resonance imaging; computed tomography of the head, chest, abdomen, and pelvis; laparotomy; bronchoscopy; gastroscopy; and colonoscopy. Information for the diagnostic test procedures was taken from the point of initial patient contact until the determination of metastatic disease. RESULTS: The primary cancer site was found in four (7.1%) of the 56 cases in the study and could not be classified as curable by systemic means. The average cost of diagnosis was $17,973, with 19.6% of the patients surviving for more than 1 year. The mean survival period was 8.1 months. A total of 410 tests were performed with only four tests correctly identifying the location of the primary tumor. CONCLUSIONS: Once a potentially curable malignancy has been excluded, there is little justification to support extensive diagnostic evaluation of the patient. Substantial costs are incurred and survival is often not significantly affected. It was estimated that 1.2 million new cancer cases would have occurred during 1994, with approximately 10% of these patients presenting with cancer of unknown primary origin. Based on cost assessments, investigation of these patients would exceed $1.5 billion. This clinical scenario is one where attention to outcome, clinical management, and expense should be carefully considered.

The effect of duration of intervention and locus of control on dietary change.

Scientific evidence supports a relationship between diet and the incidence of cancer. This finding has resulted in dietary recommendations that have been disseminated to the public. To reduce actual cancer incidence, these recommendations must lead to dietary changes among the population. We compared two brief dietary interventions with a longer term intervention and found that all three interventions produced significant reductions of calories, fat, fiber intake, and weight. The duration of the intervention did not significantly affect the magnitude of these reductions. We also found that health locus of control did not affect dietary change. Participants who initially were found to have an internal locus of control, or who subsequently internalized their locus of control during the period of observation, did not demonstrate a significant change in their intake of any of the nutrients measured when compared to participants with an external locus of control. Thus, we suggest a brief dietary intervention as a feasible and effective mechanism to produce progressive incremental dietary changes in a large population.

Breast cancer screening and compliance and evaluation of lesions.

It appears that screening mammography certainly is of value in women over age 50, and although controversy exists regarding screening of women under 50 years of age for breast cancer, the authors believe that this strategy is the most reasonable one for women 40 to 64 years of age at this time. Additionally, it is important for physicians to remember to encourage their patients to undergo cancer screening evaluation. Encouragement by physicians is an important factor in increasing cancer screening rates.

The effects of NSAIDs on breast cancer prognostic factors.

There are several risk factors involved in the pathogenesis of breast cancer. The role of non-steroidal anti-inflammatory drugs (NSAIDs) in the development of breast cancer has not been fully clarified. In order to investigate the impact of NSAIDs ingestion on prognostic factors of breast cancer we studied a total of 341 women with invasive carcinoma of the breast who presented between March and September 1993 to the Breast Cancer Clinic of the H. Lee Moffitt Cancer Center in Tampa, Florida. We noted that ingestion of NSAIDs was inversely associated with the size of the primary tumor, the lymph node status, and the number of involved axillary nodes. ingestion of NSAIDs may impact favorably on factors that determine the prognosis and clinical outcome of women with breast cancer.

Nutrition and cancer prevention.

Of all cancers in the United States, 35% are estimated to be caused by dietary factors and may be preventable. Diets high in fat or calories, for example, are said to be associated with five of the six most common cancers: breast, colorectal, pancreatic, prostatic, and uterine. Conversely, some dietary components such as vitamin A, in fruits and vegetables, and fiber may help protect against certain cancers. Obesity may confer a small risk of breast cancer on a woman, but women with upper body fat localization are at significantly higher risk of developing breast cancer and endometrial cancer.

Breast cancer surveillance--a cost-effective strategy.

The effectiveness of a surveillance program for breast cancer recurrence in extending survival is predicated on two assumptions: 1) most recurrences are detected at an early stage at surveillance visits; and 2) the early treatment of recurrence offers a better chance of cure or longer survival. However, the data suggest that neither of these two assumptions is correct, and that postoperative follow-up of patients with breast cancer is expensive and does not significantly extend survival.

Diet, obesity, fat distribution and cancer in women.

Thirty-five percent of all cancers in the United States are estimated to be caused by dietary factors and may be preventable. Diets high in fat or calories, for example, are said to be associated with five of the six most common cancers: breast, colorectal, pancreatic, prostatic, and uterine. Conversely, some dietary components such as vitamin A in fruits and vegetables and fiber may help protect against certain cancers. Although some of these findings are controversial, the dietary guidelines they engender are not, as the recommendations are healthy for other reasons as well. Obesity may confer a small risk of breast cancer on a woman, but women with upper body fat localization are at significantly higher risk of developing breast cancer. This risk appears to be reduced with weight loss.

Serum ferritin and stool occult blood and colon cancer screening.

A group of 531 participants age 50 years or older were evaluated for colonic polyps and malignancy with stool occult blood testing, hemoglobin, hematocrit, serum ferritin, flexible fiberoptic sigmoidoscopy, and colonoscopy. Screening revealed 1 colorectal cancer, 2 malignant polyps, 30 hyperplastic polyps, 69 adenomatous polyps, 4 villous adenomas, and 2 villous components. Low serum ferritin, an indicator of iron deficiency without anemia, improved the detection of colonic malignancies and polyps when used in combination with stool occult blood testing. The program was acceptable to participants and attrition was low; the attrition rate for the screening program at 1 year was 14.5%.

Use of ceruloplasmin levels to monitor response to therapy and predict recurrence of breast cancer.

Ceruloplasmin (CP), an acute phase reactant, has been found to be elevated in patients with various tumors including breast cancer. We found that the CP level was elevated in 89% of 103 patients with metastatic breast cancer. In 27 patients with measurable metastatic disease that responded to treatment the mean CP level fell by 35% (p less than 0.001) and in 22 patients whose disease progressed on treatment, the mean CP level rose by 44% (p less than 0.001). Of those patients with Stage II breast cancer that were treated with adjuvant chemotherapy, only 6% of patients with a normal post mastectomy CP level have recurred, whereas 44% of patients with an elevated post mastectomy CP level have recurred (p less than 0.01). In following patients with breast cancer, we noted that in those patients that recurred, the CP level became elevated 16-34 weeks prior to any clinical evidence of metastases. We also noted that the CP level became elevated after initially falling in patients receiving adjuvant chemotherapy and on occasion, the initially elevated CP level did not even fall. These circumstances may represent resistant microscopic disease, so that changing to a noncross-resistant chemotherapeutic regimen might be appropriate.

Malignant tumors of the small intestine.

Primary malignant tumors of the small intestine are uncommon. The average annual incidence rate over a period of 30 years in Saskatchewan was 0.7 and 0.6 per 100,000 for male and females, respectively. The 209 patients who comprise the series represent 1.6% of the total number who had gastrointestinal cancers over the same period. The distribution of the tumors by site and histologic type is described. Both carcinoid and adenocarcinomatous tumors of the small intestine are associated with a high incidence of primary malignant neoplasms in other sites (17.0 and 20.3%, respectively). One patient with Peutz-Jeghers syndrome is of interest because of the malignant change which occurred in more than one of the small bowel polyps and because of consequent liver metastases. The reason for the poor prognosis in noncarcinoid small bowel malignant neoplasms is probably due to late diagnosis. The five-year disease-free survival in these tumors was 22.5%. Malignant carcinoids had a better overall five-year survival rate of 64%. For those confined to the bowel wall, the five-year survival rate was 73%, compared to 59% for those extending to nodes or metastasizing to distant organs.

Successful pregnancy following continuous treatment with combination chemotherapy before conception and throughout pregnancy.

A 21-year-old woman with diffuse histiocytic lymphoma received combination chemotherapy continuously for 16 months before conception and throughout pregnancy. Procarbazine and BCNU were given for 5 months before conception and throughout the first and second trimesters, and streptozotocin was given throughout the third trimester. A male infant who was phenotypically and genotypically normal was delivered. The authors reviewed the literature regarding chemotherapeutic agents given during the first trimester of pregnancy. Although most chemotherapeutic agents are teratogenic in the animal model, the incidence of teratogenicity of chemotherapeutic agents given to humans in the first trimester of pregnancy is 12.7%. This represents a fivefold increase in teratogenicity. As yet the administration of chemotherapeutic agents in the second and third trimesters has not resulted in teratogenicity. This information may help the physician when deciding whether to treat pregnant patients with chemotherapeutic agents during the first trimester or whether to continue treatment when the patient has become pregnant while receiving these agents.

Cancer patients' insight into their treatment, prognosis, and unconventional therapies.

The authors interviewed 190 patients with metastatic cancer to determine their insight into their disease, treatment and prognosis. They also explored their attitudes to religion, their guilt feelings, and the persons with whom they discussed their condition. The authors also examined the feelings of 315 patients with a diagnosis of cancer toward unconventional therapies. It was found that only 55% of the patients were aware that their cancer had spread, and only 48% knew the location of their metastases. The majority of patients seemed satisfied with the amount of information they received from their physician although 38% of the patients believed their knowledge about their cancer was inadequate. Patients were optimistic about their treatment in that 37% thought it would cure them and 60% thought it would control their metastatic disease. A third of the patients had become more religious since learning they had cancer, but only 6% of the patients saw the development of cancer as a form of punishment. About 25% of the patients thought that either Laetrile, vitamins, or special diets could cure cancer, and 70% said they would take these forms of treatment if available, although only 7% were taking or had taken an unconventional therapy.

Obesity, body fat distribution, and sex hormones in breast cancer patients.

This study addresses the relationship between female sex hormones, obesity, body fat distribution, and breast cancer. Increasing obesity correlated with a progressive fall in sex hormone-binding globulin (SHBG) level and an increase in testosterone level. Premenopausal breast cancer patients were found to have significantly lower levels of SHBG compared with age-matched and weight-matched controls. This difference in SHBG level was not noted in postmenopausal breast cancer patients. The SHBG level decreased with increasing upper body fat localization in breast cancer patients and controls. This effect was more marked in breast cancer patients which may explain our earlier finding that women with upper body fat localization are at increased risk for developing breast cancer.

Estimate of breast cancer risk reduction with weight loss.

Upper body fat localization has been associated with an increased risk of cancer. This study demonstrated that 64.2% of 124 women with at least a 4.5-kg weight loss decreased their upper body fat localization, as measured by a reduction in their suprailiac-thigh skin fold ratio and other skin fold thicknesses associated with upper body fat localization. Based on a risk model previously developed for breast cancer and upper body fat localization, a reduction in estimated breast cancer relative risk of 45% was calculated for the entire group of women who lost 4.5 kg or more in weight. Greater weight loss further reduced upper body fat localization and estimated breast cancer risk based on this model.

Variation in body fat distribution and breast cancer risk in the families of patients with breast cancer and control families.

BACKGROUND: The pattern of body fat distribution in women has been correlated with the risk of developing breast and endometrial cancer. The authors determined whether body fat distribution varied between first-degree relatives of patients with breast cancer and in cancer-free families by comparing the body fat distribution of first-degree relatives of patients with breast cancer with age and Quetelet Index-matched controls. METHODS: Fifty-six first-degree relatives of newly diagnosed patients with breast cancer were compared with 56 controls (non-cancer family members) matched for age and Quetelet Index and were studied for variation in body fat distribution. Anthropometric measurements were taken for the abdomen, thigh, suprailiac, subscapular, biceps, and triceps skinfold thickness; waist and hip circumference; weight; and height. The distribution of body measurements and derived ratios in both case and control family members were compared using the Student t test. RESULTS: A significant variation in body fat distribution occurred among first-degree relatives in breast cancer and control families. In families with a history of breast cancer, first-degree family members were found to have significantly greater waist:hip ratio (P < 0.001) compared with controls without family history matched for age and Quetelet Index. Other variables indicating upper body fat localization, such as abdomen and suprailiac skinfold were significantly greater in family members of patients with breast cancer compared with controls. CONCLUSIONS: A marked variation occurred in body fat localization among first-degree relatives of patients with breast cancer and in cancer-free families. This finding implies a variation in breast cancer risk in these families. Identifying family members with upper body fat distribution in breast cancer families would allow targeting of these individuals for energetic screening and risk factor reduction interventions.

Specific immunotherapy of advanced renal carcinoma: evidence for the polyclonality of metastases.

Autologous, irradiated (10,000 rads) tumor cells mixed with C. parvum were given weekly to 14 patients with metastatic renal carcinoma. The tumor tissue had been cryopreserved with DMSO. No significant toxicity was produced. Four patients underwent objective responses, and a fifth had prolonged stabilization (27+ months). Varying responses occurred simultaneously in different metastatic lesions within the same patient. Responding patients usually had an excellent ambulatory status and received greater than 20 x 10(7) tumor cells.

Serum cholesterol reduction with tamoxifen.

The serum cholesterol levels of 123 consecutively and newly diagnosed women with Stage I and II breast cancer taking tamoxifen were compared with a control group of 81 consecutively newly diagnosed women with Stage I and II breast cancer who were not taking a hormonal treatment or supplement. Other factors that were evaluated were age, menopausal status, tumor size, weight, height, Quetelet index, and smoking and alcohol intake history. The mean cholesterol change in patients on tamoxifen (34.2 +/- 3.6 mg/dl) was significantly greater than controls (1.0 +/- 4.1 mg/dl) (P less than 0.001). Serum cholesterol fell by more than 10 mg/dl in 72.9% of women on tamoxifen vs. 35.1% of controls and by more than 40 mg/dl in 39.9% of women on tamoxifen vs. 12.6% of controls. Multivariate analysis revealed that tamoxifen administration (P less than 0.0001), initial cholesterol level (P = 0.001), and age (P = 0.04) were significant factors in producing a decrease in serum cholesterol. The administration of tamoxifen as adjuvant therapy to women with newly diagnosed breast cancer resulted in a significant fall in serum cholesterol. This effect of tamoxifen on the serum cholesterol may prove to be an additional benefit in the form of reduced cardiovascular risk in these women.