Life events and breast cancer prognosis.

OBJECTIVE--To determine whether psychosocial stress, in the form of adverse life events and social difficulties, depressive illness, or lack of confiding relationships, shortens the postoperative disease free interval in breast cancer patients. DESIGN--Prospective follow up of a cohort of newly diagnosed breast cancer patients for 42 months after primary surgical treatment, using a life events and social difficulties schedule (LEDS) and assessment of depressive symptomatology (DSM-III). SETTING--Patients recruited from breast clinics in Southampton and Portsmouth were interviewed in their homes. PATIENTS--204 women (83% of 246 consecutive cases) treated either by mastectomy or wide excision followed by radiotherapy interviewed four, 24, and 42 months after operation. MAIN OUTCOME MEASURES--Hazard ratios for relapse of breast cancer in relation to various measures of psychosocial stress. Relapse was defined as local recurrence or distant metastasis, or both, with histological or radiological confirmation and timed from the month when clinical symptoms began. RESULTS--After adjustment for age and axillary lymph node involvement, the hazard ratio associated with severe life events or social difficulties (excluding "own health" ones), or both, during the year before breast cancer surgery was 0.43 (95% confidence interval 0.20 to 0.93); for those during the follow up period it was 0.88 (0.48 to 1.64). For prolonged major depression before surgery and during the follow up period, hazard ratios were 1.26 (0.49 to 3.26) and 0.85 (0.41 to 1.79) respectively. For absence of a full confidant the figures were 0.93 (0.42 to 2.09) and 0.86 (0.38 to 1.93). CONCLUSION--These results give no support to the theory that psychosocial stress contributes to relapse of breast cancer.     

Adjuvant chemotherapy for breast cancer: side effects and quality of life.

In a trial of postoperative adjuvant chemotherapy women with primary breast cancer and spread to one or more axillary nodes were randomised to receive a six-month course of either the single agent chlorambucil or the five-drug combination of chlorambucil, methotrexate, fluorouracil, vincristine, and adriamycin. On completing the treatment 47 patients were asked to fill in questionnaires at home on the side effects of treatment and its influence on the quality of their life. Side effects including nausea, vomiting, malaise, and alopecia had been severe enough to interfere with their lifestyle in 9 (42%) of the patients who had received the single agent and 19 (79%) of those who had received multiple-drug treatment. Various other side effects were reported by a few patients. Seven (29%) of the patients who had received the multiple-drug schedule voluntarily added that the treatment had been "unbearable" or "could never be gone though again." The proportion of patients who had experienced severe side effects while receiving the treatment was considerable; hence such adjuvant chemotherapy is justifiable only if it will substantially improve a patient''s prognosis.     

Adjuvant radiotherapy for early breast cancer: patterns of practice in Ontario.

OBJECTIVE: To determine the number of different radiation schedules used in Ontario to treat women with node-negative breast cancer after lumpectomy and axillary dissection. DESIGN: Retrospective survey. SETTING: Princess Margaret Hospital, Toronto, and regional centres of the Ontario Cancer Treatment and Research Foundation (in Hamilton, London, Ottawa, Windsor and Thunder Bay). PATIENTS: A total of 551 of 1624 consecutive patients with node-negative breast cancer having undergone lumpectomy and axillary dissection who were eligible but did not participate in the Ontario Clinical Oncology Group randomized clinical trial and who received adjuvant breast irradiation between April 1984 and February 1989. OUTCOME MEASURES: Schedules of radiotherapy received. RESULTS: Forty-eight different radiotherapy schedules were identified. Total doses ranged from 4000 to 6600 cGy and the number of fractions from 15 to 30. Several different schedules were preferred: 322 patients (58.5%) received 4000 cGy in 15 or 16 fractions to the whole breast over 3 weeks plus a local boost of 1250 cGy to the primary site in 5 fractions over 1 week; 66 patients (12.0%) received 4000 cGy in 15 or 16 fractions over 3 weeks to the whole breast plus a local boost of 1000 cGy to the primary site in 4 or 5 fractions over 1 week; and 63 patients (11.5%) received 5000 cGy in 25 fractions to the whole breast in 5 weeks, without a boost. CONCLUSIONS: The practice of adjuvant radiotherapy for early breast cancer in Ontario varies. The optimal radiation regimen for patients after lumpectomy should be determined through randomized clinical trials.     

Natural history and prognosis of recurrent breast cancer.

Patterns of recurrent disease were analysed in 603 patients with breast cancer. The time of onset, frequency of recurrence, and survival after recurrence were not influenced by age or menopausal state. While survival after local recurrence was longer than survival after distant metastasis, the time to onset of local and distant disease followed an identical pattern, indicating that local recurrence should be regarded as a manifestation of systemic disease. Postoperative radiotherapy did not affect the time of onset of local recurrence. We suggest that patients with local recurrence should receive both systemic and local treatment and that controlled trials of chemotherapeutic agents in these patients might be valuable in finding the most effective drug combinations to be used as adjuvant treatment after mastectomy.     

External validation of a measurement tool to assess systematic reviews (AMSTAR)

Background

Thousands of systematic reviews have been conducted in all areas of health care. However, the methodological quality of these reviews is variable and should routinely be appraised. AMSTAR is a measurement tool to assess systematic reviews.

Methodology

AMSTAR was used to appraise 42 reviews focusing on therapies to treat gastro-esophageal reflux disease, peptic ulcer disease, and other acid-related diseases. Two assessors applied the AMSTAR to each review. Two other assessors, plus a clinician and/or methodologist applied a global assessment to each review independently.

Conclusions

The sample of 42 reviews covered a wide range of methodological quality. The overall scores on AMSTAR ranged from 0 to 10 (out of a maximum of 11) with a mean of 4.6 (95% CI: 3.7 to 5.6) and median 4.0 (range 2.0 to 6.0). The inter-observer agreement of the individual items ranged from moderate to almost perfect agreement. Nine items scored a kappa of >0.75 (95% CI: 0.55 to 0.96). The reliability of the total AMSTAR score was excellent: kappa 0.84 (95% CI: 0.67 to 1.00) and Pearson''s R 0.96 (95% CI: 0.92 to 0.98). The overall scores for the global assessment ranged from 2 to 7 (out of a maximum score of 7) with a mean of 4.43 (95% CI: 3.6 to 5.3) and median 4.0 (range 2.25 to 5.75). The agreement was lower with a kappa of 0.63 (95% CI: 0.40 to 0.88). Construct validity was shown by AMSTAR convergence with the results of the global assessment: Pearson''s R 0.72 (95% CI: 0.53 to 0.84). For the AMSTAR total score, the limits of agreement were −0.19±1.38. This translates to a minimum detectable difference between reviews of 0.64 ‘AMSTAR points’. Further validation of AMSTAR is needed to assess its validity, reliability and perceived utility by appraisers and end users of reviews across a broader range of systematic reviews.     

Genetic variability of proto-oncogenes for breast cancer risk and prognosis

This paper summarizes the results of a study on human breast cancers performed mainly at the Centre René Huguenin in collaboration with other American and French groups, and supported in part by a Grant from the Association pour la Recherche sur le Cancer (ARC) Villejuif. During this work, the following conclusions emerged: c-myc proto-oncogene amplification is a common alteration in ductal invasive tumors, more frequently found in recurrent and metastatic tumors, suggesting a role for c-myc in tumor progression. However, in the current state of our study, it does not appear to be linked to prognosis; parts of the short arm of chromosome 11 are deleted in 20% of tumors resulting in hemizygosity for several genes (c-ha-ras, beta globin, pTH, calcitonin, catalase). These deletions seem to be linked with aggressiveness of tumors; a restriction fragment length polymorphism (RFLP) study of c-ha-ras has shown a significant association of the frequency of rare ha-ras alleles in cancer patients compared to that of normal individuals. Although this result is currently a matter of controversy, further studies must be independently repeated to be conclusive; -- another RFLP was found in c-mos proto-oncogene, which is detected only in patients with breast cancers or other types of tumors. The molecular basis for this RFLP has been elucidated. The significance of this association is unknown.