Entry into clinical trials in breast cancer: the importance of specialist teams. Scottish Breast Cancer Focus Group and Scottish Cancer Therapy Network

The aim of this study was to identify the factors influencing entry of women with invasive breast cancer into clinical trials in Scotland. Women diagnosed during 1987 and 1993 were identified from cancer registry data records and their case notes reviewed. Entry into clinical trials was recorded, along with clinical and demographic data for 4688 patients. In 1987, the proportion of women entering clinical trials was 12.3% and, allowing for shorter follow-up, this appeared unchanged in 1993. Patients seen by surgeons with a high case load and those referred to an oncologist were approximately seven times and three times, respectively, more likely to enter a clinical trial (P < 0.0001). The area of Scotland (Health Board) where the woman was first treated also influenced study entry (P < 0.0001), whereas social deprivation had no effect (P = 0.93). Older women, especially those over 80 years of age, were less likely to enter studies (P = 0.05). Extending the management of patients by specialist multidisciplinary teams should increase recruitment into clinical trials and help to identify better treatments for women with breast cancer.     

Cutaneous malignant melanoma in Scotland: incidence, survival, and mortality, 1979-94. The Scottish Melanoma Group

OBJECTIVE: To determine the changing incidence of and mortality from cutaneous malignant melanoma in Scotland from 1979 to 1994. DESIGN: Detailed registration of clinical and pathological features, surgical and other treatment, and follow up of all cases of cutaneous malignant melanoma diagnosed from 1979 to 1994 and registered with specialist database for Scotland. SETTING: Scotland. SUBJECTS: 6288 patients with invasive primary cutaneous malignant melanoma diagnosed between 1 January 1979 and 31 December 1994. RESULTS: The annual age standardised incidence of cutaneous malignant melanoma rose significantly from 3.5 to 7.8 per 100,000 per year in men and from 6.8 to 12.3 per 100,000 per year in women (P < 0.001 for both). World standardised rates increased from 2.7 to 6.0 per 100,000 per year in men and 4.6 to 8.50 per 100,000 in women. The incidence of melanoma continued to increase significantly in men of all ages during the study, but the rate stabilised in women after 1986. Mortality from cutaneous malignant melanoma was 1.3 per million per annum in men in 1979, rising to 2.3 per million per annum in 1994 (P < 0.01); it was 2.4 per million per annum in women in 1979, falling to 1.9 per million per annum in 1994 (P = 0.09). The underlying mortality trends showed a continuing rise for men but a downward trend for women that was not significant (P = 0.09). In men, melanoma free survival was 69% at 5 years and 61% at 10 years; in women the corresponding rates were 82% and 75%. Younger patients had higher survival rates, which were not entirely explained by thinner tumours. Over the 15 year period, survival rates improved by 12% overall, only partly owing to thinner tumours. CONCLUSIONS: In Scotland the incidence of melanoma in women has stabilised, while mortality associated with melanoma in women shows a downward trend.     

Effect of social class on tumour size at diagnosis and surgical treatment in Danish women with breast cancer

This study examines the effect of socio-economic inequalities on the tumour size at diagnosis and the choice of surgical treatment in Danish women with breast cancer. The Danish Breast Cancer Cooperative Group (DBCG) registers all women with breast cancer in Denmark and provides clinical register data on tumour size and surgical treatment for 1594 women <75 yr diagnosed with breast cancer between 1991 and 1996. A questionnaire including questions on social class was sent to the women. The tumour size at diagnosis (an indicator of access to treatment) and the surgical procedure (lumpectomy or mastectomy) for patients who were potential candidates for lumpectomy were the main outcome measures examined. Social class was not associated with tumour size at diagnosis. The tumour size was associated with age and the existence of a mammographic screening program in the county. However, treatment was strongly related to social class. Among women considered candidates for lumpectomy 77% underwent lumpectomy in the highest social class, compared to 50% in the lowest social class. Treatment was associated with age, tumour size and hospital status. It was concluded that the study showed no socio-economic inequalities related to access to health services as measured by tumour size, though significant social differences were found regarding treatment.     

Spectroscopic and thermodynamic evidence for a complex denaturation mechanism of bovine beta-lactoglobulin A

PURPOSE/OBJECTIVES: To investigate the patterns of functioning and psychosocial adjustment of midlife and older women following surgery for breast cancer. Differences between those who received follow-up adjuvant therapy and those who did not also were compared. DESIGN: 2 x 3 mixed design with one between-groups factor (type of treatment) and one within-subjects factor (time). SETTING: Four midwestern hospitals. SAMPLE: 46 patients with breast cancer who are age 55 or older. METHODS: Baseline data about presurgical functional status and other variables were obtained during the first week after surgery. Follow-up data were obtained at six weeks, three months, and six months postsurgery. Data were collected via telephone interviews and mailed questionnaires. MAIN RESEARCH VARIABLES: Functional status, patient symptomatology, quality of life (QOL), demands of illness, and type of treatment (surgery only versus surgery plus adjuvant therapy). FINDINGS: No differences existed between the two treatment groups at baseline, with the exception of lower functional status reported by the surgery-only group. In the surgery-only group, functional status improved significantly from six weeks to three months postsurgery. The most frequently reported symptoms of both groups included fatigue and pain. CONCLUSIONS: These results suggest that both groups did equally well, regardless of whether they received adjuvant therapy (radiation or chemotherapy). Neither QOL nor demands of illness differed between the two groups, nor did these scores change significantly over time following surgery. IMPLICATIONS FOR NURSING PRACTICE: These findings suggest that women undergoing surgery for breast cancer, whether they receive adjuvant therapy or not, may have functional and psychosocial needs that could be effectively addressed by nursing interventions pre- and postsurgery.     

A phase II trial and pharmacokinetic analysis of 96-hour infusional paclitaxel in patients with metastatic colorectal cancer

AIMS: To carry out a retrospective study of male breast cancer over a 22-year experience. METHODS: Data from 121 male patients with breast cancer treated between the years 1972 and 1994 at the Surgical Clinic of Ankara Oncology Hospital were reviewed. Distribution of cases according to stage was: 2.5% stage I, 28.9% stage II, 55.4% stage III and 13.2% stage IV (AJCC staging method). The surgical treatment for 23 of the patients (19%) was Halsted's radical mastectomy or modified radical mastectomy. Seventy-three cases (60.3%) had total mastectomy without axillary node dissection and 25 (20.7%) had local tumour excision only. Seventy-two of 121 patients had adjuvant treatment. RESULTS: In general the prognosis of men with breast cancer was worse than for women. In the analysis of patients in stages I, II and III-A (operable disease group), the 5-year survival rates were 73% in axillary node-negative patients and 77% in those with tumours sized under 5 cm (P<0.001). In these patients, univariate analysis demonstrated that axillary status (relative risk of death in positive status vs. negative=3.6), tumour size (relative risk in T3 vs. T1-2=2), surgical treatment type (relative risk in simple mastectomy vs. radical mastectomy=1.9) and adjuvant chemotherapy (relative risk if no chemotherapy=1.4) were statistically significant factors associated with survival. CONCLUSIONS: Cox's regression model revealed that axillary status, tumour size and type of surgical treatment were the most important independent prognostic factors (P<0.001).     

The importance of the lumpectomy surgical margin status in long-term results of breast conservation

BACKGROUND: The impact of the surgical margin status on long-term local control rates for breast cancer in women treated with lumpectomy and radiation therapy is unclear. METHODS: The records of 289 women with 303 invasive breast cancers who were treated with lumpectomy and radiation therapy from 1972 to 1992 were reviewed. The surgical margin was classified as positive (transecting the inked margin), close (less than or equal to 2 mm from the margin), negative, or indeterminate, based on the initial biopsy findings and reexcision specimens, as appropriate. Various clinical and pathologic factors were analyzed as potential prognostic factors for local recurrence in addition to the margin status, including T classification, N classification, age, histologic features, and use of adjuvant therapy. The mean follow-up was 6.25 years. RESULTS: The actuarial probability of freedom from local recurrence for the entire group of patients at 5 and 10 years was 94% and 87%, respectively. The actuarial probability of local control at 10 years was 98% for those patients with negative surgical margins versus 82% for all others (P = 0.007). The local control rate at 10 years was 97% for patients who underwent reexcision and 84% for those who did not. Reexcision appears to convey a local control benefit for those patients with close, indeterminate, or positive initial margins, when negative final margins are attained (P = 0.0001). Final margin status was the most significant determinant of local recurrence rates in univariate analysis. By multivariate analysis, the final margin status and use of adjuvant chemotherapy were significant prognostic factors. CONCLUSIONS: The attainment of negative surgical margins, initially or at the time of reexcision, is the most significant predictor of local control after breast-conserving treatment with lumpectomy and radiation therapy.     

High-dose therapy with cytostatic agents as primary treatment of advanced breast cancer

Thousands of women with breast cancer have received high dose chemotherapy prior to the results from controlled clinical trials being known. As one of these patients the author reviews and discusses the results of the first randomised study from South Africa. High dose therapy with autologous stem cell support was compared with conventional chemotherapy in 90 young women with metastatic aggressive breast cancer. Though survival was short in both groups the disease free survival was doubled in the high dose group. A significant increase was found in response rate, duration of response and survival. Data from America show the cost effectiveness of this treatment to be comparable to that of other life-saving therapies. A comparison is made with the absolute and relative survival benefit of simvastatin treatment. A Norwegian White Paper on high dose therapy does not include advanced breast cancer in the planned trial protocols. It is argued that future health planning should give high priority to the treatment of advanced breast cancer in young women.     

Dietary pectin with high viscosity lowers plasma and liver cholesterol concentration and plasma cholesteryl ester transfer protein activity in hamsters

The aim of this retrospective cohort study was to investigate whether survival of patients with breast cancer has changed over the period 1975-89. A total of 2604 women diagnosed as having invasive breast cancer at a clinical oncology unit in London were followed up for between 5 and 20 years. Patients were divided into four groups according to menstrual status (pre or post) and the staging of cancer (operable or inoperable). For each group, survival from diagnosis was compared between three consecutive 5-year cohorts, both with and without adjustments made for relevant prognostic factors. No temporal patterns were found in patients with inoperable cancer, in whom the survival rate was consistently low. Of women with operable cancers, differences were seen only among post-menopausal women, for whom the best survival patterns were seen in patients diagnosed between 1985-89. This is probably due to tamoxifen being commonly prescribed as adjuvant treatment for this cohort of patients. We cannot explain an apparently worse survival in the group of patients presenting in the early 1980s compared with that observed in the late 1970s.     

Breast carcinoma survival analysis for African American and white women in an equal-access health care system

BACKGROUND: This retrospective review of breast carcinoma cases in the Department of Defense (DoD) Central Tumor Registry evaluated differences in survival patterns between African American and white women treated in U.S. military health care facilities. The study examined the effects of age, stage of cancer, tumor size, grade, lymph node involvement, waiting time between diagnosis and first treatment, marital status, military dependent status, alcohol usage, tobacco usage, and family history of cancer. METHODS: Researchers reviewed the tumor registry records of 6577 women (5879 whites and 698 African Americans) diagnosed with breast carcinoma. The patients, ages 19-97 years, were diagnosed between 1975 and 1994. A hazard ratio (relative risk of mortality) model compared African American and white patients, adjusting for various combinations of covariates; impact of independent variables on the risk of death; prognostic factors significantly associated with survival; disease free and overall survival times; effects of ethnicity, stage, and age on survival; and trends in stage at diagnosis. A P value (2-sided) of less than 0.05 was considered statistically significant. RESULTS: After adjustment for age, the risk of death was 1.45 (95% confidence interval [CI], 1.20-1.76) times greater for African American women than for white women. Adjustment for stage reduced the risk to 1.41 (95% CI, 1.16-1.70); further adjustment for demographic variables and most clinical variables had no effect. Still, African American women treated in the military health care facilities had a better survival rate than African American women represented in the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute. In our study, the 5-year risk of death, from any cause, was 1.37 for African American women with breast carcinoma; in other words, the mortality rate for African American women was 24.77% compared with 18.08% for white women. In the latest SEER data, the 5-year relative risk of death for African American women compared with white women is 1.86. The mortality rate in SEER is 34.2% for African American women and 18.4% for white women. The survival rate for white DoD beneficiaries is comparable to that for white women in SEER. CONCLUSIONS: These observations suggest that ready access to medical facilities and the full complement of treatment options that are standard for all DoD patients improve survival rates for African American women. However, a significant unexplained difference in survival still exists between African American and white military beneficiaries.     

The impact of age, marital status, and physician-patient interactions on the care of older women with breast carcinoma

Understanding why older women with breast carcinoma do not receive definitive treatment is critical if disparities in mortality between younger and older women are to be reduced. With this in mind, the authors studied 302 women age > or =55 years with early stage breast carcinoma. Data were collected from surgical records and in telephone interviews with the women. The main outcome was receipt of definitive primary tumor therapy, defined either as modified radical mastectomy or as breast-conserving surgery with axillary dissection followed by radiation therapy. The majority (56%) of the women underwent breast-conserving surgery and axillary dissection followed by radiation therapy. After statistical control for four variables (comorbidity, physical function, tumor size, and lymph node status), patients' ages, marital status, and the number of times breast carcinoma specialists discussed treatment options were significantly associated with the receipt of definitive primary tumor therapy. The authors concluded that when older women have been newly diagnosed with breast carcinoma and there is clinical uncertainty as to the most appropriate therapies, patients may be better served if they are offered choices from among definitive therapies. In discussing therapies with them, physicians must be sensitive to their fears and concerns about the monetary costs and functional consequences of treatment in relation to the expected benefits.     

GABAergic stimulation regulates the phenotype of hippocampal interneurons through the regulation of brain-derived neurotrophic factor

PURPOSE: Information concerning the differences between older and younger women with breast cancer, treated with standard therapy, is lacking from many prospective series. The purpose of this study is to identify factors that influence treatment decisions and determine if women age 65 and older are treated differently than younger women. The outcomes of older women would then be compared to younger to determine if treatment differences influence outcome. METHODS AND MATERIALS: The records of 558 women with early invasive breast cancer who were treated with breast conserving surgery and radiation therapy were retrospectively reviewed. Four hundred thirty-two women under the age of 65 (range: 24-64) and 126 women age 65 and older (range: 65-85) were assessed for treatment differences including breast reexcision, extent of axillary dissection, extent of breast and nodal irradiation, and the use of chemotherapy or hormonal therapy. Differences in the treatment of the two groups were determined and the end points of local control, disease-free survival, and overall survival were compared. Median follow-up was 5.5 years. RESULTS: The two treatment groups had identical pathologic TNM staging with the exception that 21% of the older age group and 5% of the younger group did not undergo axillary dissection. Women age 65 and older were less likely to have a reexcision, extensive axillary dissection, chemotherapy, or nodal irradiation. They were more likely to receive hormonal therapy. Reexcision in older women was positively influenced by a family history of breast cancer and negatively influenced by a history of previous malignancy. None of the patients who were treated without and axillary dissection suffered a regional recurrence. Although local control was better in older patients, there were no differences in disease-free or overall survival for the two groups. DISCUSSION: The findings of this study reveal that older patients have significant treatment differences as compared to younger patients; however, despite these differences, similar local control and survival were achieved at 5 to 10 years. With the expected survival of older women increasing, the prospective evaluation of treatment options for older women should be considered.     

Family history and treatment outcome in young women after breast-conserving surgery and radiation therapy for early-stage breast cancer

PURPOSE: To evaluate the safety and efficacy of breast-conserving therapy for young women with a family history (FH) suggestive of inherited breast cancer susceptibility. MATERIALS AND METHODS: A total of 201 patients aged 36 or younger at diagnosis treated with breast-conserving surgery and radiation therapy (> or = 60 Gy) for early-stage breast cancer were categorized by FH. FH was considered positive in 29 patients who, at the time of diagnosis, had a mother or sister previously diagnosed with breast cancer before age 50 or ovarian cancer at any age. Clinical, pathologic, and demographic variables; sites of first failure; disease-free survival; and overall survival (OS) were compared between FH-positive and -negative groups. Median follow-up time was 11 years. RESULTS: Patient and tumor features were similar between those with and without an FH. Regression analysis of sites of first failure at 5 years demonstrated a risk ratio (RR) of 5.7 for opposite breast cancer for FH-positive patients. Rates of local, regional, and distant failure and disease-free survival or OS did not differ between FH-positive and -negative patients. Age at diagnosis and Ashkenazi heritage were not significantly predictors of patterns of failure. CONCLUSION: Breast-conserving surgery combined with radiation therapy is not associated with a higher rate of local recurrence, distant failure, or second (non-breast) cancers in young women with an FH suggestive of inherited breast cancer susceptibility compared with young women without an FH. However, their increased risk of opposite breast cancer should be taken into account when considering breast conservation as a treatment option.     

Evaluation of tryptamine in an impinger and on XAD-2 for the determination of hexamethylene-based isocyanates in spray-painting operations

We have investigated the relationship between immunohistochemically determined p53 status and outcome in 277 women with node-positive primary breast cancer who, following tumour excision and axillary clearance, were randomised to receive either 6 cycles of cyclophosphamide/methotrexate/S-fluorouracil (CMF) (n = 130) or no such post-operative treatment (n = 147). Follow-up data (median = 9 years) were available on all patients. A significant association was found between p53 status and survival. Patients with p53-positive tumours had a less favourable outcome than those with p53-negative disease. Women receiving adjuvant CMF chemotherapy had a significantly more favourable outcome compared to those who did not. The effect was seen both in women with p53-positive and p53-negative tumours; multivariate analysis showed relative risks for overall survival attributable to chemotherapy of 2.3 (95% CI 1.2-4.3) for women with p53-positive tumours and of 2.1 (95% CI 1.4-3.0) for those with p53-negative tumours. Thus, adjuvant chemotherapy with CMF is associated with a survival benefit in women with node-positive breast cancer irrespective of immunohistochemically determined p53 status.     

Statistical modelling of breast cancer incidence and mortality rates in Scotland

The interpretation of time trends in disease rates can be facilitated using estimable contrasts from age-period-cohort models. Cohort and period trends in breast cancer incidence and mortality rates in Scotland were investigated using contrasts that measure the changes in the linear trends. These contrasts were compared with estimates obtained from mortality rates in the USA and Japan. A significant moderation of both breast cancer incidence and mortality rates was observed in Scotland, associated with cohorts of women born after the Second World War compared with women born between the two world wars. The moderation of breast cancer mortality among cohorts born after 1925 compared with cohorts born before 1925 that was observed in the USA and Japan was also observed in this study. This moderation is not present in the incidence rates. The relative decline in the risk of breast cancer seen in younger cohorts seems to be contradictory to the temporal pattern present among breast cancer risk factors. It may well be that the alteration of eating patterns as a result of rationing in the wartime and immediate post-war period, and the subsequent influence on certain breast cancer risk factors probably produced by such changes, may have had some influence on the development of healthier girls and women. Such speculation could be addressed in a well-designed epidemiological study. There have been no changes in the mortality rate trends with period in Scotland, although the changes in the incidence rate trends with period are consistent with an increase in registration coverage.     

Breast cancer care in older women: sources of information, social support, and emotional health outcomes

BACKGROUND: The authors studied older women with breast cancer and asked: 1) where do older women get information regarding breast cancer care and how helpful do they perceive each of these sources to be? and 2) what aspects of social support are associated with older women's general and breast cancer specific emotional health outcomes? METHODS: To be eligible, women had to be at least 55 years of age and newly diagnosed with TNM Stage I or II breast cancer. Data were collected from women's surgical records and a 35-minute, computer-assisted telephone interview. RESULTS: Nearly all women rated information that was provided by their breast cancer physicians as very or somewhat helpful. Written materials provided by breast cancer physicians also were frequently rated as very or somewhat helpful. Women's marital status, religious service attendance, ratings of their physicians' technical and interpersonal care, and perceptions of their own abilities to communicate with their physicians were significantly associated with both general and breast cancer specific emotional health outcomes (all P < 0.05). CONCLUSIONS: Although older women obtained information regarding breast cancer from a variety of sources, they relied heavily on their physicians for information. To care most effectively for this group of patients, an increased understanding of the relation between the processes and outcomes of breast cancer care is needed Identifying older women with breast cancer at risk for poor emotional health outcomes and developing methods to enhance physician-patient communication in this setting may improve these outcomes.     

Factors affecting baseline quality of life in two international adjuvant breast cancer trials. International Breast Cancer Study Group (IBCSG)

Quality of life (QL) is used to assess treatments in clinical trials but may be influenced by other factors. We analysed the impact of biomedical, sociodemographic and cultural factors on baseline QL indicators in two International Breast Cancer Study Group trials. Patients with stage II breast cancer were randomized within 6 weeks of primary surgery to various adjuvant treatments. They were asked to assess five indicators of QL at baseline. QL forms were available for 1231 (83%) of the 1475 premenopausal and 989 (82%) of the 1212 post-menopausal patients, who were from nine countries and spoke seven languages. Culture (defined as language/country groups) had a statistically significant impact on baseline QL measures. Premenopausal patients with poor prognostic factors showed a tendency to report worse QL, with oestrogen receptor status as an independent predictor for mood (P = 0.0005). Older post-menopausal patients reported better emotional wellbeing (P = 0.002), mood (P = 0.002), and less effort to cope (P = 0.0009) compared with younger post-menopausal patients. Co-morbidity, type of surgery, treatment assignment and sociodemographic factors showed a statistically significant impact in post-menopausal patients only. Cultural and biomedical factors influenced baseline QL and should be considered when evaluating the impact of treatment on QL in international breast cancer clinical trials.     

Treatment of breast cancer after 70 years of age. Report of 1143 cases

STUDY AIM: Breast cancer is the most frequent type of cancer in women, increasing in frequency with the elderly. In Europe, a third of new breast cancers occur in women over 70 years of age. The aim of this retrospective study was to analyse the tumoural lesions and therapeutic results in a female population over 70, treated in the same medical centre over a 15-year period. PATIENTS AND METHODS: From 1978 to 1992, 1,143 female patients aged 70 or over were treated for a unilateral breast cancer without metastases and followed-up during a mean 6-year period. The initial treatment was surgical in 1,012 patients: radical mastectomy in 95% of the cases with axillary node dissection in 97.6%. Adjuvant radiotherapy was performed in 289 patients and adjuvant treatment with Tamoxifen in 411 patients. The results were compared with those obtained in 2,947 patients aged 50 to 69, treated during the same period in the same medical centre. RESULTS: The 5-year survival rate in women 70 and over was 80% vs 85.5% in women aged 50 to 69 (P < 0.000001). The same rate of loco-regional recurrences and metastases occurred in both populations. In the patients who initially underwent surgery, after multivariate analysis according to the Cox model, the prognosis factors (similar to those observed in the group of younger women) were: the number of involved nodes (P = 0.000001), the clinical size of the tumour (P = 0.00001), the histological grade (P = 0.01), and the estrogen receptors (P = 0.02). CONCLUSIONS: In this series, the treatment was focused on surgery complemented with adjuvant radiotherapy according to node invasion and adjuvant hormonotherapy according mostly to hormonal receptors. However, the complete treatment could not be applied to all cases: only 50% of patients with node involvement were irradiated. The 5-year survival rate lower than that of younger patients may be attributed to incomplete adjuvant treatment. Specific controlled trials taking into account quality of life had to be undertaken in elderly patients in order to adjust the treatment in relation with the patients' age and physiological condition.     

Breast cancer survival and treatment in health maintenance organization and fee-for-service settings

BACKGROUND: Enrollment in health maintenance organizations (HMOs) has increased rapidly during the past 10 years, reflecting a growing emphasis on health care cost containment. To determine whether there is a difference in the treatment and outcome for female patients with breast cancer enrolled in HMOs versus a fee-for-service setting, we compared the 10-year survival and initial treatment of patients with breast cancer enrolled in both types of plans. METHODS: With the use of tumor registries covering the greater San Francisco-Oakland and Seattle-Puget Sound areas, respectively, we obtained information on the treatment and outcome for 13,358 female patients with breast cancer, aged 65 years and older, diagnosed between 1985 and 1992. We linked registry information with Medicare data and data from the two large HMOs included in the study. We compared the survival and treatment differences between HMO and fee-for-service care after adjusting for tumor stage, comorbidity, and sociodemographic characteristics. RESULTS: In San Francisco-Oakland, the 10-year adjusted risk ratio for breast cancer deaths among HMO patients compared with fee-for-service patients was 0.71 (95% confidence interval [CI] = 0.59-0.87) and was comparable for all deaths. In Seattle-Puget Sound, the risk ratio for breast cancer deaths was 1.01 (95% CI = 0.77-1.33) but somewhat lower for all deaths. Women enrolled in HMOs were more likely to receive breast-conserving surgery than women in fee-for-service (odds ratio = 1.55 in San Francisco-Oakland; 3.39 in Seattle). HMO enrollees undergoing breast-conserving surgery were also more likely to receive adjuvant radiotherapy (San Francisco-Oakland odds ratio = 2.49; Seattle odds ratio = 4.62). CONCLUSIONS: Long-term survival outcomes in the two prepaid group practice HMOs in this study were at least equal to, and possibly better than, outcomes in the fee-for-service system. In addition, the use of recommended therapy for early stage breast cancer was more frequent in the two HMOs.     

Does the placement of surgical clips within the excision cavity influence local control for patients treated with breast-conserving surgery and irradiation

PURPOSE: A number of authors have demonstrated the importance of using surgical clips to define the tumor bed in the treatment planning of early-stage breast cancer. The clips have been useful in delineating the borders of the tangential fields, especially for very medial and very lateral lesions as the boost volume. If surgical clips better define the tumor bed, then a reduction in true or marginal recurrences should be appreciated. We sought to compare the incidence of breast recurrence in women with and without surgical clips, controlling for other recognized prognostic factors. METHODS AND MATERIALS: Between 1980 and 1992, 1364 women with clinical Stage I or II invasive breast cancer underwent excisional biopsy, axillary dissection, and definitive irradiation. Median follow-up was 60 months. Median age was 55 years. Seventy-one percent of patients were path NO, 22% had one to three nodes, and 7% had > than four nodes. Sixty-one percent were ER positive and 44% PR positive. Margin status was negative in 62%, positive in 10%, close in 9%, and unknown in 19%. Fifty-seven percent of women underwent a reexcision. Adjuvant chemotherapy + tamoxifen was administered in 29%, and tamoxifen alone in 17%. Surgical clips were placed in the excision cavity in 556 patients, while the other 808 did not have clips placed. All patients had a boost of the tumor bed. Patients had their boost planned with CT scanning or stereo shift radiographs. No significant differences between the two groups were noted for median age, T stage, nodal status, race, ER/PR receptor status, region irradiated, or tumor location. Patients without clips had negative margins less often, a higher rate of unknown or positive margins and more often received no adjuvant therapy compared to patients with surgical clips. RESULTS: Twenty-five and 27 patients with and without surgical clips, respectively, developed a true or marginal recurrence in the treated breast. The actuarial probability of a breast recurrence was 2% at 5 years and 5% at 10 years for patients without clips compared to 5 and 11%, respectively, for patients with clips (p=0.01). Comparing the breast recurrence rates for patients with and without clips there was no significant difference for the following factors: chemotherapy, tamoxifen, negative, positive or close margins, reexcision, N1, and central or inner primary. Increased rates of breast recurrence were noted for patients with clips for the following variables: no adjuvant treatment (p < 0.001), unknown margins (p < 0.001), a single excision (p = 0.003), path NO (p = 0.001), and outer location (p= 0.02). A forward stepwise multivariate analysis for all 1364 patients was performed using the aforementioned variables as well as the presence or absence of surgical clips and the primary surgeon. The surgeon (p = 0.03) and no adjuvant treatment (p = 0.01) significantly influenced breast recurrence. For patients with surgical clips the 10 year isolated breast recurrence rate was 21% for a single surgeon vs. 6% in the remainder of the group (p = 0.01). For patients with clips, this surgeon had unknown margins in 48% of cases compared to 10% overall (p = 0.001). Excluding this surgeon from analysis the isolated breast recurrence for patients with clips was 6 vs. 5% for patients without clips (p = 0.18). CONCLUSIONS: Overall, there was a significant difference in the 10-year breast recurrence rate favoring women without clips despite more adverse prognostic factors. There was no difference in the breast recurrence rate for patients with or without surgical clips if careful attention to margin status was addressed. Failure to ink the surgical specimen resulting in unknown margins cannot be compensated for with the placement of .