Diagnosis delay in Libyan female breast cancer

ABSTRACT: BACKGROUND: To study the diagnosis delay and its impact on stage of disease among women with breast cancer on Libya METHODS: 200 women, aged 22 to 75 years with breast cancer diagnosed during 2008--2009 were interviewed about the period from the first symptoms to the final histological diagnosis of breast cancer. This period (diagnosis time) was categorized into 3 periods: <3 months, 3--6 months, and >6 months. If diagnosis time was longer than 3 months, the diagnosis was considered delayed (diagnosis delay). Consultation time was the time taken to visit the general practitioner after the first symptoms. Retrospective preclinical and clinical data were collected on a form (questionnaire) during an interview with each patient and from medical records. RESULTS: The median of diagnosis time was 7.5 months. Only 30.0% of patients were diagnosed within 3 months after symptoms. 14% of patients were diagnosed within 3--6 months and 56% within a period longer than 6 months. A number of factors predicted diagnosis delay: Symptoms were not considered serious in 27% of patients. Alternative therapy (therapy not associated with cancer) was applied in 13.0% of the patients. Fear and shame prevented the visit to the doctor in 10% and 4.5% of patients, respectively. Inappropriate reassurance that the lump was benign was an important reason for prolongation of the diagnosis time. Diagnosis delay was associated with initial breast symptom(s) that did not include a lump (p < 0.0001), with women who did not report monthly self examination (p < 0.0001), with old age (p = 0.004), with illiteracy (p = 0.009), with history of benign fibrocystic disease (p = 0.029) and with women who had used oral contraceptive pills longer than 5 years (p = 0.043). At the time of diagnosis, the clinical stage distribution was as follows: 9.0% stage I, 25.5% stage II, 54.0% stage III and 11.5% stage IV.Diagnosis delay was associated with bigger tumour size (p <0.0001), with positive lymph nodes (N2, N3; p < 0.0001), with high incidence of late clinical stages (p < 0.0001), and with metastatic disease (p < 0.0001). CONCLUSIONS: Diagnosis delay is very serious problem in Libya. Diagnosis delay was associated with complex interactions between several factors and with advanced stages. There is a need for improving breast cancer awareness and training of general practitioners to reduce breast cancer mortality by promoting early detection. The treatment guidelines should pay more attention to the early phases of breast cancer. Especially, guidelines for good practices in managing detectable of tumors are necessary.     

Risk factors for breast cancer in women biopsied for benign breast disease: A nested case-control study

Aim: Women with a history of benign breast disease are at increased risk of subsequent breast cancer. However, few studies have examined whether established breast cancer risk factors other than histology are associated with an altered risk of breast cancer in women with benign breast disease. We used a nested case-control design within a large, multi-center cohort of women biopsied for benign breast disease (BBD) to estimate odds ratios for breast cancer in association with exposure to a range of personal and lifestyle factors. Methods: Cases were women biopsied for BBD who subsequently developed breast cancer; controls were individually matched to cases on center and age at diagnosis and were women biopsied for BBD who did not develop breast cancer in the same follow-up interval as that for the cases. After excluding women with prevalent breast cancer, 1357 records (661 case records and 696 records) were available for analysis. We used conditional logistic regression to obtain crude and multivariable-adjusted estimates of the association between specific factors and risk of breast cancer. Results: In multivariable analyses age at first live birth, number of pregnancies, and postmenopausal status were inversely associated with risk of breast cancer. The odds ratio for women with age at first birth <25 years and ≥3 pregnancies, relative to nulliparous women, was 0.49, 95% confidence interval 0.13–0.79, and that for postmenopausal women relative to premenopausal women was 0.60, 95% CI 0.37–0.99. Conclusions: Further study of personal factors influencing the risk of breast cancer in women with BBD may help to identify subgroups of the population at increased risk of invasive disease.     

Management of women at increased risk for breast cancer: preliminary results from a new program

OBJECTIVE: To examine the characteristics of malignant tumours that develop in women undergoing surveillance for increased risk for breast cancer and to identify presentation patterns in order to determine the respective roles of mammography, clinical breast examination (CBE) and breast self-examination (BSE). SETTING: Breast Diagnostic Clinic and Familial Breast Cancer Clinic at Toronto-Sunnybrook Regional Cancer Centre. PARTICIPANTS: A total of 1044 women evaluated for breast cancer risk from Oct. 1, 1990, to Dec. 31, 1996, of whom 381 were categorized as being at high risk, 204 as being at moderate risk, 401 as being at slightly increased risk and 58 as being at no appreciably increased risk. PROGRAM COMPONENTS: Comprehensive review and discussion of risk factors, clinical assessment, surveillance recommendations that include mammography, CBE and BSE, genetics consultation (Familial Breast Cancer Clinic) and psychosocial support. Data are captured prospectively, updated at each visit and audited every 3 to 6 months. PROGRAM OUTCOMES: During the study period breast cancer was diagnosed in 24 patients, 12 in the high-risk group, 4 in the moderate-risk group and 8 in the group at slightly increased risk. The mean age at diagnosis was 47 (range 32 to 82) years. Ten cases of cancer were diagnosed during surveillance (incident cancer), 5 in women under age 50. The mean length of time from initial assessment to diagnosis was 28.6 (range 12 to 51) months. Of the 24 women, 17 reported a family history of breast cancer. The mean age at diagnosis in this cohort was 45.5 years, and the diagnosis was made under age 50 in 10 patients (59%). The mean earliest age at which breast cancer was diagnosed in a family member was 42.5 years. CONCLUSIONS: These preliminary results suggest that surveillance of women at increased risk for breast cancer may be useful in detecting disease at an early stage. The regular performance of mammography, CBE and BSE appears necessary to achieve these results.     

Mammography screening in the county of Fyn. November 1993-December 1999

This report covers the outcome of the first three invitation rounds of the organised mammography screening programme in the county of Fyn. The programme started in November 1993, and the third invitation round ended on 31 December 1999. The screening takes place either at a special clinic located at University Hospital Odense or in a mobile unit. Women living in and around the city of Odense are examined at the clinic (about 55%), while the rest are examined in the mobile unit. Two-view mammography is used at the first screening. Women with dense breast tissue will continue to have two-view mammography (about 60%), whereas the rest will have singleview mammography at the subsequent screens. All screening images are exposed at the mammography-screening clinic and evaluated with double reading in the clinic. The programme targets women aged 50-69, except those undergoing treatment for breast cancer or going for regular check-ups following breast cancer. Based on the updated population register, the IT-Centre of the county of Fyn issues the invitations. Invited are all women aged 50-69 and living in the county of Fyn when their general practitioners' patients are invited. During the first 3 invitation rounds, 136,079 screening tests were made. Of these, 129,375 tests were made in the women aged 50-69 targeted by the programme. In addition, 6682 screening tests were made in women aged 70 and above, and 22 screening tests were made in women below the age of 50. As a consequence of the mammography screening 2657 assessments were made, 1145 women had surgery, 782 women were diagnosed with invasive breast cancer, and 109 women were diagnosed with ductal carcinoma in situ. A participation rate for the first invitation round was calculated immediately after the end of the round based on the number of participants divided by the number of women invited. This percentage was 88%. Invitation data are, however, not stored. It is therefore not possible now to calculate the participation rates in previous invitation rounds based on the same method. We have therefore chosen to calculate the participation rate as the coverage, i.e. the number of participants divided by the average number of women in the county of Fyn during a given invitation round. Calculated in this way, 84% participated in the first round, 84% in the second round, and 82% in the third round. It should be remembered that these figures do not take into account that some women are not invited because they 1) were undergoing current treatment for breast cancer or going for regular check-ups following breast cancer, or 2) did not participate in the previous round (and never actively informed the programme that they wanted an invitation to the next invitation round), relevant only for the second and third invitation round. For the second and third invitation rounds, the programme only invited women who participated in the previous invitation round, asked the clinic for an invitation, or entered the target population since the last invitation round. Therefore the participation rate in the second invitation round among actually invited women will be close to 94%, as 94% of those participating in the first round came for the second round. For the third invitation round, the participation rate among actually invited women will be close to 96%, as 96% of those participating in the first and second rounds came for the third round. One per cent of the participants in the first invitation round were diagnosed with invasive breast cancer or ductal carcinoma in situ. The detection rate was 0.5% in both the second and third invitation rounds. Ductal carcinoma in situ cases constituted 14% of the detected cases in the first and second rounds, and 10% in the third round. The percentage of invasive breast cancer 10 mm of less was 38%, 31%, and 32%, respectively, and 68%, 74%, and 73%, respectively, were node-negative. The screening programme of the county of Fyn fulfilled all the quality assessment parameters specified by the European guidelines on breast cancer screening, except two. The proportionate interval cancer rate was higher than specified in the guidelines, probably mainly due to the fact that the Fyn programme operates without early recalls. The proportion of stage II+ cancers was higher than specified in the guidelines, which seems, however, to be due to inconsistency between some of the performance indicators in the European guidelines. This analysis of the outcome from the first three invitation rounds of the mammography screening programme in the county of Fyn thus showed that it is a programme of high quality with a favourable profile of the prognostic indicators. The screening programme is hopefully well on its way to reducing breast cancer mortality in the county of Fyn.     

Is needle-directed breast biopsy overused?

We undertook this study of needle-localized breast biopsy--a frequently done surgical procedure--to examine current practice patterns and to determine if the technique is overused in any group of patients. From a retrospective review of medical records of all patients who had needle-localized breast biopsy at a teaching hospital between June 1, 1988, and October 31, 1990, we found that a total of 125 were done: 24 biopsy specimens showed malignancy (19%). Mammographic indications for biopsy were microcalcification (n = 62, or 50%), mass or density (n = 60, or 48%) and mass and calcifications (n = 3, or 2%). Indications for biopsy in patients with cancer were microcalcification (14 patients) and mass or density (10 patients). The incidence of malignancy increased with age. In patients younger than 40 years, no biopsy showed malignancy. Only 2 of 30 biopsies done in patients younger than 50 showed cancer (7%). Breast cancer was most frequently discovered in patients in the seventh and eighth decades of life, and this group accounted for 75% of "positive" biopsies. Needle-localized breast biopsy is a useful technique in the early diagnosis of breast cancer. Although indications for the procedure should remain liberal, in women younger than 50, the percentage of biopsies that reveal malignancy is low.     

Cervical intraepithelial neoplasia grade III (CIN III) and invasive cervical carcinoma: the yawning gap revisited and the treatment of risk

In a 3-year study of the population of Southampton and south-west Hampshire there were 10 times as many cases of CIN III compared with invasive squamous carcinoma (700 compared with 70). The peak incidence of CIN III per 1000 screened women years was in those aged 25-29 years, which was 20 years earlier than the peak incidence of invasive cervical cancer per 1000 women years at risk. Ninety percent of CIN III was diagnosed in women under 50 years. There were 14 cases of cervical glandular intraepithelial neoplasia grade III (CGIN III), three coexisting with CIN III, all in women aged under 50 years: the gap between intraepithelial and invasive lesions was not seen for glandular neoplasia. Although referral was for at least moderate dyskaryosis in 86.8% of women with CIN III or CGIN III, most had been screened previously, either having had mild abnormalities requiring repeat cytology (39.8%) or negative cytology (34.5%). Only 12 women aged > or = 50 years had previous negative cytology: 21.4% compared with 35.6% of women aged < 50 years (P = 0.034). The results of this study suggest that the best opportunity for preventing invasive squamous cell carcinoma lies in screening women aged 20-39 years when the incidence of CIN III in the screened population is highest and before the peak incidence of invasive disease. The results also indicate the importance of repeated screening and follow up of minor cytological abnormalities in the detection of CIN III. The benefit of screening must be regarded as a treatment of risk, since it is almost certain that a high proportion of CIN III regresses or persists unchanged.     

Mammographic screening and mortality from breast cancer: the Malm? mammographic screening trial.

STUDY OBJECTIVE--To determine whether mortality from breast cancer could be reduced by repeated mammographic screening. DESIGN--Birth year cohorts of city population separately randomised into study and control groups. SETTING--Screening clinic outside main hospital. PATIENTS--Women aged over 45; 21,088 invited for screening and 21,195 in control group. INTERVENTIONS--Women in the study group were invited to attend for mammographic screening at intervals of 18-24 months. Five rounds of screening were completed. Breast cancer was treated according to stage at diagnosis. END POINT--Mortality from breast cancer. MEASUREMENTS AND MAIN RESULTS--All women were followed up and classed at end point as alive without breast cancer, alive with breast cancer, dead from breast cancer, or dead from other causes. Cause of death was taken from national mortality registry and for patients with breast cancer was validated independently. Mean follow up was 8.8 years. Altogether 588 cases of breast cancer were diagnosed in the study group and 447 in the control group; 99 v 94 women died of all causes and 63 v 66 women died of breast cancer (no significant difference; relative risk 0.96 (95% confidence interval 0.68 to 1.35)). In the study group 29% more women aged less than 55 died of breast cancer (28 v 22; relative risk 1.29 (0.74 to 2.25)). More women in the study group died from breast cancer in the first seven years; after that the trend reversed, especially in women aged greater than or equal to 55 at entry. Overall, women in the study group aged greater than or equal to 55 had a 20% reduction in mortality from breast cancer (35 v 44; relative risk 0.79 (0.51 to 1.24)). OTHER FINDINGS--In the study group 100 (17%) cancers appeared in intervals between screenings and 107 (18%) in non-attenders; 51 of these women died from breast cancer. Cancers classed as stages II-IV comprised 33% (190/579) of cancers in the study group and 52% (231/443) in the control group. CONCLUSIONS--Invitation to mammographic screening may lead to reduced mortality from breast cancer, at least in women aged 55 or over.     

The relationship between breast cancer and augmentation mammaplasty: an epidemiologic study

Surgical implantation of breast prostheses for cosmetic purposes has become increasingly popular, and by 1981, it was estimated that three-quarters of a million women had had such an operation. The long-term potential risks, particularly of breast cancer, of such procedures have not been properly investigated. To evaluate the potential breast cancer risk, we have conducted a retrospective cohort study of 3111 women followed through various public and medical records for a total of 18,476 person-years, with a median of 6.2 years per person. The cases of breast cancer were detected by means of a computerized match with the Los Angeles County Cancer Surveillance Program, a population-based cancer registry. Overall, 15.7 breast cancer cases were expected and 9 were observed, a nonsignificant deficit [standardized incidence ratio (SIR) = 57 percent, 95 percent confidence limits: 26 percent, 109 percent]. The cancers were generally diagnosed at an early stage. Among the 573 women aged 40 or older at implantation, 7.1 cases were expected and 8 were observed (SIR = 113 percent). In women whose implants were performed before the age of 40, only 1 case was observed whereas 8.6 cases were expected (SIR = 12 percent, 95 percent confidence limits: 0.3 percent, 65 percent), a significant difference. These data do not support an increased risk of breast cancer following augmentation mammaplasty. The low breast cancer rate in women having augmentation mammaplasty at a young age that many such women may have a reduced amount of breast tissue, but data on this are unavailable.     

Screening for cervical intraepithelial neoplasia in north east Scotland shows fall in incidence and mortality from invasive cancer with concomitant rise in preinvasive disease.

OBJECTIVE--To assess the effect of screening for cervical intraepithelial neoplasia on the incidence of and mortality from invasive squamous cell carcinoma of cervix in north east Scotland and to discover why cases of invasive cancer still occur. DESIGN--(a) Analysis of data on cases of cervical intraepithelial neoplasia obtained from the cytology data bank; (b) analysis of data on 612 women presenting with invasive squamous cancer during 1968-91, obtained from cancer registry and hospital records; (c) analysis of death rates obtained from the registrar general''s (Scotland) annual reports, the Information Services Division of the Home and Health Department (Scotland), and local records for 1974-91; (d) case-control studies on 282 cases of invasive cancer and 108 deaths which occurred in 1982-91. Cases were matched with two controls both for age and for having a negative smear test result at the time of presentation of the case. SETTING--North east Scotland (Grampian region, Orkney, and Shetland). SUBJECTS--Women (n = 306,608) who had had cervical smear tests between 1960 and 1991. RESULTS--There had been a substantial increase in cases of cervical intraepithelial neoplasia grade III since 1982. The incidence of invasive cancer has fallen since the start of screening in 1960, the fall occurring mainly in the well screened age group 40-69 years. There was a rise in women aged under 40 and over 70. Women with invasive disease seen between 1982 and 1991 mostly presented at stage I. Of these, half were unscreened, one third were poorly screened, 11% were found in retrospect to have had abnormal cells, 3% had recurrence of disease after treatment for cervical intraepithelial neoplasia grade III, and 3% were lost to follow up. Death rates had fallen, most noticeably in women aged 45-64, who had had the opportunity to be screened and rescreened. There was a disturbing rise in deaths among women under 45. Most deaths (65%) occurred in unscreened women. Case-control studies showed that the longer the time and absence of a smear test before presentation the higher was the risk of invasive cancer and of death. CONCLUSIONS--Screening has been effective in reducing the incidence of and mortality from cervical cancer in north east Scotland. Most cases and deaths occurred in unscreened women or in those who had had few smears at long intervals. An increase in cases of cervical intraepithelial neoplasia grade III in women screened for the first time occurred during 1982-91.     

Coronary artery surgery: are women discriminated against?

OBJECTIVE--To determine whether the sex differences in access to cardiac surgery observed in the United States exist in the United Kingdom. DESIGN--Retrospective analysis of routinely collected data. SETTING--South West Thames and North West Thames regional health authorities. SUBJECTS--8564 patients discharged from hospital with a principal diagnosis of coronary heart disease in 1987-8 in South West Thames region and 15243 discharges in North West Thames region in 1990-1. MAIN OUTCOME MEASURES--Performance of angiography or coronary artery bypass surgery. RESULTS--In all age groups and among patients with a principal diagnosis of either angina or chronic ischaemia men were significantly more likely than women to undergo revascularisation in both regions. Using multiple logistic regression to control for potential clinical and demographic confounders, the male to female odds ratio for revascularisation among all cases was 1.59 (95% confidence interval 1.25 to 2.03) in South West Thames region and 1.47 (1.32 to 1.63) in North West Thames region. CONCLUSION--There appears to be a systematic difference in the treatment received by men and women in the United Kingdom. The reasons for this are uncertain.     

CA 15.3 as a tumour marker in breast cancer

CA 15.3 is an antigenic determinant associated with human mammary carcinomas. Two murine monoclonal antibodies have been raised against the determinants, and an immunoradiometric assay (IRMA-Kit, Centocor, USA) has been developed to determine the antigen levels in plasma of cancer patients. Based on the 99% confidence limit of healthy women, plasma values above 30 U/ml are considered abnormal. Plasma samples from 357 women were examined in the present study. Healthy females (n = 84) ranged below the cut-off level between less than 10 and 29 U/ml. Higher values were found in 12.5% of benign breast diseases and in 23.6% of breast cancer patients, including all stages. Depending on the stage of the disease, there were elevated levels in 11% of operable breast cancer patients preoperatively, in 7% of the cases with no evidence of disease after primary treatment and in 63.5% of patients with disseminated mammary carcinoma. In metastasized breast cancer the frequency and the degree of abnormal titers were closely related to the extent of the metastatic disease. Follow-up examinations of 63 patients under cytotoxic therapy showed CA 15.3 changes correlating well with the clinical course in up to 90% of the antigen positive cases. The present data indicate that CA 15.3 may be useful in the surveillance of breast cancer patients. However in our study one third of the patients with metastatic breast cancer did not show any increase in CA 15.3 and must be regarded as antigen negative.     

Retrospective study of reasons for improved survival in patients with breast cancer in east Anglia: earlier diagnosis or better treatment.

OBJECTIVES: To investigate the recent fall in mortality from breast cancer in England and Wales, and to determine the relative contributions of improvements in treatment and earlier detection of tumours. DESIGN: Retrospective study of all women with breast cancer registered by the East Anglian cancer registry and diagnosed between 1982 and 1989. SUBJECTS: 3965 patients diagnosed 1982-5 compared with 4665 patients diagnosed 1986-9, in three age groups 0-49, 50-64, > or = 65 years, with information on stage at diagnosis and survival. MAIN OUTCOME MEASURES: Three year relative survival rates by time period, age group, and stage; relative hazard ratios for each time period and age group derived from Cox''s proportional hazards model, adjusted for single year of age and stage. RESULTS: Survival improved in the later time period, although there was little stage specific improvement. The proportion of early stage tumours increased especially in the 50-64 year age group, and adjustment for stage accounted for over half of the improvement in survival in women aged under 65 years. CONCLUSION: Over half of the drop in mortality in women aged under 65 years seems to be attributable to earlier detection of tumours, which has been observed since the mid-1980s. This could have resulted from an increase in breast awareness predating the start of the breast screening programme.     

Is mammography indicated for women with defective BRCA genes? Implications of recent scientific advances for the diagnosis, treatment, and prevention of hereditary breast cancer

About 5% of breast cancer patients have inherited their disease because of a mutation in genes encoding either the BRCA-1 or BRCA-2 proteins. Inheriting one of these mutations confers a 50% to 87% risk of breast cancer. Many physicians faced with such a patient would, at a minimum, suggest increased and earlier screening for breast cancer by routine mammography.[1] Normally, regular mammographic screening combined with appropriate and prompt treatment can reduce mortality from breast cancer by 30% in women aged 50-59 years and by about 14%-18% in women aged 40-49. There are no controlled clinical trials for screening young women who have multiple first-degree relatives developing breast cancer before age 45, or those known to carry BRCA-1 or BRCA-2 mutations. In fact, recent advances point out that BRCA-1 and BRCA-2 gene products are needed to repair radiation damage to DNA.[4,5] Based on this finding, I propose that women with defective BRCA genes are likely to have an inordinate sensitivity to radiation, and this raises a question about the advisability of routinely screening these women by frequent mammography.     

California's male suicide rate at record high.

Breast cancer is the most commonly occurring cancer in women and, until recently surpassed by lung cancer, was the leading cause of cancer-related death in women. It is the leading cause of death in women aged 39 to 44 years. The American Cancer Society has estimated that there will be 135,000 new cases of breast cancer and 42,300 breast cancer-related deaths in 1988. It is now predicted that breast cancer will develop in one out of every ten women in the United States. Given the clinical and public health significance of breast cancer, annual screening with mammography and clinical breast examination is recommended for women aged 50 and older to reduce breast cancer mortality.     

Survival with bladder cancer,evaluation of delay in treatment,type of surgeon,and modality of treatment.

OBJECTIVE--To determine whether length of delay before treatment; specialty and grade of the surgeon; and use made of surgery, radiotherapy, and chemotherapy influenced the survival of patients with cancer of the bladder, after adjusting for case severity. DESIGN--Retrospective cohort study. SETTING--South East and South West Thames health regions. PATIENTS--609 men aged under 75 resident in the South Thames regions who had been registered as new cases of bladder cancer in 1982, 35 of whom were excluded, leaving 574 eligible patients. Analysis was based on 75% retrieval rate for case notes. MAIN OUTCOME MEASURES--Duration of survival from date of diagnosis of the bladder tumour. RESULTS--10 prognostic variables were used to adjust for case severity. The median delay from referral to first treatment was 48 (interquartile range 27-84) days. Treatment after a short delay was associated with shorter survival because of the early treatment of more severe cases. Consultants treated 68% of patients, trainee surgeons treated less severe cases. Initial treatment was by a urologist in 67% of cases, but the specialty of the surgeon was not associated with prognosis. The associations of radiotherapy, cystectomy, and systemic chemotherapy with survival were interpreted in terms of selection bias as well as therapeutic effect. CONCLUSION--Case severity was the most important influence on survival and influenced length of delay before treatment, grade and specialty of the surgeon, and main treatment allocation. After adjusting for case severity variations in these processes of care were not strongly associated with variations in survival.     

Human small breast epithelial mucin: the promise of a new breast tumor biomarker

Breast cancer remains one of the most frequently diagnosed cancers today. In developed countries, one in eight women is expected to present with breast cancer within her lifetime and an estimated 1,000,000 cases are detected each year worldwide (Canadian Cancer Statistics, http://www.cancer.ca/vgn/images/ portal/cit_86751114/14/33/1959864 11niw_stats2004_en.pdf). For women with recurrent disease, the median time of survival is about 2 years. Despite optimal surgery, adjuvant irradiation, hormonal treatment, and chemotherapy, approximately 30% of patients with localized breast cancer finally develop distant metastases. Early detection, which enables intervention at a localized and potentially curable stage, remains a central goal in breast cancer treatment. Indeed, the 5-year survival rate for women with breast cancer has been shown to increase dramatically when the disease is diagnosed at an early stage: from less than 25% in women with disseminated cancer to about 75% in patients with regional disease and over 95% in women with a localized tumor (Breast Cancer Facts and Figures, 2001-2002, http://www.cancer.org/downloads/STT/BrCaFF 2001.pdf). Unfortunately, only 60% of all breast cancers are diagnosed at a local stage. Any improvement in early detection through identification of tumor biomarkers would have a significant impact on reducing overall breast cancer mortality.     

Frequent loss of the BLID gene in early-onset breast cancer

The BH3-like motif-containing inducer of cell death (BLID) is an intronless gene localized on 11q24.1. Loss of that region has frequently been reported in early-onset breast cancer and is significantly associated with poor prognosis and reduced survival. Downregulation of BLID is associated with younger age, triple-negative phenotype, and reduced disease-free and overall survival of breast cancer patients. In this study, we investigated allelic loss of BLID in breast tumor specimens from 78 women with invasive breast cancer using 2 dinucleotide polymorphic markers closely linked to the BLID gene (no intragenic marker for BLID is available). Seventy-three cases were informative. Overall, loss of heterozygosity (LOH) at the BLID locus was detected in 32% of the informative cases (23/73). However, in patients 40 years old and younger, LOH was detected in 50% of the cases (9/18). Patients aged 40 years and younger were significantly more likely to experience LOH than those aged 41-55 years (p = 0.04). Specifically, the odds of BLID loss for patients aged 40 years and younger were 3.7 times the odds of loss for patients aged 41-55 years (95% CI, 1.1-13). Our findings suggest a tumor suppressor role of the BLID gene in early-onset breast cancer.     

Relation between socioeconomic deprivation and pathological prognostic factors in women with breast cancer.

OBJECTIVE--To investigate the relation between socioeconomic deprivation and pathological prognostic factors in women with breast cancer as a possible explanation for socioeconomic differences in survival. DESIGN--Retrospective analysis of data from cancer registry and from pathology and biochemistry records. SETTING--Catchment areas of two large teaching hospitals in Glasgow. SUBJECTS--1361 women aged under 75 who had breast cancer diagnosed between 1980 and 1987. MAIN OUTCOME MEASURES--Tumour size, axillary lymph node status, histological grade, and oestrogen receptor concentration in relation to deprivation category of area of residence. RESULTS--There was no significant relation between socioeconomic deprivation and four pathological prognostic factors: 93 (32%) women in the most affluent group presented with tumours less than 20 mm in size compared with 91 (31%) women in the most deprived group; 152 (48%) of the most affluent group presented with negative nodes compared with 129 (46%) of the most deprived group; 23 (22%) of the most affluent group presented with grade I tumours compared with 12 (17%) of the most deprived group; and 142 (51%) of the most affluent group had a low oestrogen receptor concentration at presentation compared with 148 (52%) of the most deprived group. None of these differences was statistically significant. CONCLUSIONS--Differences in survival from breast cancer by socioeconomic deprivation category could not be accounted for by differences in tumour stage or biology. Other possible explanations, such as differences in treatment or in host response, should be investigated.     

Variations in the treatment of early-stage breast cancer in Quebec between 1988 and 1994

BACKGROUND: The influence of organizational factors on the process and outcomes of the treatment of breast cancer has been extensively investigated. Although the quality of care is presumed to be better in larger centres, evidence is inconsistent. This study was conducted to determine whether therapies for patients with breast cancer varied according to hospital caseload. METHODS: Women newly diagnosed between 1988 and 1994 with early-stage node-negative primary breast cancer were randomly selected from the Quebec tumour registry and the Quebec hospital discharge database. Data were collected from medical charts, and only women having undergone dissection of the axilla were included in the analyses. Logistic regression analysis was used to adjust for case mix and organizational variables. RESULTS: The final sample included 1259 patients with node-negative stage I or II primary breast cancer. The proportion of women who underwent breast-conserving surgery increased significantly with hospital caseload (from 78.0% in hospitals admitting fewer than 25 new cases each year to 88.0% in those admitting 100 patients or more; p for trend < 0.001). This trend remained significant even after statistical adjustment for case mix and organizational factors (p for trend = 0.001). Of the 1039 women who underwent breast-conserving surgery 965 (92.9%) received radiotherapy. Use of systemic adjuvant therapy (tamoxifen or chemotherapy, or both) increased with the number of patients treated in a given centre (from 60.1% to 68.5%), but this trend disappeared after adjustment for case mix and other factors. The proportion of patients receiving systemic adjuvant therapy consistent with published consensus guidelines tended to increase with caseload for those treated in hospitals participating in multicentre clinical trials but decrease with caseload for patients in hospitals not involved in clinical research. INTERPRETATION: The care of patients in Quebec with early-stage breast cancer is characterized by a high prevalence of both breast-conserving surgery and systemic adjuvant therapy. Large centres, especially those actively involved in clinical research, rapidly adopt innovative therapeutic modalities.