Robot-assisted nipple-sparing mastectomy: systematic review.

BACKGROUND: The growing volume of studies of robot-assisted nipple-sparing mastectomy requires critical assessment. This review synthesizes the data on safety, feasibility, oncological and cosmetic outcomes, and patient-reported outcome measures (PROMs) for robot-assisted nipple-sparing mastectomy. METHODS: A systematic review was performed using MEDLINE, MEDLINE In-Process/ePubs, Embase/Embase Classic, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, LILACS, PubMed, ClinicalTrials.Gov, WHO ICTRP and the grey literature. Original studies reporting on patients with breast cancer or at increased risk of breast cancer undergoing robot-assisted nipple-sparing mastectomy were included. Risk of bias was assessed using the Institute of Health Economics Case Series Quality Appraisal Checklist. RESULTS: Of 7177 titles screened, eight articles were included, reporting on 249 robot-assisted nipple-sparing mastectomies in 187 women. The indication was either therapeutic (58·6 per cent) or prophylactic (41·4 per cent), with immediate reconstruction performed in 96·8 per cent. Surgical techniques followed a similar approach, with variations in incision, robot models, camera and insufflation. Postoperative morbidity included skin complications, lymphocele, infection, seroma, haematoma and skin ischaemia/necrosis. Complications specific to the nipple-areolar complex included ischaemia and necrosis. There were two conversions owing to haemorrhage, but no intraoperative deaths. Three patients had positive margins. Follow-up time ranged from 3·4 to 44·8 months. Locoregional recurrences were not observed. PROMs and objective cosmetic outcomes were reported inconsistently. Data on nipple sensitivity were not reported. CONCLUSION: Robot-assisted nipple-sparing mastectomy is feasible with acceptable short-term outcomes but it remains in the assessment phase.

ANTECEDENTES: El volumen creciente de estudios en los que se realiza una mastectomía con preservación de pezón asistida por robot requiere una evaluación crítica. Esta revisión sintetiza la seguridad, factibilidad y los resultados oncológicos, estéticos y percibidos por la paciente (patient-reported outcome measures, PROMs) tras la mastectomía con preservación del pezón asistida por robot. MÉTODOS: Se realizó una revisión sistemática utilizando Medline, Medline In-Process/ePubs, Embase/Embase Classic, el registro Cochrane Central de ensayos clínicos, la base de datos Cochrane de revisiones sistemáticas, LILACS, PubMed, ClinicalTrials.Gov, WHO ICTRP y la literatura gris (desde su inicio hasta el 3/5/2020). Se incluyeron los estudios originales en los que se realizaba una mastectomía con preservación de pezón asistida por robot en pacientes con cáncer de mama o con un aumento del riesgo de cáncer de mama. La posibilidad de sesgo se evaluó mediante la lista de verificación para la evaluación de la calidad de series de casos del Instituto de Economía de la Salud (Institute of Health Economics). RESULTADOS: De 7.177 artículos identificados, se seleccionaron 8 con 249 mastectomías con preservación de pezón asistidas por robot en 187 mujeres. La indicación fue terapéutica (58,6%) o profiláctica (41,4%) y la reconstrucción se realizó de forma inmediata en el 96,8% de los casos. La mediana de seguimiento más larga fue de 19 meses (rango 1,3-44 meses), y no se detectaron recidivas locorregionales. La técnica quirúrgica siguió un esquema similar, con diferencias en la incisión, modelo de robot, cámara e insuflación. Las complicaciones incluyeron complicaciones cutáneas, como necrosis, linfocele, infección de heridas, hematoma, seroma y necrosis del pezón. Hubo dos conversiones por hemorragia, pero ningún caso de mortalidad intraoperatoria. La presentación de datos respecto a los PROMs y los resultados cosméticos fue irregular. CONCLUSIÓN: La mastectomía con preservación de pezón asistida por robot es segura, factible y tiene resultados oncológicos aceptables a corto plazo. El procedimiento sigue siendo experimental y es preciso evaluar los resultados oncológicos a largo plazo y los PROMs en ensayos prospectivos comparativos y aleatorizados.

How do the characteristics of breast cancer diagnostic assessment programmes influence service delivery: A mixed methods study.

Diagnostic assessment programmes (DAPs) coordinate multidisciplinary teamwork (MDT), and improve wait times and patient satisfaction. No research has established optimal DAP design. This study explored how DAP characteristics influence service delivery. A mixed methods case study of four breast cancer DAPs was conducted including qualitative interviews with health-care providers and retrospective chart review. Data were integrated using multiple approaches. Twenty-three providers were interviewed; 411 medical records were reviewed. The number of visits and wait times from referral to diagnosis and consultation were lowest at a one-stop model. DAP characteristics (rural-remote region, human resources, referral volume, organisation of services, adherence to service delivery targets and one-stop model) may influence service delivery (number of visits, wait times). MDT, influenced by other DAP characteristics (co-location of staff, patient navigators, team functioning), may also influence service delivery. While the one-stop model may be ideal, all sites experienced similar and unique challenges. Further research is needed to understand how to optimise the organisation and delivery of DAP services. Measures reflecting individual, team and patient-reported outcomes should be used to assess the effectiveness and impact of DAPs in addition to more traditional measures such as wait times.

Cost analysis of breast cancer diagnostic assessment programs.

OBJECTIVES: Diagnostic assessment programs (daps) appear to improve the diagnosis of cancer, but evidence of their cost-effectiveness is lacking. Given that no earlier study used secondary financial data to estimate the cost of diagnostic tests in the province of Ontario, we explored how to use secondary financial data to retrieve the cost of key diagnostic test services in daps, and we tested the reliability of that cost-retrieving method with hospital-reported costs in preparation for future cost-effectiveness studies. METHODS: We powered our sample at an alpha of 0.05, a power of 80%, and a margin of error of ±5%, and randomly selected a sample of eligible patients referred to a dap for suspected breast cancer during 1 January-31 December 2012. Confirmatory diagnostic tests received by each patient were identified in medical records. Canadian Classification of Health Intervention procedure codes were used to search the secondary financial data Web portal at the Ontario Case Costing Initiative for an estimate of the direct, indirect, and total costs of each test. The hospital-reported cost of each test received was obtained from the host-hospital's finance department. Descriptive statistics were used to calculate the cost of individual or group confirmatory diagnostic tests, and the Wilcoxon signed-rank test or the paired t-test was used to compare the Ontario Case Costing Initiative and hospital-reported costs. RESULTS: For the 191 identified patients with suspected breast cancer, the estimated total cost of $72,195.50 was not significantly different from the hospital-reported total cost of $72,035.52 (p = 0.24). Costs differed significantly when multiple tests to confirm the diagnosis were completed during one patient visit and when confirmatory tests reported in hospital data and in medical records were discrepant. The additional estimated cost for non-salaried physicians delivering diagnostic services was $28,387.50. CONCLUSIONS: It was feasible to use secondary financial data to retrieve the cost of key diagnostic tests in a breast cancer dap and to compare the reliability of the costs obtained by that estimation method with hospital-reported costs. We identified the strengths and challenges of each approach. Lessons learned from this study have to be taken into consideration in future cost-effectiveness studies.

The surgical importance of an axillary arch in sentinel node biopsy.

PURPOSE: When Carl Langer described the aberrant axillary arch in 1846 its relevance in sentinel node biopsy (SNB) surgery could not have been contemplated. The authors define an incidence and elucidate relevance of the arch in SNB of the axilla. METHODS: A review of a database for breast and melanoma axillary SNB was carried out. The sample was 1 year at Princess Margaret Hospital, Toronto. RESULTS: Of 319 axillary SNB, 3 (0.9%) had axillary arches noted. Two were in the melanoma group (n = 59) and one in the breast (n = 260). Interestingly one arch case had an ipsilateral 'idiopathic' axillary vein thrombosis as a child. CONCLUSIONS: The authors see no reason to deviate from the practice of division of the arch at the highest level when recognised at SNB. This would abrogate the risk of concealed nodes and possible future neurovascular compression.

Factors associated with negative margins of lumpectomy specimen: potential use in selecting patients for intraoperative radiotherapy.

BACKGROUND: Lumpectomy followed by radiation is standard treatment for early breast cancer. Recently, the use of partial breast intraoperative radiation (IORT) has been developed, and patients selected for IORT should not have positive margins. This study's purpose was to identify factors predicting negative margins after lumpectomy. METHODS: Patient age, preoperative investigations, surgery, final pathology, and margin status were examined using a prospective database between 1999 and 2005. Univariate and multivariate logistic regression analysis were performed to identify patient and tumor factors predicting an increased rate of negative margins. The results were used to generate a patient selection algorithm. RESULTS: The rate of positive margins at first resection was 17% in 730 lumpectomies (708 patients). Multivariate analysis revealed that older age (P = .0006), smaller tumor size (P < .0025), type of surgery (OR = 3.4 for ultrasound vs mammogram-guided wire localization, P = .003), and having a core needle biopsy (CNB) with preoperative cancer diagnosis (P < .0001) were predictive for having a negative margin. Patients older than age 50 with a preoperative CNB showing invasive cancer less that 3 cm that can be localized under ultrasound had a negative margin rate of 98% (n = 178). These patients would be ideal for consideration of IORT. CONCLUSIONS: Negative margin rates after lumpectomy are predicted by age, tumor size, preoperative investigations, and localization technique. These variables can be used to select patients for IORT with a 2.2% chance of positive margins.

Lack of comparability between binding of monoclonal antibodies to melanoma cells in vitro and localization in vivo.

The affinity and specificity of monoclonal antibodies (MAbs) to tumor-associated antigens are often determined by in vitro assays. The specific binding of two anti-human melanoma antibodies (96.5 and ZME-018) and a control antibody (ZCE-025) to three human melanoma cell lines (DX3, A375-M, and Hs294t) was examined under in vitro conditions and compared to in vivo localization of 111In-labeled antibodies to the same cells growing as solid tumors in the subcutis of nude mice. The in vitro binding of the specific MAbs to the tumor cells did not predict in vivo localization. Under in vitro conditions, MAb ZME-018 bound to all three cell lines at levels exceeding that of 96.5, yet ZME-018 did not show superior localization to subcutaneous tumors. MAb 96.5 bound to cultured DX3 cells at levels exceeding those observed with A375-M cells. Yet, 96.5 localized better to A375-M xenografts in nude mice than to DX3 or Hs294t xenografts. Antigen expression differed between in vitro and in vivo growing cells, as evidenced by alteration in binding of 96.5 to tumor cells dissociated from solid subcutaneous tumors. Collectively, the data suggest that in vitro parameters do not predict the clinically relevant localization of MAbs to tumors.

Treatment patterns of elderly breast cancer patients at two Canadian cancer centres.

BACKGROUND: Treatment of breast cancer in elderly women is limited by declining functional status and life expectancy. The impact of providing less aggressive treatment remains controversial. This study assessed the treatment patterns of elderly breast cancer patients. METHODS: Retrospective chart review of women ≥70 y with breast cancer treated between 2004 and 2011 at two large Canadian cancer centres. Tumour and treatment characteristics were collected across three subgroups: 70-74 y (n = 314), 75-79 y (n = 233), and ≥80 y (n = 219). Comparisons were made using Chi-squared test, Fisher-Freeman-Halton exact test, or ANOVA. Disease free (DFS) and overall (OS) survival were estimated by Kaplan-Meier analysis and compared by log-rank test. RESULTS: Women ≥80 y had larger tumours that were better differentiated, hormone receptor-positive, HER2-negative, and lymph node (LN)-positive relative to younger women (p < 0.05). Women ≥80 y more frequently underwent mastectomy than breast conserving surgery and lacked LN staging (p < 0.05). Chemotherapy was provided in few patients, especially ≥80 y. Radiation therapy was provided less often in women ≥80 y despite indications. Hormone therapy was more frequently provided in women ≥80 y. Women ≥80 y had a significantly lower DFS (17.5 m) relative to women 70-74 y (31 m, p = 0.02) and 75-79 y (35 m, p = 0.006). Women ≥80 y had the lowest median OS (53 m) relative to 70-74 y (79 m, p = 0.001) and 75-79 y (75 m, p = 0.003) women. CONCLUSIONS: Women ≥80 y received less aggressive treatment than younger women and had less favourable DFS and OS. Until age-specific recommendations are available physicians must use clinical judgement and assess the tumour biology with the patient's comorbidties to make the best choice.

Breast adipose tissue concentrations of polychlorinated biphenyls and other organochlorines and breast cancer risk.

Numerous studies have examined the relationship between organochlorines and breast cancer, but the results are not consistent. In most studies, organochlorines were measured in serum, but levels in breast adipose tissue are higher and represent cumulative internal exposure at the target site for breast cancer. Therefore, a hospital-based case-control study was conducted in Ontario, Canada to evaluate the association between breast cancer risk and breast adipose tissue concentrations of several organochlorines. Women scheduled for excision biopsy of the breast were enrolled and completed a questionnaire. The biopsy tissue of 217 cases and 213 benign controls frequency matched by study site and age in 5-year groups was analyzed for 14 polychlorinated biphenyl (PCB) congeners, total PCBs, and 10 other organochlorines, including p,p'-1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene. Multiple logistic regression was used to assess the magnitude of risk. While adjusting for age, menopausal status, and other factors, odds ratios (ORs) were above 1.0 for almost all organochlorines except five pesticide residues. The ORs were above two in the highest concentration categories of PCB congeners 105 and 118, and the ORs for these PCBs increased linearly across categories (Ps for trend < or =0.01). Differences by menopausal status are noted especially for PCBs 105 and 118, with risks higher among premenopausal women, and for PCBs 170 and 180, with risks higher among postmenopausal women. Clear associations with breast cancer risk were demonstrated in this study for some PCBs measured in breast adipose tissue.

An improved statistical approach: can it clarify the role of new prognostic factors for breast cancer?

Recently, there has been a proliferation of new biomarkers, some of which may lead to an improved prognostic index or may influence treatment selection. However, there are methodological and statistical issues that require attention in assessing the role and use of these prognostic factors. Between 1977 and 1986, 1097 primary breast cancer patients were accrued for multidisciplinary research at the Henrietta Banting Breast Centre, Women's College Hospital; follow-up to 1990 is complete for 96% of the patients. Data for these patients are used here to illustrate strategies: (1) for the comparison of results from diverse assessments of biomarkers; (2) for the improved comparability of inter-laboratory results; (3) for the examination of the results from monoclonal or polyclonal antibody assays for possible clinically relevant bimodality; (4) for good statistical resolution of overlapping distributions; (5) that involve the use of quantitative values for prognostic factors whenever possible; and (6) for improved multivariate analyses. Good data handling and analyses may enable more accurate and rapid assessment of new prognostic factors, thereby expediting and improving their clinical application.

An investigation of cut-points for primary breast cancer oestrogen and progesterone receptor assays.

Oestrogen and progesterone receptor (ER and PgR) assay values are frequently used in medical decision-making for breast cancer patients. We have proposed statistical standardization of receptor assay values to improve inter-laboratory comparability, and now report the use of standardized log units (SLU) to investigate the effects of ER and PgR cut-points on time to first recurrence outside the breast (DFS). Between 1980 and 1986, there were 678 primary breast cancer patients treated at the Henrietta Banting Breast Centre (HBBC). The effects of ER and PgR cut-points were examined with multivariate analyses considering the variables: age, tumour size, nodal status, weight and adjuvant treatment. We considered receptor assay cut-points ranging from - 1.0 to + 1.0 SLU (ER between 7 and 166 fmol/mg protein; PgR between 7 and 181 fmol/mg protein). PgR was included in the multivariate prognostic models more often than ER, although patients had a better prognosis with both larger ER and PgR values. There was no best cut-point for ER or PgR, and there was strong evidence that ER and PgR should be considered as continuous rather than dichotomous (negative, positive) variables. Patient prognosis should also be more comparable with SLU.

Histopathological patterns of melanoma metastases in sentinel lymph nodes.

AIMS: Sentinel lymph node biopsy (SLNB) is an important component in the staging and treatment of cutaneous melanoma (CM). The medical literature provides only limited information regarding melanoma sentinel lymph node (SLN) histology. This report details the specific histological patterns of melanoma metastases in sentinel lymph nodes (SLNs) and highlights some key factors in evaluating SLNs for melanoma. METHODS: From 281 SLNB cases between June 1998 and May 2002, 79 consecutive cases of SLN biopsies positive for metastases from CM were retrospectively reviewed. The important characteristics of the SLNs and the metastatic foci are described. RESULTS: The median size of positive SLNs was 17 mm (range, 5-38). SLNs had a median of two metastatic foci (range, 1-11), with the largest foci being a median of 1.1 mm in size (range, 0.05-24). S-100 and HMB-45 staining was positive in 100% and 92% of the detected metastatic foci, respectively. The metastatic melanoma cells were epithelioid, spindled, and mixed in 86%, 5%, and 9% of cases. Metastatic foci were most often (86%) found in the subcapsular region of the SLN. Benign naevic cells were found coexisting in 14% of positive SLNs. CONCLUSIONS: Staining for S100 is more sensitive than HMB-45 (100% v 92%), but HMB-45 staining helped to distinguish benign naevic cells from melanoma. The subcapsular region was crucial in SLN evaluation, because it contained the metastases in 86% of cases. Evaluation of the subcapsular space should not be compromised by cautery artefacts or incomplete excision of the SLN.

Prospective phase I trial of conservative management of low rectal lesions.

The purpose of this study was to assess and function and to compare the morbidity of local excision and postoperative radiotherapy for rectal adenocarcinoma with the morbidity of abdominoperineal resection. A posterior parasacral approach was used for local excision. All patients had negative margins, and all but one were continent after completion of radiotherapy. Seven patients (29%) had either a wound infection or a fistula in the local excision group. No local failures occurred, although follow-up was only 13 months. Thirteen (50%) of the 26 patients who underwent an abdominoperineal resection developed at least one complication. Combined treatment that spares the rectal sphincters may be preferable in selected patients with low rectal cancer, if long-term disease-free survival is maintained.

The prognostic significance of lymph node metastases after preoperative chemotherapy for locally advanced breast cancer.

We compared the prognostic value of surgical lymph node staging after preoperative chemotherapy relative to other patient and tumor variables in 136 patients with locally advanced breast cancer (T3-4 and/or N2-3) who received preoperative chemotherapy followed by mastectomy and axillary dissection as part of a prospective protocol. Univariate analysis revealed that the number of metastatic lymph nodes, clinical tumor stage at presentation, clinical and pathologic response, and menopause status were significant variables associated with survival and disease-free survival, but clinical node stage at presentation and estrogen receptor status were not. The number of metastatic lymph nodes had more prognostic value than the other factors, and when evaluated by multivariate regression, surgical node staging added significantly more information to the remaining variables. Surgical staging is an important component of treatment for patients with breast cancer undergoing preoperative chemotherapy because it can provide an accurate and quantitative method for subgrouping patients with different survival rates and it can be used to compare results between preoperative chemotherapy trials.

Prostaglandin biosynthesis by gastric mucosa. II. Studies in man.

The concentration of prostaglandin E2 (PGE2) in gastric juice and the PGE2 biosynthetic capacity ( PGBC ) of mucosal biopsies were studied before and after a five-day course of acetylsalicylic acid (650 mg QID) in seven healthy subjects. Gastric juice PGE2 concentration varied between individuals, but mucosal PGBC was relatively constant. After the five-day course of acetylsalicylic acid both measurements were significantly lower. PGE2 concentration fell 49 +/- 8% and PGBC was reduced by at least 97%. The ready availability of these samples at endoscopy and the sensitivity and reproducibility of the measurements suggest that these techniques may be valuable in clinical studies of gastric function and disease.

Prostaglandin biosynthesis by gastric mucosa. I. Studies in rat.

A technique for determination of the prostaglandin E2 biosynthetic capacity ( PGBC ) of gastric mucosa is described. The effects of food deprivation and indomethacin pretreatment on PGBC were studied. Indomethacin (1 mg/kg i.p.) significantly reduced the PGBC of fundal and antral tissue. This effect was more marked in the fundal tissue. Food deprivation for up to 22 h had no effect on fundal PGBC . In the antrum, a 12-hour fast caused a significant reduction in PGBC while a 22-hour fast had no effect. These changes in PGBC may relate to the increase in susceptibility to gastric ulceration caused by fasting or indomethacin pretreatment. This technique may be applicable to clinical studies.

Breast cancer and organochlorines: a marker for susceptibility?

The incidence of breast cancer is increasing and despite extensive research efforts, the etiology of this disease is largely unknown. Most women exhibit no known risk factors except for their age and sex. It has recently been postulated that the increased breast cancer incidence might be attributed to exposure to environmental carcinogens such as the organochlorine compounds. In this article, the scientific literature with respect to this possibility is reviewed and alternative hypotheses, which may in part explain the possible role of organochlorine compounds in the etiology of breast cancer, are presented.

Alternative multivariate modelling for time to local recurrence for breast cancer patients receiving a lumpectomy alone.

Certain prognostic factors (patient and/or tumour characteristics) may be associated with low (or high) risk for local recurrence. Patients with these characteristics could be candidates for less (or more) adjuvant therapy or a less (or more) aggressive surgical approach. However, the assessment of many factors can be problematic with the standard multivariate technique-a Cox proportional hazards model and step-wise regression. We compared the results obtained when using a Cox model with those from four alternative models (exponential, Weibull, log logistic and log Normal) in step-wise and all subset regressions. Between 1977 and 1986, 293 primary invasive breast cancer patients were treated at the Henrietta Banting Breast Centre with a lumpectomy with or without an axillary dissection, and with no postoperative adjuvant therapy. The variables considered were age, lymph node status, tumour size, estrogen receptor (ER), progesterone receptor (PgR), histologic grade, nuclear grade, carcinoma in situ (CIS), amount of CIS, and presence of tumour emboli. With follow-up to 1991, nodal status was not found to be included in the step-wise Cox model, although it was in the step-wise exponential, Weibull and log Normal models, and in the best all subset models for all model types. The variables tumour emboli, ER, age, CIS and nodal status were consistently included in the best all subset regressions, regardless of model type. In the 1993 follow-up, the variables in the step-wise Cox model were tumour emboli, ER, age, CIS and nodal status. The multivariate consideration of all possible subsets of regression variables led to an earlier indication of the importance of nodal status, while the data strongly supported accelerated failure time models over the Cox model.

Outpatient percutaneous central venous access in cancer patients.

A 1-year experience of percutaneous subclavian catheterization in outpatients with cancer was reviewed to document reliability, safety, and cost. There were 763 catheter insertions attempted with prospective documentation of complications in 664 consecutive patients. Catheter insertion was successful in 722 attempts (95%). There were only 13 pneumothoraces (2%). Thirty catheters required repositioning (4%). The average catheter duration was 191 days (range: 0 to 892 days). Fifty-six catheters (8%) were removed because of suspected infection. Documented catheter sepsis occurred in 21 patients (3%); catheter site infection occurred in 8 patients (1%). Thus, only 0.22 infections per catheter year occurred during this 382 catheter-year experience. The estimated cost of catheter insertion was $562, which is one-third the estimated cost for tunneled catheters ($1,403) and for reservoir devices ($1,738). In our experience, percutaneous subclavian catheterization is a reliable, cost-effective method compared with tunneled or reservoir devices, with an equivalent incidence of catheter-related infections. The cornerstone of our success with this program is a staff dedicated to catheter care and intensive patient education. In centers where a large number of patients require central venous access, percutaneous catheterization should be the technique of choice.

Health care strategies to promote earlier presentation of symptomatic breast cancer: perspectives of women and family physicians.

BACKGROUND: Many women with symptoms suggestive of a breast cancer diagnosis delay presentation to their family physician. Although factors associated with delay have been well described, there is a paucity of data on strategies to mitigate delay. OBJECTIVES: We conducted a qualitative research project to examine factors related to delay and to identify health care system changes that might encourage earlier presentation. METHODS: Individual semi-structured interviews were conducted with women who sought care 12 weeks or more after self-detection of breast cancer symptoms and with family physicians whose practices included patients meeting that criterion. RESULTS: The women and physicians both suggested a need for clearer screening mammography guidelines for women 40-49 years of age and for better messaging concerning breast awareness. The use of additional hopeful testimonials from breast cancer survivors were suggested to help dispel the notion of cancer as a "death sentence." Educational initiatives were proposed, aimed at both increasing awareness of "non-lump" breast cancer symptoms and advising women that a previous benign diagnosis does not ensure that future symptoms are not cancer. Women wanted empathic nonjudgmental access to care. Improved methods to track compliance with screening mammography and with periodic health exams and access to a rapid diagnostic process were suggested. CONCLUSIONS: A list of "at-risk situations for delay" in diagnosis of breast cancer was developed for physicians to assist in identifying women who might delay. Health care system changes actionable both at the health policy level and in the family physician's office were identified to encourage earlier presentation of women with symptomatic breast cancer.