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.

Primary excision margins, sentinel lymph node biopsy, and completion lymph node dissection in cutaneous melanoma: a clinical practice guideline.

Background: For patients who are diagnosed with early-stage cutaneous melanoma, the principal therapy is wide surgical excision of the primary tumour and assessment of lymph nodes. The purpose of the present guideline was to update the 2010 Cancer Care Ontario guideline on wide local excision margins and sentinel lymph node biopsy (slnb), including treatment of the positive sentinel node, for melanomas of the trunk, extremities, and head and neck. Methods: Using Ovid, the medline and embase electronic databases were systematically searched for systematic reviews and primary literature evaluating narrow compared with wide excision margins and the use of slnb for melanoma of the truck and extremities and of the head and neck. Search timelines ran from 2010 through week 25 of 2017. Results: Four systematic reviews were chosen for inclusion in the evidence base. Where systematic reviews were available, the search of the primary literature was conducted starting from the end date of the search in the reviews. Where systematic reviews were absent, the search for primary literature ran from 2010 forward. Of 1213 primary studies identified, 8 met the inclusion criteria. Two randomized controlled trials were used to inform the recommendation on completion lymph node dissection.Key updated recommendations include:■ Wide local excision margins should be 2 cm for melanomas of the trunk, extremities, and head and neck that exceed 2 mm in depth.■ slnb should be offered to patients with melanomas of the trunk, extremities, and head and neck that exceed 0.8 mm in depth.■ Patients with sentinel node metastasis should be considered for nodal observation with ultrasonography rather than for completion lymph node dissection. Conclusions: Recommendations for primary excision margins, sentinel lymph node biopsy, and completion lymph node dissection in patients with cutaneous melanoma have been updated based on the current literature.

Personalizing post-treatment cancer care: a cross-sectional survey of the needs and preferences of well survivors of breast cancer.

Background: Improved treatments resulting in a rising number of survivors of breast cancer (bca) calls for optimization of current specialist-based follow-up care. In the present study, we evaluated well survivors of bca with respect to their supportive care needs and attitudes toward follow-up with various care providers, in varying settings, or mediated by technology (for example, videoconference or e-mail). Methods: A cross-sectional paper survey of well survivors of early-stage pT1-2N0 bca undergoing posttreatment follow-up was completed. Descriptive and univariable logistic regression analyses were performed to examine associations between survivor characteristics, supportive care needs, and perceived satisfaction with follow-up options. Qualitative responses were analyzed using conventional content analysis. Results: The 190 well survivors of bca who participated (79% response rate) had an average age of 63 ± 10 years. Median time since first follow-up was 21 months. Most had high perceived satisfaction with in-person specialist care (96%, 177 of 185). The second most accepted model was shared care involving specialist and primary care provider follow-up (54%, 102 of 190). Other models received less than 50% perceived satisfaction. Factors associated with higher perceived satisfaction with non-specialist care or virtual follow-up by a specialist included less formal education (p < 0.01) and more met supportive care needs (p < 0.05). Concerns with virtual follow-up included the perceived impersonal nature of virtual care, potential for inadequate care, and confidentiality. Conclusions: Well survivors of bca want specialists involved in their follow-up care. Compared with virtual follow-up, in-person follow-up is perceived as more reassuring. Certain survivor characteristics (for example, met supportive care needs) might signal survivor readiness for virtual or non-specialist follow-up. Future work should examine multi-stakeholder perspectives about barriers to and facilitators of shared multimodal follow-up care.

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.

Outcomes in Patients Treated with Post-mastectomy Chest Wall Radiotherapy without the Routine Use of Bolus.

AIMS: The use of bolus in post-mastectomy radiotherapy (PMRT) varies significantly between institutions. We report on chest wall recurrence and acute toxicity rates for PMRT patients treated with selective use of bolus. MATERIALS AND METHODS: We analysed PMRT patients who received adjuvant chest wall radiotherapy for invasive breast cancer between 2004 and 2009. Patient, tumour and cancer outcomes were collected from a prospective database, with additional radiotherapy and acute toxicity details supplemented retrospectively. Chest wall bolus was reserved for patients considered at high risk of local recurrence. RESULTS: There were 314 patients suitable for analysis: 52 received bolus, 262 did not. The mean age was 53.2 years. The median follow-up was 4.2 years. The most common T stage was T2 (37%), followed by T3/T4 (33%). There were 229 patients (73%) who had N+ disease; 213 (68%) patients had grade 3 cancer. Oestrogen receptor was positive in 176 (56%) cases, progesterone receptor was positive in 134 (43%) and HER2 receptor was positive in 24 (8%). Lymphovascular space invasion was present in 146 patients (46%), dermal invasion in 30 patients (10%) and positive margin in 14 patients (4%). The 4 year chest wall recurrence rate was 14% (95% confidence interval 5.4-26.8%) in the bolus group and only 3.5% (95% confidence interval 1.6-6.4%) in the non-bolus group. On univariate analysis, use of bolus was associated with a significant difference in chest wall recurrence (hazard ratio 3.09; 1.15-8.33; P = 0.025). However, when taking into account margin status, this significance was lost (hazard ratio = 2.45; 95% confidence interval 0.80-7.50, P = 0.12). There was a higher rate of acute grade 2 skin toxicity in patients receiving bolus compared with those without, 40% versus 21% (P = 0.01). CONCLUSIONS: The selective use of bolus resulted in a small risk of chest wall recurrence rates for low-risk patients. This suggests that the routine use of bolus in PMRT patients may be unnecessary.

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.

Systematic review of the prevalence, risk factors, diagnosis and management of meniscal injury in dogs: Part 2.

OBJECTIVE: To systematically evaluate the evidence reporting the diagnosis and management of meniscal injury in dogs with cranial cruciate ligament failure. STUDY DESIGN: Systematic literature review. MATERIALS AND METHODS: Research questions relating to the accuracy of diagnostic techniques for meniscal injury and the effects of meniscal treatment were defined. An electronic database search of PubMed and CAB Abstracts was performed during March 2015. Data were extracted for study participants, design, intervention, outcome measures and results. Studies were evaluated using a validated instrument for assessing methodological quality and assigned a Quality Index score. A level of evidence was then assigned to each study. RESULTS: Eighty-nine studies were identified. The median Quality Index score was 14 out of a possible 26. Twenty-seven studies were prospective case series, 31 retrospective case series, 16 animal research and 15 cadaveric studies. There were no class I or class II studies, 27 class III and 62 class IV studies. CONCLUSIONS: Despite a large number of publications the quality of evidence was generally low. No one study or combination of studies provided high quality evidence to support one diagnostic or surgical intervention over another for meniscal injuries in dogs with cranial cruciate ligament failure.

Systematic review of the prevalence, risk factors, diagnosis and management of meniscal injury in dogs: Part 1. [corrected].

OBJECTIVE: To systematically evaluate the evidence reporting the frequency and risk factors of meniscal injury in dogs with cranial cruciate ligament failure. STUDY DESIGN: Systematic literature review. MATERIALS AND METHODS: Research questions were defined. An electronic database search of PubMed and CAB Abstracts was performed during November 2013. Data were extracted for study participants, design, intervention, outcome measures and results. Studies were evaluated using a validated instrument for assessing methodological quality and assigned a quality index score. A level of evidence was then assigned to each study. RESULTS: Sixty-two studies were identified. The median quality index score was 14 out of a possible 26. Twenty-four studies were prospective case series, 37 retrospective case series and 1 animal research study. There were no class I or class II studies, 24 class III studies and 38 class IV studies. CLINICAL SIGNIFICANCE: Despite a large number of publications the quality of evidence was generally low. No one study or combination of studies provided high quality evidence to establish the true frequency or risk factors for meniscal injury in dogs with cranial cruciate ligament failure.

Adjuvant treatment and onset of menopause predict weight gain after breast cancer diagnosis.

PURPOSE: Weight gain is common during the first year after breast cancer diagnosis. In this study, we examined clinical factors associated with body size at diagnosis and weight gain during the subsequent year. PATIENTS AND METHODS: An inception cohort of 535 women with newly diagnosed locoregional breast cancer underwent anthropometric measurements at baseline and 1 year. Information was collected on tumor- and treatment-related variables, as well as diet and physical activity. RESULTS: Mean age was 50.3 years; 57% of women were premenopausal. Mean baseline body mass index (weight [kg] divided by height [m] squared) was 25.5 kg/m2. Overall, 84.1% of the patients gained weight. Mean weight gain was 1.6 kg (95% confidence interval, 1.2 to 1.9 kg), 2.5 kg (95% confidence interval, 1.8 to 3.2 kg) in those receiving chemotherapy, 1.3 kg (95% confidence interval, 0.7 to 1.8 kg) in those receiving tamoxifen only, and 0.6 kg (95% confidence interval, 0.01 to 1.3 kg) in those receiving no adjuvant treatment. Menopausal status at diagnosis (P = .02), change in menopausal status over the subsequent year (P = .002), axillary nodal status (P = .009), and adjuvant treatment (P = .0002) predicted weight gain in univariate analysis. In multivariate analysis, onset of menopause and administration of chemotherapy were independent predictors of weight gain (all P < or = .05). Caloric intake decreased (P < .01) and physical activity increased (P < .05) during the year after diagnosis; these factors did not explain the observed weight gain. CONCLUSION: Weight gain is common after breast cancer diagnosis; use of adjuvant chemotherapy and onset of menopause are the strongest clinical predictors of this weight gain.

Mastectomy or lumpectomy? Helping women make informed choices.

PURPOSE: To develop an instrument to help clinicians inform their patients about surgical treatment options for the treatment of breast cancer and to evaluate the impact of the instrument on the clinical encounter. METHODS: We developed an instrument, called the Decision Board, to present information regarding the benefits and risks of breast-conserving therapy (lumpectomy plus radiation therapy) and mastectomy to women with early-stage breast cancer to enable them to express a preference for the type of surgery. Seven surgeons from different communities in Ontario administered the instrument to women with newly diagnosed clinical stage I or II breast cancer over an 18-month period. Patients and surgeons were interviewed regarding acceptability of the instrument. The rates of breast-conserving surgery performed by surgeons before and after the introduction of the instrument were compared. RESULTS: The Decision Board was administered to 175 patients; 98% reported that the Decision Board was easy to understand, and 81% indicated that it helped them make a decision. The average score on a true/false test of comprehension was 11.8 of 14 (84%) (range, 6 to 14). Surgeons found the Decision Board to be helpful in presenting information to patients in 91% of consultations. The rate of breast-conserving surgery decreased when the Decision Board was introduced (88% v 73%, P =.001) CONCLUSION: The Decision Board is a simple method to improve communication and facilitate shared decision making. It was well accepted by patients and surgeons and easily applied in the community.

neu/erbB-2 amplification identifies a poor-prognosis group of women with node-negative breast cancer. Toronto Breast Cancer Study Group.

PURPOSE: It remains a challenge to predict which women with axillary node-negative (ANN) breast cancer at greatest risk of relapse may benefit most from adjuvant therapy. Increases in neu/erbB-2 have been implicated in breast cancer prognosis. Although overexpression has been investigated extensively, this study represents the first prospective assessment of the prognostic value of neu/erbB-2 DNA amplification in a cohort of women with newly diagnosed ANN. METHODS: A consecutive series of women was monitored for recurrence (median follow-up duration, 36 months) and tumors from 580 individuals were analyzed for amplification. The association of amplification with risk of recurrence was examined in survival analyses with traditional and histologic markers as prognostic factors. RESULTS: Neu/erbB-2 was amplified in 20% of cases. We found an increased risk of disease recurrence when neu/erbB-2 was amplified > or = twofold that persisted with adjustment for other prognostic factors (relative risk, 2.36; P = .002). We found some evidence that amplification was more important in patients who received chemotherapy compared with untreated patients. CONCLUSION: neu/erbB-2 amplification is an independent prognostic factor for risk of recurrence in ANN breast cancer. Women with tumors without neu/erbB-2 amplification have a good prognosis; aggressive therapy in this group is therefore difficult to justify. On the other hand, even with adjuvant chemotherapeutic treatment, women whose tumors exhibit neu/erbB-2 amplification have an increased risk of recurrence. We encourage a randomized trial to compare more aggressive adjuvant chemotherapy versus standard chemotherapy for ANN women whose tumors exhibit neu/erbB-2 amplification.

Mechanical comparison of monofilament nylon leader and orthopaedic wire for median sternotomy closure.

OBJECTIVES: To compare the mechanical properties of monofilament nylon leader and orthopaedic wire for median sternotomy closure in the dog. MATERIALS AND METHODS: Median sternotomy was performed in 14 canine cadaver sternums with the manubrium intact. The sternotomy was closed with either 80 lb monofilament nylon leader or 20G orthopaedic stainless steel wire in a peristernal figure of 8 pattern. Constructs were loaded in a servohydraulic material testing machine. Load at yield, maximum load, stiffness, displacement and mode of failure were compared between constructs subjected to a single cycle load to failure. RESULTS: No significant differences were found in load at yield, maximum load, stiffness or displacement between the monofilament nylon leader and the stainless steel wire constructs. No implant failure was evident in the stainless steel wire constructs. Four of the monofilament nylon leader constructs failed by pulling of the nylon through the crimp. CLINICAL SIGNIFICANCE: Monofilament nylon leader is mechanically comparable to stainless steel wire and potentially a suitable alternative for closure of median sternotomy in the dog.

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.