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.

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.

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.

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.

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.

Outcomes after localized axillary node recurrence in breast cancer.

BACKGROUND: Localized axillary recurrence (LAR) is an uncommon event. It is estimated to occur in 0.5% to 3% of patients when adequate axillary surgery has been performed. Although relatively sparse data exist on the outcome of patients with LAR, in the era of sentinel node biopsy (SNB) these data may have increased relevance. This study assesses the survival outcomes in these patients. METHODS: A retrospective chart review was completed. Patient age, tumor size, pathology, receptor status, and treatment of the primary breast carcinoma were reviewed. Axillary recurrence, treatment, and overall survival data were collected. RESULTS: Fifteen patients were identified with LAR that developed at a median of 77 months after their initial dissection. At the time of treatment for their LAR, all patients had completion axillary clearance and six also had a concurrent completion mastectomy. Further adjuvant treatment was individualized. Five patients (33%) have died, including all patients (3) who developed a LAR within 2 years of their initial breast cancer presentation. Ten-year overall survival is 56%. CONCLUSION: Our experience suggests early (<24 months) LAR is indicative of a poor prognosis. With multimodal treatment, ten-year overall survival is 56%.

Organochlorines and breast cancer risk by receptor status, tumor size, and grade (Canada).

OBJECTIVE: We evaluated the association between organochlorines and breast cancer subtype defined by the tumor characteristics: estrogen receptor status, progesterone receptor status, tumor size, and grade. METHODS: A case-control study was conducted from 1995 to 1997 in Kingston and Toronto, Canada. Breast adipose tissue, taken from 217 cases and 213 biopsy controls frequency-matched on age, was analysed for 14 polychlorinated biphenyl (PCB) congeners and 10 pesticides. RESULTS: Adjusting for age, geometric means of several organochlorines differed by estrogen receptor status and tumor grade (p < 0.05). Odds ratios (ORs) for each organochlorine relative to the common control group for breast cancers of differing subtype were compared using polytomous logistic regression. Although the ORs did not differ significantly by subtype, the ORs of PCBs and p, p'-1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE) were higher with risk of estrogen receptor-negative breast cancer than estrogen receptor-positive breast cancer. One of the most extreme differences was with DDE, where the OR for the association with risk of estrogen receptor-negative breast cancer was 2.4 (95% confidence interval (CI) 1.0-5.4) in the uppermost tertile relative to the lowest, whereas the corresponding OR for risk of estrogen receptor-positive breast cancer was 1.1 (95% CI 0.6-1.9). PCBs also tended to be more strongly positively associated with risk of larger and higher-grade tumors. CONCLUSIONS: The association between organochlorines and breast cancer risk did not significantly differ by subtype, but many PCBs were more strongly associated with tumors of poor prognosis.

The rate of breast-conserving surgery for early breast cancer is not influenced by the surgical strategy of excisional biopsy followed by the definitive procedure.

Increased emphasis on breast conservation and the primacy of the patient's preferences has led to the promotion and increased use of a two-step surgical strategy (definitive operation only after a final tissue diagnosis from a biopsy done on a previous visit) in the treatment of early breast cancer, with the assumption being that this is more conducive to the performance of breast-conserving surgery (BCS). We sought to test this by examining the effect of the surgical strategy (one-step versus two-step) on the operation performed (BCS versus mastectomy). A random sample of women with node-negative breast cancer diagnosed in 1991 in Ontario was drawn from the Ontario Cancer Registry database and matched to the Canadian Institute of Health Information and Ontario Health Insurance Plan databases (n = 643). This provided information on the timing and nature of all surgical procedures performed as well as patient, tumor, hospital, and surgeon characteristics. The surgical strategy was defined as either a one-step procedure (biopsy and definitive surgery performed at the same time) or a two-step procedure (surgical biopsy and pathologic diagnosis, followed by definitive surgery at a later date). The axillary lymph node dissection was used to define the definitive procedure. BCS was employed in 68% of patients, and this did not differ significantly between the one-step and two-step groups (66% versus 70%). Patients with palpable lesions had a significantly lower rate of breast conservation than those with nonpalpable lesions. Other variables associated with a lower rate of BCS were larger tumor size, presence of extensive ductal carcinoma in situ (DCIS), and central or multifocal tumors. The use of a one-step procedure was associated with a patient age of more than 50 years, a palpable mass, tumor size larger than 1 cm, previous fine needle aspiration (FNA) biopsy, absence of extensive DCIS, and surgery in an academic setting. Breast conservation was not affected by the surgical strategy used or the timing of the decision, but was associated with several accepted tumor factors. This study shows that, contrary to the opinion of some, there is a group of breast cancer patients in whom treatment in a one-step manner is appropriate.

Sentinel lymph-node biopsy after previous wide local excision for melanoma.

OBJECTIVE: To document experience with sentinel lymph-node biopsy in patients who have already undergone a wide local excision for melanoma because in many centres previous wide excision has been a contraindication for sentinel lymph-node biopsy. DESIGN: A prospective cohort study. SETTING: A tertiary care academic cancer centre. PATIENTS: One hundred patients who presented with cutaneous melanoma (depth >1 mm or Clark level IV) after having undergone wide local excision of the primary lesion that was not situated in the head or neck. The follow-up was 3 years. INTERVENTIONS: Sentinel lymph-node biopsy. Patients with truncal melanoma had preoperative lymphoscintigraphy to document the nodal basins at risk. Technetium-99m sulfur colloid (0.5-1 mCi in 0.5 mL) was injected intradermally around the scar, and the sentinel lymph node was excised with the aid of a hand-held gamma detector. OUTCOME MEASURES: Accuracy of the biopsy and false-negative rates in this setting. RESULTS: Of the 100 patients, 44 had truncal and 56 had extremity lesions. The average tumour depth was 3.47 mm and 3.07 mm respectively. Thirty-one patients had a sentinel lymph node positive for melanoma metastasis. Biopsies were positive for melanoma in 18 (41%) truncal lesions and 13 (23%) extremity lesions. There were 3 (9%) false-negative sentinel lymph-node biopsies as diagnosed by clinically evident nodal disease subsequently appearing in the nodal basin subjected to biopsy. Two occurred in patients after large rotation flap closures of truncal lesions. The third patient had a subungual melanoma of the great toe. No disease was found in the 2 nodes dissected. Two of the 3 false-negative biopsy results were obtained before serial sections and immunohistochemical staining were used to examine the sentinel lymph nodes. CONCLUSIONS: Sentinel lymph-node biopsies can successfully identify clinically occult nodal metastases in patients who have had previous wide local excision of a melanoma, but the false-negative rate in patients with rotation flap closures should be taken into consideration.

In situ duct carcinoma of the breast: clinical and histopathologic factors and association with recurrent carcinoma.

There has been a recent increase in the diagnosis of in situ duct carcinoma of the breast (DCIS) as a result of mammographic screening. DCIS is heterogeneous in appearance and likely in prognosis. There is no generally accepted model to predict progression to invasive carcinoma. We investigated the prognostic effect of clinical presentation and pathologic factors for women diagnosed with primary DCIS. A cohort of 124 patients was accrued between 1979 and 1994 and was followed to 1997; 78 had DCIS detected mammographically, and 88 underwent lumpectomy alone. In this article, we provide details about characteristics affecting the choice of primary therapeutic modality, and we examine the effects of factors on progression for the two patient subgroups. Presentation with bloody nipple discharge was associated with a significant increase in DCIS recurrence (p=0.07). The pattern of duct distribution was important: DCIS in which the involved ducts were more widely separated had a significantly greater recurrence of DCIS than when the involved ducts were more concentrated (p=0.08 for mammographically detected DCIS, p=0.07 for patients who underwent lumpectomy alone). For mammographically detected DCIS, younger patients had more DCIS recurrence (p=0.07). We found considerable heterogeneity in nuclear grade; 50% of patients exhibited more than one grade. Nuclear grade, necrosis, and architecture were not significantly associated with either recurrence of DCIS or development of invasive carcinoma. Longer follow-up will allow further evaluation of the prognostic relevance of the factors assessed.

Factors associated with local breast cancer recurrence after lumpectomy alone: postmenopausal patients.

BACKGROUND: We have been following a cohort of patients who underwent a lumpectomy without receiving adjuvant radiotherapy or adjuvant systemic therapy. We now report the experience of a postmenopausal subgroup. METHODS: The postmenopausal subgroup included 244 patients accrued between 1977 and 1986 and followed up. The end point was ipsilateral local breast cancer recurrence. The factors studied were the patient's age in years; tumor size (in mm); nodal status (N-, Nx, N+); estrogen and progesterone receptor status (< 10, - 10 fmol/mg protein); presence or absence of lymphovascular/perineural invasion; presence or absence, and type, of DCIS (none, non-comedo, comedo); percentage of DCIS; histological grade (1,2,3); and nuclear grade (1,2,3). Univariate analyses consisted of Kaplan-Meier plots and the Wilcoxon (Peto-Prentice) test statistic; the multivariate analyses were step-wise Cox and log-normal regressions. RESULTS: The median follow-up of those patients still alive was 9.1 years, and the overall relapse rate was 24% (59/244). The univariate results indicated that the characteristics of smaller tumor size, negative nodes, positive ER status, and no lymphovascular or perineural invasion were associated with significantly (P <.05) lower relapse. From the multivariate analyses, the factors lymphovascular or perineural invasion, age, and amount of DCIS were all significantly associated with local relapse with both Cox and log-normal regressions. Additionally, there was weak evidence of an association between ER (P = .08 in the Cox regression and in the log-normal) and nodal status (P = .09 in the log-normal regression) with local relapse. We also are able to define a low-risk subgroup (N-, age -65, no comedo, ER positive, no emboli) with a crude 10-year local recurrence rate of 9%. CONCLUSION: With longer follow-up, and for postmenopausal patients, there continues to be support for the theory that local relapse is affected by the factors lymphovascular or perineural invasion, age, amount of DCIS, ER, and nodal status. A low risk subgroup has been identified.

Factors affecting distant disease-free survival for primary invasive breast cancer: use of a log-normal survival model.

BACKGROUND: Invasive breast cancer is a frequently diagnosed disease that now comes with an ever expanding array of therapeutic management options. We assessed the effects of 20 prognostic factors in a multivariate context. METHODS: We accrued clinical data for 156 consecutive patients with stage 1-3 primary invasive breast cancer who were diagnosed in 1989-1990 at the Henrietta Banting Breast Center, and followed to 1995. There is complete follow-up for 91% of patients (median follow-up of 4.9 years). The event of interest was distant recurrence (for distant disease-free survival, DFS). We used Cox and log-normal step-wise regression to assess the multivariate effects of the following factors on DFS: age, tumor size, nodal status, histology, tumor and nuclear grade, lymphovascular and perineural invasion (LVPI), ductal carcinoma-in-situ (DCIS) type, DCIS extent, DCIS at edge of tumor, ER and PgR, ERICA, adjuvant systemic therapy, ki67, S-phase, DNA index, neu oncogene, and pRb. RESULTS: There was strong evidence against the Cox assumption of proportional hazards for nodal status, and nodal status was not in the Cox step-wise model. With step-wise log-normal regression, a large tumor size (P < .001), positive nodes (P = .002), high nuclear grade (P = .01), presence of LVPI (P = .03), and infiltrating duct carcinoma not otherwise specified (P = .05) were associated with a reduction in DFS. CONCLUSIONS: For nodal status, there was strong evidence against the Cox assumption of proportional hazards, and it was not included in the Cox model although it was in the log-normal model. Only traditional factors were included in the step-wise models. Thus, this statistical management of prognostic markers in breast cancer appears to be very important.

RT-PCR amplification of CK19 mRNA in the blood of breast cancer patients: correlation with established prognostic parameters.

We optimized the assay for detection of cytokeratin 19 (CK19) mRNA by the reverse transcriptase-polymerase chain reaction (RT-PCR) in blood as an index of circulating tumor cells in breast cancer patients. The limit of detection of < 1 MCF7 tumor cells per 10(6) peripheral blood leukocytes (PBL) was achieved in mixing experiments. We did not detect CK19 mRNA in control bloods (0/30) or in the blood of patients with benign breast disease (0/15). In blood samples from 109 patients with invasive breast cancer, CK19 mRNA was detected in 7/23 patients with node-negative disease, in 21/58 with node-positive disease, and in 20/28 with distant metastases. There was a significant association (P < 0.01) of CK19 positivity with distant metastatic versus both node-negative and node-positive disease, but not with any other histopathological parameter examined. In a small number of patients with distant metastases, increased intensity of the CK19 RT-PCR signal was associated with a reduced survival.

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.

Hereditary breast cancer. Risk assessment of patients with a family history of breast cancer.

OBJECTIVES: To assist family physicians in stratifying women with a family history of breast cancer as being at low, moderate, or high risk of hereditary breast cancer (HBC). To present guidelines for managing each of these risk groups. QUALITY OF EVIDENCE: A MEDLINE search was conducted from January 1976 to December 1997 using key words related to breast cancer risk factors, risk assessment, prevention, and screening. Risk stratification criteria were derived empirically and assessed using retrospective chart review. MAIN FINDINGS: Although up to 20% of women in the general population have a family history of breast cancer, less than 5% are at high risk for HBC. Certain features in a family history suggest increased risk. Women with none of these features are at low risk for HBC and should have annual clinical breast examinations and mammography at least every 2 years starting at age 50. Women with one or more features of increased risk who do not meet criteria for referral to a familial cancer clinic are at moderate risk for HBC and should begin annual mammography and clinical breast examination at age 40. Women who meet referral criteria are at high risk for HBC and should be counseled regarding referral to a familial cancer clinic for more detailed risk assessment and consideration for genetic testing. All women should be taught proper breast self-examination technique and encouraged but not pressured to practise it monthly for life. CONCLUSION: A simple algorithm can assist physicians in stratifying women into low, moderate, and high HBC risk groups. Management strategies for each group are given in this article and the two following (Heisey et al page 114 and Carroll et al page 126).