PubMed Health⌕ Search

Biomedical subjects

D R McCready

Publications and source records attributed to D R McCready.

At least 19 recordsLinked to original sources
PubMed2004

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.

Antigens, Neoplasm↗
PubMed2003

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%.

Adult↗
PubMed2001

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.

Adipose Tissue↗
PubMed2001

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.

Contraindications↗
PubMed2000

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.

Breast Neoplasms↗
PubMed2000

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.

Adult↗
PubMed2000

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.

Biomarkers, Tumor↗
PubMed2000

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.

Adipose Tissue↗
PubMed1999

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).

Adult↗
PubMed1999

Hereditary breast cancer. Identifying and managing BRCA1 and BRCA2 carriers.

OBJECTIVES: To present a strategy for identifying candidates for consideration of BRCA1 and BRCA2 mutation testing. To discuss the implications of identifying patients as BRCA1 or BRCA2 mutation carriers, and to provide recommendations for managing them. QUALITY OF EVIDENCE: A MEDLINE search from January 1990 to May 1998 was performed using the terms genetic breast screening, BRCA1, and BRCA2. The bibliographies of articles found were searched for further relevant titles. There are no published, randomized controlled clinical trials of management strategies for known BRCA carriers. Many recommendations for management are based on expert opinion only. MAIN FINDINGS: About 5% of women with breast cancer are carriers of genetic mutations. An accurate and detailed family history is the most important tool for identifying potential BRCA1 and BRCA2 mutation carriers. Women identified as carriers have a substantially increased risk of breast and ovarian cancer. Male carriers have a moderately increased risk of prostate cancer. Management strategies for carriers are not well studied but include increased surveillance, preventive surgery, chemoprevention, and lifestyle modification. CONCLUSION: Family physicians must be able to identify people at risk, to discuss management strategies, and when appropriate, to offer referral for consideration of genetic testing. There is an urgent need for research to determine the effectiveness of surveillance strategies, preventive surgery, chemoprevention, and lifestyle modification for BRCA1 and BRCA2 mutation carriers.

Adult↗
PubMed1999

Hereditary breast cancer. Psychosocial issues and family physicians' role.

OBJECTIVES: To outline the psychosocial issues in hereditary breast cancer (HBC) assessment and discuss the role of family physicians. QUALITY OF EVIDENCE: A literature search using MEDLINE, CINAHL, CancerLit, and HealthStar databases was conducted from January 1990 to April 1998, using the key words breast cancer or neoplasm and familial or hereditary, genetic testing or screening, primary care or family physician or counseling, genetic counseling, psychosocial or psychological. We found only a few studies focusing on a small number of well-studied "research families." MAIN FINDINGS: Women with a family history of breast cancer were likely to be highly interested in genetic testing for cancer risk. The benefit of testing for those with negative results is reassurance. Those found to be carriers of genetic mutations might benefit from increased surveillance and prophylactic therapy. Risks of testing include anxiety, depression, guilt, altered self-image, and insurance and employment discrimination. A family physician's role is to assess risk, to provide information and support so women can make informed choices about referral to familial cancer clinics, to offer cancer surveillance, and to provide support once genetic test results are available. CONCLUSION: Genetic testing is rapidly moving from research to clinical applications. Family physicians play an integral role in educating and managing women at risk for HBC. Physicians must prepare themselves with knowledge and counseling skills to meet the challenges of this new technology.

Adult↗
PubMed1998

Assessment of treatment for patients with primary ductal carcinoma in situ in the breast.

BACKGROUND: Current mammographic technology has resulted in increased detection of ductal carcinoma in situ (DCIS). It is necessary to assess which patients presenting with DCIS are good candidates for breast conservation and which of these patients should receive adjuvant radiation. METHODS: We accrued clinical data for 124 patients with a primary diagnosis of DCIS from 1979 through 1994. Primary therapy was a mastectomy for 18 patients, and a lumpectomy for 106 patients. Only 18 of the latter group of patients received adjuvant radiotherapy. For the 88 lumpectomy-alone patients (median follow-up, 5.2 years), we evaluated the effects of clinical (age and initial presentation) and pathologic (nuclear grade, architecture, parenchymal involvement, calcifications, and measured margins) factors on recurrence of DCIS or the development of invasive breast cancer. RESULTS: Patients who underwent lumpectomy with or without adjuvant radiotherapy (median follow-up, 5.0 years) were significantly more likely to have recurrence of DCIS (P=.05) than those who underwent mastectomy (median follow-up, 6.7 years): 18% (19/106) versus 0% (0/18), respectively; lumpectomy-alone patients experienced a 19% (17/88) rate of DCIS recurrence. All recurrent DCIS was ipsilateral. For lumpectomy-alone patients, the factors associated with ipsilateral recurrence of DCIS were extent of involvement of the parenchyma (P=.01, for univariate; P=.07, for multivariate) and initial presentation (P=.05, for univariate; P=.07, for multivariate). Eleven lumpectomy-alone patients developed invasive breast cancer (6 ipsilateral, 5 contralateral); none of the 18 lumpectomy patients who received adjuvant radiation developed invasive disease. None of the factors investigated, including primary surgery and adjuvant radiotherapy, were associated with a significant effect on the development of invasive disease. CONCLUSIONS: Longer follow-up is required to determine if the benefits of either mastectomy or radiotherapy following lumpectomy persist. There is a suggestion that patients under 40 years of age or women who present with nipple discharge might be considered for either adjuvant radiotherapy following lumpectomy or a simple mastectomy.

Adult↗
PubMed1997

The surgical and oncologic significance of the axillary arch during axillary lymphadenectomy.

An uncommon and often-overlooked anatomic variation of the latissimus dorsi muscle is the axillary arch. It is formed by an anomalous slip of the muscle that arises from the body of the latissimus dorsi but then inserts along with the pectoralis major muscle anterior to the axillary vein and neurovascular bundle. If an axillary arch is encountered during axillary lymphadenectomy, the lymph nodes posterior and lateral to the arch should be excised. Experience with a number of cases is used to consider local therapeutic and staging factors.

Aged↗
PubMed1997

Surgical management of early stage invasive breast cancer (stage I and II). Provincial Breast Disease Site Group.

GUIDELINE QUESTION: What is the optimal surgical management of early stage invasive breast cancer (stage I and II)? More specifically, what is the relative efficacy (and safety) of breast conservation therapy (lumpectomy with axillary dissection) compared with modified radical mastectomy? OBJECTIVE: To make recommendations about surgical management and techniques in the treatment of early stage invasive breast disease (stage I and II). OUTCOMES: Survival, local recurrence (for lumpectomy patients) and quality of life are the primary outcomes of interest. PERSPECTIVE (VALUES): Evidence was selected and reviewed by 6 members of the Ontario Cancer Treatment Practice Guidelines Initiative, Disease Site Group for Breast Cancer (Breast DSG). Earlier drafts of this evidence-based recommendation have been reviewed, discussed and approved by the Breast DSG, which comprises surgeons, medical oncologists, radiation oncologists, epidemiologists, a pathologist and a medical sociologist. There was no consumer participation in the development of this guideline. QUALITY OF EVIDENCE: There are 7 randomized controlled trials (RCTs) comparing breast conservation therapy with mastectomy in women with early stage breast cancer. BENEFITS: In 6 RCTs, no statistically significant differences were detected in survival rate between the mastectomy and conservative therapy (lumpectomy) groups. In 1 RCT, a statistically significant differences was detected in favour of the mastectomy arm; however, this was an early trial with substantial methodologic weaknesses. HARMS: None. PRACTICE GUIDELINE: Women with early stage invasive breast cancer (stage I and II) who are candidates for breast conservation therapy (see discussion of technical factors) should be offered the choice of either breast conservation therapy (excision of tumour with clear margins and axillary dissection) or modified radical mastectomy. The choice is an individual one for the patient, and thus she should be fully informed of the options, including the risks and benefits of each procedure. She should be informed that breast irradiation is part of the procedure for breast conservation therapy. In addition, she should be aware of the potential need for further surgery if the margins are positive. For further information about the use of radiotherapy in the management of early stage breast cancer, please refer to the Ontario Cancer Treatment Practice Guidelines Initiative's practice guideline Breast Irradiation in Women with Early Stage Invasive Breast Cancer Following Breast Conserving Surgery.

Breast Neoplasms↗
PubMed1996

Genetic counselling and testing for susceptibility to breast, ovarian and colon cancer: where are we today?

Recent advances in our understanding of the genetic characteristics of cancer will change approaches to genetic screening and counselling. Cancer results from multiple, cumulative mutations in genes that regulate cell replication and differentiation. In familial cancer a germ-line mutation is passed on in an autosomal dominant pattern, but cancer will develop in people who inherit the defect only if other mutations also occur in susceptible somatic cells. The tumour-suppressor gene known as BRCA1 is thought to affect half of those families who have an inherited breast cancer syndrome and most families with a breast and ovarian cancer syndrome. Another gene, BRCA2, is thought to affect most of the remaining families with a breast-cancer-only syndrome. Hereditary nonpolyposis colon cancer (HNPCC) is caused by mutations in surveillance genes that protect DNA from the spontaneous errors that occur during cell division. Because there are no outcome data on which to base practice guidelines for genetic screening or management of asymptomatic carriers in families at risk, testing should be restricted to research settings.

Breast Neoplasms↗