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Biomedical subjects

P Goss

Publications and source records attributed to P Goss.

At least 19 recordsLinked to original sources
PubMed2003

Management of recurrent locoregional breast cancer: oncologist survey.

Locoregional recurrence (LRR) after therapy for early breast cancer is common. A questionnaire was used to assess consensus between breast oncologists about the definition, prognosis and management of patients with LRR. The questionnaire was mailed to surgical, radiation and medical oncologists in Canada, the UK and the USA. Of 495 questionnaires, 322 (65%) were returned. Most clinicians sampled agree that disease in the skin of the chest wall, surgical scar, axilla, ipsilateral breast tumor recurrence (IBTR), infraclavicular lymph nodes, supraclavicular fossa lymph nodes and internal mammary lymph nodes constitute sites of LRR. The sites that were felt to be curable by the majority of respondents were: IBTR, surgical scar, axilla or chest wall. It was for these disease sites that local therapy was generally recommended. Irrespective of the site of recurrence, most respondents surveyed recommend initiation of a new systemic therapy at the time of LRR. While the results of this survey show general agreement regarding the definition of sites of LRR, treatment recommendations vary among oncologists. Due to the variation in sites of recurrence, time since initial diagnosis and prior therapy, the exact prognosis and optimal management of LRR remain undefined. In the absence of randomized prospective trial data, recommendations for local and systemic therapy of LRR will continue to mimic those offered at the time of initial presentation of breast cancer.

Biopsy, Needle↗
PubMed2001

Locoregionally recurrent breast cancer: incidence, risk factors and survival.

Locoregional recurrence (LRR) after therapy for early breast cancer is common. Patients with LRR can suffer both local consequences and symptoms of metastatic disease, as LRR is an independent predictor of subsequent distant metastases. Much of the available data on LRR is derived from small, single institution, retrospective studies, so marked differences in the incidence rates for LRR, it's risk factors and subsequent systemic recurrence are reported. The purpose of this review was to try and collate this data in a format that would be useful for both clinicians and their patients.

Adult↗
PubMed2001

Does treatment at the time of locoregional failure of breast cancer alter prognosis?

Locoregional recurrence (LRR) after therapy for early breast cancer is common. Patients with LRR can suffer local consequences such as bleeding, ulceration, pain and arm oedema or symptoms of metastases. Unlike existing treatment guidelines for primary tumours, both local (surgical and radiation) and systemic treatment recommendations are less well defined after LRR. The purpose of this review was to assess whether or not treatment at the time of locoregional failure ultimately alters a patient's prognosis. Unfortunately, the data from both retrospective and prospective studies are inconclusive and therefore the treatment of patients with LRR will continue to be recommended using guidelines similar to those for primary breast cancer. Future studies of factors predicting LRR and metastatic spread may allow better prognostication of patients with LRR which may in turn effect both local and systemic treatment decisions.

Adult↗
PubMed2000

E2F1 and p53 are dispensable, whereas p21(Waf1/Cip1) cooperates with Rb to restrict endoreduplication and apoptosis during skeletal myogenesis.

We describe temporal and genetic analyses of partially rescued Rb mutant fetuses, mgRb:Rb-/-, that survive to birth and reveal specific defects in skeletal muscle differentiation. We show that in the absence of Rb, these fetuses exhibit increased apoptosis, bona fide endoreduplication, and incomplete differentiation throughout terminal myogenesis. These defects were further augmented in composite mutant fetuses, mgRb:Rb-/-:p21-/-, lacking both Rb and the cyclin-dependent kinase inhibitor p21(Waf1/Cip1). Although E2F1 and p53 mediate ectopic DNA synthesis and cell death in several tissues in Rb mutant embryos, both endoreduplication and apoptosis persisted in mgRb:Rb-/-:E2F1-/- and mgRb:Rb-/-:p53-/- compound mutant muscles. Thus, combined inactivation of Rb and p21(Waf1/Cip1) augments endoreduplication and apoptosis, whereas E2F1 and p53 are dispensable during aberrant myogenesis in Rb-deficient fetuses.

Animals↗
PubMed2000

Breast cancer in women < or = 35 years: review of 1002 cases from a single institution.

BACKGROUND: Early-onset breast cancer may differ with respect to etiology, clinical features and outcome compared with breast cancer in older women. To gain further insight, we retrospectively reviewed the clinical features and outcome of women < or = 35 years with primary breast cancer seen at our institution over a 30-year period. PATIENTS AND METHODS: Charts were reviewed for women with operable breast cancer diagnosed < or = 35 years of age seen at the Princess Margaret Hospital (PMH), Toronto from 1965-1994. RESULTS: One thousand eighty-six women with non-metastatic invasive breast cancer, aged 18.3-35.6 years (median 32.1 years) were referred to PMH. Symptoms at presentation included: self-detected breast lump (83%), other breast symptom (10%), physician diagnosis (4%) and unknown (3%). Tumor size was known in 936 (>2 cm in 61%) and nodal status in 888 (lymph node positive in 52%). Modified radical mastectomy was performed in 568 (57%) and breast-conservation surgery (BCS) in 422 (42%). Five hundred sixteen (51%) patients received adjuvant radiotherapy and five hundred thirty-four (53%) adjuvant systemic therapy. Two hundred ninety-three (29%) patients had a family history of breast cancer (FH). Contralateral breast cancer (CBC) occurred more frequently in women with FH (P range 0.042-0.008). Local recurrence (LR) was 37% and 73% at 10 years in those treated by BCS with and without radiotherapy, respectively. At 10 years, disease-free survival (DFS) was 30% and overall patient survival 48%. CONCLUSIONS: In this cohort, breast cancer was usually self-diagnosed and tumors were > 2 cm at presentation in approximately two-thirds of cases, suggesting the possibilities of a delay in diagnosis, more aggressive tumors or both. Our results are compatible with the known association of breast cancer FH with increased CBC. Our data also corroborates the suggestion that positive genetic testing in this age group should lead to consideration of more aggressive ipsilateral and contralateral breast management. In those receiving adjuvant irradiation after BCS, the LR rate was high, but did not impact on overall survival.

Adolescent↗
PubMed2000

Localization to Xq27 of a susceptibility gene for testicular germ-cell tumours.

Testicular germ-cell tumours (TGCT) affect 1 in 500 men and are the most common cancer in males aged 15-40 in Western European populations. The incidence of TGCT has risen dramatically over the last century. Known risk factors for TGCT include a history of undescended testis (UDT), testicular dysgenesis, infertility, previously diagnosed TGCT (ref. 7) and a family history of the disease. Brothers of men with TGCT have an 8-10-fold risk of developing TGCT (refs 8,9), whereas the relative risk to fathers and sons is fourfold (ref. 9). This familial relative risk is much higher than that for most other types of cancer. We have collected samples from 134 families with two or more cases of TGCT, 87 of which are affected sibpairs. A genome-wide linkage search yielded a heterogeneity lod (hlod) score of 2.01 on chromosome Xq27 using all families compatible with X inheritance. We obtained a hlod score of 4.7 from families with at least one bilateral case, corresponding to a genome-wide significance level of P=0.034. The proportion of families with UDT linked to this locus was 73% compared with 26% of families without UDT (P=0.03). Our results provide evidence for a TGCT susceptibility gene on chromosome Xq27 that may also predispose to UDT.

Adolescent↗
PubMed2000

Breast cancer risk following irradiation for Hodgkin's disease.

Radiation is commonly used to treat early-stage Hodgkin's disease. As the risk of recurrent Hodgkin's disease decreases as time from treatment elapses, the risk of radiation-induced breast cancer rises. Women irradiated between the time of puberty and the age of 30 are at the highest risk. The median time to breast cancer following radiation in this age group is approximately 15 years, usually when women are aged between 30 and 40, and often before regular breast screening is implemented. Risk factors associated with breast cancer development include age at irradiation, time since treatment and the radiation dose received. Current screening for breast cancer after Hodgkin's disease is inconsistent. In this article we review breast development, mechanisms of radiation-induced carcinogenesis, and findings from retrospective studies on Hodgkin's disease and breast cancer. We also review future considerations of management, including assessment of risk awareness in these women, guidelines for follow-up and screening, and chemoprevention both during and after treatment of Hodgkin's disease. The literature reviewed was obtained from Medline using the key words: breast cancer, Hodgkin's disease and radiation-induced cancer. The search was limited to English language literature. Other sources include reference lists in books and published papers.

Adult↗
PubMed2000

Phase I/II trial of cyclophosphamide, mitoxantrone, and escalated doses of carboplatin supported by peripheral-blood stem cells in women with metastatic breast cancer.

PURPOSE: To intensify a regimen of high-dose cyclophosphamide, mitoxantrone, and carboplatin that had previously produced high complete and overall response rates in metastatic breast cancer (MBC). PATIENTS AND METHODS: Forty-four patients with a median age of 43 years (range, 25 to 57 years) and previously untreated MBC who were responding to anthracycline-based or single-agent taxane chemotherapy received cyclophosphamide 1.5 g/m(2)/d and mitoxantrone 16 mg/m(2)/d combined with escalating doses of carboplatin 200 to 500 mg/m(2)/d, each given daily from days -6 to -3. Hematopoiesis was supported by mobilized peripheral-blood stem cells infused on day 0 and by use of granulocyte-macrophage colony-stimulating factor 300 microg/d subcutaneously starting on day 1. RESULTS: A total of six dose levels of carboplatin were examined. Grades 3 and 4 toxicity occurred in 10 patients and one patient, respectively, with grade 3 toxicity occurring in only five of 31 patients treated with < or = 400 mg/m(2) of carboplatin. Major dose-limiting toxicities were cardiac, pulmonary, and renal. Four patients developed congestive heart failure: two had persistently low ejection fraction 11 and 36 months after peripheral-blood stem-cell transplantation (PBSCT), and two recovered. Hematologic recovery to an absolute neutrophil count of greater than 0.5 x 10(9)/L occurred at a median of 11 days (range, 8 to 25 days) and to a platelet count of greater than 20 x 10(9)/L at a median of 10.5 days (range, 6 to 60 days). There were two toxic deaths from sepsis: one on day 27 (level 5) and one from cardiac arrest on day 42 (level 6). CONCLUSION: The maximum-tolerated dose of carboplatin was 400 mg/m(2)/d in combination with mitoxantrone 16 mg/m(2)/d and cyclophosphamide 1,500 mg/m(2), all drugs given over 4 days. This regimen is being tested in a phase III trial of high-dose chemotherapy and PBSCT versus standard treatment.

Adolescent↗
PubMed2000

Phase III comparative study of vinorelbine combined with doxorubicin versus doxorubicin alone in disseminated metastatic/recurrent breast cancer: National Cancer Institute of Canada Clinical Trials Group Study MA8.

PURPOSE: This phase III study was performed to determine the superiority of doxorubicin (DOX) and vinorelbine (VNB) (arm 1) versus DOX alone (arm 2) in metastatic breast cancer (MBC) for overall survival (OS), time to treatment failure (TTF), toxicity, and quality of life (QOL). PATIENTS AND METHODS: Three hundred three patients were randomized to DOX 50 mg/m(2) intravenously (IV) on day 1 and VNB 25 mg/m(2) IV on days 1 and 8 (arm 1) or DOX 70 mg/m(2) IV on day 1 (arm 2). Both regimens were given every 3 weeks until a cumulative DOX dose of 450 mg/m(2). After 16 of the first 65 randomized patients experienced febrile neutropenia (FN), the doses were reduced to DOX 40 mg/m(2) on day 1 and VNB 20 mg/m(2) on days 1 and 8 versus DOX 60 mg/m(2) on day 1. Eligible patients were vinca alkaloid and anthracycline naive. Chemotherapy was first-line or second-line for MBC. RESULTS: Three patients were ineligible. Thus, 300 patients were assessable for toxicity and to determine time to disease progression (TTP), TTF, and OS. Two hundred eighty-nine patients were assessable for response, and 99 responders were assessable for response duration (RD). The response rates, QOL, and median RD, TTP, and TTF were not significantly different between the arms. Median OS was 13.8 months for arm 1 versus 14.4 months for arm 2 (P =.4). Grade 3 or 4 granulocytopenia was equivalent in both arms but more grade 3/4 neurotoxicity, mild venous toxicity, and FN were seen on arm 1. CONCLUSION: The survival with DOX and VNB is not superior to DOX alone in MBC.

Adult↗
PubMed1999

Prevalence and penetrance of BRCA1 and BRCA2 gene mutations in unselected Ashkenazi Jewish women with breast cancer.

BACKGROUND: Approximately 2.0%-2.5% of Ashkenazi Jewish women carry one of three founding mutations in the BRCA1 and BRCA2 genes, and each mutation is associated with a high lifetime risk of invasive breast cancer. We investigated the extent to which these three mutations contribute to breast cancer incidence in the Ashkenazi Jewish population. METHODS: We ascertained 457 Jewish women with prevalent cases of breast cancer who were unselected for age or family history of the disease; 412 of these women were tested for the three founder mutations (case patients). Control subjects consisted of 360 non-Jewish women with breast cancer (control patients) and 380 healthy Jewish women with no history of cancer (control subjects). RESULTS: Mutations were found in 48 (11.7%) of 412 Jewish case patients. Forty-six of 48 mutations occurred in women with early-onset breast cancer (<50 years) or a history of ovarian or early-onset breast cancer in a first-, second-, or third-degree relative. The estimated penetrance to age 70 years for breast cancer was 59.9% for the BRCA1 gene mutations and 28.3% for the BRCA2 gene mutation. Compared with Jewish control subjects, the relative risk (RR) of breast cancer for first-degree relatives of mutation carriers was 5.16 (95% confidence interval [CI] = 3.14-8. 48), but risk was also increased for relatives of noncarriers (RR = 1.66; 95% CI = 1.18-2.33). The RR of prostate cancer for first-degree relatives of Jewish case patients was 3.36 (95% CI = 1. 49-7.56). CONCLUSIONS: Approximately 12% of breast cancers in the Ashkenazi Jewish population are attributable to mutations in the BRCA1 or BRCA2 gene. Genetic testing may be useful when Jewish women with breast cancer are diagnosed before age 50 years or have a close relative with ovarian or early-onset breast cancer. An association between breast and prostate cancers was observed in our study population.

Aged↗
PubMed1999

Physical and psychological morbidity after axillary lymph node dissection for breast cancer.

PURPOSE: Alternatives to axillary lymph node dissection (ALND) are being developed amid controversy surrounding the therapeutic benefit and overall utility of this routine surgical procedure. Although potential negative side effects associated with ALND are known, we set out to examine whether these side effects contribute significantly to patient reports of quality of life and mental health. PATIENTS AND METHODS: We surveyed 222 women who had received an ALND as part of breast cancer surgery. All women underwent a physical therapy assessment of range of arm/shoulder motion and completed the Modified Post-operative Pain Questionnaire, the Pain Disability Index, the McGill Pain Questionnaire (short form), the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, and the Mental Health Inventory. RESULTS: Seventy-two percent of the women experienced arm/shoulder pain, weakness, or numbness in the week before the interview, and range of motion of the affected arm/shoulder was impaired in 73% of the women. Severity of pain was reported to be low to moderate, and younger patients experienced greater pain than older patients. Pain severity correlated positively with the number of lymph nodes removed and receipt of chemotherapy and was not significantly related to length of time since surgery or receipt of radiation therapy. Generally high levels of cancer-specific quality of life and mental health were reported. Quality of life was significantly predicted by the McGill Pain Questionnaire, and mental health was significantly predicted by the Pain Disability Index and the physical therapy assessment. CONCLUSION: Surgery-related symptoms after ALND persist for a majority of women with breast cancer and are not significantly related to time since surgery or receipt of radiation therapy. These symptoms and associated disability are significantly predictive of cancer-specific quality of life and mental health.

Axilla↗
PubMed1999

Combined results of two phase II studies of Taxol (paclitaxel) in patients with relapsed or refractory lymphomas.

This study was performed to determine the clinical activity and safety of paclitaxel in the treatment of patients with refractory or relapsing aggressive Non-Hodgkin's lymphoma (NHL). Between May 3, 1994 and February 16, 1996, 39 patients with refractory or relapsing NHL consented to be enrolled in two, multicenter, open-labelled studies to evaluate the efficacy, safety, time to progression and overall survival of paclitaxel given at a dose of 175 mg/m2 by a 3-hour IV infusion every three weeks without G-CSF use. Data from the two studies is combined. One patient, although registered, did not receive treatment. Of the remaining 38 patients, 17 men and 21 women aged 26-82 years (median 60) were given 104 courses of paclitaxel [median 2 (range 1-6)]. Seventeen patients had stage IV, 7 stage III, 8 stage II, 5 stage 1 and 1 unknown stage of disease. Histologic grades included 1 low, 33 intermediate, and 4 high. Three patients had bone marrow involvement. Median time from diagnosis to study entry was 19 months (1-160). The median number of previous chemotherapy regimens was 2 (range 1-6). Three of the 35 (8.6%) patients evaluable for response had partial remission (PR) of their disease for 1-7 months (median 2) and 11/35 (31.4%) stable disease (SD) for 1 to 19 months (median 3). All three responders and 3 of the 11 SD patients had received paclitaxel after relapsing from a CR. At analysis, nine of the 38 patients were alive. Median duration of follow up at analysis was 6 months (3 days-29 months). The estimated survival rates for all patients at 1 and 2 years are 34% and 27%, respectively (Kaplan-Meier) from the start of paclitaxel treatment. The median survival time was 5.4 months (3 days to 28+ months). Febrile neutropenia occurred in two patients. Seven (18%) patients developed a neutrophil nadir of < 0.5 x 10(9)/L and 2 (5%) patients developed a platelet nadir of < 50 x 10(9)/L. Six patients received blood transfusions. Non-hematologic toxicity was generally mild to moderate with all patients experiencing some toxicity. Twenty-seven patients experienced grade III toxicity including: alopecia (n = 19), pain (n = 9), fatigue (n = 5), nausea/vomiting (n = 3), diarrhoea (n = 2), pulmonary/shortness of breath (n = 2), anorexia (n = 1) and fluctuating levels of consciousness and somnolence (n = 1). Two patients experienced grade IV toxicity (infection, peripheral neuropathy, pain). No patient discontinued paclitaxel for a severe hypersensitivity reaction. In summary, administered as a 3-hour infusion, paclitaxel 175 mg/m2 results in mild myelotoxicity but minimal antitumor activity in patients with refractory NHL.

Adult↗
PubMed1997

Repeat expansion detection analysis of (CAG)n tracts in tumor cell lines, testicular tumors, and testicular cancer families.

The mutational expansion of triplet repeat microsatellite sequences underlies the transmission of a number of heritable neurological disorders. However, this form of microsatellite instability has not previously been observed in association with malignant disease. Because trinucleotide expansions can dramatically alter gene expression and protein function, we hypothesized that they might occur in neoplastic cells as a mechanism through which to alter cancer genes. Accordingly, we used the repeat expansion detection technique to determine whether (CAG)n triplet repeat expansions were present in DNA from malignant cells. No expansions were observed in a survey of 20 tumor cell lines derived from neoplasms of the breast, ovary, cervix, endometrium, lung, colon, placenta, or hematopoietic system. However, we did observe expanded (CAG)n tracts in DNA from 5 of 11 testicular tumor cell lines and in 1 of 11 sporadic testicular tumors. Examination of the corresponding normal DNA, when available, revealed that some of the expansions were germline in nature. To assess the possibility that (CAG)n expansions underlie some cases of inherited testicular cancer, we also analyzed germline DNA from members of five kindreds predisposed to this malignancy. An increase in (CAG)n tract size was observed in all five families and was particularly striking in one large pedigree in which expansions were observed in three of four affected siblings. These observations raise the possibility that the germline transmission of expanded (CAG)n tracts may play a role in testicular tumorigenesis.

Adenine↗
PubMed1996

Mutation analysis of the BRCA2 gene in 49 site-specific breast cancer families.

The hereditary breast cancer gene BRCA2 was recently cloned and is believed to account for almost half of site-specific breast cancer families and the majority of male breast cancer families. We screened 49 site-specific breast cancer families for mutations in the BRCA2 gene using single strand conformation analysis (SSCA) followed by direct sequencing. We found mutations in eight families, including all four families with male breast cancer. The eight mutations were small deletions with the exception of a single nonsense mutation, an all were predicted to interrupt the BRCA2 coding sequence and to lead to a truncated protein product. Other factors which predicted the presence of a BRCA2 mutation included a case of breast cancer diagnosed at age 35 or below (P = 0.01) and a family history of pancreatic cancer (P = 0.03). Two mutations were seen twice, including a 8535delAG, which was detected in two French Canadian families. Our results suggest the possibility that the proportion of site-specific breast cancer families attributable to BRCA2 may be overestimated.

Adult↗
PubMed1996

Do genetic factors explain associations between muscle strength, lean mass, and bone density? A twin study.

Are the associations between muscle strength, lean mass, and bone mineral density (BMD) genetically determined? Based on within-pair differences in 56 monozygotic (MZ) and 56 dizygotic (DZ) female twin pairs, mean age 45 yr (range 24-67), BMD was associated with lean mass, independent of fat mass and height (P < 0.05). A 10% increment in femoral neck (FN) BMD was associated with a 15% increment in lean mass (approximately 6 kg). BMD was associated with muscle strength (measured in 35 pairs) before, but not after, adjusting for lean mass. Based on age-adjusted cross-sectional analyses, same-trait correlations (+/- SE) in MZ pairs were double those in DZ pairs: FN BMD (0.62 +/- 0.08, 0.33 +/- 0.12) and lean mass (0.87 +/- 0.03, 0.30 +/- 0.11; all P < 0.001), consistent with a genetic hypothesis. The cross-trait correlation (r) between lean mass and FN BMD in the same individual was 0.43 +/- 0.06. The cross-trait cross-twin correlation between lean mass in one twin and FN BMD in the other was 0.31 +/- 0.07 in MZ pairs, approximately 75% of the cross-trait correlation (r) and 0.19 +/- 0.09 in DZ paris (P < 0.001). After adjusting for height and fat mass, the MZ and DZ cross-trait cross-twin correlations were no different (0.16 +/- 0.08 and 0.13 +/- 0.09, respectively). Therefore, genetic factors account for 60-80% of the individual variances of both FN BMD and lean mass, and > 50% of their covariance. The association between greater muscle mass and greater BMD is likely to be determined by genes regulating size.

Adult↗
PubMed1995

DICE (dexamethasone, ifosfamide, cisplatin, etoposide) as salvage therapy in non-Hodgkin's lymphomas.

Between April 1988 and April 1992 we conducted a study of DICE (dexamethasone 10 mg q6h, ifosfamide 1 g/m2, cisplatin 25 mg/m2, etoposide 100 mg/m2, and mesna uroprotection daily x 4 given every 28 days) in thirty six patients with intermediate or high-grade non-Hodgkin's lymphomas (NHL's). All patients had disease refractory to anthracycline-based chemotherapy and were ineligible for our dose intensive salvage chemotherapy program including autologous bone marrow transplant (ABMT). Twenty six men and 10 women aged 21-79 years (median 61) were given 100 courses of treatment in hospital. Twenty three patients had stage IV, 7 stage III and 6 stage II disease. Fourteen patients had bone marrow involvement and 11 had B symptoms. Thirty two patients had received only 1 previous chemotherapy regimen. After a follow-up of 1-70 months (median 7), 8 of the 34 (23%) patients evaluable for response had complete remission (CR) of their disease for 8-70+ months (med 24) and 15/34 (44%) partial remission (PR) for 2-55+ months (med 13), giving an overall response rate of 67% (23/34). Eight of the 36 patients are alive 34-70 months (median 48) after being enrolled on study, 6 of whom relapsed and responded to subsequent treatment. The estimated survival rates for all patients at 1 and 2 years are 50% and 36% respectively (Kaplan Meier). Response to prior chemotherapy was the only baseline characteristic statistically predictive (p = 0.04) of response to DICE by logistic regression analysis. Myelosuppression was the dose limiting toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗