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Steven A Narod, Kelly Metcalfe,
Henry T Lynch,
Parviz Ghadirian,
Andre Robidoux,
Nadine Tung,
Elizabeth Gaughan,
Charmaine Kim-Sing,
Olufunmilayo I Olopade,
William D Foulkes,
Mark Robson,
Kenneth Offit,
Ania Jakubowska,
Tomasz Byrski,
Tomasz Huzarski,
Ping Sun,
Jan Lubinski
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ABSTRACT: To estimate the 15-year survival following a diagnosis of stage I breast cancer among women who carry a BRCA1 mutation and to determine predictors of mortality, including the use of chemotherapy. Patients were 379 women with stage I breast cancer for whom a BRCA1 mutation had been identified, in herself or in a close family member. Patients were followed for up to 15 years from the initial diagnosis of breast cancer. Survival rates were estimated for women by age, tumor size (≤1 cm; >1 cm), ER status (±), and by chemotherapy (yes/no). 42 women died of breast cancer in the follow-up period (11.2 %). Survival rates were similar for women with cancers of size 0-1.0 cm and size 1.1-2.0 cm. Of the 267 women in the study who used chemotherapy, 21 had died (7.9 %) compared to 21 deaths among 112 women who did not receive chemotherapy (18.8 %; p = 0.002). The 15-year survival was 89.4 % for women who received chemotherapy and was 73.1 % for women who did not receive chemotherapy (p = 0.08; log rank). The adjusted hazard ratio for death following a diagnosis of stage I breast cancer associated with chemotherapy was 0.53 (95 % CI 0.28-1.07; p value 0.06) after adjusting for age of diagnosis, tumor size, and estrogen receptor status. This was statistically significant only among women with ER-negative breast cancers (HR = 0.28; 95 % CI 0.10-0.79; p = 0.02). BRCA1 positive women who are treated for stage I breast cancer with chemotherapy have better survival than those who do not receive chemotherapy. The difference cannot be explained by other prognostic factors. All women with invasive breast cancer and a BRCA1 mutation should be considered to be candidates for chemotherapy.
Breast Cancer Research and Treatment 02/2013; · 4.43 Impact Factor
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Kelly Metcalfe,
Henry T Lynch,
Parviz Ghadirian,
Nadine Tung,
Charmaine Kim-Sing,
Olufunmilayo I Olopade,
Susan Domchek,
Andrea Eisen,
William D Foulkes,
Barry Rosen,
Danny Vesprini,
Ping Sun,
Steven A Narod
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ABSTRACT: Women with a BRCA1 or BRCA2 mutation have an elevated risk of breast cancer and of contralateral breast cancer. In this study, we estimate the risk of non-synchronous ipsilateral breast cancer after a diagnosis of breast cancer in BRCA carriers and evaluate the effects of various treatments on this risk. Patients were 396 women with stage I or stage II breast cancer with an intact ipsilateral breast and for whom a BRCA1 or BRCA2 mutation had been identified in the family. Patients were followed from the initial diagnosis of cancer until the first of ipsilateral mastectomy, ipsilateral breast cancer, death or last follow-up. The 5-year actuarial risk of ipsilateral breast cancer was 5.8% (95% CI 3.2-8.4%) and the 10-year risk was 12.9% (95% CI 8.7-17.1%). Subjects who received chemotherapy had a significantly lower risk of ipsilateral breast cancer compared to those who did not receive chemotherapy (RR 0.45; 95% CI 0.24-0.84; P = 0.01). Radiotherapy was associated with a reduced risk of ipsilateral breast cancer (RR 0.28; 95% CI 0.12-0.63; P = 0.002). Oophorectomy was associated with a significant reduction in the risk of ipsilateral breast cancer (RR 0.33; 95% CI; 0.13-0.81; P = 0.02). On average, following a diagnosis of breast cancer, the annual risk of ipsilateral breast cancer risk in BRCA mutation carriers is 1.2% per year. For women treated with chemotherapy, radiation therapy or oophorectomy the risk is low, compared to women who did not receive any of these treatments.
Breast Cancer Research and Treatment 01/2011; 127(1):287-96. · 4.43 Impact Factor
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Kelly Metcalfe,
Jan Lubinski,
Henry T Lynch,
Parviz Ghadirian,
William D Foulkes,
Charmaine Kim-Sing,
Susan Neuhausen,
Nadine Tung,
Barry Rosen,
Jacek Gronwald,
Peter Ainsworth,
Kevin Sweet,
Andrea Eisen,
Ping Sun,
Steven A Narod
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ABSTRACT: Women who carry a deleterious mutation in BRCA1 or BRCA2 have high lifetime risks of breast and ovarian cancers. However, the influence of a family history of these cancers on these risks in women with BRCA mutations is unclear. We calculated cancer incidence rates for a multinational cohort comprising 3011 women with BRCA1 or BRCA2 mutations who were followed up for a mean of 3.9 years, during which time 243 incident breast or ovarian cancers were recorded. The 10-year cumulative risks of breast cancer were 18.1% (95% confidence interval [CI] = 13.3% to 22.8%) for women with a BRCA1 mutation and 15.2% (95% CI = 9.1% to 21.2%) for women with a BRCA2 mutation. Among women with a BRCA1 mutation, the risk of breast cancer increased by 1.2-fold for each first-degree relative with breast cancer before age 50 years (hazard ratio [HR] = 1.21; 95% confidence interval [CI] = 0.94 to 1.57) and the risk of ovarian cancer increased by 1.6 fold for each first- or second-degree relative with ovarian cancer (HR = 1.61; 95% CI = 1.21 to 2.14). Among women with a BRCA2 mutation, the risk of breast cancer increased by 1.7-fold for each first-degree relative younger than 50 years with breast cancer (HR = 1.67; 95% CI = 1.04 to 2.07).
CancerSpectrum Knowledge Environment 12/2010; 102(24):1874-8. · 14.07 Impact Factor
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ABSTRACT: To predict which women might suffer from abnormally high levels of anxiety and depression after receiving a positive genetic BRCA1 test result, series of pregenetic testing and postgenetic testing psychological measurements were performed. Of 3524 women who returned the psychological test sheets before receiving their genetic test result, 111 women were found to carry a BRCA1 mutation. We found that overall, anxiety does not increase in women who receive a positive BRCA1 genetic test result; however, women who experience high levels of anxiety before genetic testing continue to experience high levels of anxiety up to 1 year posttesting. There were differences in cancer-related distress in affected and unaffected women. BRCA1 carriers with a previous diagnosis of cancer had significantly higher levels of cancer-related distress at 1 month posttest than those without cancer. Our findings suggest that healthcare providers should consider including a brief pretest psychological assessment before initiating genetic testing for BRCA1 and BRCA2.
Genetic Testing and Molecular Biomarkers 05/2009; 13(3):325-30. · 1.11 Impact Factor
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ABSTRACT: In Canada, approximately 1,500 women are diagnosed with cervical cancer every year, and 581 will die of the disease (WHO/ICO Information Centre on HPV and Cervical Cancer, 2007). The importance of preventing cervical cancer is clear, as the effects that this disease has on the lives of women and their families regardless of culture, sex, nationality or country is evident. With the recent media attention and release of the Human Papillomavirus (HPV) vaccine in Canada, it is crucial that oncology nurses understand HPV, its role in the development of cervical cancer, and the HPV vaccine. A brief overview of HPV and its involvement in the development of cervical cancer will be discussed in this paper. In addition, information on the HPV vaccine and its implications, as well as the current policy for the vaccine in Canada will be addressed. It will become evident how the role of the oncology nurse, as an educator and advocate regarding the implementation of this vaccine is crucial for successful acceptance of this vaccine. Finally, future implications of the vaccine and avenues of research will be touched upon.
Canadian oncology nursing journal = Revue canadienne de nursing oncologique 01/2009; 19(2):60-4.
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ABSTRACT: Genetic testing for BRCA1/2 has psychosocial impacts including those related to views of personal health, sense of self and identity and body image. The centrality of a person's self-concept in maintaining physical and psychosocial well-being has been well recognized; however, to date research exploring altered self-concept related to carrier knowledge is limited.
The objective of the study was to develop and validate a scale to measure the self-concept among individuals testing positive for BRCA1/2 mutations.
The study was conducted in two phases: phase I: item generation and refinement and phase II: scale selection and initial validation. During phase I, scale items were generated through individual interviews and focus groups of women with BRCA1/2 mutations, including women with or without a prior diagnosis of cancer. In phase II items were selected based on several criteria resulting in a 25-item scale, which underwent a reliability analyses and preliminary validation with 115 women. A second sample of 126 women was used to conduct further validation and samples were pooled to conduct factor analysis and the final scale selection.
A 17-item self-concept scale emerged having three factors: stigma, vulnerability and mastery demonstrating evidence for an instrument with promising psychometric properties (total scale alpha=0.90).
The scale has direct relevance for research in facilitating our understanding of the specific aspects of the self, which are vulnerable to BRCA1/2 testing and which play a role in clinical outcomes, to facilitate the development and specific testing of interventions and may be used as an outcome measure. Specific measurement tools for genetic populations will ultimately assist in the clinical management of these populations.
Psycho-Oncology 01/2009; 18(11):1216-29. · 3.34 Impact Factor
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ABSTRACT: Liede A, Metcalfe K, Offit K, Brown K, Miller S, Narod SA, Moslehi R. A family with three germline mutations in BRCAl and BRCA2. Clin Genet 1998: 54: 215–218. 0 Munksgaard. 1998Several cancer genetics centres offer testing for specific BRCAl and BRCAZ mutations to Ashkenazi Jewish individuals with a family history of breast and ovarian cancers. Testing involves screening for three common mutations found in this population, namely BRCA I 185delAG, 5382insC and BRCA2 6174delT (Struewing et al., Nat Genet 1995: 11: 198–200; Roa et al., Nat Genet 1996: 14 185–187; Oddoux et al., Nat Genet 1996: 14 188–190). We have identified a large Ashkenazi Jewish kindred (W9170) with ten cases of breast cancer and four cases of ovarian carcinoma. Initially, mutation analysis for this family identified a BRCAl 185delAG mutation in the proband diagnosed with three separate primary cancers of the breast, ovary and colon. Another individual in this family diagnosed with two primary cancers of the ovary and breast, was identified as having a second mutation, BRCA I 5382insC. Subsequent work found that two sisters (cousins of the proband), both diagnosed with carcinoma of the breast, had a third mutation, BRCAZ 6174delT. These three mutations have previously been found to be more common in the Ashkenazi Jewish population (References as above). The identification of all three mutations in one family, raised new implications for the manner in which testing and counselling should be offered. In our opinion, Ashkenazi Jewish individuals in breast-ovarian cancer families should be offered complete testing for the three common Ashkenazi Jewish mutations regardless of previous identification of one of these mutations in the family.
Clinical Genetics 04/2008; 54(3):215 - 218. · 3.13 Impact Factor
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ABSTRACT: Ideally, a genetic screening program for cancer should offer testing to all women who qualify, and who wish to participate, and who might benefit from the test. As the number of preventive options for women at high risk for hereditary breast cancer expands, the demand for testing increases. However, many women do not have ready access to testing because of cost, and many others have not been recognized by their physicians to be candidates for testing. It is possible to increase women's awareness about hereditary cancer through the popular press. Genetic testing was offered to 5000 Polish women through an announcement placed in a popular women's magazine (Twoj Styl) in October 2001. A total of 5024 women who qualified received a free genetic test for three mutations in BRCA1 which are common in Poland. Out of these, 198 women (3.9%) were found to carry a BRCA1 mutation. The overall cost per mutation detected was 630 US dollars--approximately 50-100 times less than the equivalent cost in North America. Genetic counseling was offered to women with a positive test or with a significant family history of breast or ovarian cancer. The great majority of women who took part in the program expressed a high degree of satisfaction and after one year approximately two-thirds of identified mutation carriers had complied with our recommendations for breast cancer screening. We found this model of genetic testing and delivery of genetic information to be very efficient in a population in which founder mutations predominate. There is a need for similar studies in other populations.
Breast Cancer Research and Treatment 01/2007; 100(3):239-45. · 4.43 Impact Factor
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ABSTRACT: Limited attention has been given to the impact of BRCA mutation disclosure on participants' psychological reaction and cancer control compliance. We asked women (290 mutation-positive, 370 mutation-negative) from 84 hereditary breast-ovarian cancer (HBOC) families with known deleterious BRCA mutations to participate in an evaluation regarding cancer prevention recommendations before and after BRCA mutation disclosure. Both men and women (n = 780) were invited to complete a questionnaire to evaluate their psychological response to BRCA mutation disclosure. Before BRCA testing, 23.0% (152 of 660) of these women underwent prophylactic bilateral mastectomy, oophorectomy, or both; of these, 53% (80 of 152) were subsequently found to be mutation negative. After mutation disclosure, 52.9% (110 of 208) of mutation carriers and 0% (0 of 203) of noncarriers underwent prophylactic surgeries. These changes were statistically significant compared with before disclosure (P < 0.0001). The rate of transvaginal ovarian ultrasound screening was significantly increased in mutation carriers (P < 0.015) and marginally decreased in noncarriers (P = 0.063) post disclosure. Psychologically, compared with noncarriers without cancer, a significantly higher percentage of carriers, regardless of their cancer status, felt guilt about passing a mutation to their children, worried about developing additional cancer or their children developing cancer, and were concerned about health insurance discrimination. Despite these psychological consequences, carriers and noncarriers reported a positive attitude toward genetic testing.
Cancer Genetics and Cytogenetics 04/2006; 165(2):91-7. · 1.39 Impact Factor
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Jeffrey N Weitzel,
Mark Robson,
Barbara Pasini,
Siranoush Manoukian,
Dominique Stoppa-Lyonnet,
Henry T Lynch,
Jane McLennan,
William D Foulkes,
Teresa Wagner,
Nadine Tung,
Parviz Ghadirian,
Olufunmilayo Olopade,
Claudine Isaacs,
Charmaine Kim-Sing,
Pal Møller,
Susan L Neuhausen, Kelly Metcalfe,
Ping Sun,
Steven A Narod
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ABSTRACT: Women with breast cancer and a BRCA mutation have a high risk of developing a contralateral breast cancer. It is generally believed that the two cancers represent independent events. However, the extent of concordance between the first and second tumors with respect to hormone receptor expression and other pathologic features is unknown.
To determine the degree of concordance of estrogen receptor (ER) status, tumor grade, and histology in tumors from women with bilateral breast cancer and a BRCA mutation.
Women with a history of bilateral invasive breast cancers were selected from an international registry of women with BRCA1 or BRCA2 mutations. Medical records were reviewed to document the characteristics of each cancer and the treatments received.
Data were available for 286 women with bilateral breast cancer and a BRCA mutation (211 BRCA1; 75 BRCA2). The mean interval between first and second tumor was 5.1 years. The two tumors were concordant more often than expected for ER status (P < 0.0001) and for grade (P < 0.0001), but not for histology (P = 0.55). The ER status of the first tumor was highly predictive of the ER status of the second tumor (odds ratio, 8.7; 95% confidence interval, 3.5-21.5; P < 0.0001). Neither age, menopausal status, oophorectomy nor tamoxifen use was predictive of the ER status of the second tumor.
There is strong concordance in ER status and tumor grade between independent primary breast tumors in women with a BRCA mutation. The excess concordance may be due to common risk factors, genetic variation, or the existence of a preneoplastic lesion that is common to both tumors.
Cancer Epidemiology Biomarkers & Prevention 07/2005; 14(6):1534-8. · 4.12 Impact Factor
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Mary Jane Esplen,
Jon Hunter,
Molyn Leszcz,
Ellen Warner,
Steven Narod, Kelly Metcalfe,
Gord Glendon,
Kate Butler,
Alexander Liede,
Mary Anne Young,
Stephanie Kieffer,
Lisa DiProspero,
Ellen Irwin,
Jiahui Wong
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ABSTRACT: Women with a BRCA1/BRCA2 mutation experience significant challenges. These include decision-making regarding surgical options and notification to offspring and family, along with a sense of isolation, which may lead to psychological and emotional distress. The current study developed, standardized, and conducted preliminary testing of a supportive-expressive group therapy intervention designed to address these challenges.
Seventy women with a BRCA1/BRCA2 mutation recruited from familial cancer risk clinics participated in 12 sessions of supportive-expressive group therapy that lasted 6 months. Before and after measures of psychosocial functioning, knowledge, and surveillance/surgery activities were completed.
Sixty-seven women completed the intervention. Significant improvements were observed in psychosocial functioning: cancer worries (P = 0.005), anxiety (P = 0.033), and depression (P = 0.015). Knowledge level and surveillance levels were high at baseline and there were no significant changes postintervention. A significant number of women made decisions concerning prophylactic surgery (oophorectomy/mastectomy) during and after the intervention.
The feasibility of a supportive-expressive group for BRCA1/BRCA2 mutation carriers was demonstrated. Findings from the study are consistent with an effective intervention. However, further research is required using a randomized controlled study design.
Cancer 12/2004; 101(10):2327-40. · 4.77 Impact Factor
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Kelly Metcalfe,
Henry T Lynch,
Parviz Ghadirian,
Nadine Tung,
Ivo Olivotto,
Ellen Warner,
Olufunmilayo I Olopade,
Andrea Eisen,
Barbara Weber,
Jane McLennan,
Ping Sun,
William D Foulkes,
Steven A Narod
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ABSTRACT: To estimate the risk of contralateral breast cancer in BRCA1 and BRCA2 carriers after diagnosis and to determine which factors are predictive of the risk of a second primary breast cancer.
Patients included 491 women with stage I or stage II breast cancer, for whom a BRCA1 or BRCA2 mutation had been identified in the family. Patients were followed from the initial diagnosis of cancer until contralateral mastectomy, contralateral breast cancer, death, or last follow-up.
The actuarial risk of contralateral breast cancer was 29.5% at 10 years. Factors that were predictive of a reduced risk were the presence of a BRCA2 mutation (v BRCA1 mutation; hazard ratio [HR], 0.73; 95% CI, 0.47 to 1.15); age 50 years or older at first diagnosis (v <or= 49 years; HR, 0.63; 95% CI, 0.36 to 1.10); use of tamoxifen (HR, 0.59; 95% CI, 0.35 to 1.01); and history of oophorectomy (HR, 0.44; 95% CI, 0.21 to 0.91). The effect of oophorectomy was particularly strong in women first diagnosed prior to age 49 years (HR, 0.24; 95% CI, 0.07 to 0.77). For women who did not have an oophorectomy or take tamoxifen, the 10-year risk of contralateral cancer was 43.4% for BRCA1 carriers and 34.6% for BRCA2 carriers.
The risk of contralateral breast cancer in women with a BRCA mutation is approximately 40% at 10 years, and is reduced in women who take tamoxifen or who undergo an oophorectomy.
Journal of Clinical Oncology 06/2004; 22(12):2328-35. · 18.37 Impact Factor
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William D Foulkes, Kelly Metcalfe,
Ping Sun,
Wedad M Hanna,
Henry T Lynch,
Parviz Ghadirian,
Nadine Tung,
Olufunmilayo I Olopade,
Barbara L Weber,
Jane McLennan,
Ivo A Olivotto,
Louis R Bégin,
Steven A Narod
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ABSTRACT: BRCA1-related breast cancers are more frequently estrogen receptor (ER) negative than are either BRCA2-related or nonhereditary breast cancers. The relationship between ER status and other clinical features of hereditary breast cancers has not been well studied.
ER status, grade, and histological tumor type were evaluated in 1131 women with invasive breast cancer, ascertained at 10 centers in North America. There were 208 BRCA1 mutation carriers, 88 BRCA2 carriers, and 804 women without a known mutation. We stratified the patients by mutation status, grade, age, and histological type and calculated the percentage of ER-positive tumors within each stratum.
BRCA1 mutation carriers were more likely to have ER-negative breast cancers than were women in other groups, after adjustment for age, grade, and histological subtype (P < 0.001). Only 3.9% of BRCA1-related breast cancers were ER-positive cancers occurring in women in their postmenopausal years. The direction and magnitude of the change in ER status with increasing age at diagnosis in BRCA1 carriers was significantly different from in BRCA2 carriers (P(intercept) = 0.0002, P(slope) = 0.04). Notably, changes in ER status with age at diagnosis for BRCA1 carriers and noncarriers were almost identical (P(slope) = 0.98).
The strong relationship between the presence of a BRCA1 mutation and the ER-negative status of the breast cancers is neither a consequence of the young age at onset nor the high grade but is an intrinsic property of BRCA1-related cancers. The ER-negative status of these cancers may reflect the cell of origin of BRCA1-related cancers.
Clinical Cancer Research 04/2004; 10(6):2029-34. · 7.74 Impact Factor
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William D Foulkes, Kelly Metcalfe,
Wedad Hanna,
Henry T Lynch,
Parviz Ghadirian,
Nadine Tung,
Olofunmilayo Olopade,
Barbara Weber,
Jane McLennan,
Ivo A Olivotto,
Ping Sun,
Pierre O Chappuis,
Louis R Bégin,
Jean-Sébastien Brunet,
Steven A Narod
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ABSTRACT: A positive correlation between breast tumor size and the number of axillary lymph nodes containing tumor is well established. It has been reported that patients with BRCA1-related breast carcinoma are more likely than patients with nonhereditary breast carcinoma to have negative lymph node status. Therefore, the authors questioned whether the known positive correlation between tumor size and lymph node status also was present in women with BRCA1-related breast carcinomas.
The relation between the greatest dimension of the resected breast tumor (size) and the presence of positive axillary lymph nodes (expressed as a percentage of all lymph nodes examined) was evaluated in 1555 women with invasive breast carcinoma who were ascertained at 10 centers in North America between 1975 and 1997. There were 276 BRCA1 mutation carriers, 136 BRCA2 carriers, and 1143 women without a known mutation (208 BRCA1/BRCA2 noncarriers and 935 untested women). Patients were stratified according to tumor size, and odds ratios were estimated for the presence of positive lymph nodes with increasing tumor size.
A highly significant positive correlation between tumor size and the frequency of positive axillary lymph nodes was seen for BRCA1/BRCA2 noncarriers, for BRCA2 carriers, and for untested women (overall P < 0.0001 for each). In contrast, there was no clear correlation between tumor size and positive lymph node status in BRCA1 carriers (overall P = 0.20).
The relation between tumor size and lymph node status in patients with breast carcinoma appears to be different in BRCA1 carriers compared with BRCA2 carriers and noncarriers. These findings have important implications for estimating the route of metastatic spread and for evaluating the effectiveness of early diagnosis in patients with BRCA1-related breast carcinoma.
Cancer 10/2003; 98(8):1569-77. · 4.77 Impact Factor
