Risk-reducing mastectomy (RRM) is offered to women with a BRCA1 or BRCA2 pathogenic variant, however, there are limited data on the impact on breast cancer mortality.
Participants were identified ...from a registry of women with BRCA1/2 pathogenic variants. We used a pseudo-randomised trial design and matched one woman with a RRM to one woman without a RRM on year of birth, gene, and country. We estimated the hazard ratio (HR) and 95% confidence intervals (CI) for dying of breast cancer in the follow-up period.
There were 1654 women included; 827 assigned to the RRM arm and 827 assigned to the control arm. After a mean follow-up of 6.3 years, there were 20 incident breast cancers (including 15 occult cancers) and two breast cancer deaths in the RRM arm, and 100 incident breast cancers and 7 breast cancer deaths in the control arm (HR = 0.26; 95% CI 0.05-1.35; p = 0.11). The probability of dying of breast cancer within 15 years after RRM was 0.95%.
In women with a BRCA1 or BRCA2 pathogenic variant, RRM reduces the risk of breast cancer, and the probability of dying of breast cancer is low.
Background
The purpose of this study was to estimate the cumulative risks of all cancers in women from 50 to 75 years of age with a BRCA1 or BRCA2 pathogenic variant.
Methods
Participants were women ...with BRCA1 or BRCA2 pathogenic variants from 85 centers in 16 countries. Women were eligible if they had no cancer before the age of 50 years. Participants completed a baseline questionnaire and follow‐up questionnaires every 2 years. Women were followed from age 50 until a diagnosis of cancer, death, age 75, or last follow‐up. The risk of all cancers combined from age 50 to 75 was estimated using the Kaplan–Meier method.
Results
There were 2211 women included (1470 BRCA1 and 742 BRCA2). There were 379 cancers diagnosed in the cohort between 50 and 75 years. The actuarial risk of any cancer from age 50 to 75 was 49% for BRCA1 and 43% for BRCA2. Breast (n = 186) and ovarian (n = 45) were the most frequent cancers observed. For women who had both risk‐reducing mastectomy and bilateral salpingo‐oophorectomy before age 50, the risk of developing any cancer between age 50 and 75 was 9%.
Conclusion
Women with a BRCA1 or BRCA2 pathogenic variant have a high risk of cancer between the ages of 50 and 75 years and should be counselled appropriately.
Women with a BRCA1 or BRCA2 pathogenic variant have a high risk of cancer after age 50 and should be counseled appropriately.
An autosomal dominant pattern of hereditary breast cancer may be masked by small family size or transmission through males given sex-limited expression.
To determine if BRCA gene mutations are more ...prevalent among single cases of early onset breast cancer in families with limited vs adequate family structure than would be predicted by currently available probability models.
A total of 1543 women seen at US high-risk clinics for genetic cancer risk assessment and BRCA gene testing were enrolled in a prospective registry study between April 1997 and February 2007. Three hundred six of these women had breast cancer before age 50 years and no first- or second-degree relatives with breast or ovarian cancers.
The main outcome measure was whether family structure, assessed from multigenerational pedigrees, predicts BRCA gene mutation status. Limited family structure was defined as fewer than 2 first- or second-degree female relatives surviving beyond age 45 years in either lineage. Family structure effect and mutation probability by the Couch, Myriad, and BRCAPRO models were assessed with stepwise multiple logistic regression. Model sensitivity and specificity were determined and receiver operating characteristic curves were generated.
Family structure was limited in 153 cases (50%). BRCA gene mutations were detected in 13.7% of participants with limited vs 5.2% with adequate family structure. Family structure was a significant predictor of mutation status (odds ratio, 2.8; 95% confidence interval, 1.19-6.73; P = .02). Although none of the models performed well, receiver operating characteristic analysis indicated that modification of BRCAPRO output by a corrective probability index accounting for family structure was the most accurate BRCA gene mutation status predictor (area under the curve, 0.72; 95% confidence interval, 0.63-0.81; P<.001) for single cases of breast cancer.
Family structure can affect the accuracy of mutation probability models. Genetic testing guidelines may need to be more inclusive for single cases of breast cancer when the family structure is limited and probability models need to be recreated using limited family history as an actual variable.
Purpose
It is not known whether the risk of breast cancer among
BRCA1
and
BRCA2
mutation carriers after age 60 is high enough to justify intensive screening or prophylactic surgery. Thus, we ...conducted a prospective analysis of breast cancer risk in
BRCA1
and
BRCA2
mutation carriers from age 60 until age 80.
Methods
Subjects had no history of cancer and both breasts intact at age 60 (
n
= 699). Women were followed until a breast cancer diagnosis, prophylactic bilateral mastectomy or death. We calculated the annual cancer rate and cumulative incidence of breast cancer (invasive and in situ) from age 60 to age 80. We assessed the associations between hormone replacement therapy, family history of breast cancer and bilateral oophorectomy and breast cancer risk.
Results
Over a mean follow-up of 7.9 years, 61 invasive and 20 in situ breast cancers were diagnosed in the cohort. The mean annual rate of invasive breast cancer was 1.8% for
BRCA1
mutation carriers and 1.7% for
BRCA2
mutation carriers. The cumulative risk of invasive breast cancer from age 60 to 80 was 20.1% for women with a
BRCA1
mutation and was 17.3% for women with a
BRCA2
mutation. Hormone replacement therapy, family history and oophorectomy were not associated with breast cancer risk.
Conclusions
Findings from this large prospective study indicate that the risk of developing breast cancer remains high after age 60 in both
BRCA1
and
BRCA2
mutation carriers. These findings warrant further evaluation of the role of breast cancer screening in older mutation carriers.
Pericardial effusion in the patient with cancer presents a unique management problem. Although multiple methods of operative and nonoperative drainage of pericardial effusions have been described, ...surgical pericardial window remains the standard approach to long-term drainage. Selecting the patient who may benefit from an operative approach presents a difficult challenge. In the present study, we retrospectively analyzed the clinical outcome of 63 consecutive patients with malignancy who underwent surgical pericardial window for symptomatic pericardial effusion between January 1, 1990, and July 1, 2001, at City of Hope National Medical Center in order to try to determine whether the type of cancer, the presence of malignant cells in pericardial fluid, or tissue specimens or the method of surgery influenced the incidence of recurrent pericardial effusion or duration of survival.
The cohort was comprised of 15 patients with non-small cell lung cancer (NSCLC), 22 patients with breast cancer, 17 patients with hematologic malignancy, and 9 patients with other solid tumors. Pertinent clinical, laboratory, hospital stay, and outcome data including long-term follow-up were recorded. Patients were followed up until the time of last clinical follow-up or death. Univariate survival analyses were performed to determine significant clinical factors contributing to outcome.
Median follow-up was 6.6 months for the group and 8.3 months for those alive at last follow-up. Median survival rates for patients with lung, breast, hematologic, and other solid-tumor malignancies were 3.2 months, 8.8 months, 17 months, and 16.4 months, respectively. Preoperative factors that negatively correlated with survival included a diagnosis of NSCLC (p = 0.0014), the presence of a pleural effusion (p = 0.003), or positive pathologic (p = 0.02) or cytologic findings (p = 0.02).
A surgical approach to pericardial drainage is effective (< 5% failure rate) and provides an opportunity for continued therapy with the potential for relief of dyspnea and improvement in quality of life and survival in selected patients.
To describe quality-of-life (QOL) concerns particular to women with ovarian cancer and to examine whether subgroups of patients with ovarian cancer have significantly different QOL concerns.
Mailed ...survey.
Readership of an ovarian cancer newsletter.
A total of 1,383 surveys were received in response to the survey's inclusion in the November 2002 issue of Conversations! The International Newsletter for Those Fighting Ovarian Cancer, a monthly newsletter circulated to 3,300 women with ovarian cancer (response rate = 42%). Women were asked to complete the 45-item City of Hope QOL Ovarian Cancer Tool (QOL-OVCA) and a short demographic questionnaire.
Patients' QOL-OVCA scores were compared across six independent variables, including disease status, age at diagnosis, stage at diagnosis, marital status, household income, and use of alternative therapy, controlling for survival time.
Ovarian cancer survivors reported significant QOL concerns across dimensions of physical, psychological, social, and spiritual well-being.
Patients with ovarian cancer experience particular QOL concerns requiring support. Future research is needed to describe the needs of survivors in more diverse populations and to develop and test interventions that can address these QOL concerns.
Women with ovarian cancer experience QOL concerns common to other patients with cancer and some that are particular to ovarian cancer. Nurses should assess for and aggressively address these QOL concerns.
The BRCA1 and BRCA2 genes confer increased susceptibility to breast and ovarian cancer and to a spectrum of other cancers. There is controversy regarding the risk of colorectal cancer conferred by ...germline mutations in these two genes.
We followed 7015 women with a BRCA mutation for new cases of colorectal cancer. Incidence rates in carriers were compared with population-specific incidence rates, and standardised incidence ratios (SIRs) were estimated. The expected numbers of cancers were computed by multiplying person-years at risk by the appropriate age-, sex- and country-specific incidence rates from the five countries.
Twenty-one incident colorectal cancer cases were observed among all mutation carriers, compared with 23.6 cases expected. The SIR for BRCA1 carriers was 0.92 (95% confidence interval (CI), 0.54-1.40, P=0.7) and for BRCA2 carriers was 0.82 (95% CI, 0.30-1.81, P=0.7). The SIR for colon cancer was 3.81 (95% CI 1.77-7.23) for women below the age of 50 years (both genes combined) and was 0.60 (95% CI 0.33-1.00) for women aged 50 years and above.
The risk of colorectal cancer is increased in female carriers of BRCA1 mutations below the age of 50 years but not in women with BRCA2 mutations or in older women.
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