Evaluating the role of alcohol consumption in breast and ovarian cancer susceptibility using population‐based cohort studies and two‐sample Mendelian randomization analyses

PURPOSE Recent studies indicate that BRCA1 breast and ovarian tumors may have an advantageous survival. In this population-based study, the survival of carriers of a mutated BRCA1 gene was investigated. PATIENTS AND METHODS The survival of 71 BRCA1-associated cancer patients (33 breast cancer, seven breast and ovarian cancer, and 31 ovarian cancer patients from 21 families with BRCA1 germline mutations) diagnosed after 1958 was compared with that of a population-based comparison group that consisted of all other invasive breast (n = 28,281) and ovarian (n = 7,011) cancers diagnosed during 1958 to 1995, as well as an age- and stage-matched control group. RESULTS No apparent survival advantage was found for BRCA1-associated breast cancers upon direct comparison. After adjustment for age and calendar year of diagnosis, survival was equal to or worse than that of the comparison group (hazards ratio [HR], 1.5; 95% confidence interval [CI], 0.9 to 2.4). In comparison with an age- and stage-matched control group, survival again appeared equal or worse (HR, 1.5; 95% CI, 0.6 to 3.7). For BRCA1-associated ovarian cancers, an initial survival advantage was noted that disappeared with time. Due to this time dependency, multivariate analyses cannot adequately be analyzed. Compared with the age- and stage-matched control group, survival again appeared equal or worse (HR, 1.2; 95% CI, 0.5 to 2.8). CONCLUSION The results suggest that survival for carriers of a BRCA1 mutation may be similar, or worse than, that for breast and ovarian cancer in general. This finding is in accordance with the adverse histopathologic features observed in BRCA1 tumors and underlines the need for surveillance in families that carry a BRCA1 mutation.

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Diagnosis and prognosis of breast and ovarian cancer A population-based study of 234 women

Acta Oncologica ◽

10.1080/02841860310022481 ◽

2004 ◽

Vol 43 (2) ◽

pp. 175-181 ◽

Cited By ~ 9

Author(s):

Hans O. Thulesius ◽

Anna C. Lindgren ◽

Håkan L. Olsson ◽

Anders Håkansson

Keyword(s):

Ovarian Cancer ◽

Population Based ◽

Breast And Ovarian Cancer ◽

Population Based Study ◽

Diagnosis And Prognosis

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Susceptibility to breast and ovarian cancer: the role of glutathione S-transferase polymorphism

European Journal of Cancer ◽

10.1016/s0959-8049(99)81164-2 ◽

1999 ◽

Vol 35 ◽

pp. S191

Author(s):

R. Medeiros ◽

D. Pereira ◽

N. Afonso ◽

C. Lopes

Keyword(s):

Ovarian Cancer ◽

Glutathione S Transferase ◽

Breast And Ovarian Cancer

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Predictors of risk-reducing surgery intentions following genetic counseling for hereditary breast and ovarian cancer

Translational Behavioral Medicine ◽

10.1093/tbm/iby101 ◽

2018 ◽

Vol 10 (2) ◽

pp. 337-346 ◽

Cited By ~ 3

Author(s):

Mary Kathleen Ladd ◽

Beth N Peshkin ◽

Leigha Senter ◽

Shari Baldinger ◽

Claudine Isaacs ◽

...

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Genetic Counseling ◽

Cancer Risk ◽

Prophylactic Surgery ◽

Ovarian Cancer Risk ◽

Breast And Ovarian Cancer ◽

Affective Factors ◽

Risk Reducing

Abstract Risk-reducing mastectomy (RRM) and salpingo-oophorectomy (RRSO) are increasingly used to reduce breast and ovarian cancer risk following BRCA1/BRCA2 testing. However, little is known about how genetic counseling influences decisions about these surgeries. Although previous studies have examined intentions prior to counseling, few have examined RRM and RRSO intentions in the critical window between genetic counseling and test result disclosure. Previous research has indicated that intentions at this time point predict subsequent uptake of surgery, suggesting that much decision-making has taken place prior to result disclosure. This period may be a critical time to better understand the drivers of prophylactic surgery intentions. The aim of this study was to examine predictors of RRM and RRSO intentions. We hypothesized that variables from the Health Belief Model would predict intentions, and we also examined the role of affective factors. Participants were 187 women, age 21–75, who received genetic counseling for hereditary breast and ovarian cancer. We utilized multiple logistic regression to identify independent predictors of intentions. 49.2% and 61.3% of participants reported intentions for RRM and RRSO, respectively. Variables associated with RRM intentions include: newly diagnosed with breast cancer (OR = 3.63, 95% CI = 1.20–11.04), perceived breast cancer risk (OR = 1.46, 95% CI = 1.17–1.81), perceived pros (OR = 1.79, 95% CI = 1.38–2.32) and cons of RRM (OR = 0.81, 95% CI = 0.65–0.996), and decision conflict (OR = 0.80, 95% CI = 0.66–0.98). Variables associated with RRSO intentions include: proband status (OR = 0.28, 95% CI = 0.09–0.89), perceived pros (OR = 1.35, 95% CI = 1.11–1.63) and cons of RRSO (OR = 0.72, 95% CI = 0.59–0.89), and ambiguity aversion (OR = 0.79, 95% CI = 0.65–0.95). These data provide support for the role of genetic counseling in fostering informed decisions about risk management, and suggest that the role of uncertainty should be explored further.

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Increased Overall Mortality Even after Risk Reducing Surgery for BRCA-Positive Women in Western Sweden

Genes ◽

10.3390/genes10121046 ◽

2019 ◽

Vol 10 (12) ◽

pp. 1046

Author(s):

Anna Öfverholm ◽

Zakaria Einbeigi ◽

Antonia Wigermo ◽

Erik Holmberg ◽

Per Karsson

Keyword(s):

Ovarian Cancer ◽

General Population ◽

Cancer Incidence ◽

Population Based ◽

Pathology Report ◽

Breast And Ovarian Cancer ◽

Incidence And Mortality ◽

Incidence Risk ◽

Risk Reducing ◽

Overall Mortality

Women with BRCA variants have a high lifetime risk of developing breast and ovarian cancer. The aim of this study was to investigate the standard incidence ratios (SIR) for breast and ovarian cancer and standard mortality ratios (SMR) in a population-based cohort of women in Western Sweden, under surveillance and after risk reducing surgery. Women who tested positive for a BRCA variant between 1995–2016 (n = 489) were prospectively registered and followed up for cancer incidence, risk reducing surgery and mortality. The Swedish Cancer Register was used to compare breast and ovarian cancer incidence and mortality with and without risk reducing surgery for women with BRCA variants in comparison to women in the general population. SIR for breast cancer under surveillance until risk-reducing mastectomy (RRM) was 14.0 (95% CI 9.42–20.7) and decreased to 1.93 (95% CI 0.48–7.7) after RRM. The SIR for ovarian cancer was 124.6 (95% CI 59.4–261.3) under surveillance until risk reducing salpingo-oophorectomy (RRSO) and decreased to 13.5 (95% CI 4.34–41.8) after RRSO. The SMR under surveillance before any risk reducing surgery was 5.56 (95% 2.09–14.8) and after both RRM and RRSO 4.32 (95% CI 1.62–11.5). Women with cancer diagnoses from the pathology report after risk reducing surgery were excluded from the analyses. Risk reducing surgery reduced the incidence of breast and ovarian cancer in women with BRCA variants. However, overall mortality was significantly increased in comparison to the women in the general population and remained elevated even after risk reducing surgery. These findings warrant further research regarding additional measures for these women.

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Clinical Implications of the Breast Cancer Susceptibility Genes BRCA1 and BRCA2

Women s Health ◽

10.1517/17455057.1.1.027 ◽

2005 ◽

Vol 1 (1) ◽

pp. 27-34

Author(s):

Steven A Narod

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Cancer Susceptibility ◽

Cancer Chemoprevention ◽

Breast Cancer Susceptibility ◽

High Risk Population ◽

Clinical Genetics ◽

Breast And Ovarian Cancer ◽

Brca1 And Brca2 ◽

Cancer Susceptibility Genes

Genetic testing for BRCA1 and BRCA2 mutations has become an important part of the practice of medical oncology and clinical genetics over the past decade. Increasing numbers of women are requesting a genetic test so that they may better understand their personal risks of breast and ovarian cancer, and so that they may take appropriate measures to reduce the risk. Several of the risk factors can be modified, including breastfeeding and the use of oral contraceptives. A significant number of women opt for preventive mastectomy or oophorectomy, which will dramatically reduce the risks of breast and ovarian cancer. Chemoprevention with tamoxifen is still uncommon, largely due to women's fears of the side effects of the drug. A number of studies have shown that magnetic resonance imaging is superior to conventional mammography in terms of the early detection of breast cancer in the high-risk population. This article explores what is known about assessing genetic risk and the evidence supporting a range of preventive strategies.

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