Can harmful lifestyle, obesity and weight changes increase the risk of breast cancer in BRCA 1 and BRCA 2 mutation carriers? A Mini review

Abstract Background and aim The BRCA 1 and BRCA 2 genes are associated with an inherited susceptibility to breast cancer with a cumulative risk of 60% in BRCA 1 mutation carriers and of 30% in BRCA 2 mutation carriers. Several lifestyle factors could play a role in determining an individual’s risk of breast cancer. Obesity, changes in body size or unhealthy lifestyle habits such as smoking, alcohol consumption and physical inactivity have been evaluated as possible determinants of breast cancer risk. The aim of this study was to explore the current understanding of the role of harmful lifestyle and obesity or weight change in the development of breast cancer in female carriers of BRCA 1/2 mutations. Methods Articles were identified from MEDLINE in October 2020 utilizing related keywords; they were then read and notes, study participants, measures, data analysis and results were used to write this review. Results Studies with very large case series have been carried out but only few of them have shown consistent results. Additional research would be beneficial to better determine the actual role and impact of such factors.

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Cost-effectiveness of surveillance and prevention strategies in BRCA 1/2 mutation carriers.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e13051 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e13051-e13051

Author(s):

Hideko Yamauchi ◽

Chizuko Nakagawa ◽

Makoto Kobayashi ◽

Yusuke Kobayashi ◽

Toshiki Mano ◽

...

Keyword(s):

Ovarian Cancer ◽

Cost Effectiveness ◽

Cost Effective ◽

Breast And Ovarian Cancer ◽

Quality Adjustment ◽

Mutation Carriers ◽

Brca 1 ◽

Brca 2 ◽

Preference Ratings ◽

Risk Reducing

e13051 Background: Cost-effectiveness analysis is important in healthcare, especially in Japan, where preventive measures for carriers of BRCA 1/2 mutations are not covered by health insurance. Methods: We developed Markov models in a simulated cohort of women aged 35–70, and compared outcomes of surveillance with risk-reducing mastectomy at age 35 (RRM), risk-reducing salpingo-oophorectomy at age 45 (RRSO), and both (RRM&RRSO), with quality adjustment. We used breast and ovarian cancer incidence, and adverse event rates from previous studies, adjuvant chemotherapy and hormonal therapy rates from Hereditary Breast and Ovarian Cancer Registration 2015, mortality rates from the National Cancer Center Hospital, Japan Society of Clinical Oncology and Ministry of Health, Labour and Welfare, and direct costs in 2016 Japanese yen from St. Luke’s International Hospital and Keio University Hospital. We used preference ratings for both of mutation carriers and controls (without known high risk) from a published study to adjust survival for quality of life (QALYs). Discount rate was 2%. Results: Compared with surveillance, RRSO and RRM & RRSO were dominant (cost-saving and more effective) and RRM was cost effective for BRCA 1 mutation carriers. RRM and RRM & RRSO were dominant, and RRSO was cost effective for BRCA 2 mutation carriers. Among four strategies including surveillance, RRM & RRSO was the most cost effective for BRCA 1 mutation carriers and RRM was the most cost effective for BRCA 2 mutation carriers based on preference ratings of controls. Conclusions: With quality adjustment, all the preventive strategies (RRM, RRSO and RRM&RRSO) were cost effective for BRCA 1 and 2. Using QALYs from the control group, RRM & RRSO for BRCA 1 and RRM for BRCA 2 were the most cost effective. We will use this result to promote insurance coverage for BRCA mutations carriers in Japan.

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Preferences for breast cancer prevention among BRCA mutation carriers

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.17018 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 17018-17018

Author(s):

J. Jacobson ◽

P. Patel ◽

A. Bharthuar ◽

D. Hershman ◽

K. Hill ◽

...

Keyword(s):

Breast Cancer ◽

High Risk ◽

Regression Models ◽

Pairwise Comparisons ◽

Carrier Status ◽

Health States ◽

Mutation Status ◽

Logistic Regression Models ◽

Mutation Carriers ◽

Brca 1

17018 Purpose: Breast cancer screening with MRI is a new option available to patients with BRCA 1/2 mutations. We analyzed preferences for this modality and 10 other breast cancer- related health states and preventive measures among women without cancer or known high risk and women with BRCA mutations. Methods: Following IRB approval, we administered a time trade-off questionnaire to mutation carriers and to women without breast cancer or known high risk. We used Kruskal-Wallis test to compare the two groups with respect to continuous variables, chi-square tests to compare proportions, and the Wilcoxon signed rank test for pairwise comparisons. We then developed logistic regression models to analyze the association of mutation carrier status and demographic factors with willingness to trade time for each of the 11 health states. Results: Two-hundred-four women (44 mutation carriers and 160 without breast cancer or known high risk) responded to the questionnaire. Both groups assigned the highest preference rating to mammography and the next-highest to MRI, but the differences in ratings were not statistically significant. Both groups assigned the lowest preference ratings to having a child with a mutation and the next lowest to ovarian cancer. In pairwise comparisons, both groups ranked oophorectomy higher than ovarian cancer (p <0.01), but mutation carriers did not rank prophylactic mastectomy significantly differently from breast cancer (p=0.38). In the logistic regression models, mutation carrier status was not a statistically significant predictor of willingness to trade time for any health state, but younger age, lower income, and nonwhite race/ethnicity were associated with willingness to trade time for certain health states. Conclusion: Our data indicate that MRI is as acceptable as mammography to respondents, and that the preferences of BRCA 1/2 mutation carriers are similar to those of other women. Age and other demographic factors may be more important than mutation status in determining preferences. The preference ratings of individuals should not be inferred from demographic characteristics or mutation status. However, such ratings can help to clarify the quality of life implications of clinical decision-making and health care policy regarding breast cancer prevention. No significant financial relationships to disclose.

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BRCA 1 and BRCA 2 mutations in Saudi breast cancer patients (single institution).

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.26_suppl.10 ◽

2014 ◽

Vol 32 (26_suppl) ◽

pp. 10-10 ◽

Cited By ~ 2

Author(s):

Omalkhair A. M. Abulkhair

Keyword(s):

Breast Cancer ◽

Family History ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Bilateral Breast Cancer ◽

Cultural Practice ◽

Reproductive Pattern ◽

Saudi Women ◽

Brca 1 ◽

Brca 2

10 Background: Breast cancer is the commonest malignancy among Saudi females accounting for 25% of all female cancers with a median age at diagnosis of 47 years (1,2). In Saudi, breast cancer showed an increased incidence attributed to many factors such as different lifestyles, reproductive pattern, family history, which was reported to account for 59%, dietary or cultural practice of Saudi women (2,3,4,5). The multifunctional and highly penetrant BRCA 1 and BRCA 2 are the two major breast cancer pre-disposition genes, accounting for about 20% of breast cancer families (6,7). To our knowledge, the prevalence of BRCA 1 and BRCA 2 mutations in native Saudi population is sparse (8,9). Our aim is to describe the findings of BRCA mutation testing in native Saudi patients with breast cancer in a large Ministry of National Guard Health Affairs (NGHA) community-based teaching hospital. Methods: In this study, 75 out of 516 patients with breast cancer who were clinically and histopathologically diagnosed at NGHA from October 2010 to April 2014 were included. Selection criteria: aged ≤ 40 years bilateral breast cancer, triple-negative breast cancer, strongly first degree family history at young age and male breast cancer. Molecular alterations were performed by direct gene sequencing, multiple ligation – dependent probe amplification (MLPA) at Bioscentia human genetic testing in Germany. Results: 75 native Saudi were enrolled and test performed for them. 18 patients (24%) were found to have mutation of which 10 in BRCA One and six in BRCA 2. Two have both BRCA 1 and BRCA 2. Seven patients have the same with deleterious mutations in BRCA 1 gene. Two of them are mother and daughter and other five are unrelated. The mean age of breast cancer diagnosis in the mutation carriers was 38 years. Triple negative breast cancer (TNBC) diagnosed in six patients, bilateral breast cancer diagnosed in one, first-degree family history in eight and second degree in 10 patients and four with no family history. Conclusions: BRCA 1 and BRCA 2 mutations are an important contributor to the etiology of breast cancer in Saudi women. A mutation in BRCA 1, C 1648 > C p, Asn550His in exon 10 has been reported as disease causing (11) and it is found in our study in seven patients. Such mutation might be specific for Saudi, so further studies are highly recommended.

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Antitumor activity of trabectedin and lurbinectedin in germline BRCA2 carriers with metastatic breast cancer (MBC) as compared to BRCA1 carriers: Analysis of two phase II trials.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.574 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 574-574

Author(s):

Judith Balmana Gelpi ◽

Jan Antoni Lubinski ◽

Banu Arun ◽

Tomasz Byrski ◽

Melinda L. Telli ◽

...

Keyword(s):

Breast Cancer ◽

Phase Ii ◽

Single Agent ◽

Metastatic Breast ◽

Cross Resistance ◽

Hematological Toxicity ◽

Phase Ii Trials ◽

Brca 1 ◽

Brca 2 ◽

Grade 3

574 Background: BRCA 1/2-associated breast cancer share homologous recombination deficiency, but also have independent and potentially actionable roles. Novel drugs with innovative mechanism of action, lacking cross-resistance with other used agents are needed for BRCA 1/2 MBC. Trabectedin (TR) and its analog, lurbinectedin (L), have shown to be active in BRCA 1/2 MBC. This study was sought to determine if there was a difference in activity of these agents between BRCA1 and 2 carriers. Methods: Safety and efficacy in MBC BRCA 1/2 were analyzed in 2 separate phase II trials of single agent TR and L. Results: 88 patients were evaluated: 34 with TR, 54 with L. Median age: 46 and 43, respectively. Median (range) prior chemotherapy lines: TR, 4 (1-10); L, 2 (0-5). Clinical responses were seen in the 2 trials (see table) and were higher in BRCA2 than in BRCA1 (33% vs 9% with TR and 61% vs 26% with L). Main adverse event was myelosuppression (grade 3-4 neutropenia / thrombocytopenia / febrile neutropenia: TR, 62.1%/24.3%/10.8% L, 66.7%/20.4%/20.4%). Non-hematological toxicity was mostly grade 1-2: fatigue, nausea/vomiting and high transaminases (grade 3/4 TR, 40.5%, L 18.5%). Conclusions: Remarkable activity of trabectedin and lurbinectedin as single agents was observed in BRCA 2 associated MBC. This finding warrants further investigation. One potential mechanistic rationale is the role of both lurbinectedin and BRCA 2 in transcription. Safety was acceptable and manageable in both studies. Clinical trial information: NCT01525589. [Table: see text]

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Aurora-A as a Modifier of Breast Cancer Risk in BRCA 1/2 Mutation Carriers

10.21236/ada473900 ◽

2007 ◽

Author(s):

Fergus J. Couch

Keyword(s):

Breast Cancer ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Aurora A ◽

Mutation Carriers ◽

Brca 1

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Clinicogenetic care of women of BRCA mutation carrier women: prevention, diagnosis and therapy

Orvosi Hetilap ◽

10.1556/oh.2011.29131 ◽

2011 ◽

Vol 152 (23) ◽

pp. 913-918 ◽

Cited By ~ 1

Author(s):

Zsolt Nagy ◽

Mónika Csanád ◽

Katalin Tóth ◽

Szabolcs Máté ◽

József Gábor Joó

Keyword(s):

Multidisciplinary Approach ◽

Randomized Trials ◽

Brca Mutation ◽

Diagnosis And Treatment ◽

Expert Opinions ◽

Mutation Carriers ◽

The Family ◽

Brca 1 ◽

Brca 2 ◽

Brca Mutation Carriers

Predictive genetics opens a considerable perspective in the diagnostics as well as the treatment of breast and ovarian cancer. Current recommendations and guidelines for the management of BRCA 1 and BRCA 2 mutation carriers are not based on controlled randomized trials, but on expert opinions. The existing options of prevention, early diagnosis and treatment must be clearly interpreted to the patient. In the context of a dedicated genetic counseling the participation of all involved professionals (geneticist, oncologist, surgeon, gynecologist) is required. The decision-making process concerning the possibilities of prevention, diagnosis and treatment is always deeply influenced by the patient’s own experience with the cancer occurred in the family, as well as by her values and expectations of life. The focused multidisciplinary approach, with the application of results from prospective studies in cohorts of BRCA mutation carriers allow the concerned individuals to benefit from this kind of approach of medical treatment. Orv. Hetil., 2011, 152, 913–918.

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