Contralateral prophylactic mastectomy rate and predictive factors among patients with breast cancer who underwent multigene panel testing for hereditary cancer

Elsayegh, Nisreen; Webster, Rachel; Barrera, Angelica M. Gutierrez; Lin, Heather; Kuerer, Henry Mark; Litton, Jennifer K.; Bedrosian, Isabelle; Arun, Banu K.

doi:10.1002/cam4.1519

Cited by 25 publications

(27 citation statements)

References 41 publications

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“…As recently reported, having BRCA-positive breast cancer may also influence carboplatin or PARP-inhibitor drug selection. [12][13][14][15][16] A second major point of consensus, discussed in more detail in the following, is that clinical data overall fairly consistently demonstrate no increased risk of radiation toxicity or radiation-induced second cancers in germline BRCA1 or BRCA2 mutation carriers treated with standard adjuvant radiation regimens. [17][18][19][20] The absence of a radiation therapyerelated detriment among BRCA carriers may provide some reassurance regarding phenotypically similar heterozygous germline DNA repair variants, such as pathogenic PALB2 and CHEK2 alleles.…”

Section: Current Germline and Somatic Tumor Genomic Screening In Clinmentioning

confidence: 98%

The Implications of Genetic Testing on Radiation Therapy Decisions: A Guide for Radiation Oncologists

Bergom

West

Higginson

et al. 2019

International Journal of Radiation Oncology*Biology*Physics

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The advent of affordable and rapid next-generation DNA sequencing technology, along with the US Supreme Court ruling invalidating gene patents, has led to a deluge of germline and tumor genetic variant tests that are being rapidly incorporated into clinical cancer decision-making. A major concern for clinicians is whether the presence of germline mutations may increase the risk of radiation toxicity or secondary malignancies. Because scarce clinical data exist to inform decisions at this time, the American Society for Radiation Oncology convened a group of radiation science experts and clinicians to summarize potential issues, review relevant data, and provide guidance for adult patients and their care teams regarding the impact, if any, that genetic testing should have on radiation therapy recommendations. During the American Society for Radiation Oncology workshop, several main points emerged, which are discussed in this manuscript: (1) variants of uncertain significance should be considered nondeleterious until functional genomic data emerge to demonstrate otherwise; (2) possession of germline alterations in a single copy of a gene critical for radiation damage responses does not necessarily equate to increased risk of radiation-induced toxicity; (3) deleterious ataxiatelangiesctasia gene mutations may modestly increase second cancer risk after radiation therapy, and thus follow-up for these patients after indicated radiation therapy should include second cancer screening; (4) conveying to patients the difference between relative and absolute risk is critical to decision-making; and (5) more work is needed to assess the impact of tumor somatic alterations on the probability of response to radiation therapy and the potential for individualization of radiation doses. Data on radiosensitivity related to specific genetic mutations is also briefly discussed.

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Section: Current Germline and Somatic Tumor Genomic Screening In Clinmentioning

confidence: 98%

The Implications of Genetic Testing on Radiation Therapy Decisions: A Guide for Radiation Oncologists

Bergom

West

Higginson

et al. 2019

International Journal of Radiation Oncology*Biology*Physics

Self Cite

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“…As the genetic testing was restricted to BRCA1 and BRCA2, other studies will be needed to assess the impact of positive test results for moderate risk genes, such as PALB2, CHEK2, and ATM. Interestingly, a CPM uptake comparable to BRCA carriers was recently reported for non-BRCA carriers with positive multigene panel testing results [24].…”

Section: Discussionmentioning

confidence: 67%

Impact of genetic counseling on the uptake of contralateral prophylactic mastectomy among younger women with breast cancer

2019

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Background: Preoperative genetic testing affects the surgical decision-making among women with breast cancer. To avoid breast-conserving surgery and to offer the possibility of mastectomy with immediate reconstruction in high-risk patients, genetic testing for pathogenic variants in BRCA1 or BRCA2 and a pedigree-based familial breast cancer risk assessment was offered to younger women with breast cancer in Denmark. We evaluated the impact of the risk stratification through genetic counseling on the uptake of contralateral prophylactic mastectomy (CPM). Material and methods: The prospective cohort study included all women with unilateral breast cancer before the age of 45 who participated in a genetic counseling program during their primary diagnostics in the Central Denmark Region (2013-2018). Each patient was followed from the time of the genetic test result to the end of follow-up to estimate the long-term uptake of CPM as a competing risk-adjusted cumulative incidence. We compared the uptake of CPM between the various genetic risk categories, ages of onset, and family histories in a multivariable Cox proportional hazards regression model, reporting hazard ratios (HR) with two-sided 95% confidence intervals (CIs). Results: 156 females, aged 21-44, learned their genetic test result within a median of 92 days [interquartile range (IQR): 75-114]. The maximal follow-up was 3.8 years (median 1.8; IQR: 0.49-2.5), after which 33% (95% CI: 24-42%) of the patients had undergone CPM. The uptake of CPM was inversely associated with the age of onset (HR 0.92; 95% CI: 0.86-0.98) and significantly higher among BRCA carriers (HR 2.9; 95% CI: 1.3-6.8) and patients from the high risk of breast cancer families (HR 5.6; 95% CI: 1.9-16) compared to the lower genetic risk categories. Conclusion: The risk stratification obtained through genetic counseling had a considerable impact on the surgical decision-making among younger women with breast cancer at long-term follow-up.

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“…There are a number of studies that have assessed the impact of genetic testing on CRRM rates [34][35][36] . A recent study from Denmark 35 confirmed that uptake of CRRM amongst women before the age of 45 years was significantly higher in those harbouring a pathogenic variant of the BRCA1/2 gene and those from high-risk families, compared to those with a lower genetic risk.…”

Section: Discussionmentioning

confidence: 99%

The Angelina Jolie effect: Contralateral risk-reducing mastectomy trends in patients at increased risk of breast cancer

Basu

Hodson

Chatterjee

et al. 2021

Sci Rep

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Contralateral risk-reducing mastectomy (CRRM) rates have tripled over the last 2 decades. Reasons for this are multi-factorial, with those harbouring a pathogenic variant in the BRCA1/2 gene having the greatest survival benefit. On May 14th, 2013, Angelina Jolie shared the news of her bilateral risk-reducing mastectomy (BRRM), on the basis of her BRCA1 pathogenic variant status. We evaluated the impact of this news on rates of CRRM in women with increased risk for developing breast cancer after being diagnosed with unilateral breast cancer. The prospective cohort study included all women with at least a moderate lifetime risk of developing breast cancer who attended our family history clinic (1987–2019) and were subsequently diagnosed with unilateral breast cancer. Rates of CRRM were then compared between patients diagnosed with breast cancer before and after Angelina Jolie’s announcement (pre- vs. post-AJ). Of 386 breast cancer patients, with a mean age at diagnosis of 48 ± 8 years, 268 (69.4%) were diagnosed in the pre-AJ period, and 118 (30.6%) in the post-AJ period. Of these, 123 (31.9%) underwent CRRM, a median 42 (interquartile range: 11–54) days after the index cancer surgery. Rates of CRRM doubled following AJ’s news, from 23.9% pre-AJ to 50.0% post AJ (p < 0.001). Rates of CRRM were found to decrease with increasing age at breast cancer (p < 0.001) and tumour TNM stage (p = 0.040), and to increase with the estimated lifetime risk of breast cancer (p < 0.001) and tumour grade (p = 0.015) on univariable analysis. After adjusting for these factors, the step-change increase in CRRM rates post-AJ remained significant (odds ratio: 9.61, p < 0.001). The AJ effect appears to have been associated with higher rates of CRRM amongst breast cancer patients with increased cancer risk. CRRM rates were highest amongst younger women and those with the highest lifetime risk profile. Clinicians need to be aware of how media news can impact on the delivery of cancer related services. Communicating objective assessment of risk is important when counselling women on the merits of risk-reducing surgery.

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Contralateral prophylactic mastectomy rate and predictive factors among patients with breast cancer who underwent multigene panel testing for hereditary cancer

Cited by 25 publications

References 41 publications

The Implications of Genetic Testing on Radiation Therapy Decisions: A Guide for Radiation Oncologists

The Implications of Genetic Testing on Radiation Therapy Decisions: A Guide for Radiation Oncologists

Impact of genetic counseling on the uptake of contralateral prophylactic mastectomy among younger women with breast cancer

The Angelina Jolie effect: Contralateral risk-reducing mastectomy trends in patients at increased risk of breast cancer

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