Multigene assessment of genetic risk for women for two or more breast cancers

Weitzel, Jeffrey N.; Kidd, John; Bernhisel, Ryan; Shehayeb, Susan; Frankel, Paul; Blazer, Kathleen R.; Turco, D; Nehoray, Bita; McGreevy, Kim; Svirsky, Kira; Brown, Krystal; Gardiner, Anna; Daly, Mary B.; Hughes, Elisha; Cummings, Shelly; Saam, Jennifer; Slavin, Thomas P.

doi:10.1007/s10549-021-06201-y

Cited by 5 publications

(4 citation statements)

References 48 publications

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“…The lack of a statistically significant association with CBC risk for ATM PV carriers in the overall ER status and race analyses is consistent with recent studies. 48-50 However, these results should be interpreted with caution because the HRs for ATM PV carriers were > 1.5 in several subsets, including postmenopausal and NHW women with ER-positive breast cancer. By contrast, there were no CBC events among 16 African American ATM PV carriers.…”

Section: Discussionmentioning

confidence: 86%

Contralateral Breast Cancer Risk Among Carriers of Germline Pathogenic Variants inATM,BRCA1,BRCA2,CHEK2, andPALB2

Yadav

Boddicker

et al. 2023

JCO

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PURPOSE To estimate the risk of contralateral breast cancer (CBC) among women with germline pathogenic variants (PVs) in ATM, BRCA1, BRCA2, CHEK2, and PALB2. METHODS The study population included 15,104 prospectively followed women within the CARRIERS study treated with ipsilateral surgery for invasive breast cancer. The risk of CBC was estimated for PV carriers in each gene compared with women without PVs in a multivariate proportional hazard regression analysis accounting for the competing risk of death and adjusting for patient and tumor characteristics. The primary analyses focused on the overall cohort and on women from the general population. Secondary analyses examined associations by race/ethnicity, age at primary breast cancer diagnosis, menopausal status, and tumor estrogen receptor (ER) status. RESULTS Germline BRCA1, BRCA2, and CHEK2 PV carriers with breast cancer were at significantly elevated risk (hazard ratio > 1.9) of CBC, whereas only the PALB2 PV carriers with ER-negative breast cancer had elevated risks (hazard ratio, 2.9). By contrast, ATM PV carriers did not have significantly increased CBC risks. African American PV carriers had similarly elevated risks of CBC as non-Hispanic White PV carriers. Among premenopausal women, the 10-year cumulative incidence of CBC was estimated to be 33% for BRCA1, 27% for BRCA2, and 13% for CHEK2 PV carriers with breast cancer and 35% for PALB2 PV carriers with ER-negative breast cancer. The 10-year cumulative incidence of CBC among postmenopausal PV carriers was 12% for BRCA1, 9% for BRCA2, and 4% for CHEK2. CONCLUSION Women diagnosed with breast cancer and known to carry germline PVs in BRCA1, BRCA2, CHEK2, or PALB2 are at substantially increased risk of CBC and may benefit from enhanced surveillance and risk reduction strategies.

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Section: Discussionmentioning

confidence: 86%

Contralateral Breast Cancer Risk Among Carriers of Germline Pathogenic Variants inATM,BRCA1,BRCA2,CHEK2, andPALB2

Yadav

Boddicker

et al. 2023

JCO

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“…Weitzel et al have already demonstrated that mutations in PALB2 and CHEK2 are associated with having two or more breast cancers, but the same study found that neither ATM nor NBN reached statistical significance for two or more breast cancers (Weitzel, 2021). In the future, high quality longitudinal studies of moderate risk mutation carriers eventually will yield data about second primary breast cancer risk.…”

Section: Discussionmentioning

confidence: 98%

“…During the time frame of the study, for mutation carriers in PALB2 , ATM , CHEK2 , and NBN (OMIM: 602667) carriers, the NCCN Guidelines® (v.3.2019) recommended annual mammogram and consideration of breast MRI starting at age 40 but cautioned that evidence was insufficient for recommending RRM which should be “based on family history” (NCCN Clinical Practice Guidelines, 2019). Women with newly diagnosed breast cancer are increasingly offered genetic panels to explore whether they are at an increased risk for developing future breast cancers so that they can make informed decisions regarding surgical approach (Kurian, 2018; Weitzel, 2021).…”

Section: Introductionmentioning

confidence: 99%

Risk‐reducing mastectomy decisions among women with mutations in high‐ and moderate‐ penetrance breast cancer susceptibility genes

Comeaux

Culver

Lee

et al. 2022

Molec Gen & Gen Med

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Background Women harboring mutations in breast cancer susceptibility genes are at increased lifetime risk of developing breast cancer and are faced with decisions about risk management, including whether to undergo high‐risk screening or risk‐reducing mastectomy (RRM). National guidelines recommend BRCA1 or BRCA2 mutation carriers consider RRM, but that carriers of moderate penetrance mutations (e.g., ATM or CHEK2) should be managed based on family history. We aimed to investigate determinants of decision for RRM, and hypothesized that mutation status, age, family history, partner status, and breast cancer would impact RRM decision making. Methods We performed a retrospective study assessing RRM decisions for 279 women. Results Women with BRCA and moderate penetrance gene mutations, a personal history of breast cancer, or a first degree relative with a history of breast cancer were more likely to undergo RRM. Breast cancer status and age showed an interaction effect such that women with breast cancer were less likely to undergo RRM with increasing age. Conclusion Although national guidelines do not recommend RRM for moderate penetrance carriers, the rates of RRM for this population approached those for BRCA mutation carriers. Further insights are needed to better support RRM decision‐making in this population.

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“…Studies of germline BRCA1/2 pathogenic variants and contralateral breast cancer risk. The systematic review of the literature identified 15 articles (13 studies [37][38][39][40][41][42][43][44][45][46][47][48][49] and two meta-analyses 50,51 ) that inform the question of whether all patients with local recurrence or contralateral primary breast cancer should be offered BRCA1/2 testing. With the exception of one study that provides direct evidence, 38 the studies identified constitute indirect evidence in support of the recommendation that BRCA1/2 testing should be offered to patients with contralateral breast cancer or ipsilateral second breast primary.…”

Section: Literature Review and Analysismentioning

confidence: 99%

Germline Testing in Patients With Breast Cancer: ASCO–Society of Surgical Oncology Guideline

Bedrosian,

Somerfield,

Achatz

et al. 2024

JCO

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PURPOSE To develop recommendations for germline mutation testing for patients with breast cancer. METHODS An ASCO–Society of Surgical Oncology (SSO) panel convened to develop recommendations based on a systematic review and formal consensus process. RESULTS Forty-seven articles met eligibility criteria for the germline mutation testing recommendations; 18 for the genetic counseling recommendations. RECOMMENDATIONS BRCA1/ 2 mutation testing should be offered to all newly diagnosed patients with breast cancer ≤65 years and select patients >65 years based on personal history, family history, ancestry, or eligibility for poly(ADP-ribose) polymerase (PARP) inhibitor therapy. All patients with recurrent breast cancer who are candidates for PARP inhibitor therapy should be offered BRCA1/ 2 testing, regardless of family history. BRCA1/ 2 testing should be offered to women who develop a second primary cancer in the ipsilateral or contralateral breast. For patients with prior history of breast cancer and without active disease, testing should be offered to patients diagnosed ≤65 years and selectively in patients diagnosed after 65 years, if it will inform personal and family risk. Testing for high-penetrance cancer susceptibility genes beyond BRCA1/ 2 should be offered to those with supportive family histories; testing for moderate-penetrance genes may be offered if necessary to inform personal and family cancer risk. Patients should be provided enough pretest information for informed consent; those with pathogenic variants should receive individualized post-test counseling. Variants of uncertain significance should not impact management, and patients with such variants should be followed for reclassification. Referral to providers experienced in clinical cancer genetics may help facilitate patient selection and interpretation of expanded testing, and provide counseling of individuals without pathogenic germline variants but with significant family history. Additional information is available at www.asco.org/breast-cancer-guidelines .

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Multigene assessment of genetic risk for women for two or more breast cancers

Cited by 5 publications

References 48 publications

Contralateral Breast Cancer Risk Among Carriers of Germline Pathogenic Variants inATM,BRCA1,BRCA2,CHEK2, andPALB2

Contralateral Breast Cancer Risk Among Carriers of Germline Pathogenic Variants inATM,BRCA1,BRCA2,CHEK2, andPALB2

Risk‐reducing mastectomy decisions among women with mutations in high‐ and moderate‐ penetrance breast cancer susceptibility genes

Germline Testing in Patients With Breast Cancer: ASCO–Society of Surgical Oncology Guideline

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