Modifiers of Cancer Risk in BRCA1 and BRCA2 Mutation Carriers: A Systematic Review and Meta-Analysis

Friebel, Tara M.; Domchek, Susan M.; Rebbeck, Timothy R.

doi:10.1093/jnci/dju091

Cited by 190 publications

(159 citation statements)

References 71 publications

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“…However, although the prevalence of risk factors often differs across population subgroups, many breast cancer risk factors have been documented to operate across racial/ethnic groups, as would be expected from diseases with a common underlying biology (20,(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52). Although we included family history as a nonmodifiable risk factor, we did not directly test for inherited mutations in genes that increase the risk of breast cancer; these are more common causes of breast cancer in younger, premenopausal women (53). This study also has a number of strengths.…”

Section: Discussionmentioning

confidence: 99%

Population Attributable Risk of Modifiable and Nonmodifiable Breast Cancer Risk Factors in Postmenopausal Breast Cancer

Tamimi¹,

Spiegelman²,

et al. 2016

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We examined the proportions of multiple types of breast cancers in the population that were attributable to established risk factors, focusing on behaviors that are modifiable at menopause. We estimated the full and partial population attributable risk percentages (PAR%) by combining the relative risks and the observed prevalence rates of the risk factors of interest. A total of 8,421 cases of invasive breast cancer developed in postmenopausal women (n = 121,700) in the Nurses' Health Study from 1980-2010. We included the following modifiable risk factors in our analyses: weight change since age 18 years, alcohol consumption, physical activity level, breastfeeding, and menopausal hormone therapy use. Additionally, the following nonmodifiable factors were included: age, age at menarche, height, a combination of parity and age at first birth, body mass index at age 18 years, family history of breast cancer, and prior benign breast disease. When we considered all risk factors (and controlled for age), the PAR% for invasive breast cancers was 70.0% (95% confidence interval: 55.0, 80.7). When considering only modifiable factors, we found that changing the risk factor profile to the lowest weight gain, no alcohol consumption, high physical activity level, breastfeeding, and no menopausal hormone therapy use was associated with a PAR% of 34.6% (95% confidence interval: 22.7, 45.4). The PAR% for modifiable factors was higher for estrogen receptorpositive breast cancers (PAR% = 39.7%) than for estrogen receptor-negative breast cancers (PAR% = 27.9%). Risk factors that are modifiable at menopause account for more than one-third of postmenopausal breast cancers; therefore, a substantial proportion of breast cancer in the United States is preventable. modifiable factors; PAR%; postmenopausal breast cancer Abbreviations: BMI, body mass index; CI, confidence interval; ER, estrogen receptor; ER−, estrogen receptor-negative; ER+, estrogen receptor-positive; MHT, menopausal hormone therapy; PAR%, population attributable risk percentage; RR, relative risk.Breast cancer is the most common cancer among women in the United States, and it is a major cause of morbidity and mortality globally. It has been estimated that 232,340 cases of invasive breast cancer and 39,620 breast cancer deaths occur annually in the United States (1). A nearly 5-fold difference in breast cancer incidence rates exists among countries globally (2). This geographic variability in incidence rates for breast cancer suggests that differences in the prevalence rates of risk factors among countries are associated with variation in breast cancer rates. Additionally, in migration studies, incidence rates of breast cancer among the descendants of women who moved from low-incidence countries to high-incidence countries converged to those of the high-incidence countries (3-7), which suggests that modifiable lifestyle factors account for much of the global difference in incidence rates. Thus, identification of modifiable risk factors for breast cancer has important impl...

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Section: Discussionmentioning

confidence: 99%

Population Attributable Risk of Modifiable and Nonmodifiable Breast Cancer Risk Factors in Postmenopausal Breast Cancer

Tamimi¹,

Spiegelman²,

et al. 2016

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“…Retrospective studies have identified several other factors that can influence the risk of ovarian cancer such as parity, prior tubal ligation, salpingectomy and unilateral or bilateral oophorectomy (surgical removal of the ovary) (29,42,43). Women who have given birth have a reduced risk of all subtypes of ovarian cancer, with the strongest risk reduction noted for clear cell cancers, compared with women who have not given birth.…”

Section: [H2] Risk Factorsmentioning

confidence: 99%

“…(42). Tubal ligation and hysterectomy are also associated with a reduction in the risk of developing ovarian cancer; tubal ligation is associated with reduction in risk of clear cell and endometrioid carcinomas and hysterectomy is associated with reduction in risk of clear cell carcinoma (Wentzensen et al) (29,42,43).In one study, reproductive risk factors such as tubal ligation, parity of ≥2, endometriosis and younger age were more strongly associated with development of dominant ovarian tumors (meaning one ovarian tumour is at least twice as large as the tumour on the other ovary), than with non-dominant cancers which are thought to arise in the fallopian tube and are mostly HGSC (44). Also, endometriosis has been associated with endometrioid and clear cell ovarian cancer as well as low grade cancers (Wentzensen et al).…”

Section: [H2] Risk Factorsmentioning

confidence: 99%

“…In women with germline BRCA mutations, tubal ligation and breastfeeding have similarly been identified as a risk factor associated with a decreased risk of ovarian cancer (29).…”

Section: [H2] Risk Factorsmentioning

confidence: 99%

“…Two trials have demonstrated comparable outcomes for first-line surgery with adjuvant chemotherapy, compared with NACT followed by surgery and post-operative chemotherapy, with less morbidity and mortality but similar outcomes in PFS and overall survival in the group that received NACT (160,161). Data from the first study showed NACT followed by interval cytoreductive surgery is not inferior to primary cytoreductive surgery followed by chemotherapy and no significant difference in PFS (12 months) or overall survival (29)(30) months) was found between groups (160). The second study (CHORUS) in patients with advanced stage III or IV cancer randomly assigned to either primary cytoreductive surgery followed by chemotherapy (consisting of either carboplatin and paclitaxel or carboplatin alone), or to NACT (3 cycles), followed by cytoreductive surgery and three more cycles of chemotherapy (carboplatin and paclitaxel or carboplatin alone) showed a non-significant difference in overall survival between the group that received NACT (24.1 months) and those that received upfront surgery (22.6 months; 95% HR 0.87, 95% CI 0.72-1.05) (161).…”

Section: [H1]managementmentioning

confidence: 99%

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Ovarian cancer

Matulonis

Sood

Fallowfield

et al. 2016

Nat Rev Dis Primers

890

787

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Ovarian cancer is not a single disease and can be subdivided into at least five different 2 histological subtypes that have different identifiable risk factors, cells of origin, molecular compositions, clinical features and treatments. Ovarian cancer is a global problem, is typically diagnosed at late stage, and has no effective screening strategy. Standard treatments for newly diagnosed cancer consist of cytoreductive surgery and platinum-based chemotherapy. In recurrent cancer, chemotherapy, anti-angiogenic agents, and poly (ADP ribose) polymerase (PARP) inhibitors are used and immunological therapies are currently being tested. High-grade serous carcinoma (HGSC) is the most commonly diagnosed form of ovarian cancer and is typically very responsive to platinum-based chemotherapy at diagnosis. However, in addition to the other histologies, HGSCs frequently relapse and become increasingly resistant to chemotherapy.Consequently, understanding the mechanisms underlying platinum resistance and finding ways to overcome them are active areas of study in ovarian cancer. Significant progress has been made in identifying genes associated with high risk of ovarian cancer (such as BRCA1 and BRCA2) as well as a precursor lesion of HGSC called a serous tubal intraepithelial carcinoma, which hold promise for identifying individuals at high risk of developing the disease and for developing prevention strategies. Competing interestsU.A.M. has served as a consultant for AstraZeneca, ImmunoGen, Pfizer, Genentech, and Merck.

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Pregnancy After Breast Cancer in Young BRCA Carriers

Lambertini,

Blondeaux,

Agostinetto

et al. 2024

JAMA

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ImportanceYoung women with breast cancer who have germline pathogenic variants in BRCA1 or BRCA2 face unique challenges regarding fertility. Previous studies demonstrating the feasibility and safety of pregnancy in breast cancer survivors included limited data regarding BRCA carriers.ObjectiveTo investigate cumulative incidence of pregnancy and disease-free survival in young women who are BRCA carriers.Design, Setting, and ParticipantsInternational, multicenter, hospital-based, retrospective cohort study conducted at 78 participating centers worldwide. The study included female participants diagnosed with invasive breast cancer at age 40 years or younger between January 2000 and December 2020 carrying germline pathogenic variants in BRCA1 and/or BRCA2. Last delivery was October 7, 2022; last follow-up was February 20, 2023.ExposurePregnancy after breast cancer.Main Outcomes and MeasuresPrimary end points were cumulative incidence of pregnancy after breast cancer and disease-free survival. Secondary end points were breast cancer–specific survival, overall survival, pregnancy, and fetal and obstetric outcomes.ResultsOf 4732 BRCA carriers included, 659 had at least 1 pregnancy after breast cancer and 4073 did not. Median age at diagnosis in the overall cohort was 35 years (IQR, 31-38 years). Cumulative incidence of pregnancy at 10 years was 22% (95% CI, 21%-24%), with a median time from breast cancer diagnosis to conception of 3.5 years (IQR, 2.2-5.3 years). Among the 659 patients who had a pregnancy, 45 (6.9%) and 63 (9.7%) had an induced abortion or a miscarriage, respectively. Of the 517 patients (79.7%) with a completed pregnancy, 406 (91.0%) delivered at term (≥37 weeks) and 54 (10.4%) had twins. Among the 470 infants born with known information on pregnancy complications, 4 (0.9%) had documented congenital anomalies. Median follow-up was 7.8 years (IQR, 4.5-12.6 years). No significant difference in disease-free survival was observed between patients with or without a pregnancy after breast cancer (adjusted hazard ratio, 0.99; 95% CI, 0.81-1.20). Patients who had a pregnancy had significantly better breast cancer–specific survival and overall survival.Conclusions and RelevanceIn this global study, 1 in 5 young BRCA carriers conceived within 10 years after breast cancer diagnosis. Pregnancy following breast cancer in BRCA carriers was not associated with decreased disease-free survival.Trial RegistrationClinicalTrials.gov Identifier: NCT03673306

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Modifiers of Cancer Risk in BRCA1 and BRCA2 Mutation Carriers: A Systematic Review and Meta-Analysis

Cited by 190 publications

References 71 publications

Population Attributable Risk of Modifiable and Nonmodifiable Breast Cancer Risk Factors in Postmenopausal Breast Cancer

Population Attributable Risk of Modifiable and Nonmodifiable Breast Cancer Risk Factors in Postmenopausal Breast Cancer

Ovarian cancer

Pregnancy After Breast Cancer in Young BRCA Carriers

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