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Several breast cancer susceptibility genes have been discovered, but more are likely to exist. To identify additional breast cancer susceptibility genes, we used the founder population of Poland and performed whole-exome sequencing on 510 women with familial breast cancer and 308 control subjects. We identified a rare mutation in ATRIP (GenBank: NM_130384.3: c.1152_1155del [p.Gly385Ter]) in two women with breast cancer. At the validation phase, we found this variant in 42/16,085 unselected Polish breast cancer-affected individuals and in 11/9,285 control subjects (OR = 2.14, 95% CI = 1.13-4.28, p = 0.02). By analyzing the sequence data of the UK Biobank study participants (450,000 individuals), we identified ATRIP loss-of-function variants among 13/15,643 breast cancer-affected individuals versus 40/157,943 control subjects (OR = 3.28, 95% CI = 1.76-6.14, p < 0.001). Immunohistochemistry and functional studies showed the ATRIP c.1152_1155del variant allele is weakly expressed compared to the wild-type allele, and truncated ATRIP fails to perform its normal function to prevent replicative stress. We showed that tumors of women with breast cancer who have a germline ATRIP mutation have loss of heterozygosity at the site of ATRIP mutation and genomic homologous recombination deficiency. ATRIP is a critical partner of ATR that binds to RPA coating single-stranded DNA at sites of stalled DNA replication forks. Proper activation of ATR-ATRIP elicits a DNA damage checkpoint crucial in regulating cellular responses to DNA replication stress. Based on our observations, we conclude ATRIP is a breast cancer susceptibility gene candidate linking DNA replication stress to breast cancer.
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Proteínas Adaptadoras Transductoras de Señales , Neoplasias de la Mama , Proteínas de Unión al ADN , Femenino , Humanos , Proteínas Adaptadoras Transductoras de Señales/genética , Bancos de Muestras Biológicas , Neoplasias de la Mama/genética , Proteínas de Ciclo Celular/genética , Daño del ADN , Proteínas de Unión al ADN/genética , Polonia/epidemiología , Proteína de Replicación A/genética , Proteína de Replicación A/metabolismo , Reino Unido/epidemiologíaRESUMEN
BACKGROUND: Risk-reducing mastectomy (RRM) is offered to women with a BRCA1 or BRCA2 pathogenic variant, however, there are limited data on the impact on breast cancer mortality. METHODS: Participants were identified from a registry of women with BRCA1/2 pathogenic variants. We used a pseudo-randomised trial design and matched one woman with a RRM to one woman without a RRM on year of birth, gene, and country. We estimated the hazard ratio (HR) and 95% confidence intervals (CI) for dying of breast cancer in the follow-up period. RESULTS: There were 1654 women included; 827 assigned to the RRM arm and 827 assigned to the control arm. After a mean follow-up of 6.3 years, there were 20 incident breast cancers (including 15 occult cancers) and two breast cancer deaths in the RRM arm, and 100 incident breast cancers and 7 breast cancer deaths in the control arm (HR = 0.26; 95% CI 0.05-1.35; p = 0.11). The probability of dying of breast cancer within 15 years after RRM was 0.95%. CONCLUSIONS: In women with a BRCA1 or BRCA2 pathogenic variant, RRM reduces the risk of breast cancer, and the probability of dying of breast cancer is low.
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Neoplasias de la Mama , Femenino , Humanos , Neoplasias de la Mama/genética , Neoplasias de la Mama/cirugía , Mastectomía , Proteína BRCA1/genética , Proteína BRCA2/genética , Genes BRCA1 , MutaciónRESUMEN
BACKGROUND: Breast-conserving surgery (BCS) followed by adjuvant radiotherapy (RT) is a standard treatment for ductal carcinoma in situ (DCIS). A low-risk patient subset that does not benefit from RT has not yet been clearly identified. The DCISionRT test provides a clinically validated decision score (DS), which is prognostic of 10-year in-breast recurrence rates (invasive and non-invasive) and is also predictive of RT benefit. This analysis presents final outcomes from the PREDICT prospective registry trial aiming to determine how often the DCISionRT test changes radiation treatment recommendations. METHODS: Overall, 2496 patients were enrolled from February 2018 to January 2022 at 63 academic and community practice sites and received DCISionRT as part of their care plan. Treating physicians reported their treatment recommendations pre- and post-test as well as the patient's preference. The primary endpoint was to identify the percentage of patients where testing led to a change in RT recommendation. The impact of the test on RT treatment recommendation was physician specialty, treatment settings, individual clinical/pathological features and RTOG 9804 like criteria. Multivariate logisitc regression analysis was used to estimate the odds ratio (ORs) for factors associated with the post-test RT recommendations. RESULTS: RT recommendation changed 38% of women, resulting in a 20% decrease in the overall recommendation of RT (p < 0.001). Of those women initially recommended no RT (n = 583), 31% were recommended RT post-test. The recommendation for RT post-test increased with increasing DS, from 29% to 66% to 91% for DS <2, DS 2-4, and DS >4, respectively. On multivariable analysis, DS had the strongest influence on final RT recommendation (odds ratio 22.2, 95% confidence interval 16.3-30.7), which was eightfold greater than clinicopathologic features. Furthermore, there was an overall change in the recommendation to receive RT in 42% of those patients meeting RTOG 9804-like low-risk criteria. CONCLUSIONS: The test results provided information that changes treatment recommendations both for and against RT use in large population of women with DCIS treated in a variety of clinical settings. Overall, clinicians changed their recommendations to include or omit RT for 38% of women based on the test results. Based on published clinical validations and the results from current study, DCISionRT may aid in preventing the over- and undertreatment of clinicopathological 'low-risk' and 'high-risk' DCIS patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03448926 ( https://clinicaltrials.gov/study/NCT03448926 ).
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Neoplasias de la Mama , Carcinoma Intraductal no Infiltrante , Mastectomía Segmentaria , Humanos , Femenino , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/patología , Carcinoma Intraductal no Infiltrante/radioterapia , Carcinoma Intraductal no Infiltrante/cirugía , Carcinoma Intraductal no Infiltrante/patología , Persona de Mediana Edad , Radioterapia Adyuvante , Pronóstico , Estudios Prospectivos , Anciano , Estudios de Seguimiento , Recurrencia Local de Neoplasia/patología , Toma de Decisiones Clínicas , Adulto , Toma de Decisiones , Biomarcadores de TumorRESUMEN
BACKGROUND: It has not been clearly established if skin cancer or melanoma are manifestations of BRCA1 or BRCA2 mutation carrier status. Estimating the risk of skin cancer is an important step towards developing screening recommendations. METHODS: We report the findings of a prospective cohort study of 6,207 women from North America who carry BRCA1 or BRCA2 mutations. Women were followed from the date of baseline questionnaire to the diagnosis of skin cancer, to age 80 years, death from any cause, or the date of last follow-up. RESULTS: During the mean follow-up period of eight years, 3.7% of women with a BRCA1 mutation (133 of 3,623) and 3.8% of women with a BRCA2 mutation (99 of 2,584) reported a diagnosis of skin cancer (including both keratinocyte carcinomas and melanoma). The cumulative risk of all types of skin cancer from age 20 to 80 years was 14.1% for BRCA1 carriers and 10.7% for BRCA2 carriers. The cumulative risk of melanoma was 2.5% for BRCA1 carriers and 2.3% for BRCA2 carriers, compared to 1.5% for women in the general population in the United States. The strongest risk factor for skin cancer was a prior diagnosis of skin cancer. CONCLUSION: The risk of non-melanoma skin cancer in women who carry a mutation in BRCA1 or BRCA2 is similar to that of non-carrier women. The risk of melanoma appears to be slightly elevated. We suggest that a referral to a dermatologist or primary care provider for BRCA mutation carriers for annual skin examination and counselling regarding limiting UV exposure, the use of sunscreen and recognizing the early signs of melanoma might be warranted, but further studies are necessary.
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BACKGROUND: The purpose of this study was to estimate the cumulative risks of all cancers in women from 50 to 75 years of age with a BRCA1 or BRCA2 pathogenic variant. METHODS: Participants were women with BRCA1 or BRCA2 pathogenic variants from 85 centers in 16 countries. Women were eligible if they had no cancer before the age of 50 years. Participants completed a baseline questionnaire and follow-up questionnaires every 2 years. Women were followed from age 50 until a diagnosis of cancer, death, age 75, or last follow-up. The risk of all cancers combined from age 50 to 75 was estimated using the Kaplan-Meier method. RESULTS: There were 2211 women included (1470 BRCA1 and 742 BRCA2). There were 379 cancers diagnosed in the cohort between 50 and 75 years. The actuarial risk of any cancer from age 50 to 75 was 49% for BRCA1 and 43% for BRCA2. Breast (n = 186) and ovarian (n = 45) were the most frequent cancers observed. For women who had both risk-reducing mastectomy and bilateral salpingo-oophorectomy before age 50, the risk of developing any cancer between age 50 and 75 was 9%. CONCLUSION: Women with a BRCA1 or BRCA2 pathogenic variant have a high risk of cancer between the ages of 50 and 75 years and should be counselled appropriately.
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Proteína BRCA1 , Proteína BRCA2 , Predisposición Genética a la Enfermedad , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/genética , Genes BRCA2 , Mastectomía , Mutación , Neoplasias Ováricas/epidemiología , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , OvariectomíaRESUMEN
PURPOSE: Chemoprevention with a selective estrogen receptor modulator (tamoxifen or raloxifene) is a non-surgical option offered to high-risk women to reduce the risk of breast cancer. The evidence for tamoxifen benefit is based on trials conducted among predominantly postmenopausal women from the general population and on studies of contralateral breast cancer in women with a pathogenic variant (mutation hereafter) in BRCA1 or BRCA2. Tamoxifen has not been assessed as a primary prevention agent in women with an inherited BRCA mutation. METHODS: We conducted a prospective analysis of tamoxifen chemoprevention and the risk of breast cancer in women with a BRCA1 or BRCA2 mutation. Data on tamoxifen (and raloxifene) use was collected by questionnaire and updated biennially. Information on incident cancers was collected by self-report and was confirmed by medical record review. In a matched analysis, we estimated the hazard ratio (HR) and 95% confidence intervals (CI) for developing a first primary breast cancer associated with tamoxifen or raloxifene use, using Cox proportional hazards analysis. RESULTS: There were 4578 unaffected women in the cohort, of whom 137 reported tamoxifen use (3%), 83 reported raloxifene use (2%) and 12 used both drugs (0.3%). Women who used tamoxifen or raloxifene were matched 1:3 with women who used neither drug on year of birth, country of residence, year of study entry and gene (BRCA1 or BRCA2). We generated 202 matched pairs. After a mean follow-up of 6.8 years, there were 22 incident breast cancers diagnosed among tamoxifen/raloxifene users (10.9% of users) and 71 cases diagnosed among non-users (14.3% of non-users; HR = 0.64; 95% CI 0.40-1.03; P = 0.07). CONCLUSION: Chemoprevention may be an effective risk-reduction option for BRCA mutation carriers, but further studies with longer follow-up are necessary.
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Neoplasias de la Mama , Tamoxifeno , Humanos , Femenino , Tamoxifeno/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/genética , Clorhidrato de Raloxifeno/efectos adversos , Genes BRCA1 , Mutación , Factores de Riesgo , Proteína BRCA1/genética , Proteína BRCA2/genéticaRESUMEN
With widespread testing for susceptibility genes, increasing numbers of women are being identified to carry a mutation in one of many genes which renders them susceptible to cancer. The first gene to be identified (in 1994) was BRCA1 which increases a woman's risk for breast cancer (70%) and ovarian cancer (40%). The prevalence of BRCA1 gene mutations has been studied widely and in many countries, mostly in women affected with cancer. In many settings testing is offered routinely to women with serous ovarian cancer or early-onset or triple-negative breast cancer. It is preferable to identify a mutation in a healthy women prior to the diagnosis of cancer. The basic strategies for prevention include surgical prevention, chemoprevention and screening (early detection). Much progress has been made in the past two decades evaluating the benefits of these three approaches. In this commentary I provide my personal views regarding these various interventions in the context of counselling a newly diagnosed health woman with a BRCA1 mutation.
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BRCA1 and BRCA2 mutations contribute to both breast cancer and ovarian cancer worldwide. In Poland approximately 4% of patients with breast cancers and 10% of patients with ovarian cancer carry a mutation in BRCA1. The majority of mutations consist of three founder mutations. A rapid inexpensive test for these three mutations can be used to screen all Polish adults at a reasonable cost. In the region of Pomerania of North-western Poland nearly half a million tests have been performed, in large part through engaging family doctors and providing ready access to testing through the Pomeranian Medical University. The following commentary provides a history of genetic testing for cancer in Pomerania and the current approach to facilitating access to genetic testing at the Cancer Family Clinic for all adults living in the region.
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Ovarian cancer has a high case fatality rate, but patients who have no visible residual disease after surgery have a relatively good prognosis. The presence of any cancer cells left in the peritoneal cavity after treatment may precipitate a cancer recurrence. In many cases, these cells are occult and are not visible to the surgeon. Analysis of circulating tumour DNA in the blood (ctDNA) may offer a sensitive method to predict the presence of occult (non-visible) residual disease after surgery and may help predict disease recurrence. We assessed 48 women diagnosed with serous ovarian cancer (47 high-grade and 1 low-grade) for visible residual disease and for ctDNA. Plasma, formalin-fixed paraffin-embedded (FFPE) tumour tissue and white blood cells were used to extract circulating free DNA (cfDNA), tumour DNA and germline DNA, respectively. We sequenced DNA samples for 59 breast and ovarian cancer driver genes. The plasma sample was collected after surgery and before initiating chemotherapy. We compared survival in women with no residual disease, with and without a positive plasma ctDNA test. We found tumour-specific variants (TSVs) in cancer cells from 47 patients, and these variants were sought in ctDNA in their post-surgery plasma. Fifteen (31.9%) of the 47 patients had visible residual disease; of these, all 15 had detectable ctDNA. Thirty-one patients (65.9%) had no visible residual disease; of these, 24 (77.4%) patients had detectable ctDNA. Of the patients with no visible residual disease, those patients with detectable ctDNA had higher mortality (20 of 27 died) than those without detectable ctDNA (3 of 7 died) (HR 2.32; 95% CI: 0.67-8.05), although this difference was not statistically significant (p = 0.18). ctDNA in post-surgical serum samples may predict the presence of microscopic residual disease and may be a predictor of recurrence among women with ovarian cancer. Larger studies are necessary to validate these findings.
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Ácidos Nucleicos Libres de Células , Cistadenocarcinoma Seroso , Neoplasias Ováricas , Humanos , Femenino , Neoplasia Residual/genética , Recurrencia Local de Neoplasia/genética , Carcinoma Epitelial de Ovario , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/genética , OncogenesRESUMEN
BACKGROUND: Several clinical and tumour factors impact on ovarian cancer survival. It is important to evaluate if germline mutations impact long-term outcomes among patients with epithelial ovarian cancer. METHODS: We followed 1422 Ontario women with ovarian cancer. Clinical information was obtained from medical records and vital status was determined by registry linkage. Germline genetic testing was performed for 12 susceptibility genes. We estimated 20-year cancer-specific survival according to various factors. RESULTS: Twenty-year survival was inferior for women with serous cancers vs. other types (22.3% vs. 68.6%; P < 0.0001). Of the 1422 patients, 248 (17.4%) carried a germline mutation; 119 BRCA1; 75 BRCA2; 7 in a mismatch repair (MMR) gene and 47 in one of seven other genes. Among serous patients, 20-year survival was 28.9% for similar for women with a BRCA1 (28.9%), BRCA2 (21.2%) or no mutation (21.6%). Among endometrioid patients, 20-year survival was poor for women with a BRCA vs. no mutation (47.3% vs. 70.4%; P = 0.004). Six of the seven MMR mutation carriers are currently alive, while all three PALB2 mutation carriers died within 3 years of diagnosis. Among women with Stage III/IV serous cancers, 20-year survival was 9.4% for those with vs. 46.5% for those with no residual disease (HR = 2.91; 95% CI 2.12-4.09, P < 0.0001). CONCLUSIONS: The most important predictor of long-term survival was no residual disease post surgery. BRCA mutation status was not predictive of long-term survival while those with MMR mutations had excellent survival. Larger studies on PALB2 carriers are needed.
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Carcinoma Epitelial de Ovario , Mutación de Línea Germinal , Proteína BRCA2/genética , Carcinoma Epitelial de Ovario/genética , Femenino , Genes BRCA1 , Genes BRCA2 , Humanos , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , PronósticoRESUMEN
BACKGROUND: To estimate the impact of oophorectomy and other treatments on the survival of breast cancer patients with a CHEK2 mutation. METHODS: Women with Stage I-III breast cancer who were treated at 17 hospitals in Poland were tested for four founder mutations in the CHEK2 gene. 974 women (10%) were positive for a CHEK2 mutation. Control patients without a CHEK2 mutation were selected from a database of patients treated over the same time period. Information on treatments received and distant recurrences were retrieved from medical records. Treatments included chemotherapy, hormonal therapy (tamoxifen) and radiation therapy. Oophorectomies were performed for the treatment of breast cancer or for benign conditions. Dates of death were obtained from the Polish Vital Statistics Registry. Causes of death were determined by medical record review. Predictors of survival were determined using the Cox proportional hazards model. RESULTS: In all, 839 patients with a CHEK2 mutation were matched to 839 patients without a mutation. The mean follow-up was 12.0 years. The 15-year survival for CHEK2 carriers was 76.6% and the 15-year survival for non-carrier control patients was 78.8% (adjusted HR = 1.06; 95% CI: 0.84-1.34; P = 0.61). Among CHEK2 carriers, the 15-year survival for women who had an oophorectomy was 86.3% and for women who did not have an oophorectomy was 72.1% (adjusted HR = 0.59; 95% CI: 0.38-0.90; P = 0.02). Among controls, the 15-year survival for patients who had an oophorectomy was 84.5% and for women who did not have an oophorectomy was 77.6% (adjusted HR = 1.03; 95% CI: 0.66-1.61; P = 0.90). CONCLUSION: Among women with breast cancer and a CHEK2 mutation, oophorectomy is associated with a reduced risk of death from breast cancer.
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Neoplasias de la Mama , Quinasa de Punto de Control 2 , Ovariectomía , Neoplasias de la Mama/genética , Neoplasias de la Mama/cirugía , Quinasa de Punto de Control 2/genética , Femenino , Predisposición Genética a la Enfermedad , Humanos , Mutación , Modelos de Riesgos Proporcionales , Factores de RiesgoRESUMEN
PURPOSE: Many women are being offered rapid genetic testing (RGT) for cancer predisposition genes, at the time of breast cancer diagnosis prior to surgery. The goal of this study was to determine if psychosocial functioning was affected in women receiving RGT for BRCA1 and BRCA2 at the time of breast cancer diagnosis. METHODS: Participants were women with invasive breast cancer diagnosed between 2013 and 2018, at four centres in Toronto, Canada. Eligible women were referred into the study by their surgeon at the time of diagnosis. Participants received pre-test genetic counselling and were offered RGT for BRCA1 and BRCA2. Standardized questionnaires (Impact of Event Scale and Hospital Anxiety and Depression Scale) were completed before genetic counselling, and follow-up questionnaires at one-week and one-year post-genetic test result disclosure (higher scores indicate higher symptoms). RESULTS: 1007 women had RGT; 60 women (6.0%) were found to have a BRCA1 or BRCA2 mutation, 80 women (7.9%) had a VUS, and 867 (86.1%) had a negative test result. At one-week post-testing, there were no differences in distress (p = 0.32), anxiety (p = 0.14), or depression (p = 0.42) between women with a BRCA1/2 mutation and those with a negative result. At one year, there were no differences in distress (p = 0.75) or anxiety (p = 0.13) between women with a BRCA1 or BRCA/2 mutation and those with a negative result. However, women with a BRCA1 or BRCA2 mutation had significantly lower depression scores compared to women with a negative result (p = 0.03). CONCLUSION: For women who have RGT for BRCA1 and BRCA2 at the time of breast cancer diagnosis, identifying a BRCA1 or BRCA2 mutation does not impair psychosocial functioning in the short or long term.
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Neoplasias de la Mama , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/genética , Femenino , Genes BRCA2 , Predisposición Genética a la Enfermedad , Pruebas Genéticas , Humanos , Mutación , Funcionamiento PsicosocialRESUMEN
PURPOSE: Young women with breast cancer (YWBC) are an understudied population and there are limited data on risk factors for psychological morbidity early in diagnosis. We examined psychological morbidity (anxiety, depression, stress symptoms), well-being and associated risk factors. METHODS: A total of 845 women from a pan-Canadian, multicentre inception cohort study of YWBC (age ≤ 40) who completed Patient Reported Outcome Measures (PROMs) after their initial surgical consultation and prior to surgical or other treatments were included. Multivariate regression analyses identified risk factors (i.e. parenting young children) associated with psychological morbidity and whether coping self-efficacy was protective. RESULTS: Rates of clinically significant anxiety (n = 683, 69.1%) and depression (n = 422, 42.7%) were high but lower for stress symptoms (n = 67, 6.8%). Probability of anxiety was high for women with a previous history of depression (OR 2.02, P = 0.03, CI 1.09-3.74) and working full-time (OR 1.76, P = 0.05 CI 1.02-2.77). Whereas, pre-existing depression (OR 2.91, P = 0.01, CI 1.36-6.01), younger children (age ≤ 10) (OR 1.69, P = 0.05, CI 1.01-2.93), and income > $100,000 (OR 2.06, P = 0.02, CI 1.18-3.64) were risk factors for depression. Coping self-efficacy was protective with a decreased risk of anxiety (OR 0.11, P ≤ 0.01 CI 0.04-0.28), depression (OR 0.03, P ≤ .01, CI 0.01-0.16), stress symptoms (OR 0.17, P ≤ .01, CI 0.04-0.65) and higher psychosocial well-being with a gain of 19.68 points (P < 0.01) for high levels of CSE (> mean plus 1 SD). Those with lower levels of neurosis had less negative outcomes. CONCLUSION: Young women with breast cancer are vulnerable to psychological morbidity early in diagnosis, particularly those with low coping self-efficacy and may benefit from earlier supportive care.
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Neoplasias de la Mama , Autoeficacia , Adaptación Psicológica , Ansiedad/diagnóstico , Ansiedad/epidemiología , Ansiedad/etiología , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/psicología , Canadá/epidemiología , Niño , Preescolar , Estudios de Cohortes , Depresión/diagnóstico , Depresión/epidemiología , Depresión/etiología , Femenino , Humanos , Morbilidad , Calidad de Vida/psicología , Factores de Riesgo , Estrés Psicológico/epidemiología , Estrés Psicológico/etiologíaRESUMEN
BACKGROUND: Breast reconstruction is generally discouraged in women with inflammatory breast cancer (IBC). Nevertheless, reconstruction rates are increasing in this population. OBJECTIVE: We aimed to determine contemporary trends and predictors of breast reconstruction use and its impact on mortality among IBC patients. METHODS: Demographic, clinicopathologic, and follow-up data for women with non-metastatic IBC having mastectomy between 2004 and 2015 were collected from the Surveillance, Epidemiology, and End Results (SEER) 18 registries database. Rates and predictors of immediate breast reconstruction, along with survival outcomes between the breast reconstruction and no reconstruction groups were calculated. To account for selection bias, a propensity score analysis matching one reconstruction patient to three no reconstruction patients was performed. RESULTS: A total of 4076 women with non-metastatic IBC who underwent mastectomy (388 [9.5%] with breast reconstruction and 3688 [90.5%] without) were included. The proportion of women undergoing breast reconstruction and contralateral prophylactic mastectomy increased from 6.2 to 15.3% and 12.9 to 29.6%, respectively, between 2004 and 2015. Younger age, higher annual income, metropolitan residence, and bilateral mastectomy predicted breast reconstruction use. The 10-year breast cancer-specific survival was 62.9% for women having breast reconstruction and 47.6% for women not having breast reconstruction. After propensity-matched analysis, 10-year cancer-specific survival was similar between the reconstruction (56.6%) and no reconstruction (62.2%) groups (adjusted hazard ratio 0.96, 95% confidence interval 0.79-1.16; p = 0.65). CONCLUSIONS: Breast reconstruction rates continue to rise among IBC patients, particularly young women and women with access to reconstruction. Breast reconstruction is not associated with inferior breast cancer-specific survival and can be an option for select patients.
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Neoplasias de la Mama , Neoplasias Inflamatorias de la Mama , Mamoplastia , Humanos , Femenino , Mastectomía/métodos , Neoplasias Inflamatorias de la Mama/cirugía , Neoplasias de la Mama/patología , Modelos de Riesgos Proporcionales , Sistema de RegistrosRESUMEN
BACKGROUND: Prompt referral by their surgeon enables fertility preservation (FP) by young women with breast cancer (YWBC) without treatment delay. Following a FP knowledge intervention, we evaluated surgeon and patient reports of fertility discussion, FP referral offer and uptake, and FP choices and reasons for declining FP among patients enrolled in the Reducing Breast Cancer in Young Women, prospective pan-Canadian study. METHODS: Between September 2015 and December 2020, 1271 patients were enrolled at 31 sites. For each patient, surgeons were sent a questionnaire inquiring whether: (1) fertility discussion was initiated by the surgical team; (2) FP referral was offered; (3) referral was accepted; a reason was requested for any "no" response. Patients were surveyed about prediagnosis fertility plans and postdiagnosis oncofertility management. RESULTS: Surgeon questionnaires were completed for 1068 (84%) cases. Fertility was discussed with 828 (84%) and FP consultation offered to 461 (47%) of the 990 YWBC with invasive disease. Among the 906 responding YWBC, referral was offered to 220 (82%) of the 283 (33%) with invasive disease who stated that they had definitely/probably not completed childbearing prediagnosis. Of these, 133 (47%) underwent FP. The two most common reasons for not choosing FP were cost and unwillingness to delay treatment. CONCLUSIONS: Although the rates of surgeon fertility discussion and FP referral was higher than most reports, likely due to our previous intervention, further improvement is desirable. FP should be offered to all YWBC at diagnosis, regardless of perceived childbearing intent. Cost remains an important barrier to FP uptake.
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Neoplasias de la Mama , Preservación de la Fertilidad , Neoplasias , Cirujanos , Neoplasias de la Mama/cirugía , Canadá , Femenino , Humanos , Neoplasias/terapia , Estudios Prospectivos , Derivación y ConsultaRESUMEN
Approximately 1% of the Ashkenazi Jewish population carries the BRCA2 6174delT (c.5946del) pathogenic variant. It is important to have accurate knowledge of the risks of breast and ovarian cancer associated with this specific variant so that women may be counseled accordingly. In this prospective study, we estimated the risks of breast and ovarian cancer associated with the 6174delT variant compared with the risks for other pathogenic variants in the BRCA2 gene. The annual risk for developing breast cancer was significantly lower in 246 women who carried the 6174delT variant compared with 721 non-Jewish women who carried a variant at any other locus in BRCA2 (1.2% per year vs. 2.4% per year, p = 0.003). We estimated the cumulative risk of breast cancer from age 30 to 70 to be 39% for carriers of the BRCA2 6174delT variant and 61% for carriers of other BRCA2 variants. The annual risk for ovarian or fallopian tube cancer was 0.51% per year for the 233 women who carried the 6174delT variant compared to 0.22% per year for the 1128 carriers of other BRCA2 variants; the difference was not significant. Lower risks for breast cancer associated with 6174delT may not impact screening and prevention choices, however, the discussion should be based on accurate risk assessment.
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Neoplasias de la Mama , Neoplasias Ováricas , Adulto , Anciano , Alelos , Proteína BRCA2/genética , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/genética , Carcinoma Epitelial de Ovario/genética , Femenino , Humanos , Judíos/genética , Persona de Mediana Edad , Mutación , Proteínas de Neoplasias/genética , Neoplasias Ováricas/epidemiología , Neoplasias Ováricas/genética , Estudios Prospectivos , Factores de Transcripción/genéticaRESUMEN
Background BRCA1 and BRCA2 (BRCA) mutation carriers face a high lifetime risk of developing ovarian cancer. Oral contraceptives are protective in this population; however, the impact of other types of contraception (e.g. intrauterine devices, implants, injections) is unknown. We undertook a matched case-control study to evaluate the relationship between type of contraception and risk of ovarian cancer among women with BRCA mutations. Methods A total of 1733 matched pairs were included in this analysis. Women were matched according to year of birth, date of study entry, country of residence, BRCA mutation type and history of breast cancer. Detailed information on hormonal, reproductive and lifestyle exposures were collected from a routinely administered questionnaire. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) associated with each contraceptive exposure. Results Ever use of any contraceptive was significantly associated with reduced risk of ovarian cancer (OR = 0.62; 95% CI 0.52-0.75; P < 0.0001), which was driven by significant inverse associations with oral contraceptives (OR = 0.66; 95% CI 0.54-0.79; P < 0.0001) and contraceptive implants (OR = 0.30; 95% CI 0.12-0.73; P = 0.008). We observed a similar effect with use of injections (OR = 0.37; 95% CI 0.10-1.38; P = 0.14), but this did not achieve significance. No significant associations were observed between patterns of intrauterine device use and risk of ovarian cancer. Conclusions These findings support a protective effect of oral contraceptives and implants on risk of ovarian cancer among women with BRCA mutations. The possible protective effect of injections requires further evaluation.
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Neoplasias de la Mama , Neoplasias Ováricas , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias de la Mama/genética , Carcinoma Epitelial de Ovario , Estudios de Casos y Controles , Anticonceptivos Orales/uso terapéutico , Femenino , Heterocigoto , Humanos , Mutación , Neoplasias Ováricas/etiología , Neoplasias Ováricas/genética , Factores de RiesgoRESUMEN
INTRODUCTION: The role of the BRCA1 and BRCA2 genes in bladder and renal tumorigenesis is unclear. Our goal was to determine the prevalence of specific founder mutations genes BRCA1 (5328 insC, C61G and 4153 delA) and BRCA2 (C5972T) mutations in bladder and kidney cancer patients from Poland. MATERIALS AND METHODS: We genotyped 1028 patients with bladder cancer and 688 cases with kidney cancer and two control groups. RESULTS: A BRCA1 mutation (all variants combined) was detected in peripheral blood leukocytes in 5 out of 1028 (0.5%) bladder cases and in 17 of 4000 controls (0.4%) (odds ratio [OR], (OR = 1.1; 95% CI 0.42-3.11; p = 1.0). Among 688 unselected kidney cancer cases a BRCA1 mutations was reported in three patients (0.4%) (OR = 1.0; 95% CI 0.29-3.51; p = 1.0). The mutation C5972T in BRCA2 was observed in 54 bladder cancer patients (5.2%) and in 159 of 2791 healthy controls (5.7%) (OR = 0.9; 95% CI 0.66-1.26; p = 0.6). Fifty kidney cancer cases carried a BRCA2 mutation (7.3%) (OR = 1.3; 95% CI 0.93-1.80; p = 0.1). CONCLUSION: In conclusion, we found no difference in the prevalence of BRCA1 and BRCA2 founder mutations between cases and healthy controls. The mutations BRCA1 and BRCA2 seem not to play a role in bladder and kidney cancer development in Polish patients.
RESUMEN
BACKGROUND: The objective of this study was to evaluate the impact of various surgical, hormonal, and lifestyle factors on memory and attention in women with a BRCA1 or BRCA2 mutation. METHODS: BRCA mutation carriers enrolled in a longitudinal study were invited to complete an online brain health assessment tool designed to screen for cognitive deficits. Four measures of memory and executive attention were assessed individually, and an overall score was compiled adjusting for age. Exposures, including preventive surgery, hormone use, and lifestyle factors, were captured by questionnaire. Performance on each of the 5 subtasks was analyzed according to various exposures. Analysis of covariance was used to compare overall scores. RESULTS: In total, 880 women completed the online cognitive assessment. The average age of the participants was 54 years (range, 23-86 years). The mean overall test score was 54.4 (range, 0-93). The individual subtask scores declined with age at test completion (P < .0001) and increased with level of education (P ≤ .01). Women who underwent a preventive oophorectomy had a significantly higher overall score compared with women who did not undergo this surgery (55.5 vs 50.5; P = .01). Reconstructive breast surgery was also associated with a higher overall score (56.5 vs 52.3; P = .005). Chemotherapy and hormone-replacement therapy were not predictive of the overall score. CONCLUSIONS: These findings are reassuring to high-risk women who undergo early surgical menopause for their cancer predisposition. Further studies are needed to evaluate cognitive function over time when memory deficits become more prevalent.
Asunto(s)
Neoplasias de la Mama , Neoplasias Ováricas , Adulto , Anciano , Anciano de 80 o más Años , Atención , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias de la Mama/genética , Neoplasias de la Mama/cirugía , Cognición , Femenino , Predisposición Genética a la Enfermedad , Humanos , Estudios Longitudinales , Persona de Mediana Edad , Mutación , Neoplasias Ováricas/genética , Ovariectomía , Adulto JovenRESUMEN
BACKGROUND: We sought to estimate the annual risk and 25-year cumulative risk of contralateral breast cancer among women with stage 0-III unilateral breast cancer. METHODS: We identified 812,851 women with unilateral breast cancer diagnosed between 1990 and 2015 in the SEER database and followed them for contralateral breast cancer for up to 25 years. Women with a known bilateral mastectomy were excluded. We calculated the annual risk of contralateral breast cancer by age at diagnosis, by time since diagnosis and by current age. We compared risks by ductal carcinoma in situ (DCIS) versus invasive disease, by race and by oestrogen receptor (ER) status of the first cancer. RESULTS: There were 25,958 cases of contralateral invasive breast cancer diagnosed (3.2% of all patients). The annual risk of contralateral breast cancer over the 25-year follow-up period was 0.37% and the 25-year actuarial risk of contralateral invasive breast cancer was 9.9%. The annual risk varied to a small degree by age of diagnosis, by time elapsed since diagnosis and by current age. The 25-year actuarial risk was similar for DCIS and invasive breast cancer patients (10.1 versus 9.9%). The 25-year actuarial risk was higher for black women (12.7%) than for white women (9.7%) and was lower for women with ER-positive breast cancer (9.5%) than for women with ER-negative breast cancer (11.2%). CONCLUSIONS: Women with unilateral breast cancer experience an annual risk of contralateral breast cancer ~0.4% per year, which persists over the 25-year follow-up period.