RESUMO
BACKGROUND: The effect of gender-affirming testosterone therapy (TT) on breast cancer risk is unclear. This study investigated the association between TT and breast tissue composition and breast tissue density in trans masculine individuals (TMIs). METHODS: Of the 444 TMIs who underwent chest-contouring surgeries between 2013 and 2019, breast tissue composition was assessed in 425 TMIs by the pathologists (categories of lobular atrophy and stromal composition) and using our automated deep-learning algorithm (% epithelium, % fibrous stroma, and % fat). Forty-two out of 444 TMIs had mammography prior to surgery and their breast tissue density was read by a radiologist. Mammography digital files, available for 25/42 TMIs, were analyzed using the LIBRA software to obtain percent density, absolute dense area, and absolute non-dense area. Linear regression was used to describe the associations between duration of TT use and breast tissue composition or breast tissue density measures, while adjusting for potential confounders. Analyses stratified by body mass index were also conducted. RESULTS: Longer duration of TT use was associated with increasing degrees of lobular atrophy (p < 0.001) but not fibrous content (p = 0.82). Every 6 months of TT was associated with decreasing amounts of epithelium (exp(ß) = 0.97, 95% CI 0.95,0.98, adj p = 0.005) and fibrous stroma (exp(ß) = 0.99, 95% CI 0.98,1.00, adj p = 0.05), but not fat (exp(ß) = 1.01, 95%CI 0.98,1.05, adj p = 0.39). The effect of TT on breast epithelium was attenuated in overweight/obese TMIs (exp(ß) = 0.98, 95% CI 0.95,1.01, adj p = 0.14). When comparing TT users versus non-users, TT users had 28% less epithelium (exp(ß) = 0.72, 95% CI 0.58,0.90, adj p = 0.003). There was no association between TT and radiologist's breast density assessment (p = 0.58) or LIBRA measurements (p > 0.05). CONCLUSIONS: TT decreases breast epithelium, but this effect is attenuated in overweight/obese TMIs. TT has the potential to affect the breast cancer risk of TMIs. Further studies are warranted to elucidate the effect of TT on breast density and breast cancer risk.
Assuntos
Densidade da Mama , Mama , Mamografia , Testosterona , Pessoas Transgênero , Humanos , Densidade da Mama/efeitos dos fármacos , Feminino , Adulto , Testosterona/uso terapêutico , Mamografia/métodos , Mama/diagnóstico por imagem , Mama/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/diagnóstico por imagem , Índice de Massa Corporal , Procedimentos de Readequação Sexual/efeitos adversos , Procedimentos de Readequação Sexual/métodosRESUMO
Deep learning-based mammographic evaluations could noninvasively assess response to breast cancer chemoprevention. We evaluated change in a convolutional neural network-based breast cancer risk model applied to mammograms among women enrolled in SWOG S0812, which randomly assigned 208 premenopausal high-risk women to receive oral vitamin D3 20â000 IU weekly or placebo for 12 months. We applied the convolutional neural network model to mammograms collected at baseline (n = 109), 12 months (n = 97), and 24 months (n = 67) and compared changes in convolutional neural network-based risk score between treatment groups. Change in convolutional neural network-based risk score was not statistically significantly different between vitamin D and placebo groups at 12 months (0.005 vs 0.002, P = .875) or at 24 months (0.020 vs 0.001, P = .563). The findings are consistent with the primary analysis of S0812, which did not demonstrate statistically significant changes in mammographic density with vitamin D supplementation compared with placebo. There is an ongoing need to evaluate biomarkers of response to novel breast cancer chemopreventive agents.
Assuntos
Densidade da Mama , Neoplasias da Mama , Colecalciferol , Aprendizado Profundo , Suplementos Nutricionais , Mamografia , Humanos , Feminino , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/prevenção & controle , Densidade da Mama/efeitos dos fármacos , Pessoa de Meia-Idade , Colecalciferol/administração & dosagem , Adulto , Vitamina D/administração & dosagem , Pré-Menopausa , Redes Neurais de Computação , Medição de RiscoRESUMO
Whether trace metals modify breast density, the strongest predictor for breast cancer, during critical developmental stages such as puberty remains understudied. Our study prospectively evaluated the association between trace metals at Tanner breast stage B1 (n = 291) and at stages both B1 and B4 (n = 253) and breast density at 2 years post-menarche among Chilean girls from the Growth and Obesity Cohort Study. Dual-energy x-ray absorptiometry assessed the volume of dense breast tissue (absolute fibroglandular volume [FGV]) and percent breast density (%FGV). Urine trace metals included arsenic, barium, cadmium, cobalt, cesium, copper, magnesium, manganese, molybdenum, nickel, lead, antimony, selenium, tin, thallium, vanadium, and zinc. At B1, a doubling of thallium concentration resulted in 13.69 cm3 increase in absolute FGV (ß: 13.69, 95% confidence interval [CI]: 2.81, 24.52), while a doubling of lead concentration resulted in a 7.76 cm3 decrease in absolute FGV (ß: -7.76, 95%CI: -14.71, -0.73). At B4, a doubling of barium concentration was associated with a 10.06 cm3 increase (ß: 10.06, 95% CI: 1.44, 18.60), copper concentration with a 12.29 cm3 increase (ß: 12.29, 95% CI: 2.78, 21.56), lead concentration with a 9.86 cm3 increase (ß: 9.86, 95% CI: 0.73, 18.98), antimony concentration with a 12.97 cm3 increase (ß: 12.97, 95% CI: 1.98, 23.79) and vanadium concentration with a 13.14 cm3 increase in absolute FGV (ß: 13.14, 95% CI: 2.73, 23.58). Trace metals may affect pubertal breast density at varying developmental stages with implications for increased susceptibility for breast cancer.
Assuntos
Absorciometria de Fóton , Densidade da Mama , Oligoelementos , Humanos , Feminino , Chile/epidemiologia , Adolescente , Densidade da Mama/efeitos dos fármacos , Oligoelementos/análise , Oligoelementos/urina , Estudos Prospectivos , Criança , Mama/efeitos dos fármacos , Mama/crescimento & desenvolvimento , Neoplasias da Mama/epidemiologiaRESUMO
Tamoxifen prevents recurrence of breast cancer and is also approved for preventive, risk-reducing, therapy. Tamoxifen alters the breast tissue composition and decreases the mammographic density. We aimed to test if baseline breast tissue composition influences tamoxifen-associated density change. This biopsy-based study included 83 participants randomised to 6 months daily intake of placebo, 20, 10, 5, 2.5, or 1 mg tamoxifen. The study is nested within the double-blinded tamoxifen dose-determination trial Karolinska Mammography Project for Risk Prediction of Breast Cancer Intervention (KARISMA) Study. Ultrasound-guided core-needle breast biopsies were collected at baseline before starting treatment. Biopsies were quantified for epithelial, stromal, and adipose distributions, and epithelial and stromal expression of proliferation marker Ki67, oestrogen receptor (ER) and progesterone receptor (PR). Mammographic density was measured using STRATUS. We found that greater mammographic density at baseline was positively associated with stromal area and inversely associated with adipose area and stromal expression of ER. Premenopausal women had greater mammographic density and epithelial tissue, and expressed more epithelial Ki67, PR, and stromal PR, compared to postmenopausal women. In women treated with tamoxifen (1-20 mg), greater density decrease was associated with higher baseline density, epithelial Ki67, and stromal PR. Women who responded to tamoxifen with a density decrease had on average 17% higher baseline density and a 2.2-fold higher PR expression compared to non-responders. Our results indicate that features in the normal breast tissue before tamoxifen exposure influences the tamoxifen-associated density decrease, and that the age-associated difference in density change may be related to age-dependant differences in expression of Ki67 and PR.
Assuntos
Antineoplásicos Hormonais , Densidade da Mama , Neoplasias da Mama , Mamografia , Tamoxifeno , Humanos , Tamoxifeno/farmacologia , Tamoxifeno/administração & dosagem , Feminino , Densidade da Mama/efeitos dos fármacos , Pessoa de Meia-Idade , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/metabolismo , Mamografia/métodos , Adulto , Antineoplásicos Hormonais/uso terapêutico , Antineoplásicos Hormonais/administração & dosagem , Método Duplo-Cego , Receptores de Estrogênio/metabolismo , Idoso , Receptores de Progesterona/metabolismo , Mama/efeitos dos fármacos , Mama/diagnóstico por imagem , Mama/patologia , Mama/metabolismo , Antígeno Ki-67/metabolismo , Antígeno Ki-67/análise , Pós-MenopausaRESUMO
Population studies show worrisome trends towards earlier breast development, difficulty in breastfeeding, and increasing rates of breast cancer in young women. Multiple epidemiological studies have linked these outcomes with chemical exposures, and experimental studies have shown that many of these chemicals generate similar effects in rodents, often by disrupting hormonal regulation. These endocrine-disrupting chemicals (EDCs) can alter the progression of mammary gland (MG) development, impair the ability to nourish offspring via lactation, increase mammary tissue density, and increase the propensity to develop cancer. However, current toxicological approaches to measuring the effects of chemical exposures on the MG are often inadequate to detect these effects, impairing our ability to identify exposures harmful to the breast and limiting opportunities for prevention. This paper describes key adverse outcomes for the MG, including impaired lactation, altered pubertal development, altered morphology (such as increased mammographic density), and cancer. It also summarizes evidence from humans and rodent models for exposures associated with these effects. We also review current toxicological practices for evaluating MG effects, highlight limitations of current methods, summarize debates related to how effects are interpreted in risk assessment, and make recommendations to strengthen assessment approaches. Increasing the rigor of MG assessment would improve our ability to identify chemicals of concern, regulate those chemicals based on their effects, and prevent exposures and associated adverse health effects.
Assuntos
Neoplasias da Mama , Mama , Exposição Ambiental , Poluentes Ambientais , Feminino , Humanos , Animais , Neoplasias da Mama/induzido quimicamente , Mama/efeitos dos fármacos , Mama/crescimento & desenvolvimento , Exposição Ambiental/efeitos adversos , Densidade da Mama/efeitos dos fármacos , Puberdade/efeitos dos fármacos , Poluentes Ambientais/farmacologiaRESUMO
BACKGROUND: We investigated the associations of oral contraceptives (OC) with percent breast density (PD), absolute dense area (DA), nondense area (NDA), and a novel image intensity variation (V) measure in premenopausal women. METHODS: This study included 1,233 controls from a nested case-control study within Nurses' Health Study II cohort. Information on OCs was collected in 1989 and updated biennially. OC use was defined from the questionnaire closest to the mammogram date. PD, DA, and NDA were measured from digitized film mammograms using a computer-assisted thresholding technique; the V measure was obtained with a previously developed algorithm measuring the SD of pixel values in the eroded breast region. Generalized linear regression was used to assess associations between OCs and density measures (square root-transformed PD, DA, and NDA, and -untransformed V). RESULTS: OC use was not associated with PD [current vs. never: ß = -0.06; 95% confidence interval (CI), -0.37-0.24; past vs. never: ß = 0.10; 95% CI, -0.09-0.29], DA (current vs. never: ß = -0.20; 95% CI -0.59-0.18; past vs. never: ß = 0.13; 95% CI, -0.12-0.39), and NDA (current vs. never: ß = -0.19; 95% CI, -0.56-0.18; past vs. never: ß = -0.01; 95% CI, -0.28-0.25). Women with younger age at initiation had significantly greater V-measure (<20 years vs. never: ß = 26.88; 95% CI, 3.18-50.58; 20-24 years vs. never: ß = 20.23; 95% CI, -4.24-44.71; 25-29 years vs. never: ß = 2.61; 95% CI -29.00-34.23; ≥30 years vs. never: ß = 0.28; 95% CI, -34.16-34.72, P trend = 0.03). CONCLUSIONS: Our findings suggest that an earlier age at first OC use was associated with significantly greater V. IMPACT: These findings could guide decisions about the age for OC initiation.
Assuntos
Densidade da Mama/efeitos dos fármacos , Mama/patologia , Anticoncepcionais Orais/efeitos adversos , Pré-Menopausa , Adulto , Estudos de Casos e Controles , Anticoncepcionais Orais/administração & dosagem , Feminino , Humanos , Mamografia/estatística & dados numéricos , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
PURPOSE: To evaluate the effect of sulindac, a nonselective anti-inflammatory drug (NSAID), for activity to reduce breast density (BD), a risk factor for breast cancer. EXPERIMENTAL DESIGN: An open-label phase II study was conducted to test the effect of 12 months' daily sulindac at 150 mg twice daily on change in percent BD in postmenopausal hormone receptor-positive breast cancer patients on aromatase inhibitor (AI) therapy. Change in percent BD in the contralateral, unaffected breast was measured by noncontrast magnetic resonance imaging (MRI) and reported as change in MRI percent BD (MRPD). A nonrandomized patient population on AI therapy (observation group) with comparable baseline BD was also followed for 12 months. Changes in tissue collagen after 6 months of sulindac treatment were explored using second-harmonic generated microscopy in a subset of women in the sulindac group who agreed to repeat breast biopsy. RESULTS: In 43 women who completed 1 year of sulindac (86% of those accrued), relative MRPD significantly decreased by 9.8% [95% confidence interval (CI), -14.6 to -4.7] at 12 months, an absolute decrease of -1.4% (95% CI, -2.5 to -0.3). A significant decrease in mean breast tissue collagen fiber straightness (P = 0.032), an investigational biomarker of tissue inflammation, was also observed. MRPD (relative or absolute) did not change in the AI-only observation group (N = 40). CONCLUSIONS: This is the first study to indicate that the NSAID sulindac may reduce BD. Additional studies are needed to verify these findings and determine if prostaglandin E2 inhibition by NSAIDs is important for BD or collagen modulation.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Antineoplásicos/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Densidade da Mama/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Sulindaco/uso terapêutico , Idoso , Neoplasias da Mama/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Pós-MenopausaRESUMO
BACKGROUND: Menopausal hormone therapy (MHT) is a risk factor for breast cancer (BC). Evidence suggests that its effect on BC risk could be partly mediated by mammographic density. The aim of this study was to investigate the relationship between MHT, mammographic density and BC risk using data from a prospective study. METHODS: We used data from a case-control study nested within the French cohort E3N including 453 cases and 453 matched controls. Measures of mammographic density, history of MHT use during follow-up and information on potential confounders were available for all women. The association between MHT and mammographic density was evaluated by linear regression models. We applied mediation modelling techniques to estimate, under the hypothesis of a causal model, the proportion of the effect of MHT on BC risk mediated by percent mammographic density (PMD) for BC overall and by hormone receptor status. RESULTS: Among MHT users, 4.2% used exclusively oestrogen alone compared with 68.3% who used exclusively oestrogens plus progestogens. Mammographic density was higher in current users (for a 60-year-old woman, mean PMD 33%; 95% CI 31 to 35%) than in past (29%; 27 to 31%) and never users (24%; 22 to 26%). No statistically significant association was observed between duration of MHT and mammographic density. In past MHT users, mammographic density was negatively associated with time since last use; values similar to those of never users were observed in women who had stopped MHT at least 8 years earlier. The odds ratio of BC for current versus never MHT users, adjusted for age, year of birth, menopausal status at baseline and BMI, was 1.67 (95% CI, 1.04 to 2.68). The proportion of effect mediated by PMD was 34% for any BC and became 48% when the correlation between BMI and PMD was accounted for. These effects were limited to hormone receptor-positive BC. CONCLUSIONS: Our results suggest that, under a causal model, nearly half of the effect of MHT on hormone receptor-positive BC risk is mediated by mammographic density, which appears to be modified by MHT for up to 8 years after MHT termination.
Assuntos
Densidade da Mama/efeitos dos fármacos , Neoplasias da Mama/etiologia , Terapia de Reposição Hormonal/efeitos adversos , Menopausa , Idoso , Neoplasias da Mama/metabolismo , Estudos de Casos e Controles , Terapia de Reposição Hormonal/estatística & dados numéricos , Humanos , Análise de Mediação , Pessoa de Meia-Idade , Razão de Chances , Estudos Prospectivos , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Fatores de RiscoRESUMO
PURPOSE: Tamoxifen prevents breast cancer in high-risk women and reduces mortality in the adjuvant setting. Mammographic density change is a proxy for tamoxifen therapy response. We tested whether lower doses of tamoxifen were noninferior to reduce mammographic density and associated with fewer symptoms. PATIENTS AND METHODS: Women, 40-74 years of age, participating in the Swedish mammography screening program were invited to the 6-month double-blind six-arm randomized placebo-controlled noninferiority dose-determination KARISMA phase II trial stratified by menopausal status (EudraCT 2016-000882-22). In all, 1,439 women were accrued with 1,230 participants accessible for intention-to-treat analysis. The primary outcome was proportion of women treated with placebo, 1, 2.5, 5, and 10 mg whose mammographic density decreased at least as much as the median reduction in the 20 mg arm. The noninferior margin was 17%. Secondary outcome was reduction of symptoms. Post hoc analyses were performed by menopausal status. Per-protocol population and full population were analyzed in sensitivity analysis. RESULTS: The 1,439 participants, 566 and 873 pre- and postmenopausal women, respectively, were recruited between October 1, 2016, and September 30, 2019. The participants had noninferior mammographic density reduction following 2.5, 5, and 10 mg tamoxifen compared with the median 10.1% decrease observed in the 20 mg group, a reduction confined to premenopausal women. Severe vasomotor symptoms (hot flashes, cold sweats, and night sweats) were reduced by approximately 50% in the 2.5, 5, and 10 mg groups compared with the 20 mg group. CONCLUSION: Premenopausal women showed noninferior magnitude of breast density decrease at 2.5 mg of tamoxifen, but fewer side effects compared with the standard dose of 20 mg. Future studies should test whether 2.5 mg of tamoxifen reduces the risk of primary breast cancer.
Assuntos
Densidade da Mama/efeitos dos fármacos , Neoplasias da Mama/prevenção & controle , Tamoxifeno/administração & dosagem , Adulto , Idoso , Antineoplásicos Hormonais/administração & dosagem , Método Duplo-Cego , Detecção Precoce de Câncer , Feminino , Humanos , Mamografia , Pessoa de Meia-IdadeRESUMO
Hormone replacement therapy in menopause is used to improve climacteric syndrome in women whose quality of life is affected. However, given the wide variety of progestogens available, it is important to evaluate their differential benign changes (radiological, cellular, and clinical) on the breast. This review aimed to determine the different benign changes of progestogens used in postmenopausal combined hormone therapy on the breast (radiological, cellular, and clinical), in women without mammary pathology, in order to establish their safety profile. A systematic review of the literature was carried out with a balanced search strategy for the identification of relevant references in the MEDLINE, BVSalud, EMBASE, ProQuest, and Cochrane databases until November 2019. The search terms used were 'menopause' or 'hormonal replacement therapy' or 'progestins' or 'estrogen' or 'mastodynia' or 'benign breast disease' or 'mammography'. Data were collected from the 'eligible' articles by two researchers (ARF and SHA), and possible discrepancies in inclusion were resolved by consensus. A total of 1886 articles were identified; 60 full-text articles were reviewed, and 17 articles that met the inclusion criteria were included for the qualitative analysis. In conclusion, combined hormone replacement therapy is associated with benign effects on the breast, such as mastodynia and increased mammographic density.
Assuntos
Doenças Mamárias/induzido quimicamente , Mama/efeitos dos fármacos , Terapia de Reposição de Estrogênios/efeitos adversos , Pós-Menopausa/efeitos dos fármacos , Progestinas/efeitos adversos , Densidade da Mama/efeitos dos fármacos , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
Background: Higher mammographic breast density (MBD) is associated with an increased risk of breast cancer when compared with lower MBD, especially in premenopausal women. However, little is known about the effectiveness of chemoprevention agents in reducing MBD in premenopausal women without a history of breast cancer. Findings from this review should provide insight on how to target MBD in breast cancer prevention in premenopausal women with dense breasts. Methods: We searched 9 electronic databases for clinical trials in English, Spanish, French, or German published until January 2020. Articles evaluating the association of pharmacological agents and MBD were included. Data were extracted on methods, type and dose of intervention, outcomes, side effects, and follow up. Quality of the studies was assessed using the US Preventive Services Task Force criteria. Results: We identified 7 clinical trials evaluating the associations of 6 chemoprevention agents with changes in MBD in premenopausal women without history of breast cancer. The studies evaluated selective estrogen-receptor modulators (n = 1); gonadotropin-releasing hormone agonists (n = 2); isoflavones (n = 1); vitamin D (n = 1); and Boswellia, betaine, and mayo-inositol compound (n = 1). Hormonal interventions were associated with net reductions in percent density (tamoxifen [13.4%], leuprolide acetate [8.9%], and goserelin [2.7%]), whereas nonhormonal (vitamin D and isoflavone) interventions were not. However, MBD returned to preintervention baseline levels after cessation of gonadotropin-releasing hormone agonists. Conclusions: A limited number of chemoprevention agents have been shown to reduce MBD in premenopausal women. Identification of new and well-tolerated chemoprevention agents targeting MBD and larger studies to confirm agents that have been studied in small trials are urgent priorities for primary breast cancer prevention in premenopausal women with dense breasts.
Assuntos
Anticarcinógenos/uso terapêutico , Densidade da Mama/efeitos dos fármacos , Pré-Menopausa , Betaína/uso terapêutico , Boswellia , Combinação de Medicamentos , Feminino , Hormônio Liberador de Gonadotropina/agonistas , Gosserrelina/uso terapêutico , Humanos , Inositol/uso terapêutico , Isoflavonas/uso terapêutico , Leuprolida/uso terapêutico , Mamografia , Ensaios Clínicos Controlados Aleatórios como Assunto , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Tamoxifeno/uso terapêutico , Vitamina D/uso terapêutico , Vitaminas/uso terapêuticoRESUMO
PURPOSE: Low-dose tamoxifen reduces breast cancer risk, but remains untested in chest-irradiated cancer survivors-a population with breast cancer risk comparable with BRCA mutation carriers. We hypothesized that low-dose tamoxifen would be safe and efficacious in reducing radiation-related breast cancer risk. PATIENTS AND METHODS: We conducted an investigator-initiated, randomized, phase IIb, double-blinded, placebo-controlled trial (FDA IND107367) between 2010 and 2016 at 15 U.S. sites. Eligibility included ≥12 Gy of chest radiation by age 40 years and age at enrollment ≥25 years. Patients were randomized 1:1 to low-dose tamoxifen (5 mg/day) or identical placebo tablets for 2 years. The primary endpoint was mammographic dense area at baseline, 1 and 2 years. IGF-1 plays a role in breast carcinogenesis; circulating IGF-1 and IGF-BP3 levels at baseline, 1 and 2 years served as secondary endpoints. RESULTS: Seventy-two participants (low-dose tamoxifen: n = 34, placebo: n = 38) enrolled at a median age of 43.8 years (35-49) were evaluable. They had received chest radiation at a median dose of 30.3 Gy. Compared with the placebo arm, the low-dose tamoxifen arm participants had significantly lower mammographic dense area (P = 0.02) and IGF1 levels (P < 0.0001), and higher IGFBP-3 levels (P = 0.02). There was no difference in toxicity biomarkers (serum bone-specific alkaline phosphatase, lipids, and antithrombin III; urine N-telopeptide cross-links) between the treatment arms. We did not identify any grade 3-4 adverse events related to low-dose tamoxifen. CONCLUSIONS: In this randomized trial in chest-irradiated cancer survivors, we find that low-dose tamoxifen is effective in reducing established biomarkers of breast cancer risk and could serve as a risk-reduction strategy.
Assuntos
Neoplasias da Mama/prevenção & controle , Sobreviventes de Câncer/estatística & dados numéricos , Neoplasias Induzidas por Radiação/prevenção & controle , Tamoxifeno/administração & dosagem , Adulto , Biomarcadores Tumorais/análise , Mama/diagnóstico por imagem , Mama/efeitos dos fármacos , Mama/efeitos da radiação , Densidade da Mama/efeitos dos fármacos , Densidade da Mama/efeitos da radiação , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/etiologia , Relação Dose-Resposta a Droga , Feminino , Humanos , Mamografia/estatística & dados numéricos , Pessoa de Meia-Idade , Neoplasias Induzidas por Radiação/diagnóstico , Neoplasias Induzidas por Radiação/etiologia , Órgãos em Risco/diagnóstico por imagem , Órgãos em Risco/efeitos da radiação , Resultado do TratamentoRESUMO
BACKGROUND: A decrease in breast density due to tamoxifen preventive therapy might indicate greater benefit from the drug. It is not known whether mammographic density continues to decline after 1 year of therapy, or whether measures of breast density change are sufficiently stable for personalised recommendations. METHODS: Mammographic density was measured annually over up to 5 years in premenopausal women with no previous diagnosis of breast cancer but at increased risk of breast cancer attending a family-history clinic in Manchester, UK (baseline 2010-2013). Tamoxifen (20 mg/day) for prevention was prescribed for up to 5 years in one group; the other group did not receive tamoxifen and were matched by age. Fully automatic methods were used on mammograms over the 5-year follow-up: three area-based measures (NN-VAS, Stratus, Densitas) and one volumetric (Volpara). Additionally, percentage breast density at baseline and first follow-up mammograms was measured visually. The size of density declines at the first follow-up mammogram and thereafter was estimated using a linear mixed model adjusted for age and body mass index. The stability of density change at 1 year was assessed by evaluating mean squared error loss from predictions based on individual or mean density change at 1 year. RESULTS: Analysis used mammograms from 126 healthy premenopausal women before and as they received tamoxifen for prevention (median age 42 years) and 172 matched controls (median age 41 years), with median 3 years follow-up. There was a strong correlation between percentage density measures used on the same mammogram in both the tamoxifen and no tamoxifen groups (all correlation coeficients > 0.8). Tamoxifen reduced mean breast density in year 1 by approximately 17-25% of the inter-quartile range of four automated percentage density measures at baseline, and from year 2, it decreased further by approximately 2-7% per year. Predicting change at 2 years using individual change at 1 year was approximately 60-300% worse than using mean change at 1year. CONCLUSIONS: All measures showed a consistent and large average tamoxifen-induced change in density over the first year, and a continued decline thereafter. However, these measures of density change at 1 year were not stable on an individual basis.
Assuntos
Antineoplásicos Hormonais/uso terapêutico , Densidade da Mama/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/prevenção & controle , Mamografia/métodos , Tamoxifeno/uso terapêutico , Adulto , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Estudos de Coortes , Feminino , Predisposição Genética para Doença , Humanos , Pessoa de Meia-Idade , Pré-Menopausa , Fatores de Risco , Fatores de Tempo , Saúde da MulherRESUMO
PURPOSE: We investigated the associations of aspirin and other non-steroid anti-inflammatory drugs with mammographic breast density (MBD) and their interactions in relation to breast cancer risk. METHODS: This study included 3,675 cancer-free women within the Nurses' Health Study (NHS) and Nurses' Health Study II (NHSII) cohorts. Percent breast density (PD), absolute dense area (DA), and non-dense area (NDA) were measured from digitized film mammograms using a computer-assisted thresholding technique; all measures were square root-transformed. Information on medication use was collected in 1980 (NHS) and 1989 (NHSII) and updated biennially. Medication use was defined as none, past or current; average cumulative dose and frequency were calculated for all past or current users from all bi-annual questionnaires preceding the mammogram date. We used generalized linear regression to quantify associations of medications with MBD. Two-way interactions were examined in logistic regression models. RESULTS: In multivariate analysis, none of the anti-inflammatory medications were associated with PD, DA, and NDA. We found no interactions of any of the medications with PD with respect to breast cancer risk (all p-interactions > 0.05). However, some of the aspirin variables appeared to have positive associations with breast cancer risk limited only to women with PD 10-24% (past aspirin OR 1.56, 95% CI 1.03-2.35; current aspirin with < 5 years of use OR 1.82, 95% CI 1.01-3.28; current aspirin with ≥ 5 years of use OR 1.89, 95% CI 1.26-2.82). CONCLUSIONS: Aspirin and NSAIDs are not associated with breast density measures. We found no interactions of aspirin with MBD in relation to breast cancer risk.
Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Aspirina/administração & dosagem , Densidade da Mama/efeitos dos fármacos , Neoplasias da Mama/epidemiologia , Mama/diagnóstico por imagem , Adulto , Mama/citologia , Mama/efeitos dos fármacos , Mama/patologia , Neoplasias da Mama/diagnóstico por imagem , Estudos de Coortes , Feminino , Humanos , Modelos Lineares , Mamografia , Pessoa de Meia-Idade , Análise Multivariada , Risco , Inquéritos e Questionários , Estados Unidos/epidemiologiaRESUMO
Women who carry the BRCA mutation are at high lifetime risk of breast cancer, but there is no consensus regarding an effective and safe chemoprevention strategy. A large body of evidence suggests that 3,3-diindolylmethane (DIM), a dimer of indole-3-carbinol found in cruciferous vegetables, can potentially prevent carcinogenesis and tumor development. The primary aim of this prospective single-arm study was to investigate the effect of DIM supplementation on breast density, a recognized predictive factor of breast cancer risk. Participants were 23 healthy female BRCA carriers (median age 47 years; 78% postmenopausal) who were treated with oral DIM 100 mg × 1/day for 1 year. The amount of fibroglandular tissue (FGT) and background parenchymal enhancement (BPE) on magnetic resonance imaging (MRI) performed before and after the intervention was scored by two independent expert radiologists using the Breast Imaging and Reporting Data System. The results showed a decrease in the average score for FGT amount from 2.8 ± 0.8 at the onset to 2.65 ± 0.84 after 1 year (P = 0.031), with no significant change in BPE (P = 0.429). A group of DIM-untreated age- and menopausal-status-matched women from the BRCA clinic did not show a significant change in FGT amount (P = 0.33) or BPE (P = 0.814) in a parallel year. Mean estradiol level decreased from 159 to 102 pmol/l (P = 0.01), and mean testosterone level decreased from 0.42 to 0.31 pmol/l (P = 0.007). Side effects were grade 1. In conclusion, 1 year's supplementation with DIM 100 mg × 1/day in BRCA carriers was associated with a significant decline in FGT amount on MRI. Larger randomized studies are warranted to corroborate these findings.
Assuntos
Anticarcinógenos/administração & dosagem , Proteína BRCA1/genética , Proteína BRCA2/genética , Densidade da Mama/efeitos dos fármacos , Neoplasias da Mama/genética , Neoplasias da Mama/prevenção & controle , Carcinogênese/efeitos dos fármacos , Indóis/administração & dosagem , Adulto , Idoso , Anticarcinógenos/farmacologia , Feminino , Heterozigoto , Humanos , Indóis/farmacologia , Pessoa de Meia-IdadeRESUMO
INTRODUCTION: Cadmium (Cd) is a heavy metal, which is widespread in the environment and has been hypothesized to be a metalloestrogen and a breast cancer risk factor. Mammographic density (MD) reflects the composition of the breast and was proposed to be used as a surrogate marker for breast cancer. The aim of our study was to investigate association between cadmium concentration in urine and mammographic density. METHODS: A cross-sectional study included 517 women aged 40-60 years who underwent screening mammography in Lódz, Poland. Data were collected through personal interviews and anthropometric measurements. Spot morning urine samples were obtained. The examination of the breasts included both craniocaudal and mediolateral oblique views. Raw data ("for processing") generated by the digital mammography system were analysed using Volpara Imaging Software, The volumetric breast density(%) and fibrograndular tissue volume(cm3) were determined. Cadmium concentration in urine was analysed using the standard ICP-MS method. RESULTS: After adjusting for key confounders including age, BMI, family breast cancer, mammographic device, season of the year of mammography, and age at menarche, an inverse association of Cd and volumetric breast density was found, which was attenuated after further adjustment for smoking. Associations of Cd with dense volume were null. CONCLUSIONS: These findings suggest that Cd is not positively associated with breast density, a strong marker of breast cancer risk, when examined in a cross-sectional fashion.
Assuntos
Densidade da Mama/efeitos dos fármacos , Neoplasias da Mama/etiologia , Cádmio/urina , Mamografia/métodos , Adulto , Neoplasias da Mama/diagnóstico , Cádmio/toxicidade , Estudos Transversais , Feminino , Humanos , Programas de Rastreamento , Pessoa de Meia-Idade , Polônia/epidemiologia , Medição de Risco , Fatores de Risco , SoftwareRESUMO
OBJECTIVES: To investigate the effect of neoadjuvant chemotherapy (NAC) on breast tissue composition with mammographic automated volumetric measurement. METHODS: This retrospective study included 168 breast cancer patients who were treated with NAC and underwent serial mammography (pre-treatment, mid-treatment, and post-treatment) between January 2015 and October 2018. Automated volumetric measurements of the contralateral breast volume (BV), fibroglandular volume (FGV), and breast density (BD) were performed using Volpara software. BD grades were divided into 4 groups by Volpara density grade (VDG). The longitudinal changes in BV, FGV, BD, and their associated factors were evaluated. RESULTS: Repeated-measures analysis of variance demonstrated a significant reduction in BV, FGV, and BD over time (p < 0.001, p < 0.001, and p = 0.002, respectively). BV showed a greater reduction in the second half than in the first half (- 28.6 cm3 vs. - 15.2 cm3), BD showed a greater reduction in the first half than in the second half (- 0.8% vs. - 0.1%), and FGV steadily decreased (- 4.6 cm3 and - 3.9 cm3 in the first and second halves). On multivariable linear regression analysis, chemotherapy regimen was associated with BV change between pre- and post-treatment (p = 0.002); age (p = 0.024) and VDG (p = 0.027) were associated with FGV change; age (p = 0.037), VDG (p = 0.002), and chemotherapy regimen (p = 0.003) were associated with BD change. CONCLUSIONS: NAC affects breast tissue composition, reflected as reductions in BV, FGV, and BD. Mammography with automated volumetric measurement can capture quantitative changes in these breast tissue parameters during NAC. KEY POINTS: ⢠Neoadjuvant chemotherapy (NAC) affects breast tissue composition with different patterns of reduction in breast volume, fibroglandular volume, and breast density. ⢠Age, Volpara density grades, and NAC regimen were independent factors associated with breast density change between pre-treatment and post-treatment. ⢠Mammography with automated volumetric measurement enables identification of longitudinal changes in breast tissue composition.
Assuntos
Neoplasias da Mama/tratamento farmacológico , Mama/efeitos dos fármacos , Quimioterapia Adjuvante , Terapia Neoadjuvante , Adulto , Idoso , Mama/diagnóstico por imagem , Densidade da Mama/efeitos dos fármacos , Feminino , Humanos , Estudos Longitudinais , Mamografia , Pessoa de Meia-Idade , Tamanho do Órgão/efeitos dos fármacos , Análise de Regressão , Estudos Retrospectivos , SoftwareRESUMO
Background: Increased mammographic breast density (MBD) is known to be associated with an increased risk of developing breast cancer.Aims: In this study, we aimed to research the possible relationship between MBD and metformin use in postmenopausal women diagnosed with type 2 diabetes mellitus (T2DM).Method: The patients were divided into two groups: women with T2DM and who were on metformin and women who were newly diagnosed with T2DM and had not yet taken metformin. MBD types are evaluated by a specialist radiologist.Results: Among the 74 women, 32 (43.2%) were in the group that did not use metformin and 42 (56.8%) were in the group of patients using metformin. The duration of breastfeeding (p = .0003), fasting blood glucose (p = .0003) and HbA1c (p = .0006) were statistically significantly higher in the group not using metformin. The quantitative mean ranks of the group members' MBD's were 41.81 in the metformin naïve group and 34.21 in the group using metformin (p = .12).Conclusions: In conclusion, metformin has no statistically significant effect on MBD in postmenopausal female patients with T2DM.
Assuntos
Densidade da Mama/efeitos dos fármacos , Diabetes Mellitus Tipo 2/epidemiologia , Metformina/farmacologia , Pós-Menopausa , Estudos de Casos e Controles , Estudos Transversais , Diabetes Mellitus Tipo 2/diagnóstico por imagem , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/patologia , Feminino , Humanos , Mamografia , Metformina/uso terapêutico , Pessoa de Meia-Idade , Pós-Menopausa/efeitos dos fármacos , Estudos RetrospectivosRESUMO
BACKGROUND: Reduction in breast density may be a biomarker of endocrine therapy (ET) efficacy. Our objective was to assess the impact of race on ET-related changes in volumetric breast density (VBD). METHODS: This retrospective cohort study assessed longitudinal changes in VBD measures in women with estrogen receptor-positive invasive breast cancer treated with ET. VBD, the ratio of fibroglandular volume (FGV) to breast volume (BV), was measured using Volpara software. Changes in measurements were evaluated using a multivariable linear mixed effects model. RESULTS: Compared with white women (n = 191), black women (n = 107) had higher rates of obesity [mean ± SD body mass index (BMI) 34.5 ± 9.1 kg/m2 vs. 30.6 ± 7.0 kg/m2, P < 0.001] and premenopausal status (32.7% vs. 16.7%, P = 0.002). Age- and BMI-adjusted baseline FGV, BV, and VBD were similar between groups. Modeled longitudinal changes were also similar: During a follow-up of 30.7 ± 15.0 months (mean ± SD), FGV decreased over time in premenopausal women (slope = -0.323 cm3; SE = 0.093; P = 0.001), BV increased overall (slope = 2.475 cm3; SE = 0.483; P < 0.0001), and VBD decreased (premenopausal slope = -0.063%, SE = 0.011; postmenopausal slope = -0.016%, SE = 0.004; P < 0.0001). Race was not significantly associated with these longitudinal changes, nor did race modify the effect of time on these changes. Higher BMI was associated with lower baseline VBD (P < 0.0001). Among premenopausal women, VBD declined more steeply for women with lower BMI (time × BMI, P = 0.0098). CONCLUSIONS: Race does not appear to impact ET-related longitudinal changes in VBD. IMPACT: Racial disparities in estrogen receptor-positive breast cancer recurrence and mortality may not be explained by differential declines in breast density due to ET.
Assuntos
Antineoplásicos Hormonais/uso terapêutico , Densidade da Mama/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Recidiva Local de Neoplasia/epidemiologia , Obesidade/epidemiologia , Negro ou Afro-Americano/estatística & dados numéricos , Idoso , Antineoplásicos Hormonais/farmacologia , Índice de Massa Corporal , Mama/diagnóstico por imagem , Mama/efeitos dos fármacos , Mama/patologia , Mama/fisiopatologia , Densidade da Mama/fisiologia , Neoplasias da Mama/patologia , Neoplasias da Mama/fisiopatologia , Feminino , Seguimentos , Disparidades nos Níveis de Saúde , Humanos , Estudos Longitudinais , Mamografia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/fisiopatologia , Receptores de Estrogênio/análise , Receptores de Estrogênio/metabolismo , Estudos Retrospectivos , Resultado do Tratamento , População Branca/estatística & dados numéricosRESUMO
State legislation in many U.S. states, including California, mandates informing women if they have dense breasts on screening mammography, meaning over half of their breast tissue is comprised of non-adipose tissue. Breast density is important to interpret screening sensitivity and is an established breast cancer risk factor. Environmental chemical exposures may play an important role in this, especially during key windows of susceptibility for breast development: in utero, during puberty, pregnancy, lactation, and the peri-menopause. There is a paucity of research, however, examining whether environmental chemical exposures are associated with mammographic breast density, and even less is known about environmental exposures during windows of susceptibility. Now, with clinical breast density scoring being reported routinely for mammograms, it is possible to find out, especially in California, where there are large study populations that can link environmental exposures during windows of susceptibility to breast density. Density scores are now available throughout the state through electronic medical records. We can link these with environmental chemical exposures via state-wide monitoring. Studying the effects of environmental exposure on breast density may provide valuable monitoring and etiologic data to inform strategies to reduce breast cancer risk.